Hump-Nosed Pit Viper Envenomation in Western Coastal India: A Case Series.

The hump-nosed pit viper (HNPV) has historically been considered less medically significant, causing local envenomation, renal injury, and coagulopathy; however, now, it is known to cause life-threatening complications. We describe the clinical presentation, treatment, and complications of 3 confirmed HNPV bites from the state of Karnataka (southwest coastal India). Patient 1, an 88-y-old woman, reported with the live specimen and developed venom-induced consumption coagulopathy (VICC) and thrombotic microangiopathy leading to acute kidney injury requiring blood product transfusions and dialysis. Patient 2, a 60-y-old woman, reported 3 d after envenomation followed by treatment at another hospital where 30 vials of polyvalent anti-snake venom (ASV) were given. She developed VICC and acute kidney injury requiring dialysis. On Day 9 of treatment, she developed a pontine hemorrhage. She died after a transfer to another treatment center closer to her residence. Patient 3, a 25-y-old man, was brought to our emergency department 6 h after being envenomed. He received topical ayurvedic treatment before arrival. He was unconscious and found to have severe VICC with a massive middle cerebral artery infarct. All 3 patients received Indian polyvalent ASV, which does not cover HNPV envenomation, clearly demonstrating the absence of paraspecificity and neutralization in a clinical setting. To our knowledge, Hypnale hypnale envenomation has not previously been reported from Karnataka state. The diagnosis of HNPV envenomation in a country without snake venom detection kits, under-reporting despite serious complications, financial burdens on rural populations afflicted, and poor outcomes due to the lack of a specific antivenom are discussed.

Venom-Induced Consumption Coagulopathy Following Hump-Nosed Pit Viper (Genus: Hypnale) Envenoming in Sri Lanka: Uncertain Efficacy of Fresh Frozen Plasma.

INTRODUCTION: Hump-nosed pit vipers (Hypnale spp) cause the highest number of venomous snakebites in Sri Lanka. Bites commonly cause local envenoming leading to local pain, swelling, and necrosis of the site of the bite. Acute kidney injury is the most common systemic manifestation, and some patients develop venom-induced consumption coagulopathy (VICC). Genus Hypnale comprises 3 species. Of them, H hypnale is found in Sri Lanka and the Western Ghats region of India. The other 2 (H nepa and H zara) are endemic species in Sri Lanka. METHODS: This study included 500 patients with hump-nosed viper bites studied prospectively over 4.5 y starting June 2014. All patients were assessed and the data were collected by the principal investigator (primary data). A subgroup of patients who developed VICC is described. There were 2 groups, including proven (patients with the specimen of the snake) and probable (specimen of snake not available) bites. RESULTS: Thirty (n=500; 6%) patients developed VICC; of them, 17 (3%) were proven cases, and 13 (2%) were probable cases. In both groups, 24 (80%) recovered, 2 (7%) progressed to chronic kidney disease, 1 (3%) died of severe hemostatic dysfunction, and 3 (10%) were lost to follow-up. Systemic bleeding was observed in 16 patients (53%), including hematuria (microscopic and gross) in 8 (27%) and venipuncture bleeding in 5 (17%). Eleven (37%) developed local bleeding at the site of the bite. Fresh frozen plasma was administered to 20 patients (67%), among whom only 11 (55%) experienced early correction of VICC. In both groups, 15 (50%) developed acute kidney injury, and 2 (7%) progressed to chronic kidney disease. Microangiopathic hemolysis was observed in 18 patients (60%) and thrombocytopenia in 16 (53%). Thrombotic microangiopathy was detected in 13 patients (43%), of whom 10 (33%) developed hemolytic uremic syndrome and 2 (7%) had thrombotic thrombocytopenic purpura. Of patients with VICC in the proven group, 94% (n=16) was caused by H hypnale and 1 (6%) was caused by H zara. In the proven group, median international normalized ratio was 3.7 (interquartile range 1.6-5.0); in the probable group, it was 5.0 (interquartile range 2.1-5.4). CONCLUSIONS: We found that 6% of patients develop hemostatic dysfunction after hump-nosed viper bites. However, which patients will develop coagulopathy or die of envenoming is unpredictable. Reliable and accessible treatments are unmet essential needs because antivenoms for these bites are currently not available in the country. Therapy with fresh frozen plasma has doubtful efficacy in early correction of VICC and needs further evaluation.

