Thromboelastography with Platelet Studies (TEG® with PlateletMapping®) After Rattlesnake Envenomation in the Southwestern United States Demonstrates Inhibition of ADP-Induced Platelet Activation As Well As Clot Lysis

Abstract

Introduction Hematologic effects of North American rattlesnake envenomation can include fibrinogenolysis and thrombocytopenia, depending on species, geography, and other variables. During treatment, these effects are routinely monitored through assessment of fibrinogen concentrations and platelet counts. However, these tests provide no information about fibrinolysis or platelet dysfunction, both of which can also occur with venom from some species. Methods This was a retrospective chart review of patients admitted to a quaternary care academic hospital (Banner -University Medical Center Phoenix) in the southwestern United States for treatment of rattlesnake envenomation, over an approximately 1year period from March 2017 through April 2018. Patients who had thromboelastography with platelet studies (TEG® with PlateletMapping®) during their care were included. Results Twelve patients were identified for this study. Four patients exhibited inhibition of ADP-induced platelet activation: one had normal fibrinogen and platelet count, two had concurrent hypofibrinogenemia, and one had concurrent thrombocytopenia. Crotalidae polyvalent immune Fab (ovine) reversed platelet inhibition in the single patient for whom serial thromboelastographs were available. Fibrinolysis was present in seven patients and resolved in the two patients with serial thromboelastographs. Conclusions Inhibition of ADP-induced platelet aggregation and fibrinolysis occurred independent of hypofibrinogenemia and thrombocytopenia, indicating fibrinogen concentration (or protime) and platelet count monitoring alone is insufficient to assess the extent of hematologic toxicity in rattlesnake envenomation. Crotalidae polyvalent immune Fab (ovine) reversed platelet inhibition in one case, suggesting platelet inhibition could also be used in treatment decisions. Fibrinolysis could also be reversed, although the timing to antivenom administration was less clear.

In vitro evaluation of canine whole blood with the addition of Crotalus atrox (Western Diamondback Rattlesnake) venom and antivenom using thromboelastography

“…4,8,10,11,[20][21][22][23] This study confirmed this finding and supports the conclusion that TEG is useful for coagulation assessment in envenomated patients and can be used in addition to traditional coagulation parameters, such as prothrombin time, activated partial thromboplastin time, activated clotting time, and platelet counts to assess coagulation status in these patients. 4,8,10,11,[20][21][22][23] In TEG analyses, the R value evaluates initial fibrin formation and depends on clotting factors VIII, IX, XI, and XII. 4,22,25 The North American antivenom product normalized the R value compared to the negative controls, meaning that the product neutralized the venom's effects on these clotting factors.…”

“…3,8,9,16,17 Crotalus atrox venom has been shown to cause VICC, which is characterized by lack of thrombus formation and depletion of fibrinogen without disseminated intravascular coagulation. 2,3,[8][9][10][11]16,17,[21][22][23] By normalizing time to clot formation and reversing the venom's fibrinolytic effects, the North American product could, in theory, help combat the development or progression of VICC in envenomated patients better than the Argentinian product at these doses if it performed similarly in vivo.…”

“…TEG has been utilized previously to document and monitor coagulation changes in cases of envenomation before and after treatment 4,8,10,11,20–23 . Studies have shown that patients envenomated by pit vipers were most likely to be hypocoagulable on TEG analysis, meaning that they have lower coagulation potential than normal patients, which may or may not relate to in vivo coagulation 4,8,10,11,20–23 .…”

Correlations between rotational thromboelastometry (ROTEM) and standard coagulation tests following viper snakebites

“…Our findings support those of other studies addressing coagulopathy after snakebites using ROTEM. 17 – 19 Additionally, we found moderate correlations between ROTEM parameters and the results of standard coagulation tests and platelet counts.…”

SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock

“…Using TEG with platelet mapping (TEG/PM), a case series of rattlesnake bites in North America revealed inhibition of ADP-induced platelet activation which was reversed by Crotalidae polyvalent immune Fab (ovine). Fibrinolysis was present and resolved in patients for whom serial thromboelastographs were available (Kang and Fisher, 2020).…”