Venom-induced Consumption Coagulopathy Research Articles

Clinical characteristics of snake envenomation-related acute kidney injury in South Korea.

Acute kidney injury (AKI) is a common complication of bites by Viperidae snakes. The main venomous snakes in South Korea are members of the Viperidae family, but there is limited information on snake-bite induced AKI in South Korea. Therefore, we investigated snake envenomation-related AKI and the performance of surrogate baseline creatinine to diagnose true AKI. This retrospective, case-control study divided 71 patients with baseline serum creatinine into two groups according to the development of envenomation-related AKI determined based on Kidney Disease Improving Global Outcome Classification. The incidence of AKI was 14.1% with 10% having stage-3 AKI. During hospitalization, the AKI group did not develop venom-induced consumption coagulopathy more frequently than did the non-AKI group. Only one patient needed renal replacement therapy, and no patients died. The serum creatinine concentration at presentation underestimated the incidence of AKI, while the lowest creatinine concentration during hospitalization overestimated the incidence of AKI. After discharge, the incidence of chronic kidney disease did not increase in the AKI group. Snake envenomation-related AKI is characterized by a relatively lower incidence and severity, has no correlation with coagulation disturbance, and has favorable short- and long-term outcomes in South Korea. Based on this study, it is recommended that future envenomation-related AKI studies would utilize the baseline creatinine for diagnosing AKI. If not, envenomation-related AKI studies should include the definition of baseline creatinine used to diagnose AKI and report bias if a baseline creatinine surrogate is used.

Progress on improving animal welfare and experiment translatability using an animal model of venom induced consumption coagulopathy

Progress on improving animal welfare and experiment translatability using an animal model of venom induced consumption coagulopathy

Handheld point-of-care devices for snakebite coagulopathy: a scoping review.

Venom induced consumption coagulopathy (VICC) is a common complication of snakebite that is associated with hypofibrinogenaemia, 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 standardised, 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 prioritise certain devices for clinical validation studies. Four small studies have evaluated a POC international normalised ratio (INR) device in patients with Australian Elapid, Daboia russelii and Echis carinatus envenoming. All of these studies used POC INR devices that rely on a thrombin substrate endpoint, which, unlike laboratory-based INR measurement, is known to underestimate INR in patients with hypofibrinogenaemia. Seventeen commercially available POC devices for measuring INR, activated clotting time (ACT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, and fibrin(ogen) degradation products (FDP) have been reviewed. POC INR devices that detect fibrin clot formation, as well as a novel POC device that quantifies fibrinogen were identified, that 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.

Utility of Three Serum Biomarkers for Early Detection of Systemic Envenoming Following Viper Bites in Sri Lanka

BackgroundEarly detection of systemic envenoming is critical for early antivenom therapy to minimise morbidity and mortality from snakebite. We assessed the diagnostic utility of three serum biomarkers in the early detection of systemic envenoming in viper bites in rural Sri Lanka. MethodsAll confirmed snakebite patients admitted to Teaching Hospital Anuradhapura from July 2020 to June 2021 were included. On admission, blood was collected for venom concentrations, prothrombin time (PT)/international normalised ratio (INR), fibrinogen, serum creatinine (sCr), and three serum biomarkers - secretory phospholipase A2 (sPLA2), neutrophil gelatinase-associated lipocalin (sNGAL) and clusterin (sClu). Systemic envenoming was defined by the presence of venom-induced consumption coagulopathy, neurotoxicity, acute kidney injury or the presence of non-specific clinical effects. ResultsA total of 237 confirmed snakebite patients (Russell’s viper,72; Hump-nosed viper,80; non-venomous snakes,31; and unidentified bites,54) with sufficient pre-antivenom serum samples were recruited [median age: 42y (interquartile range: 29-53y); males: 173 (73%)]. Systemic envenoming occurred in 68 (94%) Russell’s viper bites, 48 (60%) hump-nosed viper bites and 45 (83%) unidentified bites. The median sPLA2 activity was 72nmol/ml/min (IQR: 30–164) for Russell’s viper envenoming, 12nmol/ml/min (IQR:9–16) for hump-nosed viper envenoming and 11nmol/ml/min (IQR:9-14) for non-venomous bites. There was no difference in sNGAL and sCLu between the three groups. The median sPLA2 activity of patients with systemic envenoming was 16nmol/min/mL (IQR:11–59nmol/min/mL) compared to 11 nmol/min/mL(IQR:9–14nmol/min/mL) in patients without systemic envenoming; difference between medians of 5nmol/min/mL (95% CI:4–12nmol/min/mL). The AUC-ROC of admission sPLA2 was the best predictor of systemic envenoming in all snakebites (AUC-ROC 0.72, 95% CI: 0.66 to 0.79), whereas sNGAL and sClu were poor predictors. sPLA2 was a better predictor of systemic envenoming in Russell’s viper bites (AUC-ROC 0.90, 95% CI:0.76-1.00) and in those presenting within 2h of bite. A sPLA2 activity >23.5nmol/min/ml had a sensitivity of 97% (95% CI:91-99.5%), but a low specificity of 41% (95% CI:34%-49%) in predicting systemic envenoming. A sPLA2 concentration of >46 nmol/min/ml on admission had a sensitivity of 100% (95% CI:51%-100%) and a specificity of 67% (95% CI:55%-77%) in predicting systemic envenoming in Russell’s viper bites. ConclusionsPLA2 is an early predictor of systemic envenoming following snakebite, particularly in Russell’s viper bites and in those who present early.

