Clinico-epidemiology and management of hump-nosed pit viper (Hypnale spp.) bites in dogs.

Human envenoming from the bite of the abundant hump-nosed pit viper (Hypnale spp.) (HNPV) is a frequent occurrence with victims experiencing unpleasant and sometimes life-threatening consequences. Further, clinico-pathology, treatment and management measures in HNPV envenomed dogs are under recognized. Prospective investigations were performed to assess the clinico-pathology and management options for HNPV envenomed dogs brought to the University of Peradeniya's Veterinary Teaching Hospital from January, 2012 to March 2018. We recorded the local and systemic manifestations, hematological and urinary abnormalities of 78 dogs in which HNPV bite had been witnessed by the owner. Mild swelling, extensive swelling, hemorrhagic blistering and hemorrhagic bullae at the site of bite were observed in 59%, 31%, 6% and 4% of the dogs, respectively. Some dogs were subjected to surgical excision of necrotized tissue including limb amputation. We observed the following systemic clinical effects in envenomed dogs: neurotoxicity (13%), acute kidney injury (AKI) (14%) and coagulopathy (16%). All dogs showed leukocytosis with mean white blood cell count of 25.25 × 103/µL. Mild anemia and thrombocytopenia were detected in 29% of the dogs. There was a significant correlation between extent of local tissue injuries with length of hospitalization (LH). The mean time of coagulopathy observed was 21.3 h (IQR: 8-48 h). In coagulopathic dogs, there was a strong correlation between LH and extent of local tissue injury (rs = 0.7751, P < 0.0001); LH and whole blood clotting time(CT) (rs = 1.0, P < 0.0001); PT and aPTT (rs = 0.4712, P < 0.001). LH was significantly correlated with the development of AKI (p = 0.0013). Lack of specific antivenom (AVS) for HNPV envenoming provided an opportunity to study the remaining treatment options. Therefore, the study allowed the identification of local and systemic effects, hematological abnormalities, possible supportive treatments and drawbacks of management measures for envenomed dogs.

In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIbα.

The interaction of platelet GPIbα with von Willebrand factor (VWF) is essential to initiate platelet adhesion and thrombosis, particularly under high shear stress conditions. However, no drug targeting GPIbα has been developed for clinical practice. Here we characterized anfibatide, a GPIbα antagonist purified from snake (Deinagkistrodon acutus) venom, and evaluated its interaction with GPIbα by surface plasmon resonance and in silico modeling. We demonstrated that anfibatide interferds with both VWF and thrombin binding, inhibited ristocetin/botrocetin- and low-dose thrombin-induced human platelet aggregation, and decreased thrombus volume and stability in blood flowing over collagen. In a single-center, randomized, and open-label phase I clinical trial, anfibatide was administered intravenously to 94 healthy volunteers either as a single dose bolus, or a bolus followed by a constant rate infusion of anfibatide for 24 h. Anfibatide inhibited VWF-mediated platelet aggregation without significantly altering bleeding time or coagulation. The inhibitory effects disappeared within 8 h after drug withdrawal. No thrombocytopenia or anti-anfibatide antibodies were detected, and no serious adverse events or allergic reactions were observed during the studies. Therefore, anfibatide was well-tolerated among healthy subjects. Interestingly, anfibatide exhibited pharmacologic effects in vivo at concentrations thousand-fold lower than in vitro, a phenomenon which deserves further investigation.Trial registration: Clinicaltrials.gov NCT01588132.

Review of North American pit viper antivenoms.

PURPOSE: For the first time in nearly 20 years, 2 antigen-binding fragment (Fab) antivenoms are available to treat patients who incur North American pit viper snakebites: Crotalidae polyvalent immune Fab (ovine), or simply FabAV; and Crotalidae immune F(ab')2 (equine), or simply F(ab')2. Pharmacists are in a key position for the selection, dosing, reconstitution, administration, and monitoring of antivenom therapy; however, they encounter inconsistent exposure and experience with these drugs. Thus, an updated review of the literature is necessary. METHODS: The search strategy and selection incorporated both controlled vocabulary terms and keywords to describe concepts relevant to the search. Retrieval was limited to literature published from 1997 to the present in English, Portuguese, or Spanish. RESULTS: Given the paucity of available prospective literature, the authors elected to include all prospective evidence to best describe the role of antivenom. For the primary literature review, manuscripts were excluded if they were observational studies, conference abstracts, narrative or opinion articles, letters to the editor, or in-progress studies. CONCLUSION: While there is limited evidence-based guidance on the superiority of F(ab')2 to FabAV, or vice versa, individual and regional considerations should contribute to formulary decisions. Pharmacists must play a role in the development of clinical pathways to ensure appropriate evaluation, supportive care, and antivenom procurement, administration, and monitoring.

