Antivenom Administration Research Articles

Livestock herding and Fulani ethnicity are a combined risk factor for development of early adverse reactions to antivenom treatment: Findings from a cross-sectional study in Nigeria.

BackgroundAdverse reactions to antivenom considerably complicate the clinical management of snakebite envenomed patients because it necessitates a temporary suspension of life-saving antivenom, increases costs and can compromise patient outcomes. This study sought to explore the association between cattle-herding occupation and ethnic group and the occurrence of early adverse reactions to antivenom.MethodsThis cross-sectional study was conducted between the 25th April and 11th July 2011 at the Kaltungo General Hospital in north east Nigeria. The exposure variable of cattle-herding occupation showed a strong correlation with the ethnic group variable, thus these were combined into a new variable with three categories (Fulani and herder, either Fulani or herder, and neither Fulani nor herder). The outcome variable was the occurrence of early adverse reactions, defined as any new symptoms occurring within 6 hours of antivenom administration. Odds Ratios were estimated using multivariable logistic regression models controlling for potential confounders.ResultsAmong 231 envenomed snakebite victims, the overall incidence of early adverse reactions was 11.9% (95% confidence intervals: 8.0–16.9%). Patients who were Fulani and herders had a higher incidence of early adverse reactions compared to patients who were neither Fulani nor herders (20% vs 5.7%). After adjusting for age and gender, victims who were Fulani and herders were 5.9 times more likely to have an early adverse reaction, compared to victims who were neither Fulani nor herders (95% CI: 1.88–18.59; p = 0.002).InterpretationTo the best of our knowledge, this is the first study to provide evidence of higher odds of early adverse reactions among patients from a particular occupation and/or ethnic group. We recommend that snake envenomed patients of Fulani origin be especially closely monitored for adverse reactions, that hospitals receiving these patients be appropriately resourced to manage both envenoming and adverse reactions and that premedication with adrenaline should be considered. Our findings provide an argument for speculation on the influence of immunological or lifestyle-related differences on the occurrence of early adverse reactions to antivenom.

Delays, fears and training needs: Perspectives of health workers on clinical management of snakebite revealed by a qualitative study in Kitui County, Kenya.

Key aims of the WHO Strategy to halve snakebite morbidity and mortality include health system strengthening and training of health workers. This requires knowledge of local health system needs and capacity, health worker training needs, and factors influencing health worker decision-making in snakebite management. This study explored health worker experiences and perceptions of snakebite management, both individually and in the context of their local health system.We used a qualitative study design with semi-structured interviews (n = 14) and focus group discussions (n = 4). We employed a combination of sampling strategies aiming to achieve maximum variation among key informants within resource limitations. We recruited health workers (n = 33) of varying roles from purposively selected tier 2, 3 and 4 health facilities (n = 12) and the community (tier 1) in four sub-counties in Kitui County, Kenya. We conducted inductive thematic analysis of all transcripts.The results identified that health workers recognised snake envenoming as a time-critical emergency in which delay in care seeking, sometimes exacerbated by health system referral delays, was a major barrier to effective management of patients. Clinicians strongly voiced a need for training in snakebite management, diagnosis and antivenom administration. Unexpressed needs for training were demonstrated in traditional remedy ineffectiveness, syndromic management, and critical appraisal of treatment effectiveness. Under-resourcing in antivenom, other medication, equipment, infrastructure and staffing also challenged management. Fear of snakebite and fear of antivenom, both linked to past experiences, influenced clinical decision-making.Our findings clearly indicate a need in Kitui County for training programmes that equip health workers for clinical decision-making in snakebite management. We further identify community intervention needs to facilitate prompt presentation to healthcare, including practical affordable transport solutions, and systematic health system resourcing needs. In addition, we recommend supportive supervision and further research in response to the emotional stress resulting from managing difficult cases in under-resourced settings.

