Hyperfibrinolysis After Major Trauma: Differential Diagnosis of Lysis Patterns and Prognostic Value of Thrombelastometry

ArticleinThe Journal of trauma 67(1):125-31 · August 2009with41 Reads
DOI: 10.1097/TA.0b013e31818b2483 · Source: PubMed
Abstract
The aim of this study was to diagnose hyperfibrinolysis (HF) and its pattern using thrombelastometry and to correlate the diagnosis with mortality. Furthermore, routine laboratory based and the rotational thrombelastometry analyzer (ROTEM)-derived variables were also correlated with survival. Severe trauma patients showing HF in ROTEM were consecutively enrolled in the study. Three different HF patterns were compared: fulminant breakdown within 30 minutes, intermediate HF of 30 to 60 minutes, and late HF after 60 minutes. Injury severity score (ISS), hemodynamics, hemoglobin, hematocrit, platelet count (PC), fibrinogen, and ROTEM variables at admission were analyzed. The observed mortality was compared with the predicted trauma and injury severity score mortality. Thirty-three patients were diagnosed with HF. The mean ISS was 47 +/- 14. Fulminant, intermediate, or late HF (n = 11 each group) resulted in 100%, 91%, or 73% mortality, respectively, with the best prognosis for late HF (p = 0.0031). The actual overall mortality of HF (88%) exceeded the predicted trauma and injury severity score mortality (70%) (p = 0.039). Lower PC (123 +/- 53 vs. 193 +/- 91; p = 0.034), ROTEM prolonged clot formation time [CFT, 359 (140/632) vs. 82 (14/190); p = 0.042], and lower platelet contribution to maximum clot firmness [MCF(EXTEM) - MCF(FIBTEM), 34 (20/40) vs. 46 (40/53); p = 0.026] were associated with increased mortality. ROTEM-based diagnosis of HF predicted outcome. Further independent predictors of death were combination of HF with hemorrhagic shock, low PC, and prolonged CFT in ROTEM. ROTEM-based point of care testing in the emergency room is thus able to identify prognostic factors such as prolonged CFT and low platelet contribution to clot firmness (MCF(EX) - MCF(FIB)) earlier than standard laboratory-based monitoring.
    • Furthermore, the acute and massive t-PA release induces hyperfibrino(geno)lysis [3, 4, 12, 20,[57][58][59][60][61][62]. Thromboelastometry such as ROTEM® can detect acute release of t-PA as lysis of clots formed in test tubes [57][58][59][60][61][62].
    [Show abstract] [Hide abstract] ABSTRACT: In severe trauma patients, coagulopathy is frequently observed in the acute phase of trauma. Trauma-induced coagulopathy is coagulopathy caused by the trauma itself. The pathophysiology of trauma-induced coagulopathy consists of coagulation activation, hyperfibrino(geno)lysis, and consumption coagulopathy. These pathophysiological mechanisms are the characteristics to DIC with the fibrinolytic phenotype.
    Full-text · Article · Dec 2017
    • This observation is commensurate with the concept of rebalanced hemostasis, and is in line with the fact that many of these patients undergo liver transplantation and invasive procedures without requiring blood products [9] . VETs for coagulation are increasingly used for point-of-care (POC) analysis of the complex coagulopathies that can occur during cardiac surgery, and following major trauma and orthopedic liver transplantation [10][11][12]. Thromboelastography (TEG; Haemonetics Corporation, Braintree, MA, USA) and rotational thromboelastometry (ROTEM; TEM International GmbH, Munich, Germany) are two commercially available VETs. VETs evaluate the kinetics of coagulation from initial clot formation to final clot strength and provide a composite picture reflecting the interaction of plasma, blood cells, and platelets .
    [Show abstract] [Hide abstract] ABSTRACT: Background The aims of this study were to investigate the parameters of thromboelastography (TEG) for evaluating coagulopathy and to reveal an association with disease severity and/or transfusion requirement in patients with chronic liver disease (CLD) in a clinical laboratory setting. Methods We enrolled two groups of adult patients with cirrhotic (N=123) and non-cirrhotic liver disease (N=52), as well as 84 healthy controls. Reaction time (R), kinetic time (K), α-angle (α), maximal amplitude (MA), and coagulation index (CI) were measured with kaolin-activated citrated blood with the TEG 5000 system (Haemonetics Corporation, USA). Platelet count, prothrombin time international normalized ratio (PT INR), albumin, bilirubin, and creatinine were simultaneously measured. The CLD severity was calculated by using the Child-Pugh (C-P) and Model for End-stage Liver Disease (MELD) scores. Transfusion history was also reviewed. Results All TEG parameters, PT INR, and platelet count in the cirrhotic group showed significant differences from those in other groups. At least one or more abnormal TEG parameters were identified in 17.3% and 44.7% of patients in the non-cirrhotic and cirrhotic group, respectively. Patients with cirrhotic disease had hypocoagulability. A weak correlation between R and PT INR (r=0.173) was noted. The TEG parameters could not predict CLD severity using the C-P and MELD scores. Patients with normal TEG parameters did not receive transfusion. Conclusions Clinical application of TEG measurements in CLD can be informative for investigating coagulopathy or predicting the risk of bleeding. Further studies are warranted.
