Snakebite associated thrombotic microangiopathy: a protocol for the systematic review of clinical features, outcomes, and role of interventions

Abstract

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 Electronic supplementary material The online version of this article (10.1186/s13643-019-1133-2) contains supplementary material, which is available to authorized users.

Thrombotic microangiopathy due to Bothrops erythromelas: a case report in Northeast Brazil

“…The markers of microvascular hemolysis with anemia following snakebite envenomation are not specific 13 . MAHA was reported in two tiger snake envenomations that evolved with anemia, increased lactate dehydrogenase levels, increased serum indirect bilirubin levels, and fragmented red blood cells (schizocytes) in blood smears 15 .…”

“…Plasma exchange and renal replacement treatment (RRT) after adequate antivenom administration are the main proposed treatments for TMA following snakebites 13,18 . Plasmapheresis is a nonspecific treatment used in many toxicological disorders to rapidly remove toxins from the circulation.…”

“…Plasmapheresis is a nonspecific treatment used in many toxicological disorders to rapidly remove toxins from the circulation. However, the effectiveness of this therapy in the treatment of snakebite-induced TMA is still uncertain 13 . RRT should be initiated when life-threatening changes in the fluid, electrolytes and acid-base balance are unresponsive to current medical therapy.…”

“…Thrombocytopenia together with microangiopathic hemolytic anemia is enough for the diagnosis of TMA 13 and it is caused by snake venom toxins, such as snake venom C-type lectins (Snaclecs) 9 , 14 being abundant in B. erythromelas 9 . This class of protein inhibits or activates platelets by binding to receptors such as collagens or the von Willebrand factor (VWF).…”

Clinical assessment and pathophysiology of Bothrops venom-related acute kidney injury: a scoping review

“…A study performed in adult patients after Bothrops snakebite revealed a strong predisposition to development of coagulation abnormalities (aPTT) and AKI development [14]. However, snakebite-associated TMA is a poorly understood phenomenon thus further studies are required to improve the management of these patients [108].…”