Article

Early Coagulopathy Predicts Mortality in Trauma

Authors:
  • The Karen Hospital / Kenyatta University
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Abstract

Coagulopathy and hemorrhage are known contributors to trauma mortality; however, the actual relationship of prothrombin time (PT) and partial thromboplastin time (PTT) to mortality is unknown. Our objective was to measure the predictive value of the initial coagulopathy profile for trauma-related mortality. We reviewed prospectively collected data on trauma patients presenting to a Level I trauma center. A logistic regression analysis was performed of PT, PTT, platelet count, and confounders to determine whether coagulopathy is a predictor of all-cause mortality. From a trauma registry cohort of 20103 patients, 14397 had complete disposition data for initial analysis and 7638 had complete data for all variables in the final analysis. The total cohort was 76.2% male, the mean age was 38 years (range, 1-108 years), and the median Injury Severity Score was 9. There were 1276 deaths (all-cause mortality, 8.9%). The prevalence of coagulopathy early in the postinjury period was substantial, with 28% of patients having an abnormal PT (2994 of 10790) and 8% of patients having an abnormal PTT (826 of 10453) on arrival at the trauma bay. In patients with disposition data and a normal PT, 489 of 7796 died, as compared with 579 of 2994 with an abnormal PT (6.3% vs. 19.3%; chi2 = 414.1, p < 0.001). Univariate analysis generated an odds ratio of 3.6 (95% confidence interval [CI], 3.15-4.08; p < 0.0001) for death with abnormal PT and 7.81 (95% CI, 6.65-9.17; p < 0.001) for deaths with an abnormal PTT. The PT and PTT remained independent predictors of mortality in a multiple regression model, whereas platelet count did not. The model also included the independent risk factors age, Injury Severity Score, scene and trauma-bay blood pressure, hematocrit, base deficit, and head injury. The model generated an adjusted odds ratio of 1.35 for PT (95% CI, 1.11-1.68; p < 0.001) and 4.26 for PTT (95% CI, 3.23-5.63; p < 0.001). The incidence of coagulation abnormalities, early after trauma, is high and they are independent predictors of mortality even in the presence of other risk factors. An initial abnormal PT increases the adjusted odds of dying by 35% and an initial abnormal PTT increases the adjusted odds of dying by 326%.

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... been identified as a significant risk factor for mortality in trauma patients (5,6). Therefore, managing coagulation defects has become a leading issue in trauma, and the latest guidelines recommend hemostatic resuscitation (7). ...
... The median age was 14 years (9-16 yr), and most of patients were male (68.6%; n = 639). Most injuries were related to a road collision (70.2%; n = 656) ( The median ISS was significantly higher in the TXA group (14 [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] vs 6 [2][3][4][5][6][7][8][9][10][11][12][13]; p < 0.001), and severe injuries (AIS ≥ 3) were more frequent in the TXA group in all body regions (limbs/hip 40.1% vs 13.1%; thorax 30.4% vs 17.5%; head 25.7% vs 14.9%; abdomen 16% vs 6.4%; p < 0.001). Overall mortality was 3.1% (n = 25). ...
... Among patients with no criteria for appropriate TXA use, 19.5% yet received a loading dose (Table 3). Within the group of patients presenting with appropriate TXA use criteria, those who did not receive TXA were younger (13 [8][9][10][11][12][13][14][15][16] vs 16 yr [13-17 yr]; p < 0.001) and had a lower ISS (14 [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] vs 17 [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]; p < 0.001) compared with those who did. There was no significant difference in terms of sex (p = 0.12), type of trauma (p = 0.39), or trauma mechanism (p = 0.08). ...
Article
Objectives: Describe prehospital tranexamic acid (TXA) use and appropriateness within a major trauma pediatric population, and identify the factors associated with its use. Design: Multicenter, retrospective study, 2014-2020. Setting: Data were extracted from a multicenter French trauma registry including nine trauma centers within a physician-led prehospital emergency medical services (EMS) system. Patients: Patients less than 18 years old were included. Those who did not receive prehospital intervention by a mobile medical team and those with missing data on TXA administration were excluded. Interventions: None. Measurements and main results: Nine-hundred thirty-four patients (median [interquartile range] age: 14 yr [9-16 yr]) were included, and 68.6% n = 639) were male. Most patients were involved in a road collision (70.2%, n = 656) and suffered a blunt trauma (96.5%; n = 900). Patients receiving TXA (36.6%; n = 342) were older (15 [13-17] vs 12 yr [6-16 yr]) compared with those who did not. Patient severity was higher in the TXA group (Injury Severity Score 14 [9-25] vs 6 [2-13]; p < 0.001). The median dosage was 16 mg/kg (13-19 mg/kg). TXA administration was found in 51.8% cases (n = 256) among patients with criteria for appropriate use. Conversely, 32.4% of patients (n = 11) with an isolated severe traumatic brain injury (TBI) also received TXA. Age (odds ratio [OR], 1.2; 95% CI, 1.1-1.2), A and B prehospital severity grade (OR, 7.1; 95% CI, 4.1-12.3 and OR, 4.5; 95% CI, 2.9-6.9 respectively), and year of inclusion (OR, 1.2; 95% CI, 1.1-1.3) were associated with prehospital TXA administration. Conclusions: In our physician-led prehospital EMS system, TXA is used in a third of severely injured children despite the lack of high-level of evidence. Only half of the population with greater than or equal to one criteria for appropriate TXA use received it. Conversely, TXA was administered in a third of isolated severe TBI. Further research is warranted to clarify TXA indications and to evaluate its impact on mortality and its safety profile to oversee its prescription.
... [4][5][6][7][8] This is essentially important because several previous studies reported TIC to be associated with 4-to 6-fold higher mortality. 4,[9][10][11][12][13] Another important death-related factor in hemorrhaging patients is time, including time to hemostasis, time-totreat, and time to activation of a massive transfusion protocol (MTP). 14 Therefore, a rapid and reliable method is needed that can detect and correct TIC during efforts to achieve surgical control at the bleeding site. ...
... Improved understanding of the pathophysiology of TIC has improved DCR in trauma patients. 2,[4][5][6]9,10,19 The incidence of TIC was reported to range from 25% to 35% in civilian and military trauma-related bleeding patients. 4,9 Prior to the introduction of VHA-guided therapy, CCT was used for coagulation-guided therapy in patients with TIC; however, these tests are time-consuming and they are limited in their ability to dynamically assess the coagulation cascade. ...
... 2,[4][5][6]9,10,19 The incidence of TIC was reported to range from 25% to 35% in civilian and military trauma-related bleeding patients. 4,9 Prior to the introduction of VHA-guided therapy, CCT was used for coagulation-guided therapy in patients with TIC; however, these tests are time-consuming and they are limited in their ability to dynamically assess the coagulation cascade. 3,19,28 VHA as a POCT for coagulation assessment was implemented in many countries to overcome these limitations. ...
Article
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Objective: To evaluate the effectiveness of viscoelastic hemostatic assay (VHA)-guided therapy for assessing and managing trauma-related bleeding using a multidisciplinary team approach at a level 1 trauma center. Materials and Methods: This retrospective pilot study included trauma-related hemorrhagic patients who underwent rotational thromboelastometry (ROTEM) during September 2019-May 2020. ROTEM trace results were compared with those of conventional coagulation tests (CCT). Results: Thirteen patients (median age: 29.1 years; male: 76.92%) were included. The median (range) days of ventilator support, ICU length of stay, and hospital length of stay was 4 [0-65], 5 [1-65], and 6 [1-83], respectively. ROTEM-guided therapy was applied 26 times, and was repeated in 7 cases. Of those, four cases were repeated to correct coagulopathy. The median time-to-confirmed hemostasis for ROTEM was substantially shorter than for CCT (92 minutes [70-110] vs. 287 minutes [204-354], respectively). The coagulation results from 26 ROTEM tests were also compared between those requiring and not requiring a massive transfusion protocol (MTP). MTP with ROTEM-guided therapy was activated in 6/13 cases. Following the resuscitation endpoints in traumatic shock, four of those had their median serum lactate levels decreased from 10.9 d/L (2.1-16.8) to 3.9 d/L (1.7-17.7). ROTEM traces detected cases with low fibrinogen that only required cryoprecipitate transfusion, and red blood cell and fresh frozen plasma use was less in ROTEM than in conventional MTP. Conclusion: VHA-guided therapy was shown to effectively facilitate goal-directed hemostatic resuscitation and efficient blood product use during resuscitation, definitive treatment, and postoperative intensive care.
... However, another study showed that TBI may lead to hyperfibrinolysis under specific conditions [30]. Therefore, coagulopathy associated with extracranial injuries is primarily caused by substantial blood loss (hemorrhagic shock), consumption, hypothermia, and hypoperfusion-induced metabolic acidosis, which can be further propagated by iatrogenic factors, such as fluid resuscitation (hemodilution) [32,33]. Hyperfibrinolysis appears to be closely associated with lethal hemorrhagic shock and is relatively independent of injury severity, which was corroborated in an animal model where isolated hemorrhagic shock induced tissue plasminogen activatormediated hyperfibrinolysis, whereas isolated tissue injury reduced fibrinolytic activity [34,35]. ...
Article
Full-text available
Objective Tranexamic acid (TXA) plays a significant role in the treatment of traumatic diseases. However, its effectiveness in patients with traumatic brain injury (TBI) seems to be contradictory, according to the recent publication of several meta-analyses. We aimed to determine the efficacy of TXA treatment at different times and doses for TBI treatment. Methods PubMed, MEDLINE, EMBASE, Cochrane Library, and Google Scholar were searched for randomized controlled trials that compared TXA and a placebo in adults and adolescents (≥ 15 years of age) with TBI up to January 31, 2022. Two authors independently abstracted the data and assessed the quality of evidence. Results Of the identified 673 studies, 13 involving 18,675 patients met our inclusion criteria. TXA had no effect on mortality (risk ratio (RR) 0.99; 95% confidence interval (CI) 0.92–1.06), adverse events (RR 0.93, 95% Cl 0.76–1.14), severe TBI (Glasgow Coma Scale score from 3 to 8) (RR 0.99, 95% Cl 0.94–1.05), unfavorable Glasgow Outcome Scale (GOS < 4) (RR 0.96, 95% Cl 0.82–1.11), neurosurgical intervention (RR 1.11, 95% Cl 0.89–1.38), or rebleeding (RR 0.97, 95% Cl 0.82–1.16). TXA might reduce the mean hemorrhage volume on subsequent imaging (standardized mean difference, -0.35; 95% CI [-0.62, -0.08]). Conclusion TXA at different times and doses was associated with reduced mean bleeding but not with mortality, adverse events, neurosurgical intervention, and rebleeding. More research data is needed on different detection indexes and levels of TXA in patients with TBI, as compared to those not receiving TXA; although the prognostic outcome for all harm outcomes was not affected, the potential for harm was not ruled out. Trial registration The review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42022300484).
... Coagulopathy frequently occurs early in the postinjury period and is an independent predictor of mortality. Compared to patients whose initial prothrombin time (PT) and activated partial thromboplastin time (aPTT) are normal, trauma patients have 35% and 326% increased risk of mortality when their initial PT and aPTT are abnormal, respectively [19]. It is important to emphasize that trauma-induced coagulopathy, also called acute traumatic coagulopathy, is distinct from massive transfusion coagulopathy that occurs in the context of loss and dilution coagulopathy [20,21] or disseminated intravascular coagulation [22]. ...
Article
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The lectin complement pathway (LP) is an important effector arm of innate immunity and exemplary pattern recognition artist that draws a fine line between friend and foe (host defense) and between innocuous and noxious (homeostasis). Intriguingly , the proteolytic activity of the LP is attributed to proteolytic enzymes, called mannan-binding lectin (MBL)-associated ser-ine proteases (MASPs). MASPs are central components of the LP that resemble the serine proteases, C1r and C1s, of the classical complement pathway (CP). Recently, the MASPs' important role in the coagulation cascade was unmasked by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [1-6]. MASPs (mainly MASP-1) are actually key elements that connect both complement and coagulation systems [7]. So far, research into complement-coagulation interactions focusing merely on MASP inhibition had offered promising targets for novel preventive and therapeutic strategies [8]. Conversely , here I propose that the fibrinolytic activity of MASPs can be explored in the management of bleeding disorders.
... Sammy et al., in a meta-analysis of the published literature, found that while multiple factors affect the mortality of older patients, demographics (age and gender), pre-existing comorbidities and injury severity and mechanism were significantly predictive of death [12]. A second systematic review conducted by Hashmi et al. concluded that overall mortality in geriatric trauma patients increases with age, with the 74 and older age group having twice the odds of mortality as compared to those in 65-74 age range; other studies had similar findings [13][14][15][16][17][18].Anemia, too, has been implicated as yet another risk factor for mortality [4]. Although these studies included all the mechanisms and levels of severity of injury in the older patients, our results are in agreement with their analysis as older age (75-85), higher ISS and having more than one comorbidity were associated with death in our study. ...
Article
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Background: In geriatric trauma patients, higher mortality rate is observed compared to younger patients. A significant portion of trauma sustained by this age group comes from low-energy mechanisms (fall from standing or sitting). We sought to investigate the outcome of these patients and identify factors associated with mortality. Methods: A retrospective review of 1285 geriatric trauma patients who came to our level 1 trauma center for trauma activation (hospital alert to mobilize surgical trauma service, emergency department trauma team, nursing, and ancillary staff for highest level of critical care) after sustaining low-energy blunt trauma over a 1-year period. IRB approval was obtained, data collected included demographics, vital signs, laboratory data, injuries sustained, length of stay and outcomes. Patients were divided into three age categories: 65–74, 75–84 and >85. Comorbidities collected included a history of chronic renal failure, COPD, Hypertension and Myocardial Infarction. Results: 1285 geriatric patients (age > 65 years) presented to our level 1 trauma center for trauma activation with a low-energy blunt trauma during the study period; 34.8% of the patients were men, 20.5% had at least one comorbidity, and 89.6% were white. Median LOS was 5 days; 37 (2.9%) patients died. Age of 85 and over (OR 3.44 with 95% CI 1.01–11.7 and 2.85 with 95% CI 1.0–6.76, when compared to 65–74 and 75–84, respectively), injury severity score (ISS) (OR 1.08, 95% CI 1.02 to 1.15) and the presence of more than one comorbidity (OR 2.68, 95% CI 1.26 to 5.68) were independently predictive of death on multi-variable logistic regression analysis. Conclusion: Age more than 85 years, higher injury severity score and the presence of more than one comorbidity are independent predictors of mortality among geriatric patients presenting with low-energy blunt trauma.