Thrombotic Microangiopathy Following Hypnale zara (Hump-Nosed Pit Viper) Envenoming: The First Known Case Report from Sri Lanka.

A 65-y-old previously healthy farmer developed thrombotic microangiopathy (TMA) comprising the triad of acute kidney injury, microangiopathic haemolysis, and thrombocytopenia after a proven Hypnale zara (hump-nosed pit viper) bite. He developed coagulopathy, which was treated with fresh frozen plasma, and underwent 8 cycles of hemodialysis. He is being followed up in the nephrology clinic for acute kidney injury. TMA caused by Hypnale hypnale, the commonest species of genus Hypnale, has previously been reported, but this is the first known case of TMA following a bite by H zara, the endemic species in Sri Lanka.

White-Lipped Tree Viper (Cryptelytrops albolabris) Envenomation in an American Viper Keeper.

BACKGROUND: Snakebites are common in many regions of the United States. Bites from exotic species, however, are rare. The white-lipped tree viper, Cryptelytrops (formerly Trimeresurus) albolabris, is a pit viper native to Southeast Asia. Bites are common in countries such as Myanmar, India, Thailand, Indonesia, and China. In this report, we describe an envenomation in an American viper keeper. CASE REPORT: A healthy 28-year-old right-handed man who collects venomous snakes experienced a bite to the distal left thumb from a neonatal C. albolabris while feeding it. Upon arrival to the Emergency Department 30 min after the bite, the patient complained of significant pain and swelling that had progressed across his entire hand. He also experienced nausea, lightheadedness, mild dyspnea, and a burning sensation in his lungs. After discussing the risks and benefits, we elected to treat with five vials of Thai Red Cross Green Pit Viper antivenin. The patient was also treated with intravenous fluids, parenteral opioids, and ondansetron. He received an additional five vials due to worsening hematologic laboratory values. His laboratory tests normalized and his local findings improved significantly. He was asymptomatic at discharge and at multiple follow-up visits. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Envenomation by C. albolabris is characterized by local tissue injury and hematotoxicity. Supportive care and specific antivenom therapy comprise the management of these bites. This case reminds physicians that not all bites that present to the hospital will be from native snakes and helps direct emergency physicians to specific expertise and uncommon antivenoms.

Galatrox is a C-type lectin in Bothrops atrox snake venom that selectively binds LacNAc-terminated glycans and can induce acute inflammation.

Previous studies indicate that snake venom contains glycan-binding proteins (GBPs), although the binding specificity and biological activities of many of these GBPs is unclear. Here we report our studies on the glycan binding specificity and activities of galatrox, a Bothrops atrox snake venom-derived GBP. Glycan microarray analysis indicates that galatrox binds most strongly to glycans expressing N-acetyllactosamine (LacNAc), with a significant preference for Galß1-4GlcNAcß over Galß1-3GlcNAcß compounds. Galatrox also bound immobilized laminin, a LacNAc-dense extracellular matrix component, suggesting that this GBP can bind LacNAc-bearing glycoproteins. As several endogenous mammalian GBPs utilize a similar binding LacNAc binding preference to regulate neutrophil and monocyte activity, we hypothesized that galatrox may mediate B. atrox toxicity through regulation of leukocyte activity. Indeed, galatrox bound neutrophils and promoted leukocyte chemotaxis in a carbohydrate-dependent manner. Similarly, galatrox administration into the mouse peritoneal cavity induced significant neutrophil migration and the release of pro-inflammatory cytokines IL-1α and IL-6. Exposure of bone marrow-derived macrophages to galatrox induced generation of pro-inflammatory mediators IL-6, TNF-α, and keratinocyte-derived chemokine. This signaling by galatrox was mediated via its carbohydrate recognition domain by activation of the TLR4-mediated MyD88-dependent signaling pathway. These results indicate that galatrox has pro-inflammatory activity through its interaction with LacNAc-bearing glycans on neutrophils, macrophages and extracellular matrix proteins and induce the release of pro-inflammatory mediators.

Life threatening intracerebral haemorrhage following saw-scaled viper (Echis carinatus) envenoming--authenticated case report from Sri Lanka.

