Snakebite Associated Thrombotic Microangiopathy and Recommendations for Clinical Practice

Abstract

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.

Longitudinal Metabolomics and Lipidomics Analyses Reveal Alterations Associated with Envenoming by Bothrops asper and Daboia russelii in an Experimental Murine Model

“…The metabolite heme was increased in the plasma of mice injected by these venoms. This is likely the result of venom-induced intravascular hemolysis whose pathogenesis might be related to the formation of microthrombi, owing to the procoagulant components present in these venoms [ 36 , 37 , 38 , 39 ], which in turn may contribute to a thrombotic microangiopathy associated with hemolysis [ 40 ]. The heme iron may contribute to the generation of reactive oxygen species, which are known to play a role in tissue alterations in snakebite envenoming [ 41 ].…”

Disseminated Intravascular Coagulation: The Past, Present, and Future Considerations

“…Notably, since the targets of venom toxins are the clotting factors, venom toxins can cause thrombosis and thrombotic microangiopathy. 84 In such cases, hemotoxic venoms can be classified as thrombotic categories. 88…”

“…83 Venom toxin is a historical biologic substance that still poses problems, namely, venom-induced consumptive coagulopathy worldwide. 84 Toxins vary among snakes but in some snake bites, venom toxins promote consumptive coagulopathy. 85 The most relevant procoagulant toxins are metalloproteinases that activate prothrombin, factor V, factor X, or thrombin-like enzymes.…”

Snakebite Envenoming: A Comprehensive Review on Epidemiology, Diagnosis, Potential Treatments Role of Proteomics and Bioinformatics

“…Venoms are made up of protein combinations of various complexities as a direct consequence of Strong Darwinian selection resulting in fast progression. These protein complexes can either work independently or as part of a combined phenotype to slay or slaughter the prey or unintentional victim [37,38]. Venom, both within and across species, appears to be a property shared across all taxonomic groups; even though these characteristics exhibit only in terms of the number of genes that encode poisons, there is a modest level of genetic complexity.…”

“…transcutaneous bites without envenoming) inflicted these bites, resulting in negligible or no symptoms. A professional herpetologist can identify the snake species if the dead snake or an image of it is available [38,50]. Snakebite victims and spectators can provide useful information if they can describe their symptoms in detail and identify characteristic patterns (syndromes) in their symptoms.…”