... 13,14) It has been previously reported that abnormalities in select parameters, including platelet count, prothrombin time (PT), active partial thromboplastin time (APTT), and fibrinogen, fibrinogen/fibrin degradation product (FDP), and D-dimer levels are predictors of poor prognosis in TBI patients. [15][16][17][18] However, although coagulation and fibrinolytic parameters change during the acute phase of TBI, most studies have reported a combination of early and delayed coagulopathy. 19 at 3 months after injury) outcomes and found that it was significantly higher in the poor than in the good outcome cases from admission to 3, 6, and 12 h after injury (Fig. 3). ...
Article
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Coagulopathy, a common complication of traumatic brain injury (TBI), is characterized by a hypercoagulable state developing immediately after injury, with hyperfibrinolysis and bleeding tendency peaking 3 h after injury, followed by fibrinolysis shutdown. Reflecting this timeframe, the coagulation factor fibrinogen is first consumed and then degraded after TBI, its concentration rapidly decreasing by 3 h post-TBI. The fibrinolytic marker D-dimer reaches its maximum concentration at the same time. Hyperfibrinolysis in the acute phase of TBI is associated with poor prognosis via hematoma expansion. In the acute phase, the coagulation and fibrinolysis parameters must be monitored to determine the treatment strategy. The combination of D-dimer plasma level at admission and the level of consciousness upon arrival at the hospital can be used to predict the patients who will "talk and deteriorate." Fibrinogen and D-dimer levels should determine case selection and the amount of fresh frozen plasma required for transfusion. Surgery around 3 h after injury, when fibrinolysis and bleeding diathesis peak, should be avoided if possible. In recent years, attempts have been made to estimate the time of injury from the time course of coagulation and fibrinolysis parameter levels, which has been particularly useful in some cases of pediatric abusive head trauma patients. Fullsize Image
... TIC is a multi-phenotypic disease state that comprises disorders of coagulation and inflammation, and describes the overall failure of the coagulation system to maintain haemostasis after major injury. TIC is associated with significantly poorer outcomes, including increased need for massive transfusion and development of organ failure and a 3-fourfold increased risk of death [13][14][15][16]. ...
Article
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Background Fibrinogen is the first coagulation protein to reach critical levels during traumatic haemorrhage. This laboratory study compares paired plasma samples pre- and post-fibrinogen replacement from the Fibrinogen Early In Severe Trauma studY (FEISTY; NCT02745041). FEISTY is the first randomised controlled trial to compare the time to administration of cryoprecipitate (cryo) and fibrinogen concentrate (Fg-C; Riastap) in trauma patients. This study will determine differences in clot strength and fibrinolytic stability within individuals and between treatment arms. Methods Clot lysis, plasmin generation, atomic force microscopy and confocal microscopy were utilised to investigate clot strength and structure in FEISTY patient plasma. Results Fibrinogen concentration was significantly increased post-transfusion in both groups. The rate of plasmin generation was reduced 1.5-fold post-transfusion of cryo but remained unchanged with Fg-C transfusion. Plasminogen activator inhibitor 1 activity and antigen levels and Factor XIII antigen were increased post-treatment with cryo, but not Fg-C. Confocal microscopy analysis of fibrin clots revealed that cryo transfusion restored fibrin structure similar to those observed in control clots. In contrast, clots remained porous with stunted fibres after infusion with Fg-C. Cryo but not Fg-C treatment increased individual fibre toughness and stiffness. Conclusions In summary, our data indicate that cryo transfusion restores key fibrinolytic regulators and limits plasmin generation to form stronger clots in an ex vivo laboratory study. This is the first study to investigate differences in clot stability and structure between cryo and Fg-C and demonstrates that the additional factors in cryo allow formation of a stronger and more stable clot.
... Furthermore, they significantly influence coagulation after severe trauma [24]. The incidence of coagulation disorders after trauma is high and is considered an independent predictor of mortality [25]. Even mildly diminished platelet activation seems to be a sign of coagulopathy associated with increased mortality in trauma patients [26]. ...
Article
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Background: Accidents and injuries are the leading causes of mortality in young people. CD4+ regulatory T cells (CD4+ Tregs), Th17 cells and platelets could be identified as key players in post-traumatic immunological dysfunction, which is a common cause of late mortality in trauma patients. The mechanisms of activation of these cell types and their interaction remain mostly unclear. Since CD69 is not only a leukocyte marker but has also immunoregulatory functions, we postulate a role for CD69 after trauma. The present study investigates the expression of CD69 on CD4+ Tregs and Th17 cells, as well as the posttraumatic expansion of platelets and hemostatic function. Subgroup analysis was performed to assess the differences between polytrauma patients with and without severe traumatic brain injury (TBI). Methods: In this non-interventional prospective clinical trial, we analyzed sequential blood samples over a period of 10 days from 30 patients after multiple traumas with an ISS ≥ 16. Platelet function was assessed by rotational thromboelastometry (ROTEM analysis). CD4+ Tregs and Th17 cells were stained with surface markers and analyzed by flow cytometry. Results: We were able to demonstrate a significantly increased expression of CD69 on CD4+ Tregs after trauma. Subgroup analysis revealed that the absence of severe TBI is associated with a significantly higher expression of CD69 on CD4+ Tregs and on Th17 cells. Platelets expanded and showed signs of dysfunction, while an overall tendency of posttraumatic hypercoagulation was detected. Conclusions: Our results support the concept of injury-specific immune responses and add to a further understanding of the complex pathophysiology of post-traumatic immune dysfunction.
... Low levels of coagulation factors, as seen by longer global coagulation times, may also be a risk factor for bleeding and mortality in patients with sepsis. In critically unwell patients, a prothrombin time or partial thromboplastin time ratio of 1.5 was observed to predict severe bleeding and higher death 34,35 . ...
Article
Despite advances in antibiotic treatment, mechanical ventilation, fluid resuscitation, and blood glucose control, sepsis continues to be a leading cause of death in critical care units. To present, no effective treatment regimens for the routine management of septic patients exist. The core pathophysiology of sepsis is influenced by the substantial interaction between inflammation and coagulation. As a result, medicines that reduce the activation of both inflammation and coagulation may help to improve sepsis outcomes. Heparin, in addition to its well-known anticoagulant properties, also has immunomodulatory capabilities and prevents glycocalyx from shedding. As a result, heparin appears to be such an agent. Anticoagulant therapy should be given at the right time, as immunothrombosis plays an important role in the initial host defense against bacterial growth. We explore the scientific and clinical evidence that supports the use of heparin in sepsis. Heparin's usage in the treatment of sepsis is currently debatable. Future heparin treatment trials for sepsis should focus on the most critically ill subjects, where benefit is most likely to be shown.
... In patients with severe trauma, the process of coagulopathy begins within a few minutes after injury, and previous studies reported 25-35% of trauma patients had already developed coagulopathy on hospital arrival [4][5][6]. Coagulopathy can result in increased transfusion volume and mortality [7]. ...
Article
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Background: We aimed to examine the association of pelvic fracture sites with the minimum fibrinogen level within 24 h after hospital arrival. Methods: We conducted a single-center cohort study using health records review. We included patients with pelvic fractures transported by ambulance to a tertiary-care hospital from January 2012 to December 2018 and excluded those transported from other hospitals or aged younger than 16 years. The pelvic fracture was diagnosed and confirmed by trauma surgeons and/or radiologists. We classified the fracture sites of the pelvis as ilium, pubis, ischium, acetabulum, sacrum, sacroiliac joint diastasis, and pubic symphysis diastasis, and each side was counted separately except for pubic symphysis diastasis. We performed linear regression analysis to evaluate the association between pelvic fracture sites and the minimum fibrinogen level within 24 h of arrival. Results: We analyzed 120 pelvic fracture patients. Their mean age was 47.3 years, and 69 (57.5%) patients were men. The median Injury Severity Score was 24, and in-hospital mortality was 10.8%. The mean minimum fibrinogen level within 24 h of arrival was 171.4 mg/dL. Among pelvic fracture sites, only sacrum fracture was statistically significantly associated with the minimum fibrinogen level within 24 h of arrival (estimate, -34.5; 95% CI, -58.6 to -10.4; p = 0.005). Conclusions: Fracture of the sacrum in patients with pelvic fracture was associated with lower minimum fibrinogen levels within 24 h of hospital arrival and the requirement of blood transfusion.
... Trauma-induced coagulopathy (TIC) develops in approximately one-quarter to one-third of severely injured and hemorrhaging trauma patients [3]. Importantly, these patients suffer from worse outcomes including a lower likelihood of survival [4][5][6][7]. Mechanistically, evidence supports that TIC is a multi-factorial failure in vascular homeostasis generally characterized by an early hypocoagulable state contributing to ongoing hemorrhage, followed by a later hypercoagulable and hyperinflammatory state predisposing survivors to thromboembolic complications and organ failure [8••, 9, 10]. Although TIC is often exacerbated by concomitant dilutional and consumptive coagulopathy, TIC develops prior to resuscitative efforts and is characterized by a spectrum of adaptive and maladaptive alterations to clot formation and breakdown and cellular behavior, including that of platelets [11]. ...
Article
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Purpose of Review To review the role of platelet transfusion in resuscitation for trauma, including normal platelet function and alterations in behavior following trauma, blood product transfusion ratios and the impact of platelet transfusion on platelet function, platelet function assays, risks of platelet transfusion and considerations for platelet storage, and potential adjunct therapies and synthetic platelets. Recent Findings Platelets are a critical component of clot formation and breakdown following injury, and in addition to these hemostatic properties, have a complex role in vascular homeostasis, inflammation, and immune function. Evidence supports that platelets are activated following trauma with several upregulated functions, but under conditions of severe injury and shock are found to be impaired in their hemostatic behaviors. Platelets should be transfused in balanced ratios with red blood cells and plasma during initial trauma resuscitation as this portends improved outcomes including survival. Multiple coagulation assays can be used for goal-directed resuscitation for traumatic hemorrhage; however, these assays each have drawbacks in terms of their ability to measure platelet function. While resuscitation with balanced transfusion ratios is supported by the literature, platelet transfusion carries its own risks such as bacterial infection and lung injury. Platelet supply is also limited, with resource-intensive storage requirements, making exploration of longer-term storage options and novel platelet-based therapeutics attractive. Future focus on a deeper understanding of the biology of platelets following trauma, and on optimization of novel platelet-based therapeutics to maintain hemostatic effects while improving availability should be pursued. Summary While platelet function is altered following trauma, platelets should be transfused in balanced ratios during initial resuscitation. Severe injury and shock can impair platelet function, which can persist for several days following the initial trauma. Assays to guide resuscitation following the initial period as well as storage techniques to extend platelet shelf life are important areas of investigation.
... In our study, coagulopathy significantly increased mortality in patients emergently admitted with blunt chest wall trauma. This finding is supported by Macleod et al., who conducted a retrospective trauma study including greater than 10,000 patients that showed that prothrombin time and partial thromboplastin time independently predicted all-cause mortality [45]. Floccard et al. elucidated the pathogenic mechanisms involved in traumainduced coagulopathy as demonstrated by reductions in protein C activity and factor V early after injury [46]. ...
Article
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Background: Blunt thoracic trauma is responsible for 35% of trauma-related deaths in the United States and significantly contributes to morbidity and healthcare-related financial strain. The goal of this study was to evaluate factors influencing mortality in patients emergently admitted with the primary diagnosis of blunt chest wall trauma. Methods: Adults emergently admitted for blunt chest trauma were assessed using the National Inpatient Sample Database, 2004–2014. Data regarding demographics, comorbidities, and outcomes were collected. Relationships were determined using univariable and multivariable logistic regression models. Results: In total, 1120 adult and 1038 elderly patients emergently admitted with blunt chest trauma were assessed; 46.3% were female, and 53.6% were male. The average ages of adult and elderly patients were 46.6 and 78.9 years, respectively. Elderly and adult patients both displayed mortality rates of 1%. The regression model showed HLOS and several comorbidities as the main risk factors of mortality Every additional day of hospitalization increased the odds of mortality by 9% (OR = 1.09, 95% CI = 1.01–1.18, p = 0.033). Mortality and liver disease were significantly associated (OR = 8.36, 95% CI = 2.23–31.37, p = 0.002). Respiratory disease and mortality rates demonstrated robust correlations (OR = 7.46, 95% CI = 1.63–34.11, p = 0.010). Trauma, burns, and poisons were associated with increased mortality (OR = 3.72, 95% CI = 1.18–11.71, p = 0.025). The presence of platelet/white blood cell disease correlated to higher mortality. (OR = 4.42, 95% CI = 1.09–17.91, p = 0.038).
... An estimated, 25% of severely injured patients arrive in emergency departments with trauma-induced coagulopathy (TIC) [1]; this relatively high incidence of acute hypocoagulopathy in trauma patients has driven an expanded investigation into the use of VHAs. TIC has been reported to be an independent predictor of mortality [2], as well as a risk factor for multisystem organ failure and higher transfusion requirements [3][4][5]. Given the point-of-care nature and fast turn-around time for results, many trauma centers consider VHAs as the standard of care for all severely injured trauma patients on arrival to an emergency department and/or trauma center. ...
Article
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The application of viscoelastic hemostatic assays (VHAs) (e.g., thromboelastography (TEG) and rotational thromboelastometry (ROTEM)) in orthopedics is in its relative infancy when compared with other surgical fields. Fortunately, several recent studies describe the emerging use of VHAs to quickly and reliably analyze the real-time coagulation and fibrinolytic status in both orthopedic trauma and elective orthopedic surgery. Trauma-induced coagulopathy—a spectrum of abnormal coagulation phenotypes including clotting factor depletion, inadequate thrombin generation, platelet dysfunction, and dysregulated fibrinolysis—remains a potentially fatal complication in severely injured and/or hemorrhaging patients whose timely diagnosis and management are aided by the use of VHAs. Furthermore, VHAs are an invaluable compliment to common coagulation tests by facilitating the detection of hypercoagulable states commonly associated with orthopedic injury and postoperative status. The use of VHAs to identify hypercoagulability allows for an accurate venous thromboembolism (VTE) risk assessment and monitoring of VTE prophylaxis. Until now, the data have been insufficient to permit an individualized approach with regard to dosing and duration for VTE thromboprophylaxis. By incorporating VHAs into routine practice, orthopedic surgeons will be better equipped to diagnose and treat the complete spectrum of coagulation abnormalities faced by orthopedic patients. This work serves as an educational primer and up-to-date review of the current literature on the use of VHAs in orthopedic surgery.
