Snakebite associated thrombotic microangiopathy: a systematic review of clinical features, outcomes, and evidence for interventions including plasmapheresis

PLoS Negl Trop Dis. 2020 Dec 8;14(12):e0008936. doi: 10.1371/journal.pntd.0008936. eCollection 2020 Dec.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / therapy
  • Animals
  • Antivenins / therapeutic use*
  • Australia / epidemiology
  • Daboia / metabolism*
  • Female
  • Humans
  • Male
  • Plasmapheresis*
  • Prevalence
  • Prospective Studies
  • Retrospective Studies
  • Snake Bites / blood
  • Snake Bites / complications*
  • Snake Bites / therapy
  • Thrombotic Microangiopathies / blood
  • Thrombotic Microangiopathies / etiology*
  • Thrombotic Microangiopathies / therapy
  • Viper Venoms / adverse effects*

Substances

  • Antivenins
  • Viper Venoms

Grants and funding

T. N. was financially supported by a University Postgraduate Research Scholarship and Menzies School of Health Research support funds. G.I. is supported by a National Health and Medical Research Council Senior Research Fellowship 1154503. The funders and sponsors played no role in the design or reporting of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.