Criteria for empiric treatment of hyperfibrinolysis after trauma

Abstract

Background Recent studies identify a survival benefit from the administration of antifibrinolytic agents in severely injured trauma patients. However, identification of hyperfibrinolysis requires thromboelastometry, which is not widely available. We hypothesized that analysis of patients with thromboelastometry-diagnosed hyperfibrinolysis would identify clinical criteria for empiric antifibrinolytic treatment in the absence of thromboelastometry. Methods From 11/2010 – 3/2012, serial blood samples were collected from 115 critically-injured patients on arrival to the emergency department of an urban level I trauma center. Rotational thromboelastometry (ROTEM®) was performed to assess viscoelastic properties of clot formation in the presence and absence of aprotinin to identify treatable hyperfibrinolysis. In 20 patients identified with treatable hyperfibrinolysis, clinical predictors were investigated using receiver-operator characteristic analysis. Results Of 115 patients evaluated, 20% had hyperfibrinolysis, defined as an admission maximal clot lysis ≥10% reversible by aprotinin treatment. Patients with hyperfibrinolysis had significantly lower temperature, pH, and platelet counts, and higher INR, PTT, and D-dimer. Hyperfibrinolysis was associated with multiorgan failure (63.2% vs. 24.6%, p=0.004) and mortality (52.2% vs. 12.9%, p<0.001). We then evaluated all non-ROTEM clinical and laboratory parameters predictive of hyperfibrinolysis using receiver-operator characteristic analysis to evaluate potential empiric treatment guidelines. The presence of hypothermia (temperature ≤36.0), acidosis (pH ≤7.2), relative coagulopathy (INR ≥1.3 or PTT ≥30), or relative thrombocytopenia (platelet count ≤200) identified hyperfibrinolysis with 100% sensitivity and 55.4% specificity (area under the curve 0.777). Conclusions Consideration of empiric antifibrinolytic therapy is warranted for critically-injured trauma patients who present with acidosis, hypothermia, coagulopathy, or relative thrombocytopenia. These clinical predictors identified hyperfibrinolysis with 100% sensitivity while simultaneously eliminating 46.6% of inappropriate therapy compared to the empiric treatment of all injured patients. These criteria will facilitate empiric treatment of hyperfibrinolysis for clinicians without access to thromboelastography. Level of evidence Prognostic study, Level I

Dynamics of fibrinogen in acute phases of trauma

“…This rapid t-PA release from endothelial cells activates the conversion of plasminogen to plasmin and induces hyper-fibrino(geno)lysis [12,16,46,47]. Shockinduced hyper-fibrino(geno)lysis are confirmed as lysis of clot formed in its test tube by thromboelastometry, such as ROTEM®, and is a predictor for massive bleeding and death [48][49][50][51][52][53]. Typical hyper-fibrino(geno)lysis detected via thromboelastometry is infrequent and is associated with very high mortality rates [48,51,53].…”

“…Shock-induced hyper-fibrino(geno)lysis is diagnosed via thromboelastometry [48][49][50][51][52][53]. However, the technique requires more than 30 min to evaluate hyperfibrino(geno)lysis [48][49][50][51][52][53].…”

Viscoelastic point-of-care testing to assist with the diagnosis, management and monitoring of haemostasis: a systematic review and cost-effectiveness analysis

“…126 There are also some published data indicating that the risk of death from bleeding increases at levels of clot lysis < 7.5% (at 30 minutes post maximum clot strength) which is generally regarded as normal. 127,128 The ROTEM FIBTEM assay and the TEG functional FIB assay use a reagent that is specific for the fibrin polymerisation process, which declines more rapidly than FIB levels as measured in the laboratory. 129 This adds the potential to detect the pathology at an earlier stage in its evolution to the time gained from using POC testing compared with laboratory-based testing.…”

Management of traumatic haemorrhage – the European perspective

“…Thus, antifibrinolytic therapy should be initiated based on pragmatic clinical aspects, such as pronounced shock, hypothermia and substantial tissue trauma rather than guided by visco-elastic tests ( Figs. 1 and 2) [48].…”