... Mortality was also higher in coagulopathic patients, especially in patients with more severe injuries (i.e., ISS > 45) [9]. Similarly, McLeod et al. demonstrated that abnormal conventional coagulation tests (CCTs), such as PT and PTT, predicted mortality after adjusting for older age, ISS, base deficit, admission systolic blood pressure, and neurologic examination/severity of head injury [10]. Traumatic coagulopathy was therefore recognized as an integral component of the pathophysiology in severely injured and bleeding patients. ...
Article
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Purpose of Review Coagulopathy is present in nearly 25% of severely injured patients and increases significantly with administration of massive transfusion of blood products. The cell-based model of hemostasis provides a background on which the current understanding of Acute Traumatic Coagulopathy (ATC) is managed. Recent Findings Viscoelastic Hemostatic Assays (VHAs) generate results that identify severely injured trauma patients at risk for large-volume blood transfusion, coagulation deficiencies, and increased mortality that are available more quickly than Conventional Coagulation Tests (CCTs). Viscoelastic-guided resuscitation during hemorrhage was recently described and demonstrated no difference in 24-h survival and free of massive transfusion. Summary VHAs are potentially valuable in early detection of patients at risk for massive resuscitation and severe coagulopathy. This review will address the ACT, clinical data supporting VHA utilization in trauma patients, and limitations in scientific knowledge of viscoelastic testing.
... 1,7) Previous studies have reported abnormalities in various parameters such as platelet count, PT, APTT, plasma fibrinogen levels, FDP, and D-dimer as predictors of poor outcome in patients with TBI. 4,[28][29][30] However, although coagulation and fibrinolytic parameters change dynamically during the acute phase of TBI, most studies have shown a mixture of early and delayed coagulopathy in TBI. 31) In a study by Nakae et al. 20) of isolated adult TBI patients within 1 h of injury, among coagulation and fibrinolysis parameters, a high D-dimer level was an independent risk factor for poor prognosis at all time points from admission to 12 h after injury. ...
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Coagulopathy is a common sequela of traumatic brain injury. Consumptive coagulopathy and secondary hyperfibrinolysis are associated with hypercoagulability. In addition, fibrinolytic pathways are hyperactivated as a result of vascular endothelial cell damage in the injured brain. Coagulation and fibrinolytic parameters change dynamically to reflect these pathologies. Fibrinogen is consumed and degraded after injury, with fibrinogen concentrations at their lowest 3-6 h after injury. Hypercoagulability causes increased fibrinolytic activity, and plasma levels of D-dimer increase immediately after traumatic brain injury, reaching a maximum at 3 h. Owing to disseminated intravascular coagulation in the presence of fibrinolysis, the bleeding tendency is highest within the first 3 h after injury, and often a condition called "talk and deteriorate" occurs. In neurointensive care, it is necessary to measure coagulation and fibrinolytic parameters such as fibrinogen and D-dimer routinely to predict and prevent the development of coagulopathy and its negative outcomes. Currently, the only evidence-based treatment for traumatic brain injury with coagulopathy is tranexamic acid in the subset of patients with mild-to-moderate traumatic brain injury. Coagulation and fibrinolytic parameters should be closely monitored, and treatment should be considered on a patient-by-patient basis.
... Most of these coagulation biomarkers have been related to a worse prognosis: thrombomodulin [111,112], plasminogen activator inhibitor 1 [113], vWf [114][115][116], ADAMTS-13 [116][117][118], and thrombocytopenia [119,120]. A prolonged coagulation time is frequent in critically ill patients, and prothrombin time and activated partial thromboplastin time have been found to be predictors of sepsis and mortality [107,121]. Hemolysis (free hemoglobin) [122] and D-dimers (excessive coagulation activation) [107,123] have also been demonstrated as survival predictors. Scoring systems such as sepsis-induced coagulopathy [124] and Overt-DIC scoring systems [125] have been described to predict coagulopathy in patients with associated disorders. ...
Article
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The pathophysiology of sepsis alters drug pharmacokinetics, resulting in inadequate drug exposure and target-site concentration. Suboptimal exposure leads to treatment failure and the development of antimicrobial resistance. Therefore, we seek to optimize antimicrobial therapy in sepsis by selecting the right drug and the correct dosage. A prerequisite for achieving this goal is characterization and understanding of the mechanisms of pharmacokinetic alterations. However, most infections take place not in blood but in different body compartments. Since tissue pharmacokinetic assessment is not feasible in daily practice, we need to tailor antibiotic treatment according to the specific patient’s pathophysiological processes. The complex pathophysiology of sepsis and the ineffectiveness of current targeted therapies suggest that treatments guided by biomarkers predicting target-site concentration could provide a new therapeutic strategy. Inflammation, endothelial and coagulation activation markers, and blood flow parameters might be indicators of impaired tissue distribution. Moreover, hepatic and renal dysfunction biomarkers can predict not only drug metabolism and clearance but also drug distribution. Identification of the right biomarkers can direct drug dosing and provide timely feedback on its effectiveness. Therefore, this might decrease antibiotic resistance and the mortality of critically ill patients. This article fills the literature gap by characterizing patient biomarkers that might be used to predict unbound plasma-to-tissue drug distribution in critically ill patients. Although all biomarkers must be clinically evaluated with the ultimate goal of combining them in a clinically feasible scoring system, we support the concept that the appropriate biomarkers could be used to direct targeted antibiotic dosing.Graphical Abstract ADAMTS-13 a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13, ALAT alanine amino transferase, APACHE IV Acute Physiology and Chronic Health Evaluation-IV, aPPT activated partial thromboplastin time, ASAT aspartate amino transferase, AT antithrombin, Ca-V-O2 oxygen content difference, arterial-venous, CRP C-reactive protein, ELAM endothelial leukocyte adhesion molecule, ICAM intercellular adhesion molecule, IL interleukin, INR international normalized ratio, LBP lipopolysaccharide-binding protein, MCP monocyte chemoattractant protein, mHLA monocytic human leukocyte antigen, MIF migration inhibitory factor, MIP macrophage inflammatory protein, PAI plasminogen activator inhibitor, PCO2 partial pressure of carbon dioxide, PT prothrombin time, RRT renal replacement therapy, SAPSS III Simplified Acute Physiology Score-III, sO2 oxygen saturation, SOFA Sequential [Sepsis-related] Organ Failure Assessment, sTREM soluble triggering receptor expressed on myeloid cells 1, TLR toll-like receptor, TNF tumor necrosis factor, VCAM vascular cell adhesion molecule, VEGF vascular endothelial growth factor, vWf von Willebrand factor
... Coagulopathy is a bleeding disorder that impairs clot formation, causing excessive bleeding and leading to life-threatening events [1,2]. Several factors contribute to this hypocoagulability, including coagulation factor inhibition, platelet dysfunction, fibrinogen consumption, and hyperfibrino(geno)lysis [3][4][5][6]. Among those causes, inflammation through endothelial and immune system activation is presumed to be a key initiator that contributes to the underlying mechanism of both sepsis-induced and trauma-induced coagulopathy (TIC) [5][6][7][8][9][10]. ...
Article
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Critical illness leads to rapid fibrinogen consumption, hyperfibrinolysis, and coagulopathy that exacerbates bleeding and increases mortality. Immune cell activation and inflammation are associated with coagulopathy after injury but play an undetermined role. We performed high dimensional immunophenotyping and single-cell imaging flow cytometry to look for a pathophysiological mechanism governing the effects of leukocyte-associated inflammation on fibrinogen function. Fibrinogen was oxidized early, followed by its degradation after 3 h of lipopolysaccharides (LPS)-induced sterile inflammation in a rat model in vivo. Fibrinogen incubated with human leukocytes activated by TNFα was similarly oxidized, and later proteolyzed after 3 h in vitro. TNFα induced mitochondrial superoxide generation from neutrophils and monocytes, myeloperoxidase (MPO)-derived reactive oxygen species (ROS) from neutrophils, and nitric oxide from lymphocytes and monocytes. Inhibition of mitochondrial superoxide prevented oxidative modification and proteolysis of fibrinogen, whereas inhibition of MPO attenuated only fibrinogen proteolysis. Quenching of both mitochondrial superoxide and MPO-derived ROS prevented coagulopathy better than tranexamic acid. Collectively, these findings indicate that neutrophil and monocyte mitochondrial superoxide generation can rapidly oxidize fibrinogen as a priming step for fibrinogen proteolysis and coagulopathy during inflammation.
... There is a developing interest in using VHAs to aid in goal-directed BCT of the bleeding trauma patient as close to the scene of injury as possible, whether that injury occurred in the far-forward combat area, or the civilian austere or urban environments [44,45]. Incidence of TIC has been reported in 24-36% of all trauma admissions to the emergency department, further increasing the importance and usability of POC VHAs in prehospital environments for improved results upon arrival [46][47][48][49][50]. The use of versatile and portable VHAs in the urban environment have been increasingly adopted for the immediate use in trauma resuscitation scenes and in studies concerning prehospital resuscitation [51,52]. ...
Article
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Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy—especially in austere or challenging environments—is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.
... Later on, a hypercoagulable state predominates associated with venous thromboembolism and multiple organ failure [18]. The presence of TIC has been demonstrated to be an independent predictor for increased organ dysfunction, infection, and overall mortality [19,20]. ...
Article
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There are well-established protocols for venous thromboembolism prophylaxis in many patients with a variety of medical and surgical conditions. However, no studies have been published regarding therapeutic anticoagulation in polytrauma patients, who usually present with multiple injuries including vascular injuries and solid organ injuries, which would require therapeutic anticoagulation that increases the risk of bleeding from abdominal solid organ injuries. Here, we present the case of a 45-year-old male, who had a motor vehicle collision and was found to have a grade III splenic injury and had to be started on therapeutic anticoagulation due to popliteal artery injury repair. Our patient was anticoagulated with low-molecular-weight heparin. He had no bleeding complications, and his splenic injury was successfully managed nonoperatively.
... Это особенно справедливо для педиатрической практики, поскольку организм ребенка имеет колоссальные резервы, которые позволяют ему не только выжить, но и выздороветь даже в тех случаях, когда смерть представляется непредотвратимой. Имеется значительное количество исследований, свидетельствующих о том, что многие клинико-лабораторные признаки могут использоваться как предикторы исхода, однако работы, посвященные поиску интегральных показателей, позволяющих выявить пациентов группы высокого риска, отсутствуют [3][4][5][6][7][8][9][10][11]. ...
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Introduction. Severe polytrauma is the most common cause of deaths in children, but there are currently no objective criteria for predicting the outcome of severe polytrauma in pediatric ICU patients and identifying a high-risk group. Objectives of the study is to identify the features of clinical and laboratory status and intensive care measures in children with severe polytrauma, which determine the outcome of a critical condition. Materials and methods. Design: A retrospective cohort multicenter uncontrolled study. 230 children were examined. The age of patients was 9.5 (4-14) years. The score on the Abbreviated Injury Score (AIS) was 34 points, the Pediatric Traumatic Score (PTS) - 5 (2-8) points. As a primary outcome, the duration of control mechanical ventilation and ICU length of stay were evaluated. Secondary outcome was divided into recovery, presence of neurological deficiency and death. Results. Minimum duration of treatment in ICU is noted with shortterm sedation during the day, an AIS score of less than 30 points and a PTS score of more than 5 points. The presence of intracranial hematoma (ICH) is associated with a doubling of treatment duration in ICU. The maximum statistically significant difference in mean values was revealed when assessing the effect on the outcome of the following features: catecholamine index (F = 109.4; p = 0.000); transfusion volume of freshly frozen plasma (F = 42.0; p = 0.000) and transfusion volume of erythrocytes (F = 33.4; p = 0.000). Conclusions. The need for prolonged sedation, an AIS score of more than thirty points, a PTS score of more than five points, and the presence of ICH is associated with an increase ICU length of stay and adverse outcome. The use of high doses of catecholamines and massive blood transfusion on the first day of treatment in ICU are independent predictors of the death of polytrauma in children.
... There is a developing interest in using VHAs to aid in goal-directed BCT of the bleeding trauma patient as close to the scene of injury as possible, whether that injury occurred in the far-forward combat area, or the civilian austere or urban environments [44,45]. Incidence of TIC has been reported in 24-36% of all trauma admissions to the emergency department, further increasing the importance and usability of POC VHAs in prehospital environments for improved results upon arrival [46][47][48][49][50]. The use of versatile and portable VHAs in the urban environment have been increasingly adopted for the immediate use in trauma resuscitation scenes and in studies concerning prehospital resuscitation [51,52]. ...
Article
Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy—especially in austere or challenging environments—is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.
... Haemorrhage after trauma is a leading cause of preventable mortality worldwide [1]. Haemorrhaging trauma patients frequently present with trauma-induced coagulopathy (TIC), which is associated with increased transfusion requirements and mortality [2,3]. TIC can manifest with hypocoagulable, hypercoagulable or mixed characteristics [4]. ...
Article
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Background: Trauma-induced coagulopathy (TIC) is a life-threatening condition associated with high morbidity and mortality. TIC can present with different coagulation defects. In this study, the aim was to determine the effect of shock duration on TIC characteristics. We hypothesized that longer duration of shock leads to a more hypocoagulable rotational thromboelastometry (ROTEM) profile compared to a shorter duration of shock. Methods: Male B57BL/6J(c) mice (n = 5-10 per group) were sedated and mechanically ventilated. Trauma was induced by bilateral lower limb fractures and crush injuries to the liver and small intestine. Shock was induced by blood withdrawals until a mean arterial pressure of 25-30 mmHg was achieved. Groups reflected trauma and shock for 30 min (TS30) and trauma and shock for 90 min (TS90). Control groups included ventilation only (V90) and trauma only (T90). Results: Mice in the TS90 group had significantly increased base deficit compared to the V90 group. Mortality was 10% in the TS30 group and 30% in the TS90 group. ROTEM profile was more hypocoagulable, as shown by significantly lower maximum clot firmness (MCF) in the TS30 group (43.5 [37.5-46.8] mm) compared to the TS90 group (52.0 [47.0-53.0] mm, p = 0.04). ROTEM clotting time and parameters of clot build-up did not significantly differ between groups. Conclusions: TIC characteristics change with shock duration. Contrary to the hypothesis, a shorter duration of shock was associated with decreased maximum clotting amplitudes compared to a longer duration of shock. The effect of shock duration on TIC should be further assessed in trauma patients.