    Full-text · Article · May 2017
    • It is recommended to embed administration of the antifibrinolytic agent in an overall therapy plan for treating coagulopathy, since in the course of HF the consumption of fibrinogen may frequently increase to such an extent that complete defibrination results. This fibrinogen depletion has to be compensated for once HF has been overcome[35]or in other words, the antifibrinolytic agent should be applied before fibrinogen is administered whenever HF is suspected[36]. For polytrauma patients the Austrian Society for Anaesthesiology, Resuscitation and Intensive Care (ÖGARI) and European guidelines[2,3]recommend early administration of TXA (in the shock room at the latest).
    [Show abstract] [Hide abstract] ABSTRACT: Uncontrolled massive bleeding with subsequent derangement of the coagulation system is a major challenge in the management of both surgical and seriously injured patients. Under physiological conditions activators and inhibitors of coagulation regulate the sensitive balance between clot formation and fibrinolysis. In some cases, excessive and diffuse bleeding is caused by systemic activation of fibrinolysis, i. e. hyperfibrinolysis (HF). Uncontrolled HF is associated with a high mortality. Polytrauma patients and those undergoing surgical procedures involving organs rich in plasminogen proactivators (e. g. liver, kidney, pancreas, uterus and prostate gland) are at a high risk for HF. Antifibrinolytics, such as tranexamic acid (TXA) are used for prophylaxis and treatment of bleeding caused by a local or generalized HF as well as other hemorrhagic conditions. TXA is a synthetic lysine analogue that has been available in Austria since 1966. TXA is of utmost importance in the prevention and treatment of traumatic and perioperative bleeding due to the resulting reduction in perioperative blood loss and blood transfusion requirements. The following article presents the different fields of application of TXA with particular respect to indications and dosages, based on a literature search and on current guidelines.
    Full-text · Article · Apr 2017
    • Assessment of clinical status, intubation, adequate ventilation, and fluid resuscitation are important treatment options to prevent and treat hypoxia, hypoventilation, and hypotension[5,6]. Coagulopathy is an important problem after TBI[7], and thrombelastometry (TEM) has been used to assess coagulation after trauma[8][9][10]as well as after TBI[11,12]. The goal of this retrospective analysis of prospectively collected data was to assess whether the early use of TEM would lead to improved outcomes as suggested in an earlier study on trauma patients[12].
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: Posttraumatic coagulopathy worsens outcomes of patients with severe traumatic brain injury (TBI). This study aimed to investigate whether the early use of thrombelastometry (TEM) was associated with better outcomes after TBI. Methods: Between 3/2002 and 4/2012 17 Austrian centers enrolled TBI patients into 2 observational studies that focused on effects of guideline compliance (n = 400) and on prehospital and early hospital management (n = 777), respectively. Data on trauma severity, clinical status, prehospital and hospital treatment, and outcomes were collected prospectively. Information on use or non-use of TEM was missing in 278 cases. Data from patients with hopeless prognosis and patients with moderate TBI were excluded. Two groups of patients were created: the “TEM group” (TEM used within the first 2 hours after admission, n = 211) and the “no-TEM group” (211 matched patients selected from 610 possible cases). Demographic data and data on trauma severity, treatment and outcome were compared. Logistic regression models, corrected for the effects of age, Glasgow Coma Scale (GCS) scores, and Injury Severity Score (ISS) were constructed. A p-value of <.05 was considered statistically significant. Results: Age, sex, trauma mechanisms, and treatment were not significantly different. The “TEM group” had higher trauma severity. However, hospital mortality was significantly lower (20% vs. 31%, p = 0.01) Logistic regression revealed that use of TEM, age, ISS and GCS score had significant influences upon hospital mortality and long-term outcome. Conclusions: The early use of TEM is associated with significantly better outcomes after severe TBI.
    Full-text · Article · Jan 2017 · Scandinavian Journal of Trauma Resuscitation and Emergency Medicine
    • It can, however, help to prevent unnecessary fibrinogen consumption caused by fibrinolysis. In our study, 1 g of TxA was given to patients with multiple injuries immediately after intravenous access Median time [min, max] Time to EP arrival (after injury) 18 min [4, 65] Time to TxA administration (after injury) 32 min [17, 85] Time to TxA administration (after EP arrival) 15 min [7, 53] Time to hospital arrival (after injury) 74 min [31, 140] Time to hospital arrival (after EP arrival) 56 min [25, 128] Time to hospital arrival (after TxA administration) 37 min [10, 85] was established and the study blood samples had been taken. Although TxA has no current marketing indication for use among major trauma patients, it is commonly used in clinical practice, and its administration is recommended by current guidelines [20].