De Novo Assessment and Review of Pan-American Pit Viper Anticoagulant and Procoagulant Venom Activities via Kinetomic Analyses.

Snakebite with hemotoxic venom continues to be a major source of morbidity and mortality worldwide. Our laboratory has characterized the coagulopathy that occurs in vitro in human plasma via specialized thrombelastographic methods to determine if venoms are predominantly anticoagulant or procoagulant in nature. Further, the exposure of venoms to carbon monoxide (CO) or O-phenylhydroxylamine (PHA) modulate putative heme groups attached to key enzymes has also provided mechanistic insight into the multiple different activities contained in one venom. The present investigation used these techniques to characterize fourteen different venoms obtained from snakes from North, Central, and South America. Further, we review and present previous thrombelastographic-based analyses of eighteen other species from the Americas. Venoms were found to be anticoagulant and procoagulant (thrombin-like activity, thrombin-generating activity). All prospectively assessed venom activities were determined to be heme-modulated except two, wherein both CO and its carrier molecule were found to inhibit activity, while PHA did not affect activity (Bothriechis schlegelii and Crotalus organus abyssus). When divided by continent, North and Central America contained venoms with mostly anticoagulant activities, several thrombin-like activities, with only two thrombin-generating activity containing venoms. In contrast, most venoms with thrombin-generating activity were located in South America, derived from Bothrops species. In conclusion, the kinetomic profiles of venoms obtained from thirty-two Pan-American Pit Viper species are presented. It is anticipated that this approach will be utilized to identify clinically relevant hemotoxic venom enzymatic activity and assess the efficacy of locally delivered CO or systemically administered antivenoms.

Venomous Snakebites in Canada: A National Review of Patient Epidemiology and Antivenom Usage.

INTRODUCTION: There are 3 pit viper species in Canada. Limited Canadian literature exists on the epidemiology of venomous snakebites and the treatment patterns with antivenom. This study described the epidemiology, the utilization of antivenom, and estimated expenditures due to forfeited antivenom for pit viper envenomations in Canada. METHODS: A retrospective review of the Health Canada Special Access Program records to generate descriptive statistics. Data are presented as mean±SD (range), as appropriate. RESULTS: The geographic distribution of Canadian pit viper species is presented. There were 99 envenomations reported in Canada from January 2009 to December 2015. The number of envenomations per year was 14±6 (6-21). CroFab and Antivipmyn are used in Canada to treat envenomations. The number of vials for patient treatment was 17±12 (3-66) and 16±9 (6-42) for CroFab and Antivipmyn, respectively. Antivenom stock usage for patient treatment varied across the country with provincial means reported for British Columbia (33%), Alberta (37%), Saskatchewan (27%), and Ontario (71%). The costs incurred secondary to forfeited stock where estimated as: $1,280,000 USD in British Columbia, $255,000 in Alberta, $60,000 in Saskatchewan, and $0 in Ontario. CONCLUSIONS: The absolute number of annual envenomations is small and the 3 Crotalinae species are limited to relatively narrow geographic areas in British Columbia, Alberta, Saskatchewan, and Ontario. The utilization of antivenom in the treatment of patients revealed that regions where the western and prairie rattlesnake reside forfeited a substantial amount of antivenom from 2009 to 2015. Organizations responsible for maintaining antivenom supplies on a provincial or regional level could use these data to guide antidote stocking and reduce costs.

Resource Utilization After Snakebite Severity Score Implementation into Treatment Algorithm of Crotaline Bite.

BACKGROUND: Crotaline envenomation clinical manifestations vary considerably among patients. Current recommendations for treatment with Crotalidae polyvalent immune Fab require assessment of envenomation control. Determining control of envenomation, particularly when patients are evaluated by different providers in separate clinical settings, can be difficult. OBJECTIVE: To determine if a difference in total vials of Crotalidae antivenin therapy exists between pre-protocol and post-Snakebite Severity Score (SSS) protocol. METHODS: Retrospective medical record review at an academic medical and regional Level I trauma center. Resource utilization in patients with a diagnosis of "snakebite" was compared between patients treated pre- and post-SSS protocol implementation. RESULTS: One hundred forty-six patients were included in the evaluation. One hundred twenty-seven (87.0%) patients received antivenin, n = 80 (90.9%) in the pre-protocol group and n = 47 (81.0%) in the post-protocol group. Median total number of antivenin vials per patient was lower in the post-protocol group than the pre-protocol group, 16 (10-24 interquartile range) vs. 12 (10-16 interquartile range), p = 0.006. This decreased utilization correlates to an approximate $13,200 savings per patient. Hospital and intensive care unit length of stay, opioid use, incidence of blood product transfusion, need for surgical intervention, or need for intubation were not different between groups. CONCLUSIONS: A snakebite protocol with SSS utilization to guide antivenin administration results in significantly decreased antivenin therapy in snakebite patients without increase in other health care utilization.