... Coagulopathy frequently complicates trauma, and, if untreated, it is associated with increased mortality; hence, the utilization of blood products is a key component of DCR [8,10,11,59]. Moreover, in polytrauma patients with TBI, coagulopathy has been associated with further progression of post-traumatic cerebral hematomas and unfavorable neurological outcomes [60,61]. ...
Article
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Managing the acute phase after a severe traumatic brain injury (TBI) with polytrauma represents a challenging situation for every trauma team member. A worldwide variability in the management of these complex patients has been reported in recent studies. Moreover, limited evidence regarding this topic is available, mainly due to the lack of well-designed studies. Anesthesiologists, as trauma team members, should be familiar with all the issues related to the management of these patients. In this narrative review, we summarize the available evidence in this setting, focusing on perioperative brain protection, cardiorespiratory optimization, and preservation of the coagulative function. An overview on simultaneous multisystem surgery (SMS) is also presented.
... Traumatic injuries represent 10% of the disease burden worldwide and particularly trauma-induced hemorrhage which is the most preventable cause of mortality among injured patients [1][2][3][4]. Around one-fourth of trauma patients are susceptible to develop acute coagulopathy and those with uncontrolled hemorrhage are at increased risk of hemorrhagic shock and mortality [4][5][6][7][8]. Therefore, early management of acute traumatic coagulopathy and hemorrhagic shock improves outcomes [5,9]. ...
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Background Prehospital administration of tranexamic acid (TXA) to injured patients is increasing worldwide. However, optimal TXA dose and need of a second infusion on hospital arrival remain undetermined. We investigated the efficacy and safety of the second in-hospital dose of TXA in injured patients receiving 1 g of TXA in the prehospital setting. We hypothesized that a second in-hospital dose of TXA improves survival of trauma patients. Methods A prospective, double-blind, placebo-controlled randomized, clinical trial included adult trauma patients receiving 1 g of TXA in the prehospital settings. Patients were then blindly randomized to Group I (second 1-g TXA) and Group II (placebo) on hospital arrival. The primary outcome was 24-h (early) and 28-day (late) mortality. Secondary outcomes were thromboembolic events, blood transfusions, hospital length of stay (HLOS) and organs failure (MOF). Results A total of 220 patients were enrolled, 110 in each group. The TXA and placebo groups had a similar early [OR 1.000 (0.062–16.192); p = 0.47] and late mortality [OR 0.476 (95% CI 0.157–1.442), p = 0.18].The cause of death (n = 15) was traumatic brain injury (TBI) in 12 patients and MOF in 3 patients. The need for blood transfusions in the first 24 h, number of transfused blood units, HLOS, thromboembolic events and multiorgan failure were comparable in the TXA and placebo groups. In seriously injured patients (injury severity score > 24), the MTP activation was higher in the placebo group (31.3% vs 11.10%, p = 0.13), whereas pulmonary embolism (6.9% vs 2.9%, p = 0.44) and late mortality (27.6% vs 14.3%, p = 0.17) were higher in the TXA group but did not reach statistical significance. Conclusion The second TXA dose did not change the mortality rate, need for blood transfusion, thromboembolic complications, organ failure and HLOS compared to a single prehospital dose and thus its routine administration should be revisited in larger and multicenter studies. Trial registration ClinicalTrials.gov Identifier: NCT03846973.
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Trauma-induced coagulopathy (TIC) is a risk factor for death and is associated with deviations in thrombin generation. TIC prevalence and thrombin levels increase with age. We assayed in vivo and ex vivo thrombin generation in injured patients (n = 418) to specifically investigate how age impacts thrombin generation in trauma and to address the prognostic ability of thrombin generation. Biomarkers of thrombin generation were elevated in young (< 40 years) and older (≥ 40 years) trauma patients. In vivo thrombin generation was associated with Injury Severity Score (ISS) and this association was stronger in young than older patients. In vivo thrombin generation decreased faster after trauma in the young than the older patients. Across age groups, in vivo thrombin generation separated patients dying/surviving within 30 days at a level comparable to the ISS score (AUC 0.80 vs. 0.82, p > 0.76). In vivo and ex vivo thrombin generation also predicted development of thromboembolic events within the first 30 days after the trauma (AUC 0.70–0.84). In conclusion, younger trauma patients mount a stronger and more dynamic in vivo thrombin response than older patients. Across age groups, in vivo thrombin generation has a strong ability to predict death and/or thromboembolic events 30 days after injury.
Article
Introduction: Thromboelastography (TEG)-derived maximum amplitude-reaction time (MA-R) ratio that accounts for both hypocoagulable and hypercoagulable changes in coagulation is associated with poor outcomes in adults. The relationship between these TEG values and outcomes has not been studied in children. Methods: In a retrospective cohort study, a level I pediatric trauma center database was queried for children younger than 18 years who had a TEG assay on admission between 2016 and 2020. Demographics, injury characteristics, and admission TEG values were recorded. The MA-R ratio was calculated and divided into quartiles. Main outcomes included mortality, transfusion within 24 hours of admission, and thromboembolism. A logistic regression model was generated adjusting for age, Injury Severity Score, injury mechanism, admission shock, and Glasgow Coma Scale. Results: In total, 657 children were included, of which 70% were male and 75% had blunt mechanism injury. The median (interquartile range) age was 11 (4-14) years, the median (interquartile range) Injury Severity Score was10 (5-22), and in-hospital mortality was 7% (n = 45). Of these patients, 17% (n = 112) required transfusion. Most R and MA values were within normal limits. On unadjusted analysis, the lowest MA-R ratio quartile was associated with increased mortality (15% vs. 4%, 5%, and 4%, respectively; p < 0.001) and increased transfusion need (26% vs. 12%, 16%, and 13%, respectively; p = 0.002) compared with higher quartiles. In the logistic regression models, a low MA-R ratio was independently associated with increased in-hospital mortality (odds ratio [95% confidence interval], 4.4 [1.9-10.2]) and increased need for transfusion within 24 hours of admission (odds ratio [95% confidence interval], 2.0 [1.2-3.4]) compared with higher MA-R ratio. There was no association between MA-R ratio and venous thromboembolic events (venous thromboembolic event rate by quartile: 4%, 2%, 1%, and 3%). Conclusion: Although individual admission TEG values are not commonly substantially deranged in injured children, the MA-R ratio is an independent predictor of poor outcome. Maximum amplitude-reaction time ratio may be a useful prognostic tool in pediatric trauma; validation is necessary. Level of evidence: Therapeutic/Care Management; Level III.
Chapter
Viscoelastic hemostatic assays (VHAs) have been proposed as an alternative strategy for coagulopathy monitoring, transfusion, and resuscitation guidance in critically injured and ill patients. Viscoelastic monitoring (VEM) assays provide information to assess platelet function, rate of clot formation, clot strength, stability, and dissolution in a short amount of time and while taking into account a whole blood sample. Several systems are available on the market. In this chapter, the basis of hemostasis and coagulopathy will be reviewed in a trauma patient, most commonly utilized viscoelastic monitoring systems are introduced, and the value of viscoelastic monitoring in care for the injured and bleeding patient is discussed.
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Abdominal traumatism (AT) produces lesions in the wall or in the content (viscera, mesos, vascular ducts, biliopancreatic, urinary tract). The abdomen can be injured in isolation, although about a third of pediatric polytraumatisms are associated with AT. AT implies a high vital risk due to two circumstances: hemorrhage due to injury to solid organs or blood vessels and peritonitis due to perforation of hollow viscera. The global mortality varies between 5 and 15% and reaches 50% in the lesion of the great vessels. Management of these injuries is key to patient survival.
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Non-compressible torso haemorrhage (NCTH) (i.e., bleeding from anatomical locations not amenable to control by direct pressure or tourniquet application) is a leading cause of potentially preventable death after injury. In select trauma patients with infra-diaphragmatic NCTH-related hemorrhagic shock or traumatic circulatory arrest, occlusion of the aorta proximal to the site of hemorrhage may sustain or restore spontaneous circulation. While the traditional method of achieving proximal aortic occlusion included Emergency Department thoracotomy (EDT) with descending thoracic aortic cross-clamping, resuscitative endovascular balloon occlusion of the aorta (REBOA) affords a less invasive option when thoracotomy is not required for other indications. In this manuscript, we review the innovation, pathophysiologic effects, indications for, and technique of EDT and partial, intermittent, and complete REBOA in injured patients, including recommended methods for reversing aortic occlusion. We also discuss advantages and disadvantages of each of these methods of proximal aortic occlusion and review studies comparing their effectiveness and safety for managing post-injury NCTH. We conclude the above by providing recommendations as to when each of these methods may be best when indicated to manage injured patients with NCTH.
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: Fasciola hepatica, which is common in the world, is a zoonotic trematode that affects the liver of many animals, especially sheep and cattle. In this study, it was aimed to determine the changes that may occur in the coagulation profile in cattle with Fasciola hepatica detected. The material of the study consisted of 282 cattle on farms. Within the scope of the study, according to the clinical and laboratory results of these cattle; 20 cattle were included in the diseased group and 20 cattle were included in the healthy group. After the general clinical examination of the animals to be studied, stool and blood samples were taken. Stool samples taken from these animals Fasciola spp. Sedimentation-zinc sulfate flotation method was used to determine the eggs. In addition, Fasciola hepatica antibodies from serum samples were investigated by ELISA method. Coagulation profiles were examined from blood samples taken into tubes with Na-citrate. As a result of the coagulation analysis, it was determined that positive samples caused prolongation in activated partial thromboplastin time (aPTT), Prothrombin time (PT) and INR (International Normalized Ratio) . In conclusion, it was concluded that chronic fasciolosis may cause significant changes in hematological and hemostatic parameters in cattle.
Chapter
Providing the inside track on how the experts approach and deal with real-world clinical scenarios, Challenging Concepts in Anaesthesia selects specific challenging cases that are encountered in everyday clinical practice but do not have simple answers. A case-based guide to challenging areas in anaesthesia and pain management, this resource covers the major sub-specialty areas in both fields. Complex cases are comprehensively examined from a multidisciplinary perspective with detailed consideration given to management options and the contemporary evidence base behind these decisions. Mapped to the Royal College of Anaesthetists' matrix for CME and the FRCA syllabus, it is effective as both a revision aid and as a reference during workplace-based assessments, and it highlights critical information through the use of boxed features: 'Learning points', 'Clinical tips', 'Evidence-base'. Each chapter has been reviewed by a national or international expert in the field who has also provided an 'Expert commentary', giving a unique insight into how today's opinion leaders confront and deal with the very same management challenges that all clinicians can potentially face on a daily basis.
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An important aim of viscoelastic testing (VET) is to implement transfusion algorithms based on coagulation test results to help reduce transfusion rates and improve patient outcomes. Establishing a rapid diagnosis and providing timely treatment of coagulopathy is the cornerstone of management of severely bleeding patients in trauma, postpartum hemorrhage, and major surgery. As the nature of acute bleeding and trauma leads to an unstable and tenuous physiologic state, conventional coagulation tests (CCTs) are too slow to diagnose, manage, and also course correct any hemostatic abnormalities that accompany an acute critical illness. Viscoelastic point-of-care tests strongly correlate with results from standard laboratory tests but are designed to enable clinicians to make timely, informed bleeding management decisions when time to intervene is critical. These assays provide an individualized and goal-oriented approach to patient blood management and are increasingly becoming involved in transfusion algorithms. The scope of this review aims to evaluate the current literature on VETs and their impact on actionable outputs in clinical decision making and their relationship to CCT.
Chapter
Trauma induced coagulopathy comprises a challenging clinical spectrum complicating the management of the traumatically injured patient. Identification followed by expeditious management of coagulopathy is paramount in achieving patient stability. This chapter details the pathophysiology and complexities of managing coagulopathy in the trauma population. Venous thromboembolism and prophylaxis strategies constantly challenge the clinician when managing the burden of traumatic injury. Understanding the risk factors and navigating the clinical challenges are critical to prevention of venous thromboembolism.KeywordsTrauma induced coagulopathyViscoelastic hemostatic assayDamage control resuscitationAnticoagulant reversalVenous thromboembolism prophylaxis
Article
Background: Viscoelastically guided coagulation factor concentrate-based algorithms for the treatment of trauma-induced coagulopathy include the administration of prothrombin complex concentrates (PCCs). However, the exact role of PCC preparations in this context is a matter of debate. Particularly, the ideal diagnostic trigger for their administration and potential differences between heparin-containing and heparin-free preparations remain unclear. We investigated the hypothesis that 2 different PCCs might have distinct influences on in vitro blood coagulation. Methods: We conducted a direct comparison of 2 commercially available PCC preparations (the heparin-containing Beriplex P/N and the heparin-free Cofact) in an in vitro hemodilution model. Sole fibrinogen substitution served as the control group. To characterize the hemostatic changes, we utilized conventional coagulation tests, a thrombin generation assay (TGA), and 2 different viscoelastic hemostatic assays (VHAs; ROTEM delta and ClotPro). Results: Irrespective of the diagnostic assay used, no significant differences between the 2 PCC groups were observed. Fibrinogen levels remained stable from the baseline throughout every dilution level. The control group already showed an increased endogenous thrombin potential (ETP; nM·L-1·min-1) at all dilution levels compared to baseline (baseline, 2829.4 (432.8); 40% dilution, 4211.7 (391.6); 60% dilution, 4290.9 (300.8); 80% dilution, 3861.4 (303.5); all P < .001). Spiking with both PCC preparations led to a further-pronounced thrombin elevation in comparison to the control group (ETP at 40% dilution, PCC1: 4913.3 [370.2], PCC2: 4988.1 [265.7]; 60% dilution, PCC1: 5174.5 [234.7], PCC2: 5390.4 [334.9]; 80% dilution, PCC1: 5253.8 [357.9], PCC2: 5392.6 [313.4]; all P < .001). Conventional coagulation tests did not mirror the TGA results. Despite increased thrombin generation, prothrombin time was significantly prolonged at all dilution levels for the control group, and both PCC groups exhibited significant prolongations at the 60% and 80% dilution levels (all P < .001) compared to baseline. Similarly, VHA did not depict the thrombin elevation. Furthermore, descriptive analyses revealed relevant differences between the 2 VHA devices, particularly at baseline. Conclusions: Both PCC preparations (ie, irrespective of heparin content) induced significant elevation of thrombin generation, which was not depicted by conventional coagulation tests or VHA. Our in vitro results suggest that diagnostic assays routinely used to guide PCC administration might not adequately reflect thrombin generation in bleeding patients.