Echis coloratus envenomation in children: a retrospective case series

Background Antivenom has been used successfully to treat systemic and progressive, local manifestations of envenomations inflicted by Echis coloratus, the second most common cause of snake envenomation in Israel. There is a paucity of published data regarding the use of monovalent (equine) immunoglobulin G antivenom in children. This study describes outcomes from the regimen used in two large, tertiary care pediatric centers. Methods A retrospective chart review of children admitted with definite or probable signs of Echis coloratus envenomation to Sourasky (Tel Aviv) and Soroka (Be’er Sheva) Medical Centers from January 1st 2008–to June 1st 2019. Extracted data included age, location of bite, time to hospital arrival, laboratory test results, complications, time to antivenom administration if indicated, adverse effects of the antivenom, and outcomes. Indications for antivenom were: diagnosis of Echis coloratus as the etiology of envenomation, local and systemic signs e.g. skin puncture wounds, swelling of the involved limb, local hematoma, and abnormal coagulation blood test results. Results During the study period, 11 children were treated with intravenous Echis coloratus antivenom. Median age was 9 years and 10 of 11 patients were male. Two patients underwent fasciotomy; in one, compartment syndrome was diagnosed by pressure measurement, and in the second, clinically. One patient developed mild urticaria 30 min after initiation of the antivenom; the treatment was stopped and then restarted at a slower rate after he was treated with hydrocortisone and diphenhydramine. No further adverse reactions were observed. Conclusions In children, Echis coloratus antivenom appeared to be effective and safe for the treatment of systemic and progressive local manifestations of envenomation by Echis coloratus.

The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming.

A global strategy, under the coordination of the World Health Organization, is being unfolded to reduce the impact of snakebite envenoming. One of the pillars of this strategy is to ensure safe and effective treatments. The mainstay in the therapy of snakebite envenoming is the administration of animal-derived antivenoms. In addition, new therapeutic options are being explored, including recombinant antibodies and natural and synthetic toxin inhibitors. In this review, snake venom toxins are classified in terms of their abundance and toxicity, and priority actions are being proposed in the search for snake venom metalloproteinase (SVMP), phospholipase A2 (PLA2), three-finger toxin (3FTx), and serine proteinase (SVSP) inhibitors. Natural inhibitors include compounds isolated from plants, animal sera, and mast cells, whereas synthetic inhibitors comprise a wide range of molecules of a variable chemical nature. Some of the most promising inhibitors, especially SVMP and PLA2 inhibitors, have been developed for other diseases and are being repurposed for snakebite envenoming. In addition, the search for drugs aimed at controlling endogenous processes generated in the course of envenoming is being pursued. The present review summarizes some of the most promising developments in this field and discusses issues that need to be considered for the effective translation of this knowledge to improve therapies for tackling snakebite envenoming.

Case Report: Treatment of a Severe Puff Adder Snakebite Without Antivenom Administration

ABSTRACT.Antivenoms are the treatment of choice for managing lethal snakebites. However, antivenoms may not be available in instances where non-native vipers are kept in captivity. We report a case of a puff adder (Bitis arietans) bite treated without antivenom. A 23-year-old man was bitten on his left hand by a puff adder that he illegally kept in his house. The swelling spread rapidly to the upper arm and there was a risk of bleeding, suggesting the need for antivenom administration, but this could not be acquired because of lack of stock. We initiated fluid resuscitation and administered recombinant thrombomodulin (rTM) to prevent venom-induced consumption coagulopathy. In addition, hyperbaric oxygen (HBO) treatment was also performed to reduce local swelling. The patient recovered without complications after the multidisciplinary treatment. Further studies are needed to prove the safety and efficacy of rTM administration and HBO therapy as an adjunct or alternative therapy with antiserum for fatal snakebite.

The application of laboratory-based analytical tools and techniques for the quality assessment and improvement of commercial antivenoms used in the treatment of snakebite envenomation.

Snakebite envenomation is a public health problem of high impact, particularly for the developing world. Antivenom, which contains whole or protease-digested immunoglobulin G, purified from the plasma of hyper-immunized animals (mainly horses), is the mainstay for the treatment of snakebite envenomation. The success of antivenom therapy depends upon its ability to abrogate or reduce the local and systemic toxicity of envenomation. In addition, antivenom administration must be safe for the patients. Therefore, antivenom manufacturers must ensure that these products are effective and safe in the treatment of envenomations. Antivenom efficacy and safety are determined by the physicochemical characteristics of formulations, purity of the immunoglobulin fragments and antibodies, presence of protein aggregates, endotoxin burden, preservative load, and batch to batch variation, as well as on the ability to neutralize the most important toxins of the venoms against which the antivenom is designed. In this context, recent studies have shown that laboratory-based simple analytical techniques, for example, size exclusion chromatography, sodium dodecyl sulphate polyacrylamide gel electrophoresis, mass spectrometry, immunological profiling including immuno-turbidimetry and enzyme-linked immunosorbent assays, Western blotting, immune-chromatographic technique coupled to mass spectrometry analysis, reverse-phase high performance liquid chromatography, spectrofluorometric analysis, in vitro neutralization of venom enzymatic activities, and other methodologies, can be applied for the assessment of antivenom quality, safety, stability, and efficacy. This article reviews the usefulness of different analytical techniques for the quality assessment of commercial antivenoms. It is suggested that these tests should be applied for screening the quality of commercial antivenoms before their preclinical and clinical assessment.

