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

[This corrects the article DOI: 10.1371/journal.pntd.0009657.].

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

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.

"Bad things come in small packages": predicting venom-induced coagulopathy in Bothrops atrox bites using snake ontogenetic parameters.

Introduction: Snake venom composition shows significant inter- and intra-species variation. In the case of the viperid species Bothrops atrox, responsible for the majority of snakebites in the Amazon region, geographical and ontogenetic variables affect venom composition, with ecological and medical implications. Previous studies had shown that venom from neonate and juvenile Bothrops specimens have a higher in vitro coagulant activity. The aim of this investigation was to assess the association of clinical outcomes, such as venom-induced coagulopathy and local complications, with B. atrox ontogenetic variables.Methods: This study explored the relationship between some clinical parameters in patients suffering envenomations by B. atrox in the Amazon and several morphometric parameters of the snake specimens causing the bites.Results: There were 248 specimens confirmed as agents of envenomation, mostly female snakes (70.5%) and classified as juveniles (62.7%). Patients bitten by neonates compared to adult snakes [OR = 2.70 (95%CI 1.15-6.37); p = .021] and by snakes with white tail tip [OR = 1.98 (95%CI 1.15-3.41); p = .013] were more likely to develop coagulopathy. Time from patient admission to the unclottable blood reversion was not affected by the snake gender (p = .214) or age (p = .254). Patients bitten by neonate (p = .024) or juvenile snakes (p < .0001) presented a lower frequency of moderate to severe edema, as compared to those bitten by adult snakes. In agreement with experimental observations, patients bitten by neonates and by snakes with a white tail tip were more likely to develop coagulopathy than those bitten by adult snakes. In contrast, envenomations by adult snakes were associated with a higher incidence of severe local edema.Conclusion: Despite these variations, no difference was observed in the time needed to recover blood clotting in these patients after Bothrops antivenom administration.

Low accuracy of microscopic hematuria in detecting coagulopathy from Bothrops pit viper bites, Brazilian Amazon.

Introduction: The common lancehead snakes (Bothrops atrox) are responsible for up to 90% of snakebites in the Amazon, especially in remote areas. The prevalence of microhematuria is similar to that of coagulopathy in B. atrox envenomation in the Amazon. Thus, this study aimed to assess the reliability of microhematuria as an inexpensive and simple alternative to detect snake-induced consumption coagulopathy. Methods: We analyzed samples from patients with confirmed B. atrox envenomation in terms of plasma fibrinogen and microhematuria (>3 red blood cells per high power field) in order to access the reliability of microhematuria to detect snakebite-induced coagulopathy, within 12 hours from admission. Results: A total of 186 patients were recruited. From the total, 85.5% of patients had hypofibrinogenemia and only about 50% (n = 94) had a microscopic examination of urine within 12 hours where microhematuria was present in 39 (41.5%). Diagnostic performance showed 38.6% sensitivity and 36.4% specificity (cutpoint 200 mg/dL). No clear association was seen between microhematuria and hypofibrinogenemia (r: -0.10; p: .34). Conclusion: In this study, microhematuria presented poor diagnostic performance to detect coagulopathy. Further studies are necessary to screen inexpensive and simple alternative diagnostic tools.

Accuracy of the Lee-White Clotting Time Performed in the Hospital Routine to Detect Coagulopathy in Bothrops atrox Envenomation.

Snake envenomation is a major public health problem in Brazil. Systemic complications that may arise from snakebites are mainly related to coagulopathy. The Lee-White clotting time (LWCT) is a simple and inexpensive test and available even in remote health facilities. However, the diagnostic value of such test needs to be evaluated to accurately diagnose coagulopathy in the clinical practice. This study aimed to assess the reliability of the LWCT performed in hospital routine to diagnose venom-induced coagulopathy. We studied 186 patients admitted at the Tropical Medicine Foundation Dr. Heitor Vieira Dourado in Manaus, Amazonas, Brazil, with Bothrops envenomation diagnosis. At admission, blood samples were collected for performing LWCT and the concentration of fibrinogen. Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios, diagnostic odds ratio, and accuracy were calculated with 95% confidence intervals. From the total, 85.5% had hypofibrinogenemia. The sensitivity of the LWCT to the diagnosis of hypofibrinogenemia was 78.0% and the specificity 40.7%. The accuracy of the test was 72.6%, and patients with a prolonged LWCT had 2.4 higher odds of developing hypofibrinogenemia. In addition, the LWCT was also compared with venom antigen levels and systemic hemorrhage. The LWCT showed moderate sensitivity to detect consumption coagulopathy and constitutes a valuable tool for the diagnosis of Bothrops snake envenomation and indication of antivenom therapy.

Experimental Bothrops atrox envenomation: Efficacy of antivenom therapy and the combination of Bothrops antivenom with dexamethasone.

Bothrops atrox snakes are the leading cause of snake bites in Northern Brazil. The venom of this snake is not included in the antigen pool used to obtain the Bothrops antivenom. There are discrepancies in reports on the effectiveness of this antivenom to treat victims bitten by B. atrox snakes. However, these studies were performed using a pre-incubation of the venom with the antivenom and, thus, did not simulate a true case of envenomation treatment. In addition, the local lesions induced by Bothrops venoms are not well resolved by antivenom therapy. Here, we investigated the efficacy of the Bothrops antivenom in treating the signs and symptoms caused by B. atrox venom in mice and evaluated whether the combination of dexamethasone and antivenom therapy enhanced the healing of local lesions induced by this envenomation. In animals that were administered the antivenom 10 minutes after the envenomation, we observed an important reduction of edema, dermonecrosis, and myonecrosis. When the antivenom was given 45 minutes after the envenomation, the edema and myonecrosis were reduced, and the fibrinogen levels and platelet counts were restored. The groups treated with the combination of antivenom and dexamethasone had an enhanced decrease in edema and a faster recovery of the damaged skeletal muscle. Our results show that Bothrops antivenom effectively treats the envenomation caused by Bothrops atrox and that the use of dexamethasone as an adjunct to the antivenom therapy could be useful to improve the treatment of local symptoms observed in envenomation caused by Bothrops snakes.

Scorpion envenoming caused by Tityus cf. silvestris evolving with severe muscle spasms in the Brazilian Amazon.

Scorpion stings are a public health problem in the Brazilian Amazon. However, detailed clinical characterization with the proper animal identification is scarce. Here we report a confirmed case of envenoming by Tityus cf. silvestris in the Brazilian Amazon. The case evolved with generalized muscle spasms and was treated with antivenom and supportive therapy, requiring intensive care unit admission. The patient evolved favourably and was discharged after 9 days of hospitalization.