The Epidemiology and Clinical Features of Deinagkistrodon acutus Envenomation: A Retrospective Study from a Medical Center in Hangzhou, Southeast China.

Deinagkistrodon acutus envenomation is one of the most common types of venomous snakebite in China and causes a series of envenomating effects on its victims. However, more specific information on the characteristics of D. acutus envenomation is rare in the English literature. Therefore, we aimed to give a detailed description of the epidemiological and clinical features of patients with D. acutus envenomation. Patients who were admitted with D. acutus envenomation between January 2018 and December 2021 were enrolled in this retrospective study. The data on demographics, clinical manifestations, laboratory features, management, and outcomes were collected. A total of 158 cases of D. acutus envenomation were enrolled. Men (n = 121; 76.6%) and rural populations (n = 133; 84.2%) were the high-risk groups, and most incidents (n = 141; 89.2%) happened between May and September. The specific effect was tissue necrosis at bite site, which occurred in 72 patients (45.6%). Other envenomation effects include extensive limb swelling, blistering, wound bleeding, and coagulopathy. In the envenomed patients, 155 (98.1%) received antivenom, 47 (29.7%) needed operations, 20 (12.7%) required intensive care, and one died. Deinagkistrodon acutus envenomation is a common snakebites emergency in Hangzhou area. A high rate of tissue necrosis at bite site and venom-induced consumption coagulopathy are the characteristics of D. acutus envenomation. Although the mortality rate is low, some patients still require intensive care.

Hemocoagulation Conditions Associated with Venom-Induced Consumption Coagulopathy due to Snakebite in Humans

Highlights:1. This review comprehensively highlighted aspects of hematologic abnormalities in snakebites, a topic that remains understudied globally.2. This review contributes insights into the field of snakebite research and improves the management of snakebites by examining the diverse effects of different types of snakebites on hemocoagulation status. Abstract Snakebite remains an underreported health hazard worldwide. The most common effects of snakebite envenomation globally are hematological disorders, with venom-induced consumption coagulopathy (VICC) being the most prevalent and significant condition. This review aimed to explore the hematological aspects of snakebite, with a focus on snakebite-induced consumption coagulopathy. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through a search across several databases, namely PubMed, ScienceDirect, and Google Scholar. The inclusion criteria for this review were studies on snakebite envenomation in humans with a discussion of relevant cases. Additionally, the included studies were conducted between 2010 and 2023 and published in the English language. Studies on animal models were excluded. We used the keywords “venom-induced consumption coagulopathy AND snake" in the search. The critical appraisal was performed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports and the Mixed Methods Appraisal Tool (MMAT). The findings were presented as a qualitative synthesis of 14 articles covering 316 patients and various snakebite types. The studies on snakebite came from various countries, but mostly from Sri Lanka. The snake types exhibited variation, with certain species existing only in specific areas. The subjects fell into different age groups, from children to the elderly. The majority of the subjects were male. The subjects' youngest age was 6 years old, while the oldest was 70 years old. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were the most discussed variables. Some of the studies demonstrated an increase in PT and APTT, although other studies reported contrasting findings. In conclusion, certain types of snakebite have a different impact on the hemocoagulation status.

