Severe acute kidney injury following Sri Lankan <i>Hypnale</i> spp. envenoming is associated with thrombotic microangiopathy

Wijewickrama, Eranga; Gooneratne, Lalindra V; Gnanathasan, Ariaranee; Gawarammana, Indika; Gunatilake, Mangala

doi:10.1080/15563650.2020.1810695

Cited by 15 publications

(23 citation statements)

References 27 publications

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“…However, we found TMA reported in 10-15% of Australian elapid envenomings, and 5.4% of proven and probable Hypnale bites in Sri Lanka, in studies with a low risk of selection bias. Consistent with these findings, a recent prospective cohort study from Sri Lanka published after our last database search date reported a prevalence of 11% TMA in a total of 103 proven Hypnale envenomings, applying our definition of TMA in this systematic review [94].…”

Section: Discussionsupporting

confidence: 83%

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

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 83%

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

et al. 2020

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“…We found that snakebite-associated TMA developed in a subset of patients with VICC, presenting with MAHA, and typically delayed thrombocytopenia. Whilst our study is confined to Australian snakebites alone, our findings, together with the few international cohort studies available, support the premise that TMA occurs in a diverse range of venomous snake types worldwide, but exclusively in association with VICC [5,6,8,9]. Increasing age was clearly associated with an increased likelihood of developing TMA.…”

Section: Discussionsupporting

confidence: 75%

“…Our detailed manual review of TMA case medical records partially relied on routinely collected clinical information. Whilst possible confounders for AKI such as concurrent nephrotoxic medicines are not able to be completely ruled out, (e.g., anti-inflammatory medicines), our findings, together with existing studies on snakebite-associated TMA support TMA being the predominant cause of AKI in snakebite [5,7]. Hypotension and prior collapse occurred in only a minority of AKI patients and indeed was less common in those with TMA than in those with VICC but not TMA, a finding which we cannot explain.…”

Section: Discussioncontrasting

confidence: 39%

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Snakebite-associated thrombotic microangiopathy: an Australian prospective cohort study [ASP30]

Noutsos

Currie

Isoardi

et al. 2021

Clinical Toxicology

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Background: Snakebite-associated thrombotic microangiopathy (TMA) occurs in a subset of patients with venom-induced consumption coagulopathy (VICC) following snakebite. Acute kidney injury (AKI) is the commonest end-organ manifestation of TMA. The epidemiology, diagnostic features, outcomes, and effectiveness of interventions including therapeutic plasma-exchange (TPE), in snakebite-associated TMA are poorly understood. Methods: We reviewed all patients with suspected or confirmed snakebite recruited to the Australian Snakebite Project (2004-2018 inclusive), a prospective cohort study, from 202 participating Australian hospitals across the country. TMA was defined as anemia with schistocytosis. Results: 2069 patients with suspected snakebite were enrolled, with 1158 (56.0%) systemically envenomed, of which 842 (72.7%) developed VICC, from which 104 (12.4%) developed TMA. Of those systemically envenomed, TMA occurred in 26% (13/50) taipan, 17% (60/351) brown, and 8% (16/197) tiger snakebites. Thrombocytopenia was present in 90% (94/104) of TMA cases, and a further eight (8%) had a > 25% decrease in platelets from the presentation. Patients with TMA were significantly older than non-TMA patients with versus 41 [24-55] years, median [IQR], p < 0.0001). AKI developed in 94% (98/104) of TMA patients, with 34% (33/98) requiring dialysis (D-AKI). There were four deaths. In D-AKI TMA cases, eventual dialysis-free survival (DFS) was 97% (32/33). TPE was used in five D-AKI cases, with no significant difference in DFS or time to independence from dialysis. >90-day follow-up for 25 D-AKI cases (130 person-years) showed no end-stage kidney disease but 52% (13/25) had ! stage 3 chronic kidney disease (CKD). Conclusion:Our findings support a definition of snakebite-associated TMA as anemia with schistocytosis and either thrombocytopenia or >25% drop in platelet count. AKI occurring with snakebite-associated TMA varied in severity, with most achieving DFS, but with a risk of long-term CKD in half. We found no evidence of benefit for TPE in D-AKI.

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“…The comparison of admission clotting assays for patients with correctly identified coagulopathy by 20WBCT (true positive) and coagulopathy missed by 20WBCT (false negative) (Figs 6 and 7 ) demonstrates that the 20WBCT is less effective at identifying less severe coagulopathy. This concern has been raised by authors in Sri Lanka that have reported that the mild coagulopathy, common to systemic envenoming by the Hump-nosed pit viper ( Hypnale hypnale ), is usually not detected by 20WBCT [ 31 , 39 ]. Figs 6 and 7 support this finding, demonstrating that the 20WBCT performs better at detecting severe coagulopathy, or so-called ‘complete consumption coagulopathy’ [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy—A systematic review and meta-analysis of diagnostic test accuracy

et al. 2021

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Background The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming. Methods and findings Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen <100 mg/dL was 0.72 (CI 0.58 to 0.83), the specificity was 0.94 (CI 0.88 to 0.98) and the SROC AUC was 0.93 (0.91 to 0.95). Both analyses that used INR and fibrinogen as the reference test displayed considerable heterogeneity. Conclusions In the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom.

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Severe acute kidney injury following Sri Lankan Hypnale spp. envenoming is associated with thrombotic microangiopathy

Cited by 15 publications

References 27 publications

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

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

Snakebite-associated thrombotic microangiopathy: an Australian prospective cohort study [ASP30]

The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy—A systematic review and meta-analysis of diagnostic test accuracy

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