101 Thromboelastography versus Conventional Coagulation Tests in Pit Viper Envenomation and Antivenom Response

Abstract

Pit viper envenomations represent a significant burden of disease worldwide, leading to severe hematologic derangements such as venom-induced consumptive coagulopathy (VICC). Recognizing this problem, the WHO recently launched a campaign to cut snake bite deaths in half by 2030. Immediacy in detection and treatment of coagulopathy with antivenom is paramount to reducing morbidity and mortality. Traditionally, administration of the pit viper antivenom, CroFab®, has been based on clinical signs and symptoms and conventional coagulation tests (CCT) such as fibrinogen, PT, PTT and INR. The purpose of this study was to assess the efficacy of TEG in detecting response to antivenom administration. Blood samples from 25 healthy adult volunteers were mixed with different concentrations of western diamondback rattlesnake (Crotalus atrox) venom (50% and 100% LD50). Each group of envenomated blood samples was treated with 4, 6, and 10 vial equivalents (vialeq) of CroFab®. All samples were assessed with CCTs including: PT, PTT, INR and Fibrinogen, as well as with TEG measures of reaction time (R), amplification (k), rate of clot formation (alpha angle), and clot strength (MA). Data was analyzed to determine the rate of return to normal range CCT and TEG values as a surrogate for return to normal coagulation. For the 50% LD50 group, CCT parameters of PT, PTT and INR returned to normal in 24%-32% of samples across all CroFab® doses. For the same group, 72% of Fibrinogen samples returned to normal at 4 vialeq with a max of 88% at 10 vialeq. TEG parameters R, k, alpha angle and MA returned to normal at a rate of 80%-96% across all CroFab doses. For the 100% LD50 group, CCT parameters of PT, PTT, and INR had a maximum of 24% return to normal for all CroFab® doses. For the same group, 16% of Fibrinogen samples returned to normal at 4 vialeq with a max of 88% at 10 vialeq. TEG parameters showed incremental increases towards normal range with 92-96% of samples in range at 10 vialeq. Pit viper envenomations are a global health threat with significant morbidity and mortality and suboptimal methods to guide the utilization of the expensive and often limited CroFab® antivenom. In this in vitro model, TEG was shown to be more sensitive than CCTs in tracking antivenom-induced recovery from VICC. Additionally, our findings represent a step towards developing a dose-response curve for antivenom administration with the potential to reduce both the amount of antivenom used and the side effects associated with its use.