Snakebite-associated thrombotic microangiopathy: a spotlight on pharmaceutical interventions

ABSTRACT

Introduction

Snakebite is a neglected public health issue causing death and disability, disproportionately affecting tropical and subtropical resource poor countries globally. Snakebite-associated thrombotic microangiopathy (TMA) occurs in a subset of snakebites and is associated with acute kidney injury (sometimes requiring renal replacement therapy) and a risk of chronic kidney disease.

Areas covered

This expert review synthesizes current evidence on therapeutic interventions in snakebite-associated TMA via PubMed search for cohort studies and randomized controlled trials (RCTs) in snakebite-associated TMA from 1970 to October 2022.

Expert opinion

There are no interventional RCTs in snakebite-associated TMA. Recent cohort studies from Sri Lanka, India, and Australia report clinical and laboratory endpoint outcomes for intervention with antivenom and therapeutic plasma-exchange (TPE). TPE is a resource intense and costly treatment using large volumes of blood donor plasma. There is no consistent evidence supporting TPE in snakebite-associated TMA with respect to patient survival, dialysis-free survival, or hospital length of stay. Antivenom is the standard of care for patients with snake envenoming, but there is no specific evidence of benefit in snakebite-associated TMA. Emerging new therapies in snakebite more broadly are untested in snakebite-associated TMA. RCTs are needed to improve the evidence for treatment of snakebite-associated TMA.

KEYWORDS:

• acute kidney injury
• antivenom
• fresh frozen plasma
• schistocytes
• snakes
• snakebite
• therapeutic plasma exchange
• thrombotic microangiopathies

Article highlights

• Snakebite-associated thrombotic microangiopathy (TMA) occurs in a broad range of envenoming snake species globally, in a subset of patients presenting with venom-nduced consumption coagulopathy (VICC).

• Whilst the majority of patients survive, outcomes vary between different studies globally, and it is associated with acute kidney injury which often requires renal replacement therapy, with a risk of death and chronic kidney disease.

• Antivenom is the gold standard of care for all snake envenomings, although there is no consistent evidence that antivenom prevents or treats TMA specifically.

• Therapeutic plasma exchange (TPE) has been used to treat snakebite-associated TMA, but it is resource intense, consuming very large volumes of blood donor fresh frozen plasma, and with no consistent evidence that it improves overall survival or dialysis free survival.

• Emerging new therapeutics in snakebite envenoming more broadly include monoclonal antibodies and small molecule toxin inhibitors, but these are currently untested in human clinical trials.

• We recommend clinical randomized controlled trials as best placed to address the evidence gap in effectiveness of treatments for this medically important complication of snakebite.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

GK Isbister is supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (1154503)