Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor

Abstract

Bleeding is a common hemostatic disorder that occurs in Bothrops envenomations. We evaluated the changes in coagulation, fibrinolysis components, and platelets in Bothrops atrox envenomations with bleeding. This is an observational study with B. atrox snakebite patients (n = 100) treated in Manaus, Brazilian Amazon. Bleeding was recorded on admission and during hospitalization. We found that the platelet count in our patients presented a weak correlation to tissue factor, factor II, and plasminogen. Tissue factor presented weak correlation to factor V, II, D-dimer, plasminogen, alpha 2-antiplasmin, and moderate correlation to fibrinogen and fibrin/fibrinogen degradation product (FDP). Patients with systemic bleeding (n = 20) presented low levels of factor V, II, fibrinogen, plasminogen, and alpha 2-antiplasmin, and high levels of tissue factor and FDP compared to those without bleeding. Patients with only local bleeding (n = 41) and without bleeding showed similar levels of hemostatic factors. Thrombocytopenia was observed mainly in patients with systemic bleeding and increased levels of serum venom. No association was found between venom levels and systemic bleeding, or between venom levels and clinical severity of envenomation. This is the first report that shows the participation of the extrinsic coagulation pathway in the consumption coagulopathy of B. atrox envenomations with systemic bleeding due to tissue factor release.

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

“…Envenomed patients present increased prothrombin time (PT) and activated partial thromboplastin time (aPTT), with low level of fibrinogen. Factors II, V, VII, X, XIII also decrease [43,47,48]. Factors involved in the intrinsic pathway (factors VIII, IX, XI, XII) are less frequently reduced [47,48].…”

“…Thrombocytopenia and unclottable blood on admission are independently associated with systemic bleeding during hospitalization for B. atrox et B. jararaca envenomation [29,43,44].…”

“…Clinical studies in patients bitten by B. jararaca evidenced that systemic bleeding is more frequent in patients with thrombocytopenia than in patients with blood incoagulability [45,46]. By contrast, thrombocytopenia is an infrequent event in envenomations in the Amazon, mainly caused by B. atrox [28,43]. A negative correlation was found between the number of platelets and the mean platelet volume on patient admission for an envenomation by B. atrox, suggesting peripheral platelet destruction, which tends to increase the mean platelet volume [29].…”

“…Unclottable blood due to consumption coagulopathy and defibrinogenation usually occurs within one hour [16]. In contrast, patients with only local bleeding and without bleeding may often show normal levels of hemostatic factors and fibrinolysis parameters [43].…”

“…Owing to its low cost, simplicity and good correlation with plasma fibrinogen concentration, the 20 min whole blood clotting test (20WBCT) is an effective and reliable method for evaluation of hemostatic status in the primary care centers without laboratory [51]. In-creased levels of plasma TF are detected and may contribute to the intravascular generation of thrombin as suggested by high levels of thrombin-antithrombin complexes, leading to a transient hypercoagulable state, then to incoagulability and systemic bleeding [43,45,52].…”