Synergistic effect of serine protease inhibitors and a bothropic antivenom in reducing local hemorrhage and coagulopathy caused by Bothrops jararaca venom

Snakebite accidents are a public health problem that affects the whole world, causing thousands of deaths and amputations each year. In Brazil, snakebite envenomations are caused mostly by snakes from the Bothrops genus. The local symptoms are characterized by pain, swelling, ecchymosis, and hemorrhages. Systemic disturbances can lead to necrosis and amputations. The present treatment consists of intravenous administration of bothropic antivenom, which is capable of reversing most of the systemic symptoms, while presenting limitations to treat the local effects, such as hemorrhage and to neutralize the snake venom serine protease (SVSP). In this context, we aimed to evaluate the activity of selective serine protease inhibitors (pepC and pepB) in combination with the bothropic antivenom in vivo. Further, we assessed their possible synergistic effect in the treatment of coagulopathy and hemorrhage induced by Bothrops jararaca venom. For this, we evaluated the in vivo activity in mouse models of local hemorrhage and a series of in vitro hemostasis assays. Our results showed that pepC and pepB, when combinated with the antivenom, increase its protective activity in vivo and decrease the hemostatic disturbances in vitro with high selectivity, possibly by inhibiting botropic proteases. These data suggest that the addition of serine protease inhibitor to the antivenom can improve its overall potential.

Challenges in the Management of an Echis coloratus Adult Snakebite Victim at a Tertiary Care Hospital: A Case Report

Patient: Male, 18-year-oldFinal Diagnosis: Snakebite envenomationSymptoms: CoagulopathyMedication:—Clinical Procedure: Anti snake venomSpecialty: General and Internal Medicine • Toxicology • Tropical MedicineObjective:Unusual clinical courseBackground:The World Health Organization has set clear guidelines for the management of snakebite envenomation. However, challenges have been reported in the clinical application of guidelines, such as identification of the biting snake, hypersensitivity reactions to the antivenom, and influence of repeated antivenom administration during hospital stay. This report aims to discuss how these challenges can affect patient management and to highlight improvement opportunities.Case Report:An 18-year-old man presented to the Emergency Department without remarkable signs of envenomation following a snakebite. An initial dose of antivenom was given despite the misidentification of snake species. An allergic reaction developed and was successfully managed. Following admission, the coagulation profile and local tissue reaction worsened. Upon consulting the Drug and Poison Information Center, it was discovered that a subtherapeutic dose of antivenom was administered. The patient was rechallenged after the administration of premedication. Coagulation profile could not be maintained; therefore, 2 extra doses of antivenom were administered, resulting in sustained improvement in local tissue reaction and coagulation profile.Conclusions:First, victims presenting without signs and symptoms of envenomation may benefit from close monitoring for late presentation of envenomation signs. Second, dosing guidelines are suggested to consider Institute of Safe Medication Practices recommendations for order sets to reduce the possibility of medication errors. Third, premedication may be an effective alternative in patients who develop allergic reaction to the locally produced equine antivenom in the setting of absent goat-derived antivenom. Lastly, antivenom administration should be titrated to patient response even if it occurs over several days.

Paediatric cases of Ceylon krait (Bungarus ceylonicus) bites and some similar looking non-venomous snakebites in Sri Lanka: Misidentification and antivenom administration

Ceylon krait (Bungarus ceylonicus) of the family Elapidae is a highly venomous endemic species inhabiting in the wet zone and some parts of the intermediate climatic zones of Sri Lanka. Clinical records of its bites are rare and limited to five case reports in the literature. It is of interest to note that there are several non-venomous snakes in Sri Lanka having similar morphological appearance to kraits causing identification difficulties which lead to unnecessary and unindicated administration of antivenom. We report two paediatric cases of proven Ceylon krait bites and three adult patients with similar looking non-venomous snakebites. These children were 1½ and 13 years old and developed neuroparalysis without progressing to respiratory failure and recovered. Both the children were administered Indian polyvalent antivenom which has not developed against endemic Ceylon krait venom. The two adult patients also received antivenom due to the misidentification without clinical and laboratory evidence of envenoming.

Acute Exposure to European Viper Bite in Children: Advocating for a Pediatric Approach.

