Rotational thromboelastometry and endothelial-derived extracellular vesicle changes in thrombotic microangiopathy versus other envenoming syndromes following hump-nosed pit viper envenoming

INTRODUCTION: Thrombotic microangiopathy is an uncommon complication of snakebite with unclear pathophysiology. We explore the mechanisms of venom-induced consumption coagulopathy, thrombotic microangiopathy and acute kidney injury in hump-nosed pit viper bites. METHODS: A prospective observational study was conducted at District General Hospital Horana, Sri Lanka (June 2023 to December 2024). Thirty-five patients were recruited, including: local envenoming alone (20), venom induced consumption coagulopathy (2), thrombotic microangiopathy (5) and acute kidney injury without thrombotic microangiopathy (8). Laboratory tests were performed every 12 hours, and rotational thromboelastometry (delta and platelet) and flow cytometry for extracellular vesicles at the earliest diagnosis of envenoming. RESULTS: All thrombotic microangiopathy cases developed severe acute kidney injury, with 4/5 requiring dialysis. All eight cases of isolated acute kidney injury had mild kidney dysfunction that resolved. The international normalized ratio was normal in patients with thrombotic microangiopathy and acute kidney injury, however rotational thromboelastometry revealed coagulation abnormalities, including fibrinogen dysfunction despite normal fibrinogen levels, in patients with thrombotic microangiopathy. Isolated acute kidney injury had mild to moderate rotational thromboelastometry abnormalities. Endothelial-derived extracellular vesicles were proportionally highest in the thrombotic microangiopathy (median 12.6%) group. Red cell-derived extracellular vesicles were raised in thrombotic microangiopathy and isolated acute kidney injury groups. DISCUSSION: Thrombotic microangiopathy and severe acute kidney injury are associated in hump-nosed pit viper envenoming. Rotational thromboelastometry revealed coagulation abnormalities, missed by conventional coagulation testing. Thrombotic microangiopathy in hump-nosed pit viper envenoming was associated with raised endothelial- and red cell-derived extracellular vesicles. CONCLUSION: Rotational thromboelastometry is more sensitive than conventional coagulation testing for detecting coagulopathy and the associated risk of developing thrombotic microangiopathy and AKI in hump-nosed viper bites. Endothelial injury may be a factor in the pathogenesis of thrombotic microangiopathy in hump-nosed pit viper envenoming.