Comparative Evaluation of Whole Blood Clotting Test as a Diagnostic Predictor of Venom Induced Consumption Coagulopathy in Hemotoxic Snake Bite

Comparative Evaluation of Whole Blood Clotting Test as a Diagnostic Predictor of Venom Induced Consumption Coagulopathy in Hemotoxic Snake Bite

The identification of a novel compound heterozygous mutation in hereditary human coagulation factor VII deficiency following a bamboo leaf green snake bite.

Hereditary factor VII (FVII) deficiency is an uncommon autosomal recessive disorder associated with mutations in the F7 gene, and laboratory investigations usually reveal isolated prolongation in prothrombin time (PT)/international normalized ratio (INR). Venom-induced consumptive coagulopathy (VICC) is distinguished by the activation of the coagulation pathway, which is triggered by procoagulant toxins in snake venom. Diagnosing snakebites in patients with hereditary FVII deficiency presents a challenge because prolonged time PT/INR is considered the most valuable diagnostic method for VICC. Therefore, it is possible that certain patients may not promptly receive an accurate diagnosis of hereditary FVII deficiency. We present a pedigree featuring hereditary FVII deficiency, which was diagnosed through Sanger sequencing, following a bamboo leaf green snake bite.

The Identification of a Novel Compound Heterozygous Mutation in Hereditary Human Coagulation Factor VII (FVII) Deficiency Following a Bamboo Leaf Green Snake Bite

Hereditary factor VII (FVII) deficiency is an uncommon autosomal recessive disorder associated with mutations in the F7 gene and laboratory investigations usually reveal isolated prolongation in prothrombin time (PT)/International normalized ratio (INR). Venom-induced consumptive coagulopathy (VICC) is distinguished by the activation of the coagulation pathway, which is triggered by procoagulant toxins in snake venom. Diagnosing snakebites in patients with hereditary FVII deficiency presents a challenge due to the fact that prolonged time PT/ INR is considered the most valuable diagnostic method for VICC. Therefore, it is possible that certain patients may not promptly receive an accurate diagnosis of hereditary FVII deficiency. We present a pedigree featuring hereditary FVII deficiency, which was diagnosed through Sanger sequencing, following a bamboo leaf green snake bite.

A case of acquired thrombotic microangiopathy secondary to Russell’s viper bite

Russell’s viper is one of the ‘big four’ most dangerous poisonous snakes in India. The farmer and snakes, especially the Russell's viper, coexist in tenuous relationship in the ecosystem. The clinical manifestations of viper bite are localized pain and swelling, coagulopathy, and renal impairment. The venom induced consumption coagulopathy (VICC) following Russell’s viper bite can result in a syndrome consistent with thrombotic microangiopathy (TMA), manifesting with thrombocytopenia, microangiopathic hemolytic anemia (MAHA) and acute kidney injury (AKI). TMA is rarely reported as a complication of Russell’s viper envenoming. Our patient, a farmer, was bitten by Russell’s viper and was brought to a nearby hospital within an hour. He was administered anti-snake venom (ASV) and supportive therapy. As his renal function declined, he was transferred to our hospital. He developed thrombocytopenia, and MAHA as evidenced by progressive anemia, schistocytes on peripheral smear, increased levels of lactate dehydrogenase (LDH), and AKI unresponsive to fluid management and diuretic administration. He was managed with sustained low-efficiency dialysis (SLED) and therapeutic plasma exchange (TPE). After three cycles of TPE and seven cycles of SLED over the next three weeks, the patient recovered completely and has been asymptomatic for more than six-months during follow up. The case is reported for rarity of TMA in the Russell’s viper envenomation, and the role of TPE in such cases.

Clinical characteristics of snakebite patients attending a tertiary hospital in Hangzhou, southeast China.

Venomous snakebite is a neglected yet an important public health problem in China, and few studies have focused on them so far. The aim of this study is to investigate clinical characteristics of snakebites patients in a tertiary hospital in Hangzhou, southeast China. A total of 416 snakebite cases were included in this retrospective study. The data were collected from the medical records including demographics, clinical manifestations, management and outcomes. Of the 416 patients with venomous snakebites, 248 were male, and the average age was 54.6 years. The majority of cases occurred in rural in May to September. Out of all the venomous bites, Gloydius brevicaudus accounted for the highest percentage (55.3%). Hands were the most vulnerable site to snakebites (47.4%). Patients had clinical manifestations of pain (100%), swelling (100%), wound necrosis (25.7%), hemorrhagic blister (18.3%), and blister (8.7%). Three hundred and ninety-two patients received antivenom administration, and most were treated within six hours after bites. Twenty-six patients received surgical treatments, and 90 patients developed venom-induced consumption coagulopathy. No deaths have occurred in this study. Hangzhou is one of the regions with high affecting of snakebites in China. The results of this study will increase the understanding of the clinical characteristics of venomous snakebites in Hangzhou area.

