Background: Thrombotic microangiopathy is an uncommon complication of snake envenoming associated with a subset of snakebite cases presenting with venom-induced consumption coagulopathy. It presents with microangiopathic haemolytic anaemia and thrombocytopenia. Available studies are predominantly small retrospective observational studies only. Renal end organ injury appears common. It has variably been likened to either thrombotic thrombocytopenic purpura or atypical haemolytic uraemic syndrome. Many studies report acute kidney injury, with dialysis required in a subset of patients. Some studies suggest a role for treatment with plasmapheresis. Interpretation of the literature is complicated by variable nomenclature and historically poor case definitions of both venom-induced consumption coagulopathy and thrombotic microangiopathy associated with snake envenoming.
Methods: The main objective of this systematic review is to synthesise the worldwide experience of snakebite-associated thrombotic microangiopathy with respect to its features and outcomes, and collate any evidence for the role of plasmapheresis as treatment. A predetermined case definition of confirmed or suspected snakebite with either blood film evidence of microangiopathic haemolytic anaemia or histological evidence of thrombotic microangiopathy will be used. This case definition will determine the search terms and study inclusion criteria. Relevant studies will be identified by electronic database, published conference abstracts, and grey literature search. This systematic review will be performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. The quality of included studies will be assessed by a proposed tool for evaluating the methodological quality of case reports and case series. Results will be reported by a descriptive synthesis with a focus on the presenting features; outcomes of acute kidney injury, dialysis-free survival, other end organ damage, and overall survival; and any evidence of a role for treatment with plasmapheresis. The quality of accumulated evidence will be assessed via the Grading of Recommendations, Assessment, Development, and Evaluations framework.
Discussion: It is anticipated that eligible studies will consist of small observational studies. Evidence gathered from this review will provide the first broader understanding of the clinical features, outcomes, prognosis, and management of snakebite-associated thrombotic microangiopathy.
Systematic review registration: PROSPERO CRD42019121436.
Keywords: Acute kidney injury; Anaemia; Envenoming; Haemolysis; Microangiopathy; Plasmapheresis; Schistocytes; Snake; Thrombotic.