Article
Background : The administration of balanced component therapy has been associated with improvements in outcomes in adult trauma. There is little to no specific data to guide transfusion ratios in children. The aim of our study is to compare outcomes among different transfusion strategies in pediatric trauma patients. Methods : We conducted a (2014-2016) retrospective analysis of the Trauma Quality Improvement Program. We selected all pediatric (age<18) trauma patients who received at least one unit of packed red blood cells (PRBC) and fresh frozen plasma (FFP) within 4 hours of admission. Patients were stratified based on their FFP:PRBC transfusion ratio in the first 4 hours into: 1:1, 1:2, 1:3, and 1:3+. Primary outcomes were 24-mortality, in-hospital mortality. Secondary outcomes were complications and 24-hour PRBC transfusion requirements. Multivariable logistic regression analysis was performed. Results : A total of 1,233 patients were identified of which 637 received transfusion ratio of 1:1, 365 1:2, 116 1:3, and 115 1:3+. Mean age was 11±6y, 70% were male, ISS was 27 [20-38], and 62% sustained penetrating injuries. Patients in the 1:1 group had the lowest 24-hour mortality (14% vs. 18% vs. 22% vs. 24%; p=0.01) and in-hospital mortality (32% vs. 36% vs. 40% vs. 44%; p=0.01). No difference was found between the groups in terms of complications (22% vs. 21% vs. 23% vs. 22%; p=0.96) such as acute respiratory distress syndrome (3.3% vs. 3.6% vs. 0.9% vs. 0%; p=0.10), and acute kidney injury (3% vs. 2.2% vs. 0.9% vs. 0.9%; p=0.46). Additionally the 1:1 group had the lowest PRBC transfusion requirements (3[2-7] vs. 5[2-10] vs. 6[3-8] vs. 6[4-10]; p<0.01). On regression analysis a progressive increase in the mortality adjusted odds ratio was observed as the FFP:PRBC transfusion ratio decreased. Conclusion : FFP:PRBC ratios closest to 1 were associated with increased survival in children. The resuscitation of pediatric patients should target a 1:1 ratio of FFP:PRBC. Further studies are needed for the development of massive transfusion protocols for this age group. Level of Evidence : Level IV
Chapter
Trauma-induced coagulopathy (TIC) is an alteration in the body’s coagulation capacity that is attributable to injury and manifests in a spectrum of phenotypes which are dynamic and time dependent. One end of the spectrum is hypocoagulability, which results in poorly hemostatic clots causing difficult to control hemorrhage. The hypercoagulable end of the spectrum can result in micro- and macrovascular thrombosis leading to a deep vein thrombosis, pulmonary embolism, acute respiratory distress syndrome, and multisystem organ failure. The pathophysiology behind TIC is complex and involves an intricate interplay between diminished thrombin generation, platelet dysfunction, vascular endothelial cell dysfunction, fibrinogen depletion, and dysregulated fibrinolysis. Improved understanding of the mechanisms behind TIC will allow for more personalized and precise treatment of trauma patients.KeywordsTrauma induced coagulopathyFibrinolysisEndotheliopathy
Article
Objective:. Trauma-induced coagulopathy (TIC) is provoked by multiple mechanisms and is perceived to be one driver of massive transfusions (MT). Single laboratory values using prothrombin time (INR) or thrombelastography (TEG) are used to clinically define this complex process. We used a proteomics approach to test whether current definitions of TIC (INR, TEG, or clinical judgment) are sufficient to capture the majority of protein changes associated with MT. Methods:. Eight level I trauma centers contributed blood samples from patients available early after injury. TIC was defined as INR >1.5 (INR-TIC), TEG maximum amplitude 10 units of red blood cells in 24 hours or >4 units RBC/hour during the first 4 hours. SomaLogic proteomic analysis of 1305 proteins was performed. Pathways associated with proteins dysregulated in patients with each TIC definition and MT were identified. Results:. Patients (n = 211) had a mean injury severity score of 24, with a MT and mortality rate of 22% and 12%, respectively. We identified 578 SOMAscan analytes dysregulated among MT patients, of which INR-TIC, TEG-TIC, and Clin-TIC patients showed dysregulation only in 25%, 3%, and 4% of these, respectively. TIC definitions jointly failed to show changes in 73% of the protein levels associated with MT, and failed to identify 26% of patients that received a massive transfusion. INR-TIC and TEG-TIC patients showed dysregulation of proteins significantly associated with complement activity. Proteins dysregulated in Clin-TIC or massive transfusion patients were not significantly associated with any pathway. Conclusion:. These data indicate there are unexplored opportunities to identify patients at risk for massive bleeding. Only a small subset of proteins that are dysregulated in patients receiving MT are statistically significantly dysregulated among patients whose TIC is defined based solely on laboratory measurements or clinical assessment.
Article
Monitoring of the coagulation function has applications in many clinical settings. Routine coagulation assays in the clinic are sample-consuming and slow in turnaround. Microfluidics provides the opportunity to develop coagulation assays that are applicable in point-of-care settings, but reported works required bulky sample pumping units or costly data acquisition instruments. In this work, we developed a microfluidic coagulation assay with a simple setup and easy operation. The device continuously generated droplets of blood sample and buffer mixture and reported the temporal development of blood viscosity during coagulation based on the color appearance of the resultant droplets. We characterized the relationship between blood viscosity and color appearance of the droplets and performed experiments to validate the assay results. In addition, we developed a prototype analyzer equipped with simple fluid pumping and economical imaging module and obtained similar assay measurements. This assay showed great potential to be developed into a point-of-care coagulation test with practical impact.
Article
Background: Vessels are not frequently affected in traumatology and isolated vascular trauma (VT) is rare; therefore, there is a lack of reliable and current data on the incidence and mortality. Objective: This article reports on the status of VT in trauma care of the severely injured in Germany based on selected references and data from our own published analyses and current studies from the data of the TraumaRegister DGU® (TR-DGU). Material and methods: Selected review of the literature and report on 2 retrospective assessments of datasets of the TR-DGU. Records with moderate to severe VT in the injury pattern were compared to records of cases without VT (non-VT) with the same injury severity. Target parameters were morbidity, mortality and parameters of the clinical course and prognosis. Results: The 2002-2012 database evaluation (TR-DGU Project-ID 2013-011) revealed an impact of allocation and level of care of the trauma centers on expected mortality (EM) and observed mortality (OM) in 2961 cases with VT among 42,326 severely injured patients (7%). The difference between OM and EM in VT was + 3.4% vs. ± 0.1% in non-VT. Due to an OM in severe VT of 33.8% vs. 16.4% in non-VT with identical injury severity, the subsequent analysis of 2008-2017 (TR-DGU Project-ID 2018-045) was initiated. The sub-stratification of isolated, main and concomitant VT could show a significant effect of the treatment level, allocation and transport on the OM in the treatment reality. A relevant mismatch of OM to EM could only be shown in VT, on average ca. + 2% and in high-risk constellations with VT up to + 29% as a measure for the relevance of VT in trauma care. Conclusion: These results indicate a substantial need for further optimization of emergency care of severely injured patients with VT, where VT vigilance, allocation, transportation and a low threshold early re-allocation can be derived as starting points.
Article
Background Transcatheter arterial embolization (TAE) for acute renal hemorrhage (RH) under coagulopathic conditions with N-butyl-2 cyanoacrylate (NBCA) is rarely described in the literature, and a consensus on the efficacy and safety of NBCA under this condition has not been reached. Purpose To evaluate the efficacy and safety of TAE using NBCA Glubran 2 in the treatment of acute RH under coagulopathic conditions. Materials and methods 8 patients underwent TAE with NBCA Glubran 2 for acute RH under coagulopathic conditions were collected. Results One patient presented with severe coagulopathy, and three presented with severe RH and hemodynamic instability. NBCA Glubran 2 was employed as the sole embolic material in six patients. In the remaining two patients, NBCA Glubran 2 was employed for secondary embolization. Under coagulopathic conditions, both technical success and clinical success were achieved in treating acute RH with NBCA Glubran 2 in all patients. During a mean follow-up time of 30.1 months, neither persistent nor recurrent active hemorrhage required repeat endovascular or surgical treatment for hemostasis. No Glubran 2-related complications occurred. In addition, there was no significant difference between the evaluated glomerular filtration rate level before and one week after Glubran 2 embolization (p=0.88; CI, -32.4 to 37.4). Conclusion TAE with NBCA Glubran 2 may be a safe alternative treatment for the management of RH under coagulopathic conditions. In particular, this method appears to be a potentially attractive alternative when conventional embolic materials fail in patients with ongoing hemodynamic instability or even under severe coagulopathic conditions.
Article
Background: Fibrinogen is the first coagulation factor to decrease after massive hemorrhage. European massive transfusion guidelines recommend early repletion of fibrinogen; however, this practice has not been widely adopted in the US. We hypothesize that hypofibrinogenemia is common at hospital arrival and is an integral component of trauma-induced coagulopathy. Study design: This study entailed review of a prospective observational database of adults meeting the highest-level activation criteria at an urban level 1 trauma center from 2014 through 2020. Resuscitation was initiated with 2:1 red blood cell (RBC) to fresh frozen plasma (FFP) ratios and continued subsequently with goal-directed thrombelastography. Hypofibrinogenemia was defined as fibrinogen below 150 mg/dL. Massive transfusion (MT) was defined as more than 10 units RBC or death after receiving at least 1 unit RBC over the first 6 hours of admission. Results: Of 476 trauma activation patients, 70 (15%) were hypofibrinogenemic on admission, median age was 34 years, 78% were male, median New Injury Severity Score (NISS) was 25, and 72 patients died (15%). Admission fibrinogen level was an independent risk factor for MT (odds ratio [OR] 0.991, 95% CI 0.987-0.996]. After controlling for confounders, NISS (OR 1.034, 95% CI 1.017-1.052), systolic blood pressure (OR 0.991, 95% CI 0.983-0.998), thrombelastography angle (OR 0.925, 95% CI 0.896-0.954), and hyperfibrinolysis (OR 2.530, 95% CI 1.160-5.517) were associated with hypofibrinogenemia. Early cryoprecipitate administration resulted in the fastest correction of hypofibrinogenemia. Conclusion: Hypofibrinogenemia is common after severe injury and predicts MT. Cryoprecipitate transfusion results in the most expeditious correction. Earlier administration of cryoprecipitate should be considered in MT protocols.
Article
Critically injured persons suffer trauma, hemorrhage, and high mortality. A subset of such patients develops early coagulation dysfunction characterized as acute traumatic coagulopathy (ATC), with a poor prognosis. The mechanisms contributing to ATC remain incompletely understood. Notwithstanding some successes in conducting clinical trials in early traumatic coagulopathy, conducting clinical research in ATC is ethically and logistically challenging. In vitro studies cannot capture the complex pathophysiological interplay between blood, vasculature, and organ systems relevant to ATC. Animal models are therefore vital for understanding ATC and to test interventions. Previous systematic reviews of animal models of ATC covered progress up to 2014. The current review aimed to extend that coverage to the end of 2021. A structured systematic search of MEDLINE/PubMed was carried out and identified 56 relevant publications. Unlike in previous reviews, where pig models predominated, rat and pig models contributed equally (19 studies each), and non-human primate models entered the field. Most studies now featured defined trauma (39 of 56), and hemorrhage controlled by pressure or volume (42 studies), with some documenting that both were necessary to induce ATC. Most studies documented coagulopathy using clotting or viscoelastometric assays and created an endogenous coagulopathy not dependent on iatrogenic dilution. As before, the diversity of species and experimental protocols may limit the translatability of the identified studies. Thus, while animal research has become more aligned to clinical realities since 2014, further efforts are required to unravel ATC mechanisms and enable the prediction and evaluation of optimal clinical interventions.
Article
Background: Traumatic acute subdural hematomas (aSDHs) are common, life-threatening injuries often requiring emergency surgery. Objective: To develop and validate the Richmond acute subdural hematoma (RASH) score to stratify patients by risk of mortality after aSDH evacuation. Methods: The 2016 National Trauma Data Bank (NTDB) was queried to identify adult patients with traumatic aSDHs who underwent craniectomy or craniotomy within 4 h of arrival to an emergency department. Multivariate logistic regression modeling identified risk factors independently associated with mortality. The RASH score was developed based on a factor's strength and level of association with mortality. The model was validated using the 2017 NTDB and the area under the receiver operating characteristic curve (AUC). Results: A total of 2516 cases met study criteria. The patients were 69.3% male with a mean age of 55.7 yr and overall mortality rate of 36.4%. Factors associated with mortality included age between 61 and 79 yr (odds ratio [OR] = 2.3, P < .001), age ≥80 yr (OR = 6.3, P < .001), loss of consciousness (OR = 2.3, P < .001), Glasgow Coma Scale score of ≤8 (OR = 2.6, P < .001), unilateral (OR = 2.8, P < .001) or bilateral (OR = 3.9, P < .001) unresponsive pupils, and midline shift >5 mm (OR = 1.7, P < .001). Using these risk factors, the RASH score predicted progressively increasing mortality ranging from 0% to 94% for scores of 0 to 8, respectively (AUC = 0.72). Application of the RASH score to 3091 cases from 2017 resulted in similar accuracy (AUC = 0.74). Conclusion: The RASH score is a simple and validated grading scale that uses easily accessible preoperative factors to predict estimated mortality rates in patients with traumatic aSDHs who undergo surgical evacuation.
Article
Introduction: Trauma-induced coagulopathy (TIC) is a form of coagulopathy unique to trauma patients and is associated with increased mortality. The complexity and incomplete understanding of TIC have resulted in controversies regarding optimum management. This review aims to summarise the pathophysiology of TIC and appraise established and emerging advances in the management of TIC. Methods: This narrative review is based on a literature search (MEDLINE database) completed in October 2020. Search terms used were "trauma induced coagulopathy", "coagulopathy of trauma", "trauma induced coagulopathy pathophysiology", "massive transfusion trauma induced coagulopathy", "viscoelastic assay trauma induced coagulopathy", "goal directed trauma induced coagulopathy and "fibrinogen trauma induced coagulopathy'. Results: TIC is not a uniform phenotype but a spectrum ranging from thrombotic to bleeding phenotypes. Evidence for the management of TIC with tranexamic acid, massive transfusion protocols, viscoelastic haemostatic assays (VHAs), and coagulation factor and fibrinogen concentrates were evaluated. Although most trauma centres utilise fixed-ratio massive transfusion protocols, the "ideal" transfusion ratio of blood to blood products is still debated. While more centres are using VHAs to guide blood product replacement, there is no agreed VHA-based transfusion strategy. The use of VHA to quantify the functional contributions of individual components of coagulation may permit targeted treatment of TIC but remains controversial. Conclusion: A greater understanding of TIC, advances in point-of-care coagulation testing, and availability of coagulation factors and fibrinogen concentrates allows clinicians to employ a more goal-directed approach. Still, hospitals need to tailor their approaches according to available resources, provide training and establish local guidelines.