Hypothetical Interventions to Prevent Acute Kidney Injury After Humpnosed Pit Viper Bite

Abstract: Even though the Hump-nosed pit viper bite is the commonest venomous snake bite in Sri Lanka, antivenoms with specific activity against it are not available. Acute kidney injury (A.K.I.) is an important systemic complication accounting for mortality. Therapeutic plasma exchange (TPE) and fresh frozen plasma (F.F.P.) are two interventional options hypothesized to prevent A.K.I. This is by TPE at-tenuating venom antigenemia and F.F.P. by inhibiting nephrotoxic renal injury by immunomodulation, and the additional benefit of replenishment of depleted clotting factors triggered by venom-induced con-sumption coagulopathy implicated in the multifactorial mechanisms of renal injury. Routine interventions on all envenomed patients are not justifiable owing to the rarity and sporadic occurrence of systemic complications, and only patients with coagulopathy should be selected for interventions. The benefit of preventing A.K.I. is most likely with early intervention at the inception of coagulopathy.

Neutralization, by a polyspecific antivenom, of the coagulopathy induced by the venom of Bothrops asper: Assessment by standard coagulation tests and rotational thromboelastometry in a murine model

Venom-induced consumption coagulopathy and thrombocytopenia are common and potentially severe manifestations of viperid snakebite envenoming since they contribute to local and systemic hemorrhage. Therefore, the assessment of the efficacy of antivenoms to neutralize coagulopathic and thrombocytopenic toxins should be part of the preclinical evaluation of these drugs. To evaluate the efficacy of the polyvalent (Crotalinae) antivenom produced in Costa Rica, in this study we have used a mouse model of coagulopathy and thrombocytopenia induced by the venom of Bothrops asper, based on the bolus intravenous (i.v.) injection of venom. When venom and antivenom were incubated before injection, or when antivenom was administered i.v. immediately after venom injection, venom-induced hemostatic alterations were largely abrogated. We also studied the recovery rate of clotting parameters in conditions where antivenom was administered when mice were coagulopathic. Some parameters recovered more rapidly in antivenom-treated mice than in control envenomed animals, but others showed a spontaneous recovery without antivenom. This is due to a rapid clearance of plasma venom levels in these experimental conditions. This implies that models based on the bolus i.v. injection of venom have limitations for assessing the effect of antivenom in the recovery of clotting alterations once coagulopathy has developed. It is suggested that alternative models should be developed based on a slower systemic absorption of venom. Overall, our findings provide a protocol for the preclinical evaluation of antivenoms and demonstrate that the polyvalent antivenom is effective in neutralizing the toxins of B. asper venom responsible for coagulopathy and thrombocytopenia.

Long-term health manifestations of hump-nosed pit viper (Genus: Hypnale) bites

Introduction The hump-nosed pit viper (Genus: Hypnale) is a highly medically significant snake in Sri Lanka, responsible for the majority of venomous snakebites (22–77%). They are found throughout Sri Lanka and the Western Ghats region of India. The venom can lead to two types of effects: acute and long-term. Acutely, bites often result in local symptoms, with less common systemic effects such as acute kidney injury, venom-induced consumption coagulopathy, and thrombotic microangiopathy. Methods We conducted a prospective observational study at Teaching Hospital Ratnapura, Sri Lanka, spanning six years, starting in June 2015. Patients bitten by hump-nosed pit vipers were followed up for two years, with assessments every three months to identify long-term effects. Data was gathered through interviewer-administered questionnaires. Results Out of 728 patients bitten by hump-nosed pit vipers, 22 (3%) were lost to follow-up. Forty-four (6.2%) experienced long-term effects, including chronic kidney disease (24; 3.4%), chronic wounds (five; 0.7%), amputations (five; 0.7%), fasciotomy-related wounds (four; 0.6%), and psychological illnesses (four; 0.6%). There were nine (1.3%) deaths in this group. Among those with chronic effects, 27 (61%) were males, and 17 (39%) were females, with ages ranging from 29 to 82 years (mean 57.6 years). The time it took to diagnose acute kidney injury from the snakebite was 18 h (interquartile range: 15–23.5 h), while the time to diagnose chronic kidney disease was 69 days (interquartile range: 64–74.75 days). In these patients, the estimated glomerular filtration rate was 29.3 mL/min/1.73 m2 (interquartile range: 14–50.75 mL/min/1.73 m2). Among the patients who did not develop long-term complications (662; 91%) 660 (90.7%) experienced local effects, and 82 (11.3%) developed systemic manifestations, including acute kidney injury in 60 (8%) and coagulopathy in 35 (5%). Conclusion Following hump-nosed pit viper bites, a subset of patients may experience long-term health complications, including chronic kidney disease, chronic ulcers, amputations, fasciotomy-related wounds, and psychological illnesses, with chronic kidney disease being the most frequently observed among these manifestations.