Viper bite is an uncommon but serious cause of envenoming in Europe, especially in children. Our study aim is to better describe and analyze the clinical course and treatment of viper bite envenoming in a pediatric population. We retrospectively reviewed 24 cases of pediatric viper bites that were admitted to the Pediatric Emergency Department and the Pediatric Intensive Care Unit of the Bambino Gesù Children Hospital in Rome between 2000 and 2020. Epidemiological characteristics of the children, localization of the bite, clinical and laboratory findings, and treatment approaches were evaluated. The median age of the patients was 4.2 years, with male predominance. Most cases of viper bite occurred in the late summer. Most patients required admission to the ward for prolonged observation. The most common presenting signs were pain, local oedema, and swelling. Patients with a high severity score also had a significantly higher white blood cell count and an increase of INR, LDH, and CRP levels. No fatality was reported. Viper bite envenomation is a rare pediatric medical emergency in Italy but may sometimes be severe. A new pediatric severity score may be implemented in the screening of children with viper bites to favor a selective and prompt administration of antivenom.

Neurological and Systemic Manifestations of Severe Scorpion Envenomation.

Scorpion envenomation is a life-threatening toxicological emergency and considered as a major public health problem, especially in endemic regions (India, Africa, Latin America); it is generally characterized by low resources and tropical or subtropical weather. Scorpion envenomation is especially fatal in the first hours, usually due to respiratory and/or cardiovascular collapse. The neurologic manifestations, triggered by multiple neurotoxic mechanisms, are varied and complex and mostly reported in children. The aim of this review is to clarify the epidemiologic characteristics and clinical manifestations as well as diagnosis and management of neurologic complications following scorpion envenomation. The management of patients with severe clinical forms is based on early recognition of the sting, antivenom serum administration, and cardiorespiratory and systemic support.

The synthetic varespladib molecule is a multi-functional inhibitor for PLA2 and PLA2-like ophidic toxins

BackgroundThe treatment for snakebites is early administration of antivenom, which can be highly effective in inhibiting the systemic effects of snake venoms, but is less effective in the treatment of extra-circulatory and local effects. To complement standard-of-care treatments such as antibody-based antivenoms, natural and synthetic small molecules have been proposed for the inhibition of key venom components such as phospholipase A2 (PLA2) and PLA2-like toxins. Varespladib (compound LY315920) is a synthetic molecule developed and clinically tested aiming to block inflammatory cascades of several diseases associated with high PLA2s. Recent studies have demonstrated this molecule is able to potently inhibit snake venom catalytic PLA2 and PLA2-like toxins. MethodsIn vivo and in vitro techniques were used to evaluate the inhibitory effect of varespladib against MjTX-I. X-ray crystallography was used to reveal details of the interaction between these molecules. A new methodology that combines crystallography, mass spectroscopy and phylogenetic data was used to review its primary sequence. ResultsVarespladib was able to inhibit the myotoxic and cytotoxic effects of MjTX-I. Structural analysis revealed a particular inhibitory mechanism of MjTX-I when compared to other PLA2-like myotoxin, presenting an oligomeric-independent function. ConclusionResults suggest the effectiveness of varespladib for the inhibition of MjTX-I, in similarity with other PLA2 and PLA2-like toxins. General significanceVarespladib appears to be a promissory molecule in the treatment of local effects led by PLA2 and PLA2-like toxins (oligomeric dependent and independent), indicating that this is a multifunctional or broadly specific inhibitor for different toxins within this superfamily.

Population pharmacokinetics of Pseudechis porphyriacus (red-bellied black snake) venom in snakebite patients

Objectives Understanding the time course of venom exposure in snakebite patients is important for the optimisation of treatment including antivenom dose and timing. We aimed to investigate the pharmacokinetics of red-bellied black snake (RBBS; Pseudechis porphyriacus) venom in envenomed patients. Methods Timed venom concentration data were obtained from patients with RBBS envenomation recruited to the Australian Snakebite Project (ASP), including demographics and antivenom treatment. Venom concentrations were measured using an enzyme immunoassay. Data were modelled using NONMEM version 7.3. Uncertainty in venom “dose” was accounted for by arbitrarily fixing the average amount to 1 mg and incorporating between-subject variability on relative bioavailability. A scale parameter for venom clearance was implemented to account for the rapid venom clearance following antivenom dosing. A sensitivity analysis was performed to determine the magnitude of venom clearance amplification. Results There were 457 venom concentrations in 114 patients (median age 41, 2–90 y; 80 male). Antivenom was administered to 54 patients a median of 4.2 h post-bite (0.67 to 32 h). A one-compartment model with first-order absorption and elimination provided the best description of the data. The estimated clearance and volume of distribution were 5.21 L/h and 39.9 L, respectively. The calculated elimination half-life of P. porphyriacus venom from the final pharmacokinetic model was 5.35 ± 0.36 h. The variability in the relative dose of injected venom was 140%. Antivenom administration increased venom clearance by 40-fold. Ten patients showed evidence of a double peak in the absorption profile. Conclusion The information on the exposure time of venom in the body following envenomation will help improve treatment and the timing of antivenom.