Chapter
This chapter outlines the current approach and the evolution in the assessment of trauma patients from a familiar “ABC” approach to the “MABCD” approach adopted throughout this textbook. The sequence of assessment, intervention and then progression through subsequent stages is explained and the rationale outlined. Each section has a brief overview of key points that is dealt with more fully in the dedicated chapters that follow, with key papers outlining core principles highlighted within this overview. The focus is mainly on clinical signs and their interpretation as they relate to traumatic injuries.
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Trauma remains the leading cause of death worldwide, with the two leading causes of traumatic deaths being direct neurotrauma and haemorrhage. Many deaths from neurotrauma result from primary brain injury (up to 50%), the effects of which cannot be mitigated against other than for public health measures such as encouraging cyclists to wear helmets. This leaves haemorrhage as the leading cause of preventable trauma deaths. Specific haemorrhagic injuries (such as massive disruption of the aorta or great vessels) are unsurvivable, and death is almost instantaneous; however, these form a minority of haemorrhage related deaths in the population. This chapter discusses major haemorrhage and its management.
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Trauma remains the leading cause of death in North America in those 40 years of age and younger [1], and those 35 years and younger globally [2]. On a global scale severe trauma contributes to approximately one in ten deaths across all ages accounting for more than 5.8 million fatalities per year [3, 4]. Death due to haemorrhage remains the primary cause in about 40% of these potentially preventable deaths [5], and trauma induced coagulopathy (TIC) develops in about ten to 25% of these patients (Fig. 15.1). The presence of acute traumatic coagulopathy (ATC), a component of TIC, increases the odds ratio towards mortality almost nine-fold, and is unrelated to transfusion practice [6]. These patients also have a higher incidence of multi-system organ failure, prolonged hospital and intensive care stay as well as increased blood utilisation [7–9]. Death from exsanguination occurs within 2–3 h (median time) after presentation and accounts for nearly 50% of trauma death [5, 10, 11]. Early recognition and treatment of TIC, along with massive transfusion guidelines, represent an opportunity to improve outcomes in trauma resuscitation [6].
Article
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Coagulation abnormalities can pose a threat to hemorrhaging patients and to attempts at surgical correction. We have shown that 97.2% of our 180 patients who died of trauma had evidence of coagulation defects prior to fluid or blood treatment. Twelve of 180 patients could not be cross-matched due to inability of their blood to coagulate in the tube. Clinically 50% of these patients had excessive oozing from venipuncture sites, and 28% had excessive hematoma formation not associated with vascular injury. The most frequently abnormal test was the prothrombin time, in 97% of patients followed by platelet count in 72%, and partial thromboplastin time in 70%. The greatest degree of coagulation abnormality occurred in patients with head trauma, followed in decreasing order by gunshot wounds, blunt trauma, and stab wounds to the body. Because 97.2% of the patients had abnormal coagulation studies prior to fluid and blood replacement, this abnormality most likely was due to disseminated intravascular coagulation. We propose using the tube-clot test to give a rapid indication of coagulation in traumatized patients while awaiting laboratory test results.
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Severe hemostatic defects that occur during massive transfusion are related to the volume of blood transfused, preexisting hemostatic abnormalities, concomitant pathologic changes, and therapeutic maneuvers. The relative role of each factor in the bleeding can be rapidly determined by using routine clinical laboratory tests. This determination requires an understanding of the properties of selected clotting factors, what coagulation screening tests measure, how these tests behave as the levels of factors change, and test profiles characteristic of different defects. Screening tests include platelet count, prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen level. These tests are generally available on an emergent basis and can be completed within 25 minutes. The pattern associated with hemodilution is universal in massive transfusion. Patterns characteristic of the other pathologic processes that may be encountered are simply superimposed on the characteristics of hemodilution. Successful management of the contributing causes of bleeding depends on the administration of the appropriate blood components in the dose necessary to ensure that the levels of platelets and clotting factors are returned to and maintained at hemostatic levels.
Article
Massive transfusion may cause abnormalities of electrolytes, clotting factors, pH, and temperature and may occur in a scenario of refractory coagulopathy and irreversible shock. Identification of correctable variables to improve survival is complicated by the interplay of this pathophysiology. Temperature may be an under-appreciated problem in the genesis of coagulopathy. In vitro studies have demonstrated that platelet function and vascular response are critically temperature-dependent. We reviewed the records of 45 trauma patients without head injury or co-morbid medical illness who required massive transfusions. The mean Injury Severity Score was 55 +/- 6, a mean of 22.5 +/- 5 units of blood was transfused, and mortality was 33%. Nonsurvivors were more likely to have had penetrating injury (88% versus 55%), received more transfusions (26.5 +/- 9 versus 18.6 +/- 1, p less than 0.05), had lower pH (pH 7.04 +/- 0.06 versus 7.18 +/- 0.02, p less than 0.05), had lower core temperature (31 +/- 1 degree C versus 34 +/- 1 degree C, p less than 0.01), and had a higher incidence of clinical coagulopathy (73% versus 23%). Severe hypothermia (temperature less than 34 degrees C) occurred in 80% of the nonsurvivors and in 36% of survivors. Patients who were hypothermic and acidotic developed clinically significant bleeding despite adequate blood, plasma, and platelet replacement. Avoidance or correction of hypothermia may be critical in preventing or correcting coagulopathy in the patient receiving massive transfusion.
Article
The aim of this investigation was to determine the prognostic value of coagulation abnormalities in a defined subset of patients with acute head injury. Prothrombin time, accelerated partial thromboplastin time (APTT), thrombin clotting time, fibrinogen assay, platelet count, fibrin degradation products (FDP) were assayed in 204 patients with acute closed head injury. Their values were graded on a score 0-3 and the sum score for each patient regarded as the disseminated intravascular coagulation (DIC) score. Moderate to severe DIC scores were evident in 38% of the cohort. At least one parameter was abnormal in 71% of patients. The DIC score correlated inversely with the Glasgow coma score (GCS) ( p 0.0001). In the GCS 13-15 subset, FDP scores were significant predictors of poor outcome ( p 0.001). In the GCS 6-12 subset, the APTT score ( p 0.001), and DIC score ( p 0.0001) predicted an adverse outcome. The DIC scores were significantly abnormal in most patients who had a poor outcome, without evidence of ...
Objective: Recognizing the impact of the 1977 San Francisco study of trauma deaths in trauma care, our purpose was to reassess those findings in a contemporary trauma system. Design: Cross-sectional. Material and methods: All trauma deaths occurring in Denver City and County during 1992 were reviewed; data were obtained by cross-referencing four databases: paramedic trip reports, trauma registries, coroner autopsy reports and police reports. Measurements and main results: There were 289 postinjury fatalities; mean age was 36.8 +/- 1.2 years and mean Injury Severity Score (ISS) was 35.7 +/- 1.2. Predominant injury mechanisms were gunshot wounds in 121 (42%), motorvehicle accidents in 75 (38%) and falls in 23 (8%) cases. Seven (2%) individuals sustained lethal burns. Ninety eight (34%) deaths occurred in the pre-hospital setting. The remaining 191 (66%) patients were transported to the hospital. Of these, 154 (81%) died in the first 48 hours (acute), 11 (6%) within three to seven days (early) and 26 (14%) after seven days (late). Central nervous system injuries were the most frequent cause of death (42%), followed by exsanguination (39%) and organ failure (7%). While acute and early deaths were mostly due to the first two causes, organ failure was the most common cause of late death (61%). Conclusions: In comparison with the previous report, we observed similar injury mechanisms, demographics and causes of death. However, in our experience, there was an improved access to the medical system, greater proportion of late deaths due to brain injury and lack of the classic trimodal distribution.
Background: Recalcitrant coagulopathy "the bloody vicious cycle," produces the majority of deaths after torso trauma. A model predicting this life-threatening complication may facilitate clinical decision-making. Methods: We prospectively analyzed patients > 15 years old who received a massive transfusion (> 10 units of packed red blood cells (PRBC)/24 h) over a 2-year period. Excluding massive head injuries and pre-existing disease, the 58 study patients had a mean age = 35.4 years, Injury Severity Score (ISS) = 30.6, and PRBC = 24.2 units/24 h. Results: Defined as prothrombin time of two times that of normal laboratory controls and partial thromboplastin time as two times that of normal laboratory controls, 27 patients (47%) developed life-threatening coagulopathy. Using a multiple logistic regression model, the four significant risk factors (with odds ratio) were (1) pH < 7.10 (12.3), (2) temperature < 34degreesC (8.7), (3) ISS > 25 (7.7), and (4) systolic blood pressure < 70 mm Hg (5.8). The conditional probability of developing coagulopathy was ISS > 25 + systolic blood pressure < 70 mm Hg = 39%, ISS > 25 + temperature < 34degreesC = 49%, ISS > 25 + pH < 7.10 = 49%; with all four risk factors the incidence was 98%. Conclusion: Postinjury life-threatening coagulopathy in the seriously injured requiring massive transfusion is predicted by persistent hypothermia and progressive metabolic acidosis.
Article
We reviewed the records of 253 patients with head injury who required serial computed tomographic (CT) scans; 123 (48.6%) developed delayed brain injury as evidenced by new or progressive lesions after a CT scan. An abnormality in the prothrombin time, partial thromboplastin time, or platelet count at admission was present in 55% of the patients who showed evidence of delayed injury, and only 9% of those whose subsequent CT scans were unchanged or improved from the time of admission (P < 0.001). Among patients developing delayed injury, mean prothrombin time at admission was significantly longer (14.6 vs. 12.6 s, P < 0.001) and partial thromboplastin time was significantly longer (36.9 vs. 29.2 s, P < 0.001) than patients who did not have delayed injury. If coagulation studies at admission were normal, a patient with head injury had a 31% risk of developing delayed insults. This risk rose to almost 85% if at least one clotting test at admission was abnormal (P < 0.001). We conclude that clotting studies at admission are of value in predicting the occurrence of delayed injury. If coagulopathy is discovered in the patient with head injury early follow-up CT scanning is advocated to discover progressive and new intracranial lesions that are likely to occur.
Article
Objective: To measure the prevalence of and characterize coagulopathy in patients with blunt brain injury. Design: Retrospective observation study based on review of medical records. Setting: Acutely injured patients admitted to a level I trauma center. Patients: One hundred fifty-nine patients with evidence of blunt head trauma who had computed tomography of the brain during initial evaluation and a coagulopathy score assigned based on 5 laboratory tests: platelet count, prothrombin time, partial thromboplastin time, fibrinogen level, and d-dimer level. The disseminated intravascular coagulation score ranged from 0 (no coagulopathy) to 15 (severe coagulopathy). Only individuals with intracranial injury based on computed tomography of the brain were designated as brain injured. Main Outcome Measures: Presence of coagulopathy, progression of brain injury, and death. Results: Among the 91 patients with brain injury, 41% had coagulopathy (disseminated intravascular coagulation score ≥5). Of the 68 patients without brain injury, 25% had coagulopathy. The patients with brain injury who developed profound depletion of fibrinogen did so within 4 hours of injury. There were 28 deaths (26 in the group with brain injury and 2 in the group without brain injury). Among patients with brain injury, those with coagulopathy more frequently died (P<.05 by χ2 analysis). Patients with brain injury and coagulopathy deteriorated more frequently based on computed tomography criteria. Conclusions: After blunt brain injury, a disseminated intravascular coagulation syndrome can lead to consumptive coagulopathy that is associated with a higher frequency of death. The syndrome develops within 1 to 4 hours after injury. Therapeutic interventions need to be implemented immediately to be effective.Arch Surg. 1996;131:923-928
Background: Antithrombin III (AT III) treatment has been shown to reduce disseminated intravascular coagulation and to inhibit thrombin, which plays a central role in the activation of platelets and other inflammatory systems in conditions with severe inflammation. The objective of this study was to evaluate the influence of early and high-dose administration of AT III to patients with severe multiple injuries on the inflammatory response and outcome. Methods: In a placebo-controlled, double-blind study, 40 consecutive patients with Injury Severity Scores of 29 or greater who met the inclusion criteria were randomized to receive either AT III or placebo within 360 minutes after trauma. Twenty patients were administered AT III for a period of 4 days, aiming to achieve AT III concentrations of 140% of normal. Results: The AT III and placebo groups were comparable with respect to Injury Severity Score, age, incidence of blood pressure less than 80 mm Hg on admission, initial base deficit, and start of the test drug. The patients in the AT III group received a total of about 20,000 IU during the first 4 days. AT III levels of 130 to 140% could be achieved by this regimen, whereas in the control group the AT III concentration averaged about 70%. In the AT III group prothrombin tended to be elevated and prothrombin fragment F1+2 as well as thrombin-AT III complex tended to be lower on the first day. No differences between groups, however, could be observed with respect to partial thromboplastin time, prothrombin time, platelets, plasminogen activator inhibitor I, soluble tumor necrosis factor receptor II, neutrophil elastase, interleukin (IL)-1 receptor antagonist, IL-6, and IL-8. Mortality (15 vs. 5%), incidence of respiratory failure (55 vs. 55%), duration of mechanical ventilation (13 VS. 12 days), and length of stay in the surgical intensive care unit (19 vs. 21 days) were also similar in both treatment groups. The duration of organ failure, however, was shorter in the patients receiving AT III. Conclusion: The early and high-dose administration of AT III to patients with severe blunt trauma appears not to attenuate the posttraumatic inflammatory response or to significantly improve outcome.