    [Show abstract] [Hide abstract] ABSTRACT: Background Hyperfibrinolysis (HF) is a major contributor to coagulopathy and mortality in trauma patients. This study investigated (i) the rate of HF during the pre-hospital management of patients with multiple injuries and (ii) the effects of pre-hospital tranexamic acid (TxA) administration on the coagulation system. Methods From 27 trauma patients with pre-hospital an estimated injury severity score (ISS) ≥16 points blood was obtained at the scene and on admission to the emergency department (ED). All patients received 1 g of TxA after the first blood sample was taken. Rotational thrombelastometry (ROTEM) was performed for both blood samples, and the results were compared. HF was defined as a maximum lysis (ML) >15 % in EXTEM. ResultsThe median (min-max) ISS was 17 points (4–50 points). Four patients (15 %) had HF diagnosed via ROTEM at the scene, and 2 patients (7.5 %) had HF diagnosed via ROTEM on admission to the ED. The median ML before TxA administration was 11 % (3–99 %) vs. 10 % after TxA administration (4–18 %; p > 0.05). TxA was administered 37 min (10–85 min) before ED arrival. The ROTEM results before and after TxA administration did not significantly differ. No adverse drug reactions were observed after TxA administration. DiscussionHF can be present in severely injured patients during pre-hospital care. Antifibrinolytic therapy administered at the scene is a significant time saver. Even in milder trauma fibrinogen can be decreased to critically low levels. Early administration of TxA cannot reverse or entirely stop this decrease. Conclusions The pre-hospital use of TxA should be considered for severely injured patients to prevent the worsening of trauma-induced coagulopathy and unnecessarily high fibrinogen consumption. Trial registrationClinicalTrials.gov ID NCT01938768 (Registered 5 September 2013).
    Full-text · Article · Dec 2016
    • Davenport [41] demonstrated that EXTEM CA5 ≤ 35 mm predicted the need for MT with higher detection rate compared to INR > 1.2 (71 vs. 43 %, p < 0.001). Schochl [28], using threshold pre-established in a previous study by the same group [26] reported that both FIBTEM A10 ≤ 4 mm (ROC AUC = 0.83) and FIBTEM MCF ≤ 7 mm (ROC AUC = 0.84) were predictive of the need for MT. Lastly, Hagemo [43] demonstrated that threshold values of EXTEM CA5 ≤ 40 mm predicted MT in 72.7 % and FIB- TEM CA5 ≤ 9 mm predicted MT in 77.5 %, respectively.
    [Show abstract] [Hide abstract] ABSTRACT: IntroductionViscoelastic assays have been promoted as an improvement over traditional coagulation tests in the management of trauma patients. Rotational thromboelastometry (ROTEM®) has been used to diagnose coagulopathy and guide hemostatic therapy in trauma. This systematic review of clinical studies in trauma investigates the ROTEM® parameters thresholds used for the diagnosing coagulopathy, predicting and guiding transfusion and predicting mortality. Methods Systematic literature search was performed using MEDLINE, EMBASE and Cochrane databases. We included studies without restricting year of publication, language or geographic location. Original studies reporting the thresholds of ROTEM® parameters in the diagnosis or management of coagulopathy in trauma patients were included. Data on patient demographics, measures of coagulopathy, transfusion and mortality were extracted. We reported our findings according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Quality assessment and risk of bias were performed using Newcastle Ottawa Scale (NOS) and the quality assessment of diagnostic accuracy studies (QUADAS-2) tools, respectively. ResultsA total of 13 observational studies involving 2835 adult trauma patients met the inclusion criteria. Nine studies were prospective and four were retrospective. There were no randomized controlled trials. The quality of the included studies was moderate (mean NOS 5.92, standard deviation 0.26). Using QUADAS-2, only 1 study (7.6 %) had low risk of bias in all domains, and 9 studies (69.2 %) had low risk of applicability concerns. Outcomes from 13 studies were grouped into three categories: diagnosis of coagulopathy (n = 10), prediction of massive transfusion or transfusion guidance (n = 6) and prediction of mortality (n = 6). Overall, specific ROTEM® parameters measured (clot amplitude and lysis) in the extrinsically activated test (EXTEM) and the fibrin-based extrinsically activated test (FIBTEM) were consistently associated with the diagnosis of coagulopathy, increased risk of bleeding and massive transfusion, and prediction of mortality. Presence of hyperfibrinolysis by ROTEM® was associated with increased mortality. Conclusions Most of the evidence indicates that abnormal EXTEM and FIBTEM clot amplitude (CA5, CA10) or maximal clot firmness (MCF) diagnose coagulopathy, and predict blood transfusion and mortality. The presence of fibrinolysis (abnormal lysis index [LI30] or maximum lysis [ML]) was also associated with mortality. ROTEM® thus, may be of value in the early management of trauma patients.
    Full-text · Article · Oct 2016
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