Suspected snakebite in a tertiary referral centre in Western Sydney: a 10-year case series

ABSTRACT We aimed to determine the epidemiology and clinical management of patients presenting to an Australian tertiary emergency department (ED) with a suspected snake bite. Nepean Hospital covers a geographical area known to harbour venomous elapid snake species. A Retrospective chart review of all patients presenting to Nepean ED from 2011 to 2020 was performed. We searched the electronic medical records (eMR) for triage presentations including search terms of “snakebite”, “bite” “envenomation”, or “bite-snake” and a discharge or independent diagnosis of “snakebite” or “envenomation”. Our review identified 110 patients presenting with snakebite, of whom nine had signs or symptoms indicating envenomation. The most common envenomation syndrome was venom-induced consumption coagulopathy (VICC) and the most commonly suspected culprit snake was the Eastern Brown Snake. Our data broadly agreed with national data on epidemiology and demographics. We noted a satisfactory rate of compliance with local snake bite protocols with evidence of early diagnosis and antivenom administration. We had no cases of anaphylaxis and one case of serum sickness. Our study of a tertiary hospital experience in the management of snake bite demonstrated an appropriate adherence to national guidelines and early clinician recognition of envenomation syndromes. It also demonstrated appropriate antivenom use without obvious time delay.

Prevalence of Thrombotic Microangiopathy Among Patients With Snake Bite-Induced Hemotoxic Clinical Syndrome in the Hills of Himachal Pradesh, India

ABSTRACT Objective: Snakebite envenomation-related thrombotic microangiopathy (TMA) is observed in a subset of patients with venom-induced consumption coagulopathy (VICC). The study was planned to determine the prevalence of TMA among patients with hemotoxic envenomation admitted to a medical college hospital in Himachal Pradesh, India. Methods: This was a hospital-based open cohort observational study conducted on patients diagnosed with hemotoxic envenomation. The study period was of 1 year and patients were recruited using a nonprobability sampling method. Hemotoxic envenomation was defined as prolonged bedside 20-min whole blood clotting time (20 WBCT) following a history of snake bites. TMA was defined as the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury (AKI). Results: A total of 56 patients (32 females and 24 males) were included in the study. The prevalence of TMA was (7/56) 12.5%. Out of the seven patients with TMA, four (57.1%) patients improved without renal replacement therapy and three (42.9%) patients took referrals for getting nephrology services outside the state and hence were lost in follow-up. AKI was developed in 17 (30%) patients. Conclusion: The study demonstrated that TMA is not an uncommon entity. Investigation protocol for TMA should be included in all patients with VICC.

Comparing modified Lee and White method against 20-minute whole blood clotting test as bedside coagulation screening test in snake envenomation victims.

Twenty-minute whole blood clotting test (20WBCT) and Modified Lee and White (MLW) method are the most routinely employed bedside tests for detecting coagulopathic snake envenomation. Our study compared the diagnostic utility of MLW and 20WBCT for snakebite victims at a tertiary care hospital in Central Kerala, South India. This single-center study recruited 267 patients admitted with snake bites. 20WBCT and MLW were performed simultaneously at admission along with the measurement of Prothrombin Time (PT). The diagnostic utility of 20WBCT and MLW was determined by comparing the sensitivity (Sn), specificity (Sp), positive and negative predictive values, likelihood ratios, and accuracy at admission with an INR value > 1.4. Out of 267 patients, 20 (7.5%) patients had VICC. Amongst those who had venom-induced consumption coagulopathy (VICC), MLW was prolonged for 17 patients, (Sn 85% 95% confidence interval [CI]: 61.1-96.0) whereas 20WBCT was abnormal for 11 patients (Sn 55%, 95% CI: 32.04-76.17). MLW and 20WBCT were falsely positive for the same patient (Sp 99.6%, 95% CI: 97.4-99.9%). MLW is more sensitive than 20WBCT to detect coagulopathy at the bedside amongst snakebite victims. However, further studies are necessary for standardizing bedside coagulation tests in snakebite cases.

