Snakebite is a neglected tropical disease with significant morbidity and mortality. Thrombotic microangiopathy (TMA) is an important but poorly understood complication of snakebite associated with acute kidney injury (AKI). Numerous treatments have been attempted based on limited evidence. We conducted a systematic review of TMA following snakebite using a pre-determined case definition of blood film red cell schistocytes or histologically diagnosed TMA. The search strategy included major electronic databases and grey literature. We present a descriptive synthesis for the outcomes of AKI, dialysis free survival (DFS), other end-organ damage, overall survival, and interventions with antivenom and therapeutic plasmapheresis (TPE). This study was prospectively registered with PROSPERO (CRD42019121436). Seventy-two studies reporting 351 cases were included, predominantly small observational studies. Heterogeneity for study selection, design, reporting and outcomes were observed. The commonest envenoming species were hump-nosed vipers (Hypnale spp.), Russell’s viper (Daboia russelii) and Australian brown snakes (Pseudechis spp.). The prevalence of TMA was at least 5.4% in proven and probable Hypnale bites, and 10–15% of Australian elapid envenomings, AKI occurred in 94% (293/312) of TMA cases, excluding case reports. The majority of cases with AKI required dialysis. Included prospective and retrospective cohort studies reporting interventions and renal outcomes showed no evidence for benefit from antivenom or TPE with respect to DFS in dialysis dependant AKI. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment for quality of accumulated evidence for interventions was low. The major complication of TMA following snakebite is AKI. AKI improves in most cases. We found no evidence to support benefit from antivenom in snakebite associated TMA, but antivenom remains the standard of care for snake envenoming. There was no evidence for benefit of TPE in snakebite associated TMA, so TPE cannot be recommended. The quality of accumulated evidence was low, highlighting a need for high quality larger studies.
Snakebite is a significant and under-resourced global public health issue. Snake venoms cause a variety of potentially fatal clinical toxin syndromes, including venom-induced consumption coagulopathy (VICC) which is associated with major haemorrhage. A subset of patients with VICC develop a thrombotic microangiopathy (TMA). This article reviews recent evidence regarding snakebite-associated TMA and its epidemiology, diagnosis, outcomes, and effectiveness of interventions including antivenom and therapeutic plasma-exchange. Snakebite-associated TMA presents with microangiopathic haemolytic anaemia (evidenced by schistocytes on the blood film), thrombocytopenia in almost all cases, and a spectrum of acute kidney injury (AKI). A proportion of patients require dialysis, most survive and achieve dialysis free survival. There is no evidence that antivenom prevents TMA specifically, but early antivenom remains the mainstay of treatment for snake envenoming. There is no evidence for therapeutic plasma-exchange being effective. We propose diagnostic criteria for snakebite-associated TMA as anaemia with >1.0% schistocytes on blood film examination, together with absolute thrombocytopenia (<150 × 109/L) or a relative decrease in platelet count of >25% from baseline. Patients are at risk of long-term chronic kidney disease and long term follow up is recommended.
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