Hematologic Effects Following Crotalinae and Unknown Snake Bites in Northeast Florida

Background: Approximately 5000 snake bites are reported in the United States (US) annually with half of these patients being admitted. Crotalinae species are the most numerous; coral and imported exotic snakes cause a smaller number. Snake venoms are highly stable chemically complex mixtures of proteins. Quantity and composition vary with species and geographic location. Although enzymes contribute to the deleterious effects of the venom, the lethal components may be the smaller low molecular-weight polypeptides. Crotalinae envenomation is known to contain thrombin-like glycoproteins that can induce coagulopathy ranging from asymptomatic lab abnormality to disseminated intravascular coagulopathy (DIC) and life-threatening hemorrhage. In certain geographical areas of the United States thrombocytopenia, hypofibrinogenemia and coagulopathy are common hematological abnormalities, and ones that dictate both a reason for treatment with antivenom as well as an important monitor of therapeutic efficacy. Data on hematological abnormalities following envenomation by crotaline species in Northeast Florida/Southwest Georgia has not been reported before. Methods: We conducted a retrospective review of envenomations that presented to the University of Florida at Jacksonville from April 2013 to October 2018. Patients had to be 16 years or older without any pre-existing hematologic disorder or use of anticoagulant medications. Data including Complete Blood Count, Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT) and Fibrinogen were measured on presentation, and 4 hours after. Crotaline Fab antivenom (CroFab®) administration was noted if done. Adverse events associated with antivenom therapy, recurrence phenomena, delayed onset of symptoms, and performance of fasciotomy were also recorded. Results: Overall, 119 snakebites were evaluated. The majority were identified as Crotalinae - 25 water moccasin, copperhead or cottonmouth (Agkistrodon piscivorus, Agkistrodon contortrix) bites and 34 rattlesnake (Sistrurus miliarius, Crotalus adamanteus) bites. Male sex dominated the sample with most patients middle-aged (Table 1). More than 80% of patients arrived within 6 hours following the bite. Over 60% of patients received crotaline Fab antivenom. Results are presented in Table 2. Around 12% of patients with water moccasin, copperhead or cottonmouth (Agkistrodon piscivorus, Agkistrodon contortrix) bites had coagulopathy on admission. This compares similarly to data from South Carolina previously showing a 10.89% rate following copperhead bites (Qureshi et al. Blood 2010;116(21):4753). The rate of coagulopathy with rattlesnake bites was however much higher in North Florida at 20.6% - compared to 5.26% in the South Carolina series. Rates of DIC or severe hemorrhage were 8% for water moccasin, copperhead or cottonmouth (Agkistrodon piscivorus, Agkistrodon contortrix) bites and 5.9% for rattlesnake (Sistrurus miliarius, Crotalus adamanteus) bites. When hemostatic defects were looked at separately, the most common abnormality induced was PT/aPTT derangement, followed by hypofibrinogenemia and then thrombocytopenia. This pattern was the same as reported in South Carolina. Recurrence phenomena was observed after 4 hours in a number of patients, however the significance of this remains uncertain as most of these patients remained clinically stable without worsening symptoms. Anaphylactic reaction to the antivenom developed in one patient. Conclusions: In this sample from North Florida, deranged PT/aPTT was the most common hematologic abnormality following envenomation, followed by hypofibrinogenemia and a low rate of thrombocytopenia. Similarities with data from South Carolina were noted, although rattlesnake bites had 4 times higher incidence of coagulopathy in North Florida. DIC or severe hemorrhage was a notable toxicity, affecting 6-8% of Crotalinae cases. Hematologic effects of envenomation do seem to vary by geographic areas in the United States and physicians would benefit from local data to better manage these patients. Disclosures No relevant conflicts of interest to declare.

High levels of functional divergence in toxicity towards prey among the venoms of individual pigmy rattlesnakes

Venom is a complex molecular phenotype that shows high levels of variation in expressed proteins between individuals within and between populations. However, the functional significance of this variation in terms of toxicity towards prey is largely unknown. Here, we assessed the relative toxicity of venom from individual pygmy rattlesnakes ( Sistrurus miliarius ) on brown anoles ( Anolis sagrei ) using a novel assay involving tests of fixed doses of venom from individual snakes on individual lizards. We found high levels of functional variation between individual venoms within populations with individual differences (nested within population) explaining 3.6 times more variation in toxicity than population differences. Our results suggest a previously unappreciated adaptive significance to within-population variation in venom. They argue that selective mechanisms that maintain variation within populations may be of equal or greater importance to divergent selection leading to local adaption between populations as evolutionary explanations of venom variation within species.