BACKGROUND: Echis carinatus (Saw scaled viper {SSV}) is a venomous snake found in the parts of Middle East and Central Asia. SSV envenoming is characterized by local swelling and coagulopathy. Various bleeding manifestations are commonly seen with SSV envenoming. In contrast to other part of Asia, saw scale viper envenoming has not been reported to cause life threatening haemorrhagic manifestations in Sri Lanka. CASE PRESENTATION: We report a 19 years old healthy boy who developed massive left temporo-parietal intra cerebral haemorrhage following Echis carinatus (Saw scaled viper) bite in Sri Lanka. CONCLUSION: Although subspecies of SSV in Sri Lanka is regarded as a 'non lethal venomous snake', the occurrence of rare potentially fatal complications such as intracerebral haemorrhage should be considered in their management. This case report is intended to bring the awareness of this fatal complication of SSV envenoming in Sri Lanka.

Therapeutic outcome of quercetin nanoparticles on Cerastes cerastes venom-induced hepatorenal toxicity: a preclinical study.

Aim: The objective of this study was to investigate the therapeutic potential of quercetin (QT) and QT-loaded poly(lactic-co-glycolic acid) nanoparticles (QT-NPs) on Cerastes cerastes venom-mediated inflammation, redox imbalance, hepatorenal tissue damage and local hemorrhage. Methods: The developed QT-NPs were first submitted to physicochemical characterization and then evaluated in the 'challenge then treat' and 'preincubation' models of envenoming. Results: QT-NPs efficiently alleviated hepatorenal toxicity, inflammation and redox imbalance and significantly attenuated venom-induced local hemorrhage. Interestingly, QT-NPs were significantly more efficient than free QT at 24 h postenvenoming, pointing to the efficacy of this drug-delivery system. Conclusion: These findings highlight the therapeutic potential of QT-NPs on venom-induced toxicity and open up the avenue for their use in the management of snakebite envenoming.

Chronic kidney disease in snake envenomed patients with acute kidney injury in Sri Lanka: a descriptive study.

BACKGROUND: Data on the long-term outcomes of acute kidney injury (AKI) in envenomed patients leading to chronic kidney disease (CKD) are scarce. The aim of the study was to investigate this issue and to determine the predictive factors in developing CKD. METHODS: The records of a series of 54 patients who had AKI following a snakebite during the period 2004-2009 and who had been followed up were reviewed in the nephrology unit, Kandy, Sri Lanka. The primary outcome measure was the failure of renal functions to return to normal within 1 year. The renal histology was studied in seven patients. RESULTS: The mean age of the group was 50 years (SD 13 years) and 39 (72%) patients were men. The offending snakes were Russell's viper and hump-nosed viper in 15 (28%) and 13 (24%) patients, respectively. At 1 year, 20 patients (37%) had developed CKD (CKD group) and the rest (63%) had recovered (recovered group). The acute stage serum creatinine was high in both groups with no difference (on admission, p=0.134; on discharge, p=0.323), but the CKD group showed significantly high serum creatinine at 2 months after AKI (p=0.004). Mean duration of renal replacement therapy (RRT) of the recovered group and CKD group were 7 (SD 5) and 16 (SD 12) days, respectively (p=0.015). Renal histology of six CKD patients showed predominant glomerular sclerosis and interstitial nephritis. CONCLUSIONS: CKD is an outcome of severe AKI following snake envenoming probably predicted by the length of RRT.

[Management of the common European viper's bite--a case report]. / A keresztesvipera-marás ellátásának aktuális szempontjai egy eset kapcsán.

The common European viper is widespread throughout Europe. In Hungary it can be found mainly in the Zemplén Mountains, on the upper course of the Tisza River, and Zala and Somogy counties. Viper's bite is one of the rarest injuries that requires emergency medical care. The venom contains polypeptides and hydrolytic enzymes which have neurotoxic, cytotoxic, hemolytic and hemorrhagic effects. Local symptoms may include double points, pain, swelling, and suffusion at the site of the bite. Very occasionally, particularly in case of small children and elderly people, viper bite can cause life threatening angioedema, as well as shock and, therefore, professional medical help should always be sought preferably in a hospital that has a toxicology and poison control centre. Authors present the history of a 64-year-old nature enthusiast, who, after having been bitten by a viper, lost consciousness and experienced persistent local redness and pain. Soon after the viper bite, the patient suffered another potentially fatal accident, a stroke of lightning that he also survived. In connection with the case, authors provide an overview of the clinical symptoms caused by viper venom, and current issues of professional care.

