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

ArticleinThe Journal of trauma 67(1):125-31 · August 2009with39 Reads
DOI: 10.1097/TA.0b013e31818b2483 · Source: PubMed
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.
    • "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: Introduction: Viscoelastic 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.
    Full-text · Article · Oct 2016
    • "Impaired fibrin polymerization can also directly contribute to hyperfibrinolysis by increasing susceptibility to enzymatic degrada- tion [8,9]. Hyperfibrinolysis is strongly associated with trauma patient mortality and when significant, often predicts imminent death [10]. In addition, antifibrinolytic therapy using the lysine analogue tranexamic acid is the only therapy found to reduce mortality when given early after injury in a large randomized controlled trial [11]. "
    [Show abstract] [Hide abstract] ABSTRACT: Victims of trauma often develop impaired blood clot formation (coagulopathy) that contributes to bleeding and mortality. Fibrin polymerization is one critical component of clot formation that can be impacted by post-translational oxidative modifications of fibrinogen after exposure to oxidants. In vitro evidence suggests that Aα-C domain methionine sulfoxide formation, in particular, can induce conformational changes that prevent lateral aggregation of fibrin protofibrils during polymerization. We used mass spectrometry of plasma from trauma patients to find that fibrinogen Aα-C domain methionine sulfoxide content was selectively-increased in patients with coagulopathy vs. those without coagulopathy. This evidence supports a novel linkage between oxidative stress, coagulopathy, and bleeding after injury.
    Full-text · Article · Apr 2016
    • "Accordingly, the fibrinolytic activity achieves a peak level after reperfusion of the liver graft [169, 182]. However, hyperfibrinolysis developed during the anhepatic phase or reperfusion is self-limiting in most cases after reperfusion and not associated with increased mortality (in contrast to hyperfibrinolysis in severe trauma) [62, 167, 171, 172, 183, 184]. Therefore, hyperfibrinolysis is only treated with TXA according to our algorithm in case of severe bleeding and a LI60 EX < 85 % during the pre-anhepatic phase or a LI30 EX < 50 % during the anhepatic phase or after reperfusion (Fig. 29.2 and Chap.5, Fig. 5.5b™ is rechecked after detecting of hyperfibrinolysis and not treated with TXA if it is self-limiting. "
    [Show abstract] [Hide abstract] ABSTRACT: Hemostasis in patients with cirrhosis usually is rebalanced on a low level and therefore can quickly result in bleeding as well as in thrombosis. Both bleeding and thrombosis are associated with poor outcome. Notably, standard laboratory coagulation tests, such as prothrombin time (PT) and the international normalized ratio (INR), are not able to discriminate between hypo- and hypercoagulability, nor are they able to predict the risk of bleeding in patients with cirrhosis. Therefore, these tests are not applicable to guide hemostatic therapy in these patients, and prophylactic transfusion of fresh frozen plasma (FFP) and platelets, due to an increased INR or low platelet count, should be avoided. On the one hand, they can result in transfusion-associated circulatory overload and portal hypertension with increased bleeding and, on the other hand, in organ dysfunction and thrombosis. Accordingly, hemostatic interventions should only be performed in cases of clinically relevant bleeding. In contrast, thrombin generation assays in the presence of soluble thrombomodulin or Protac®—as well as viscoelastic hemostatic testing (VHT) such as thromboelastometry (ROTEM®) and thrombelastography (TEG®)—indicate that patients with cirrhosis tend rather to hypercoagulability with its inherent risk of thrombosis than to spontaneous bleeding. Several studies demonstrated that invasive interventions such as liver biopsy and central venous catheterization can be performed in cirrhotic patients with increased INR and low platelet count without increased incidence of bleeding risk if thromboelastometric results are normal. Furthermore, implementation of bleeding management algorithms based on thromboelastometry has been shown to reduce transfusion requirements, transfusion-associated adverse events, and liver transplant costs. First-line, calculated, thromboelastometry-guided therapy with fibrinogen and 4-factor prothrombin complex concentrate seems to be the most effective without increasing the incidence of thrombotic/thromboembolic events. Notably, patients with cirrhosis and increased INR are not “auto-anticoagulated.” Therefore, thromboprophylaxis should strongly be considered in patients with cirrhosis, despite prolonged PT and increased INR.
    Full-text · Chapter · Jan 2016 · Free Radical Biology and Medicine
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