Criteria for empiric treatment of hyperfibrinolysis after trauma

Abstract

Background: Recent studies identify a survival benefit from the administration of antifibrinolytic agents in patients with severe injury and trauma. However, identification of hyperfibrinolysis requires thromboelastography, which is not widely available. We hypothesized that analysis of patients with thromboelastography-diagnosed hyperfibrinolysis would identify clinical criteria for empiric antifibrinolytic treatment in the absence of thromboelastography.

Methods: From November 2010 to March 2012, serial blood samples were collected from 115 patients with critical injury on arrival to the emergency department of an urban Level I trauma center. Rotational thromboelastography was performed to assess viscoelastic properties of clot formation in the presence and absence of aprotinin to identify treatable hyperfibrinolysis. For 20 patients identified with treatable hyperfibrinolysis, clinical predictors were investigated using receiver operating characteristic analysis.

Results: Of the 115 patients evaluated, 20% had hyperfibrinolysis, defined as an admission maximal clot lysis of 10% or higher, reversible by aprotinin treatment. Patients with hyperfibrinolysis had significantly lower temperature, pH, and platelet counts and higher international normalized ratio, activated partial thromboplastin time, 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-rotational thromboelastography clinical and laboratory parameters predictive of hyperfibrinolysis using receiver operating characteristic analysis to evaluate potential empiric treatment guidelines. The presence of hypothermia (temperature ≤36.0°C), acidosis (pH ≤7.2), relative coagulopathy (international normalized ratio ≥1.3 or activated partial thromboplastin time ≥30), or relative thrombocytopenia (platelet count ≤200) identified hyperfibrinolysis with 100% sensitivity and 55.4% specificity (area under the curve, 0.777).

Conclusion: Consideration of empiric antifibrinolytic therapy is warranted for patients with critical injury and trauma 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 with 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 III.

Figure 1

Representative admission ROTEM® tracings for patients with hyperfibrinolysis.

Figure 2

Kaplan-Meier 24-hour survival curves showing early survival differences between patients with (dashed line) and without (solid line) hyperfibrinolysis. *p < 0.001 by log-ran test.