Snake Bite Management: A Scoping Review of the Literature.

Background:Around the world, snake bite envenomation remains an underreported human health hazard. Envenomation can cause local and systemic complications, especially when there is a lack of antivenom availability. Although there are established guidelines regarding snake bite management acute care, there is a paucity of data regarding surgical intervention and the plastic surgeon’s role treating this unique patient population.Methods:A review was conducted identifying relevant published articles involving snake bite management and treatment in PubMed and EMBASE.Results:One hundred ten articles were identified and 77 met inclusion criteria. Snake bite envenomation can result in complications that are dependent upon a variety of variables. The literature has shown the best field treatment to be timely transportation to the nearest medical facility, along with antivenom administration. The cytotoxic, hemotoxic, and neurotoxic effects of venom can cause a variety of local soft tissue and systemic complications. Surgical interventions such as fasciotomies, wound debridements, skin grafts, and tissue flaps may be necessary in these patients to optimize functional and aesthetic outcomes. Disparities in access to care in resource limited settings are discussed.Conclusions:Global health disparities and insufficient antivenom distribution create an inequality of care in snake bite patients. Plastic surgeons have an important role in managing acute and chronic complications of snake bite envenomations that can lead to improved patient outcomes.

Examination of the Efficacy and Cross-Reactivity of a Novel Polyclonal Antibody Targeting the Disintegrin Domain in SVMPs to Neutralize Snake Venom.

Snake envenomation can result in hemorrhage, local necrosis, swelling, and if not treated properly can lead to adverse systemic effects such as coagulopathy, nephrotoxicity, neurotoxicity, and cardiotoxicity, which can result in death. As such, snake venom metalloproteinases (SVMPs) and disintegrins are two toxic components that contribute to hemorrhage and interfere with the hemostatic system. Administration of a commercial antivenom is the common antidote to treat snake envenomation, but the high-cost, lack of efficacy, side effects, and limited availability, necessitates the development of new strategies and approaches for therapeutic treatments. Herein, we describe the neutralization ability of anti-disintegrin polyclonal antibody on the activities of isolated disintegrins, P-II/P-III SVMPs, and crude venoms. Our results show disintegrin activity on platelet aggregation in whole blood and the migration of the SK-Mel-28 cells that can be neutralized with anti-disintegrin polyclonal antibody. We characterized a SVMP and found that anti-disintegrin was also able to inhibit its activity in an in vitro proteolytic assay. Moreover, we found that anti-disintegrin could neutralize the proteolytic and hemorrhagic activities from crude Crotalus atrox venom. Our results suggest that anti-disintegrin polyclonal antibodies have the potential for a targeted approach to neutralize SVMPs in the treatment of snakebite envenomations.

Moderate-to-severe Vipera berus envenoming requiring ViperaTAb antivenom therapy in the UK

