Handheld Point-of-Care Devices for Snakebite Coagulopathy: A Scoping Review

Abstract

Venom-induced consumption coagulopathy (VICC) is a common complication of snakebite that is associated with hypofibrinogenemia, bleeding, disability, and death. In remote tropical settings, where most snakebites occur, the 20-minute whole blood clotting test is used to diagnose VICC. Point-of-care (POC) coagulation devices could provide an accessible means of detecting VICC that is better standardized, quantifiable, and more accurate. In this scoping review, the mechanistic reasons that previously studied POC devices have failed in VICC are considered, and evidence-based recommendations are made to prioritize certain devices for clinical validation studies. Four small studies have evaluated a POC international normalized ratio (INR) device in patients with Australian Elapid, Daboia russelii, and Echis carinatus envenoming. The devices assessed in these studies either relied on a thrombin substrate endpoint, which is known to underestimate INR in patients with hypofibrinogenemia, have been recalled due to poor accuracy, or have since been discontinued. Sixteen commercially available POC devices for measuring INR, activated clotting time, activated partial thromboplastin time, fibrinogen, D-dimer, and fibrin(ogen) degradation products have been reviewed. POC INR devices that detect fibrin clot formation, as well as a novel POC device that quantifies fibrinogen were identified, which show promise for use in patients with VICC. These devices could support more accurate allocation of antivenom, reduce the time to antivenom administration, and provide improved clinical trial outcome measurement instruments. There is an urgent need for these promising POC coagulation devices to be validated in prospective clinical snakebite studies.

Fig. 1

( A ) Overview of the site of action of procoagulant snake venom toxins on the coagulation pathway. The red boxes detail the major groups of coagulopathic venom toxins, their enzyme classification, and a nonexhaustive list of medically important snake species that utilize the toxin group. The dashed arrows indicate the site of the coagulation pathway where the major groups of coagulopathic venom toxins act. Adapted from “Coagulation Cascade,” by BioRender.com (2023). Retrieved from: https://app.biorender.com/biorender-templates . ( B ) Levels of measurement of each point-of-care device on the coagulation pathway. The green boxes detail the names and assay types of the point-of-care devices that have been included in this review. The tails of the green arrows indicate where each assay's activator acts on the coagulation pathway. The arrow heads highlight where the endpoint read of each assay exists on the coagulation pathway. Adapted from “Coagulation Cascade,” by BioRender.com (2023). Retrieved from https://app.biorender.com/biorender-templates . Ca ²⁺ , calcium; FDPs, fibrin degradation products; PL, phospholipid; TF, tissue factor.

Fig. 2

Comparison of laboratory and POC device INR by participant from previous studies (O'Rourke et al and Senthilkumaran et al 37 ). ( A ) The laboratory, i-STAT, CoaguChek S, and Alere INRatio2 INR values for 15 participants with Daboia russelii envenoming: the participants are ordered according to increasing laboratory INR values. ( B ) The laboratory, i-STAT, CoaguChek S, and Alere INRatio2 INR values for three participants with Echis carinatus envenoming. ( C ) The laboratory and i-STAT INR values for 15 participants with Australian Elapid envenoming. INR, international normalized ratio.