Article
The prospective study reported here evaluated the relationship between coagulopathy, catecholamines, and outcome in severe head trauma. Thirty-six trauma patients (10 with penetrating injuries, 26 with blunt injuries, 50% overall mortality) were evaluated. These patients had severe head trauma (Glasgow Coma Scale score < 9). Blood was analyzed for platelet count, prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen, D-dimer, antithrombin III, protein C, and protein S levels. A 24-hour urine sample was collected for vanillylmandelic acid (VMA), normetanephrine, and metanephrine determinations. A control group of five patients undergoing elective neurosurgery was also studied. Statistically significant differences between head injury survivors and nonsurvivors were present for platelet count, PT, and fibrinogen activity. There were no differences in the results of the other coagulation tests or in urinary catecholamine levels. The trauma patients differed from the elective neurosurgery patients with regard to D-dimer levels, PT, PTT, protein C levels, and urinary normetanephrine concentrations. Head trauma patients have a coagulopathy that is absent in patients following elective neurosurgical procedures. The coagulopathy may correlate with poor survival in head trauma and may be related to a catecholamine surge.
Article
To determine the effects of disseminated intravascular coagulation (DIC) and head injury on posttrauma coagulation and fibrinolysis. Case-control study. General ICU (tertiary care center) in a city hospital serving a population of 150 million people. Forty trauma victims: 15 with DIC; 25 without DIC. Measurement of six types of coagulation and fibrinolytic molecular markers (fibrinopeptide A, fibrinopeptide B beta 15-42, plasmin antiplasmin complex, D-dimer, tissue plasminogen activator antigen concentration, tissue plasminogen activator activity) immediately after trauma, 3 days later, and 6 days later. Anticoagulant treatment with gabexate mesilate at 1.45 +/- 0.06 mg/kg/hr. Fibrinopeptide A, fibrinopeptide B beta 15-42, plasmin antiplasmin complex, and D-dimer showed high values immediately after trauma and exceeded normal activity for the first 6 days. When trauma was complicated with DIC, the molecular markers showed significantly higher values than those for non-DIC patients on all days. In the head-injured patients, such effect was not noted. Tissue plasminogen activator antigen concentration and tissue plasminogen activator activity were within a normal physiologic range of variation. By contrast, tissue plasminogen activator antigen concentration increased significantly after trauma in patients with DIC. When anticoagulant treatment was found effective, it caused a reduction in fibrinopeptide A. a) Fibrinolytic shut-down and its reactivation cannot be confirmed after trauma. b) Head injury does not lead to an increase in posttrauma coagulation or fibrinolytic activity. c) DIC enhances posttrauma coagulation and fibrinolytic activity and plasminogen activator inhibitor activity can be inferred in DIC patients. d) Increase in tissue plasminogen activator antigen concentration without tissue plasminogen activator activation may be a prognostic factor indicative of DIC and its chances of improvement, and fibrinopeptide A as an assessment criterion for the effectiveness of anticoagulant treatment.
Article
We reviewed the records of 253 patients with head injury who required serial computed tomographic (CT) scans; 123 (48.6%) developed delayed brain injury as evidenced by new or progressive lesions after a CT scan. An abnormality in the prothrombin time, partial thromboplastin time, or platelet count at admission was present in 55% of the patients who showed evidence of delayed injury, and only 9% of those whose subsequent CT scans were unchanged or improved from the time of admission (P less than 0.001). Among patients developing delayed injury, mean prothrombin time at admission was significantly longer (14.6 vs. 12.6 s, P less than 0.001) and partial thromboplastin time was significantly longer (36.9 vs. 29.2 s, P less than 0.001) than patients who did not have delayed injury. If coagulation studies at admission were normal, a patient with head injury had a 31% risk of developing delayed insults. This risk rose to almost 85% if at least one clotting test at admission was abnormal (P less than 0.001). We conclude that clotting studies at admission are of value in predicting the occurrence of delayed injury. If coagulopathy is discovered in the patient with head injury early follow-up CT scanning is advocated to discover progressive and new intracranial lesions that are likely to occur.
Article
The prospective study reported here evaluated the relationship between coagulopathy, catecholamines, and outcome in severe head trauma. Thirty-six trauma patients (10 with penetrating injuries, 26 with blunt injuries, 50% overall mortality) were evaluated. These patients had severe head trauma (Glasgow Coma Scale score less than 9). Blood was analyzed for platelet count, prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen, D-dimer, antithrombin III, protein C, and protein S levels. A 24-hour urine sample was collected for vanillylmandelic acid (VMA), normetanephrine, and metanephrine determinations. A control group of five patients undergoing elective neurosurgery was also studied. Statistically significant differences between head injury survivors and nonsurvivors were present for platelet count, PT, and fibrinogen activity. There were no differences in the results of the other coagulation tests or in urinary catecholamine levels. The trauma patients differed from the elective neurosurgery patients with regard to D-dimer levels, PT, PTT, protein C levels, and urinary normetanephrine concentrations. Head trauma patients have a coagulopathy that is absent in patients following elective neurosurgical procedures. The coagulopathy may correlate with poor survival in head trauma and may be related to a catecholamine surge.
Article
Massive transfusion may cause abnormalities of electrolytes, clotting factors, pH, and temperature and may occur in a scenario of refractory coagulopathy and irreversible shock. Identification of correctable variables to improve survival is complicated by the interplay of this pathophysiology. Temperature may be an under-appreciated problem in the genesis of coagulopathy. In vitro studies have demonstrated that platelet function and vascular response are critically temperature-dependent. We reviewed the records of 45 trauma patients without head injury or co-morbid medical illness who required massive transfusions. The mean Injury Severity Score was 55 +/- 6, a mean of 22.5 +/- 5 units of blood was transfused, and mortality was 33%. Nonsurvivors were more likely to have had penetrating injury (88% versus 55%), received more transfusions (26.5 +/- 9 versus 18.6 +/- 1, p less than 0.05), had lower pH (pH 7.04 +/- 0.06 versus 7.18 +/- 0.02, p less than 0.05), had lower core temperature (31 +/- 1 degree C versus 34 +/- 1 degree C, p less than 0.01), and had a higher incidence of clinical coagulopathy (73% versus 23%). Severe hypothermia (temperature less than 34 degrees C) occurred in 80% of the nonsurvivors and in 36% of survivors. Patients who were hypothermic and acidotic developed clinically significant bleeding despite adequate blood, plasma, and platelet replacement. Avoidance or correction of hypothermia may be critical in preventing or correcting coagulopathy in the patient receiving massive transfusion.
Article
The Authors have studied five coagulation parameters (platelets count, prothrombin time, activated partial thromboplastin time, fibrinogen and fibrinogen degradation products) in 60 head traumatized patients. These parameters were alterated in a high percentage of patients. Moreover 5 patients presented laboratory values indicative of disseminated intravascular coagulation (DIC). DIC could be an important factor of mortality in the head traumatized patients. So coagulation system must be carefully evaluated in any patient with head injury.
Article
Three cases with intracranial lesions developed evidence of disseminated intravascular coagulation which was confirmed at necropsy. The factors engendering this state, including release of potent thromboplastin from neural tissue are discussed and the danger of this intermediary mechanism of disease increasing the mortality of intracranial disease is demonstrated. Careful haematological investigation of all patients with intracranial disease is therefore advised, especially if they manifest evidence of a bleeding tendency.
Article
The fibrinolytic response to trauma was investigated in 23 patients. Patients were triaged upon arrival in the emergency center into three groups; group I-patients with significant trauma who maintained normal vital signs, had a good prognosis, and tolerated the trauma well (mean injury severity score 8, range 4 to 12); group II--patients with significant trauma and transient episodes of hypotension, hypoxia, or acidosis who recovered (mean injury severity score 22, range 9 to 38); and group III--patients with profound or continued hypoxia and hypotension who eventually died of the trauma (mean injury severity score 41, range 30 to 50). Serial measurements of prothrombin time, activated partial thromboplastin time, and platelet count; concentrations of fibrinogen, plasminogen, and fibrin degradation products; and assays of euglobulin fraction fibrinolytic activity on plasminogen-free and plasminogen-rich fibrin plates were obtained on all patients. Coagulation studies documented a trauma-related coagulopathy that correlated with the degree of trauma. Plasminogen concentrations were initially depressed in all three groups; however by 24 hours group III patients were noted to have significantly elevated plasminogen concentrations while group I and group II patients had normal plasminogen concentrations. Fibrinolytic activity measured on plasminogen-free and plasminogen-rich fibrin plates was initially increased in all three groups with group III patients demonstrating the greatest increase. Over the succeeding 14 hours fibrinolytic activity returned to baseline values in group I and group II patients while group III patients demonstrated no detectable fibrinolytic activity for the remainder of the study period. This absence of fibrinolytic activity and increase in plasminogen concentrations in group III patients is thought to be caused by depletion of the intravascular plasminogen activator with the subsequent development of a hypofibrinolytic state.
Article
Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients. To examine the safety and dose-related efficacy of aprotinin, a prospective, multicenter, placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft (CABG) surgery. Two hundred eighty-seven patients were randomly assigned to receive either high-dose aprotinin, low-dose aprotinin, pump-prime-only aprotinin, or placebo. Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume. The percentage of patients requiring donor-red-blood-cell (RBC) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups (high-dose aprotinin, 54%; low-dose aprotinin, 46%; pump-prime only, 72%; and placebo, 75%; overall P = .001). The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo (high-dose aprotinin, 1.6 +/- 0.2 U; low-dose aprotinin, 1.6 +/- 0.3 U; pump-prime-only, 2.5 +/- 0.3 U; and placebo, 3.4 +/- 0.5 U; P = .0001). There was also a significant difference in total blood-product exposures among treatment groups (high-dose aprotinin, 2.2 +/- 0.4 U; low-dose aprotinin, 3.4 +/- 0.9 U; pump-prime-only, 5.1 +/- 0.9 U; placebo, 10.3 +/- 1.4 U). There were no differences among treatment groups for the incidence of perioperative myocardial infarction (MI). This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI.
Article
To determine blood products used, clinical outcomes and frequency of haemostatic complications of massive blood transfusion. Retrospective review of the medical records of patients receiving more than 10 units of blood in 24 hours at a tertiary referral hospital in 1993. Forty-three patients fulfilled this criterion. The major reasons for massive transfusion were trauma (46%; 20 patients), gastrointestinal bleeding (21%; nine patients) and leaking abdominal aortic aneurysm (14%; six patients). Blood products used, platelet count ( < 50 x 10(9)/L in first 48 h), prothrombin time (PT) and activated partial thromboplastin time (APTT) (twice normal in first 48 h), microvascular bleeding, and survival. The 43 patients used 824 units of packed cells 15.2% of the total used in 1993), 457 units of fresh frozen plasma (FFP) (17.1% of the 1993 total) and 370 units of platelets (14.8% of the 1993 total). Overall, these patients consumed 16% of the total number of units of blood product used in 1993 for 1478 transfusion episodes. The overall survival rate was 60%. Severe coagulopathy occurred in 19 patients (44%) (mortality rate, 74%), and 13 (31%) had severe thrombocytopenia ( < 50 x 10(9)/L). There was no significant correlation between the severity of coagulopathy/thrombocytopenia and total units transfused, or between the age of the units of blood and development of coagulopathy or microvascular bleeding. Severe coagulopathy is common after massive transfusions. In the absence of clear correlation with the number of units transfused, "formula" replacement with plasma and platelets is unlikely to avoid the problem. Duration of tissue hypoperfusion and platelet consumption are likely to be more important than simple haemodilution of coagulation factors.
Article
Recognizing the impact of the 1977 San Francisco study of trauma deaths in trauma care, our purpose was to reassess those findings in a contemporary trauma system. Cross-sectional. All trauma deaths occurring in Denver City and County during 1992 were reviewed; data were obtained by cross-referencing four databases: paramedic trip reports, trauma registries, coroner autopsy reports and police reports. There were 289 postinjury fatalities; mean age was 36.8 +/- 1.2 years and mean Injury Severity Score (ISS) was 35.7 +/- 1.2. Predominant injury mechanisms were gunshot wounds in 121 (42%), motorvehicle accidents in 75 (38%) and falls in 23 (8%) cases. Seven (2%) individuals sustained lethal burns. Ninety eight (34%) deaths occurred in the pre-hospital setting. The remaining 191 (66%) patients were transported to the hospital. Of these, 154 (81%) died in the first 48 hours (acute), 11 (6%) within three to seven days (early) and 26 (14%) after seven days (late). Central nervous system injuries were the most frequent cause of death (42%), followed by exsanguination (39%) and organ failure (7%). While acute and early deaths were mostly due to the first two causes, organ failure was the most common cause of late death (61%). In comparison with the previous report, we observed similar injury mechanisms, demographics and causes of death. However, in our experience, there was an improved access to the medical system, greater proportion of late deaths due to brain injury and lack of the classic trimodal distribution.
Article
To determine if the decision to pack for hemorrhage could be refined. Seventy consecutive trauma patients for whom packing was used to control hemorrhage were studied. The patients had liver injuries, abdominal vascular injuries, and bleeding retroperitoneal hematomas. Preoperative variables were analyzed and survivors compared with nonsurvivors. Packing controlled hemorrhage in 37 (53%) patients. Significant differences (p < 0.05) between survivors and nonsurvivors were Injury Severity Score (29 vs. 38), initial pH (7.3 vs. 7.1), platelet count (229,000 vs. 179,000/mm3), prothrombin time (14 vs. 22 seconds), partial thromboplastin time (42 vs. 69 seconds), and duration of hypotension (50 vs. 90 minutes). Nonsurvivors received 20 units of packed red blood cells before packing compared to 13 units for survivors. Patients who suffer severe injury, hypothermia, refractory hypotension, coagulopathy, and acidosis need early packing if they are to survive. Failure to control hemorrhage is related to severity of injury and delay in the use of pack tamponade. A specific protocol that mandates packing when parameters reach a critical limit should be considered.
Article
To measure the prevalence of and characterize coagulopathy in patients with blunt brain injury. Retrospective observation study based on review of medical records. Acutely injured patients admitted to a level I trauma center. One hundred fifty-nine patients with evidence of blunt head trauma who had computed tomography of the brain during initial evaluation and a coagulopathy score assigned based on 5 laboratory tests: platelet count, prothrombin time, partial thromboplastin time, fibrinogen level, and D-dimer level. The disseminated intravascular coagulation score ranged from 0 (no coagulopathy) to 15 (severe coagulopathy). Only individuals with intracranial injury based on computed tomography of the brain were designated as brain injured. Presence of coagulopathy, progression of brain injury, and death. Among the 91 patients with brain injury, 41% had coagulopathy (disseminated intravascular coagulation score > or = 5). Of the 68 patients without brain injury, 25% had coagulopathy. The patients with brain injury who developed profound depletion of fibrinogen did so within 4 hours of injury. There were 28 deaths (26 in the group with brain injury and 2 in the group without brain injury). Among patients with brain injury, those with coagulopathy more frequently died (P < .05 by chi 2 analysis). Patients with brain injury and coagulopathy deteriorated more frequently based on computed tomography criteria. After blunt brain injury, a disseminated intravascular coagulation syndrome can lead to consumptive coagulopathy that is associated with a higher frequency of death. The syndrome develops within 1 to 4 hours after injury. Therapeutic interventions need to be implemented immediately to be effective.