Neuroparalytic Snake Bite Masquerading as Acute Abdominal Pain in Children

Background: Neurotoxic snakebite (usually by the krait) presents with abdominal colic and chest pain as a common premonitory sign of envenomation. Being a nocturnal snake, the time of unprovoked painless biting is usually at night and the victims are individuals sleeping on the ground. Thus, history is usually not forthcoming. Snakebite causes morbidity (neuroparalytic, myopathic, vasculopathic, venom-induced consumption coagulopathy, cardiotoxic, nephrotoxic, etc.), and mortality if not given timely treatment with anti-snake venom (ASV), the only specific treatment. Clinical Description: We present four children from a rural background who were admitted successively over a month during the last rainy season. They initially became symptomatic with acute abdominal pain from midnight to early morning time and developed neuroparalytic manifestations within a few hours. On exclusion of other causes by clinical evaluation, we suspected snakebite envenomation though there was no witnessing of the event or evidence of fang bites. Investigations to rule out commonly associated organ dysfunction were ordered. Management: All children were given supportive therapy. Three cases required mechanical ventilation. The first two received ASV relatively late as the suspicion of snakebite was not considered initially. In the third case, the administration of ASV was early and the hospital stay was shorter. The fourth case received ASV at a peripheral health center and was referred in case he required ventilator support. However, his neuroparalysis did not progress to respiratory failure and he was discharged the earliest. Conclusions: Clinicians should consider snakebite in children belonging to rural areas who present with acute abdominal pain during the rainy season, and monitor for signs of neurotoxicity and other clinical manifestations of snake envenomation. A high index of suspicion should be kept, as definitive treatment with ASV results in early recovery without any sequelae, and reduces mortality.

Venom-induced consumptive coagulopathy leading to thrombotic microangiopathy following Echis carinatus sochureki bite: is snake antivenom effective?

The incidence of thrombotic microangiopathy (TMA) following snake bite is reported to be ranging from 3.6 to 15%. We report a 10-year-old boy who developed TMA and due to venom-induced consumptive coagulopathy (VICC) despite receiving adequate and timely doses of snake antivenom following a bite of saw-scaled viper (Echis carinatus sochureki). VICC was managed by plasmapheresis. Though snake bite envenomation-associated renal complications are not uncommon, possibility of TMA should be considered early during management. Our patient developed TMA with subsequent acute cortical necrosis after saw-scaled viper bite despite an adequate and timely dose of snake antivenom which emphasizes the ineffectiveness of antivenom against the venom of given snake species leading to long-term complications.

Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in Daboia siamensis and Agkistrodon halys Envenomation-Induced Thrombocytopenia.

Venom-induced thrombocytopenia (VIT) is one of the most important hemotoxic effects of a snakebite, which is often associated with venom-induced consumptive coagulopathy (VICC). Refractory thrombocytopenia without significant coagulation abnormalities has also been reported after envenomation by some viperid snakes; however, the mechanisms are not well understood and therapeutic strategies are lacking. Here, we found that patients injured by Daboia siamensis or Agkistrodon halys snakes, who were resistant to standard antivenom treatment, had developed coagulopathy-independent thrombocytopenia. Venoms from these viperid snakes, rather than from the elapid snake (Bungarus multicinctus), induced platelet surface expression of neuraminidase-1 (NEU-1), and significantly increased the desialylation of the glycoproteins on human platelets. The desialylated platelets caused by viperid snake venoms were further internalized by macrophages, which resulted in reduced platelet numbers in peripheral blood. Importantly, neuraminidase inhibitor significantly decreased viper venom-induced platelet desialylation, therefore inhibiting platelet phagocytosis by macrophages, and alleviating venom-induced thrombocytopenia. Collectively, these findings support an important role for desialylated platelet clearance in the progression of viper envenomation-induced, coagulopathy-independent thrombocytopenia. Our study demonstrates that the neuraminidase inhibitor may be a potential therapy or adjuvant therapy to treat snakebite-induced thrombocytopenia.