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

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.

Anti-hemorrhagic activity of four Brazilian vegetable species against Bothrops jararaca venom.

Around 20,000 snakebites are reported annually in Brazil and 90% of them are inflicted by species of the genus Bothrops. Intravenous administration of antibothropic antivenom neutralizes the systemic actions, but it is of little effect on the reversal of local symptoms and often induces adverse reactions, a context that drives the search for complementary treatments for snakebite accidents. Vegetable extracts with a range of antiophidian activities constitute an excellent alternative. In this study, we investigated the anti-hemorrhagic effects of Mouriri pusa Gardn. (Melastomataceae), Byrsonima crassa Niedenzu (Malpighiaceae), Davilla elliptica St. Hill. (Dilleniaceae) and Strychnos pseudoquina St. Hil. (Loganiaceae) against Bothrops jararaca venom. The methanolic extracts from M. pusa (leaves), B. crassa (leaves) and D. elliptica (leaves) showed total neutralization capacity against local hemorrhages. The amenthoflavone and quercetin fractions from B. crassa and the flavonoids fractions (quercetin and myricetin) from M. pusa and D. elliptica also showed total neutralization capacity. We conclude that flavonoids derived from myricetin, quercetin and amenthoflavone play an important role in the anti-hemorrhagic potential of these Brazilian vegetables species against B. jararaca venom.

Hemoperitoneum caused by hepatic necrosis and rupture following a snakebite: a case report with rare CT findings and successful embolization.

We report the computed tomographic and angiographic findings in the case of a recently obtained successful clinical outcome after embolization of the hepatic artery in the case of a snakebite causing hemoperitoneum associated with hepatic necrosis and rupture with active bleeding.

Gaboon viper (Bitis gabonica) envenomation resulting from captive specimens--a review of five cases.

BACKGROUND: Five cases of illegitimate bite by captive specimens of the Gaboon viper (Bitis gabonica) snake have demonstrated the dangers of keeping exotic African snakes in captivity. CASE SERIES: Four cases necessitated hospitalization for the bite and were characterized by progressive swelling of the affected limb, local necrosis and hemorrhagic edema near the wound, chest tightness and prolonged coagulation times. However, platelet counts were not altered. All patients received antivenom and had uneventful recovery, except for one who underwent amputation of a distal phalanx and one who required debridement. In the fifth case, the patient died without being able to summon help. DISCUSSION: The results of this case series emphasize the need for extreme care to be exercised with the captivity of exotic snakes, such as the Gaboon viper. The increasing popularity of this snake as a captive pet predicates the need for private collectors to have a pre-existing treatment strategy with their local emergency centers. Such arrangements may facilitate the treatment of envenomation by this snake.

Accident ofídic / Accidente ofídico / Ophidic accident

Introducció. L’accident ofídic és un motiu d’hospitalitzacióa Catalunya, sobretot en època estival. Tot i que és unmotiu d’ingrés infreqüent, presenta una mortalitat no negligible. Sobre la base d’un cas clínic, se’n revisa el maneig iel tractament, sovint desconegut.Cas clínic. Pacient de 12 anys ingressada per accident ofídic i reacció al verí amb afectació cutània local i analítica.Necessita ingrés a la unitat de cures intensives, administració de sèrum antiofídic i dessensibilització a aquestabans de l’administració subcutània.Comentaris. Es presenta el cas amb l’objectiu de revisar els criteris d’ingrés, les proves analítiques i els criteris d’administració (via i dosi) del sèrum antiofídic. (AU)

Introducción. El accidente ofídico es un motivo de hospitalizaciónen Cataluña, sobre todo en época estival. Aunque es un motivo deingreso infrecuente, presenta una mortalidad no despreciable. Enbase a un caso clínico, se intenta revisar su manejo y tratamiento,a menudo desconocido.Caso clínico. Paciente de 12 años ingresada en el centro por accidente ofídico y reacción al veneno con afectación cutánea local yanalítica. Precisa ingreso hospitalario en unidad de cuidados intensivos, administración de suero antiofídico y realización de desensibilización a este, antes de su administración subcutánea.Comentarios. Se presenta el caso con el objetivo de revisar loscriterios de ingreso, pruebas analíticas y criterios de administración (vía y dosis) del suero antiofídico. (AU)