Article
Closed head injuries account for a significant portion of the morbidity and mortality following blunt trauma. Severe closed head injuries can be complicated by the development of a coagulopathy that may worsen blood loss and delay invasive neurosurgical procedures. Awaiting the results of coagulation studies prior to initiating treatment of such a coagulopathy introduces an inherent delay that may allow worsening of the coagulation disturbance and negatively influence outcome. This study was undertaken to see if a subgroup of patients with severe closed head injuries had a high probability of developing a coagulopathy and would warrant empiric treatment with fresh frozen plasma. The records of adult patients admitted to our trauma center with a Glasgow coma score (GCS) of < or = 8 and an extracranial abbreviated injury score of < or = 2 during a 9-month period were reviewed. Patients with penetrating trauma or whose altered level of consciousness was due to sedation or shock were excluded. The presence of coagulation abnormalities was determined according to prothrombin time and partial thromboplastin time obtained on admission. The time to invasive neurosurgical procedures for both coagulopathic and noncoagulopathic patients was determined as well as the mean number of hospital days, intensive care unit days, and the mortality for each group. Eighty-one per cent of the patients with a GCS < or = 6 were coagulopathic on admission, and all patients with a GCS of 3 or 4 were coagulopathic. In contrast, no patient with a score of 7 or 8 was coagulopathic. The coagulopathic patients tended to have a higher mortality than the noncoagulopathic patients (53 versus 22%) as well as longer intensive care unit and hospital stays. The mean time to neurosurgical intervention for the coagulopathic group was 226.0 +/- 190.9 minutes versus 84.8 +/- 38.4 minutes for the noncoagulopathic patients. We conclude that patients with closed head injuries who present with a GCS of 6 or less are candidates for empiric treatment for coagulopathy. Such treatment will negate the delay of awaiting coagulation studies. Whether or not such therapy shortens the interval between admission and neurosurgical procedures or alters outcome will require prospective study.
Article
Recalcitrant coagulopathy "the bloody vicious cycle," produces the majority of deaths after torso trauma. A model predicting this life-threatening complication may facilitate clinical decision-making. We prospectively analyzed patients > 15 years old who received a massive transfusion (> 10 units of packed red blood cells (PRBC)/24 h) over a 2-year period. Excluding massive head injuries and pre-existing disease, the 58 study patients had a mean age = 35.4 years, Injury Severity Score (ISS) = 30.6, and PRBC = 24.2 units/24 h. Defined as prothrombin time of two times that of normal laboratory controls and partial thromboplastin time as two times that of normal laboratory controls, 27 patients (47%) developed life-threatening coagulopathy. Using a multiple logistic regression model, the four significant risk factors (with odds ratio) were (1) pH < 7.10 (12.3), (2) temperature < 34 degrees C (8.7), (3) ISS > 25 (7.7), and (4) systolic blood pressure < 70 mm Hg (5.8). The conditional probability of developing coagulopathy was ISS > 25 + systolic blood pressure < 70 mm Hg = 39%, ISS > 25 + temperature < 34 degrees C = 49%, ISS > 25 + pH < 7.10 = 49%; with all four risk factors the incidence was 98%. Postinjury life-threatening coagulopathy in the seriously injured requiring massive transfusion is predicted by persistent hypothermia and progressive metabolic acidosis.
Article
The aim of this investigation was to determine the prognostic value of coagulation abnormalities in a defined subset of patients with acute head injury. Prothrombin time, accelerated partial thromboplastin time (APTT), thrombin clotting time, fibrinogen assay, platelet count, fibrin degradation products (FDP) were assayed in 204 patients with acute closed head injury. Their values were graded on a score 0-3 and the sum score for each patient regarded as the disseminated intravascular coagulation (DIC) score. Moderate to severe DIC scores were evident in 38% of the cohort. At least one parameter was abnormal in 71% of patients. The DIC score correlated inversely with the Glasgow coma score (GCS) (p < 0.0001). In the GCS 13-15 subset, FDP scores were significant predictors of poor outcome (p < 0.001). In the GCS 6-12 subset, the APTT score (p < 0.001), and DIC score (p < 0.0001) predicted an adverse outcome. The DIC scores were significantly abnormal in most patients who had a poor outcome, without evidence of adverse predictors on CT. Logistic regression analysis confirmed the independent predictive capacity of APTT, FDP and DIC scores when values for GCS were fixed. Abnormal haemostatic parameters may enhance the predictive ability in subsets of patients with acute head injury defined by clinical or CT predictors.
Article
Antithrombin III (AT III) treatment has been shown to reduce disseminated intravascular coagulation and to inhibit thrombin, which plays a central role in the activation of platelets and other inflammatory systems in conditions with severe inflammation. The objective of this study was to evaluate the influence of early and high-dose administration of AT III to patients with severe multiple injuries on the inflammatory response and outcome. In a placebo-controlled, double-blind study, 40 consecutive patients with Injury Severity Scores of 29 or greater who met the inclusion criteria were randomized to receive either AT III or placebo within 360 minutes after trauma. Twenty patients were administered AT III for a period of 4 days, aiming to achieve AT III concentrations of 140% of normal. The AT III and placebo groups were comparable with respect to Injury Severity Score, age, incidence of blood pressure less than 80 mm Hg on admission, initial base deficit, and start of the test drug. The patients in the AT III group received a total of about 20,000 IU during the first 4 days. AT III levels of 130 to 140% could be achieved by this regimen, whereas in the control group the AT III concentration averaged about 70%. In the AT III group prothrombin tended to be elevated and prothrombin fragment F1+2 as well as thrombin-AT III complex tended to be lower on the first day. No differences between groups, however, could be observed with respect to partial thromboplastin time, prothrombin time, platelets, plasminogen activator inhibitor I, soluble tumor necrosis factor receptor II, neutrophil elastase, interleukin (IL)-1 receptor antagonist, IL-6, and IL-8. Mortality (15 vs. 5%), incidence of respiratory failure (55 vs. 55%), duration of mechanical ventilation (13 vs. 12 days), and length of stay in the surgical intensive care unit (19 vs. 21 days) were also similar in both treatment groups. The duration of organ failure, however, was shorter in the patients receiving AT III. The early and high-dose administration of AT III to patients with severe blunt trauma appears not to attenuate the posttraumatic inflammatory response or to significantly improve outcome.
Article
Although disseminated intravascular coagulation (DIC) and other hemocoagulative abnormalities are severe complications of head injury, their effect on clinical outcome remains unclear, particularly among children. To evaluate the frequency of hemocoagulative abnormalities and their influence on outcome among children with head injury. We conducted a prospective observational study among 60 children with head injury, immediately evaluating severity of head injury (Glasgow Coma Scale, GCS); cerebral axial tomography; prothrombin time; activated partial thromboplastin time (aPTT); fibrinogen level; concentration of fibrin-fibrinogen degradation products (FDP), and platelet count. Two months after injury, we applied the Glasgow Outcome Score (GOS). Associations with GOS were evaluated using univariate and multivariate logistic models. Among children with severe head injury, 22.2% (6/27) developed DIC, all of whom died and had shown severe brain edema. Among those with severe head injury yet without DIC, the mortality was only 14.2%. A low GOS was significantly and independently associated with a low GCS, multiple trauma, delayed aPTT, low fibrinogen level, elevated FDP and low platelet count. Brain edema was also associated with a low GOS, though not significantly. In addition to GCS, type of trauma, type of brain lesion and certain coagulation abnormalities are predictors of GOS.
Article
Recombinant activated factor VII (rFVIIa) was approved for treatment of hemorrhages in patients with hemophilia who develop inhibitors to factors VIII or IX. Conditions with increased thromboembolic risk, including trauma with or without disseminated intravascular coagulation, were considered a contraindication for the drug. The mechanism of action of rFVIIa suggests enhancement of hemostasis limited to the site of injury without systemic activation of the coagulation cascade. Therefore, use of the drug in trauma patients suffering uncontrolled hemorrhage appears to be rational. Seven massively bleeding, multitransfused (median, 40 units [range, 25-49 units] of packed cells), coagulopathic trauma patients were treated with rFVIIa (median, 120 microg/kg [range, 120-212 microg/kg]) after failure of conventional measures to achieve hemostasis. Administration of rFVIIa resulted in cessation of the diffuse bleed, with significant decrease of blood requirements to 2 units (range, 1-2 units) of packed cells (p < 0.05); shortening of prothrombin time and activated partial thromboplastin time from 24 seconds (range, 20-31.8 seconds) to 10.1 seconds (range, 8-12 seconds) (p < 0.005) and 79 seconds (range, 46-110 seconds) to 41 seconds (range, 28-46 seconds) (p < 0.05), respectively; and an increase of FVII level from 0.7 IU/mL (range, 0.7-0.92 IU/mL) to 23.7 IU/mL (range, 18-44 IU/mL) (p < 0.05). Three of the seven patients died of reasons other than bleeding or thromboembolism. The results of this report suggest that in trauma patients rFVIIa may play a role as an adjunctive hemostatic measure, in addition to surgical hemostatic techniques, and provides the motivation for controlled animal and clinical trials.
Article
Administration of large amounts of fluids to trauma patients, in the absence of surgical control, may increase bleeding, cause hypothermia and coagulopathy which may worsen the bleeding and increase morbidity and mortality. The purpose of our study is to examine the impact of prehospital fluid administration to military combat casualties on core body temperature and coagulation functions. Prospective data were collected on all cases of moderately (9 < or = ISS < or = 14) and severely (ISS > or = 16) injured victims wounded in South Lebanon, treated by Israeli military physicians and evacuated to hospitals in Israel, over a two-year period. Data regarding prehospital phase of injury (timetables, amount of fluids) and upon hospital arrival (initial core body temperature, prothrombin time [PT], partial thromboplastin time [PTT]) were examined for monotonic relation using Spearman's non-parametric test. Fifty-three moderately injured and 31 severely injured patients were included in the study. The average evacuation time for the moderately injured group was 109.3 +/- 44.8 min, and for the severely injured 100.3 +/- 38.4 min (P value=NS). The mean volume of fluids administered was 2.39 +/- 1.52 and 2.49 +/- 1.47 l, respectively (P=NS). No statistical correlation was found between core body temperature, PT or PTT, measured upon hospital arrival, and prehospital fluid treatment. In addition, no correlation was found between core body temperature on hospital arrival and prehospital time, or between prehospital fluid volumes and prehospital time. The mean core body temperature of the moderately injured patients was 36.8 degrees C, and that of severely injured was 35.8 degrees C (P=0.026). With proper control of blood loss and avoidance of excessive fluid administration, moderately and severely injured combat casualties in 'low intensity conflict' in South Lebanon can be resuscitated with fluid volumes that do not result in a coagulation deficit or hypothermia. The core body temperature on arrival at the hospital is related to the severity of the injury.
Article
Recombinant factor VIIa (rFVIIa) is used for treatment of bleeding episodes in hemophilia patients who develop inhibitors to factors VIII and IX. We tested the hypothesis that administration of rFVIIa early after injury would decrease bleeding and improve survival after experimental hepatic trauma. Anesthetized swine were cannulated for blood sampling and hemodynamic monitoring. Avulsion of left median lobe of the liver induced uncontrolled hemorrhage. After a 10% reduction of mean arterial pressure, animals were blindly randomized to receive intravenous rFVIIa (180 microg/kg) (n = 6) or placebo (n = 7). Mortality was 43% (three of seven) in controls versus 0% with rFVIIa (p = 0.08, chi2). Significantly shorter prothrombin time and higher mean arterial pressures were observed in the rFVIIa group. Intravenous administration of rFVIIa early after induction of hemorrhage shortens prothrombin time and improves mean arterial pressure. A trend toward improved survival was observed.
Article
Recombinant factor VIIa (rFVIIa) has been used to decrease bleeding in a number of settings including hemophilia, liver transplantation, intractable bleeding, and cirrhosis. Experience in the trauma setting is limited. This study was performed to determine whether rFVIIa would reduce bleeding after a grade V liver injury in hypothermic, dilutionally coagulopathic pigs when used as an adjunct to abdominal packing and to determine whether increasing the dose of the drug increased its hemostatic efficacy. Thirty animals were randomized to receive 180 microg/kg of rFVIIa, 720 microg/kg of rFVIIa, or vehicle buffer control. After laparotomy and splenectomy, animals underwent a 60% blood volume isovolemic exchange transfusion with 5% human albumin. The animals' temperature was maintained at 33 degrees C and a standardized grade V liver injury was made with a liver clamp. Thirty seconds after injury, the abdomen was packed with laparotomy sponges, resuscitation was initiated, and blinded therapy was given. Animals were resuscitated to their baseline mean arterial pressure and the study was continued for 2 hours. Serial coagulation parameters were measured at the temperature they were drawn. After the study period, surviving animals were killed, posttreatment blood loss was measured, and an autopsy was performed. Ten animals were randomized to each group. After administration of study drug, factor VII clotting activity (FVII:C) was higher in the 720 microg/kg group than in the 180 microg/kg group (p < 0.01). FVII:C was higher in both treatment groups than in the control group (p < 0.01). The mean prothrombin time was shorter in the treatment groups than in the control group (p < 0.05). Mean arterial pressure was lower in the control group than in the treatment groups throughout the study (p < 0.01). Mean blood loss was less in the treatment groups than in the control group (p = 0.03). Mortality was not different between groups. There were no differences between the groups that received rFVIIa in any measured parameters except for FVII:C. Liver injuries were similar between groups and there was no evidence of microthrombosis on lung histology. rFVIIa reduces blood loss in hypothermic, dilutionally coagulopathic pigs with grade V injuries when used as an adjunct to packing. Increasing the dose does not enhance the hemostatic effect.
Disseminated intravascular coagulation as a consequence of cerebral damage Coagulopathy and catecholamines in severe head injury
  • Fe Preston
  • Rg Malia
  • Mj Sworn
  • Wr Timperley
  • Blackburn
  • Tj Kearney
  • L Bentt
  • M Grode
  • S Lee
  • Jr Hiatt
  • Shabot
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  • Martinowitz