Introduction. Ophidic accidents are a cause for hospitalization inCatalonia, especially during summer. Despite their rarity, mortalityrate is not negligible. In this report we review the management ofophidic accidents.Case report. A 12-year-old patient was admitted to the hospital dueto an ophidic accident with severe local reaction to the venom,together with laboratory alterations, who required hospitalization in the intensive care unit and administration of antiophidic serumwith previous desensitization.Comments. The case is presented with the aim of reviewing theadmission criteria, laboratory tests and administration criteria(route and dose) of the antiophidic serum. (AU)

[Lymphoedema after an adder bite].

Bites from the adder, Vipera berus, are well known for causing local and general toxicity. We report a case of a 63-year-old female who was bitten in one of her lower extremities. She was seen twice in the emergency department with symptoms and signs consistent with severe envenomation. Despite treatment with antihistamines and corticosteroids the oedema persisted. A lymphoscintigraphy was performed showing dermal backflow in the right leg, confirming the diagnosis of lymphoedema. Based on the present case report and review of the literature antivenom therapy should be considered more actively.

Recurrent and persistent coagulopathy following pit viper envenomation.

BACKGROUND: Coagulation abnormalities following crotaline (pit viper) snakebite have traditionally been considered short-lived, but laboratory studies have rarely been reported beyond the first few days of treatment for envenomation. During the course of an antivenom clinical trial, we observed coagulation defects as late as 2 weeks following envenomation. OBJECTIVES: To document and characterize the recurrence or persistence of coagulopathy among patients envenomed by pit vipers and treated with a Fab antivenom. METHODS: Patients with moderate pit viper envenomation were enrolled in a multicenter, prospective clinical trial. A Fab-based antivenom preparation, antivenom polyvalent crotalid (ovine) Fab, was administered in all cases. Platelet count, fibrinogen level, presence of fibrin split products, prothrombin time, and partial thromboplastin time were determined before treatment and at standard intervals during the following 2 weeks. RESULTS: Of 38 patients completing the study, 20 (53%) had recurrent, persistent, or late coagulopathy 2 to 14 days after envenomation. Thrombocytopenia occurred in patients with prior thrombocytopenia; hypofibrinogenemia occurred only in those with prior hypofibrinogenemia or positive fibrin split products. No patient experienced significant spontaneous bleeding. One patient with coagulopathy developed minor bleeding following minor surgery 12 days after envenomation. CONCLUSIONS: Prolonged or recurrent coagulopathy may occur after envenomation by North American pit vipers. Patients treated with Fab-based antivenom may benefit from periodic rather than single-bolus dosing. Patients with coagulopathy should undergo close monitoring during the first 2 weeks after snakebite.

[Use of ecarin clotting time in whole blood for monitoring recombinant hirudine treatment during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia]. / Utilisation du temps de coagulation par l'écarine en sang total pour la surveillance d'un traitement anticoagulant par lépirudine (Refludan au cours de circulation extracorporelle dans un contexte de thrombopénie induite par l'héparine.

Lepirudin (Refludan is a recombinant hirudin, approved for anticoagulation treatment of heparin-induced thrombocytopenia patients with thrombosis. We report here our method for laboratory monitoring with ecarin clotting time (ECT) of hirudin therapy as anticoagulation for cardiac surgery. Ecarin is extracted from the Echis carinatus snake venom and directly converts prothrombin to its intermediate, meizothrombin. This one binds in a stoechiometric way to hirudin to be proportioned in whole blood. The activation of coagulation starts up only when the totality of the hirudin is bound to the meizothrombin. To minimize the effect of dilution related to the CEC on the prothrombin and fibrinogen levels, thus lengthening the ECT, the specimen to be tested is diluted with normal whole blood. In 1997, when we have performed our first surgery with cardiopulmonary bypass, only one team (Pötzsch et al., 1997) had described the use of the ECT in whole blood. We describe in this work our assay to dose hirudin with ECT after dilution in whole blood. This assay was used during 8 CEC among 7 patients affected with HIT (n = 6) or potentially sensitized with heparin (n = 1). Experimental conditions and interpretation of the assay are reported here. This test is fast enough to provide useful information for adjusting the dose during cardiopulmonary bypass.