Background Bites by the European adder (Vipera berus) in the UK are uncommon but potentially life threatening, and can be associated with marked limb swelling and disability. Following an interruption in Zagreb Imunološki zavod antivenom supply around 2012, the UK changed its national choice of antivenom for Vipera berus to ViperaTAb, an ovine Fab monospecific antivenom. In the absence of randomised controlled trials, we established an audit to review its use in clinical practice. Methods A prospective audit of ViperaTAb use was conducted from March 2016 until November 2020 by the UK National Poison Information Service (NPIS). Users of the NPIS online toxicology database, TOXBASE, considering the use of antivenom for V. berus envenoming were invited to discuss the case with the on-call clinical toxicology consultant. Information was collected prospectively on indications, administration, adverse reactions and outcome of patients administered ViperaTAb antivenom. Results One hundred and seventy patients were administered ViperaTAb antivenom over five years. One hundred and thirty-two were adults and 38 children (median age and range: 38, 2–87 years). Bites occurred across the UK, but most commonly in coastal regions of Wales and of South-West and East England. Median time to presentation was 2.1 (IQR 1.5–4.0) h and to antivenom administration from presentation was 2.0 (IQR 0.9–3.6) h. A minority of patients presented to hospital more than 12 h after being bitten (n = 19, 11.2%) or received antivenom more than 12 h after presenting to hospital (n = 17, 10.0%). Features of systemic envenoming were present in 64/170 (37.6%) patients, including 23 (13.5%) with anaphylaxis and 26 (15.3%) with hypotension (nine with both). Clinician assessment considered the initial antivenom to have been effective in 122/169 (72.2%) patients. Repeated dosing was common, occurring in 55/169 (32.5%), predominantly due to persisting or worsening local effects (46/51, 90.2%). There were three cases of probable early adverse reaction. No deaths occurred during the study. Complications of envenoming were rare but included four patients that underwent surgery, three patients each with acute kidney injury, mild coagulopathy, or thrombocytopenia (one severe). The median duration of hospital stay was 43.7 (IQR 22.5–66.5) h, longer for children than adults (52.5 vs 41.3 h). Conclusion ViperaTAb antivenom appears to be effective and safe and should be administered as soon as possible for patients meeting clinical criteria. Patients require close observation following antivenom to detect adverse reactions and progression or recurrence of envenoming. Close collaboration with expert NPIS consultant advice can help optimise antivenom timing, ensure repeated dosing is given appropriately, and avoid unnecessary surgical intervention. All hospitals, particularly those located in areas of relatively high incidence, should stock sufficient antivenom available at short notice, 24 h a day.

Spring poisoning hazards

Poisoning can be seasonal. Potential toxic hazards in the spring include adders, which emerge from hibernation as the weather warms. Adders may not be seen to bite a horse, but envenomation should be considered in a horse with localised limb swelling that spreads up the leg. There are several spring-flowering plants which contain toxic compounds such as cardiogenic glycosides (foxglove, lily of the valley, oleander), protoanemonin (Hellebore) and grayanotoxins (Pieris and Rhododendron). Saplings of sycamore are a spring source of hypoglycin A which causes atypical myopathy in horses. Treating plant poisoning in horses generally involves removing the plant, providing good quality food and giving supportive care. Managing the effects of adder bite is supportive, centring around administration of specific antivenom.

Coagulopathy after snake envenomation in South Korea

Objective This retrospective study investigated the nature and severity of venom-induced consumption coagulopathy (VICC) and determined the clotting factors involved in VICC in patients after envenomation by South Korea’s snakes. Additionally, we studied the effectiveness of antivenom for the treatment of VICC after envenomation. Methods Included patients were divided into three groups according to the severity of VICC (no VICC, partial VICC, and complete VICC). Data, including changes in coagulation parameters during hospitalization and clotting factors at presentation, were collected and analyzed. Results One hundred nineteen patients who presented at our emergency department within 3 h after snake envenomation were included. VICC developed in 34 patients (27 patients with partial VICC and 7 patients with complete VICC). Two of 34 patients with VICC required blood transfusions. Five patients with complete VICC had an undetectable fibrinogen concentration at presentation. Three patients with complete VICC had an unmeasurable INR and aPTT within 24 h. The median times of the most extreme values were 10 h for INR, 12 h for aPTT, and 16 h for fibrinogen after presentation in the VICC group. The D-dimer concentration peaked at a median of 63.5 h after presentation. The activities of factors II and X were significantly reduced in the complete VICC group (factor II: 88 (84-99.3)% in the non-VICC group vs. 69 (49.5–83.5)% in the complete VICC group; factor X:94 (83–102) in the non-VICC group vs. 70 (66.5–79.8)% in the complete VICC group), while there was no difference in factor V activity at presentation. The time from bite to first antivenom administration did not correlate with the time course and most extreme concentrations for fibrinogen and D-dimer within the VICC groups. Discussion and conclusion VICC occurs in approximately one-quarter of snakebite patients in South Korea; however, VICC itself does not appear to lead to clinical deterioration. Fibrinogen is an early diagnostic maker for complete VICC. Clotting factors II and X are involved in VICC. Future investigations should explore the mechanism of VICC from Korean snakebites and the effect of antivenom on VICC.

The in vitro laboratory tests and mass spectrometry-assisted quality assessment of commercial polyvalent antivenom raised against the ‘Big Four’ venomous snakes of India

India has recorded the maximum snakebite deaths in the world. Intravenous administration of polyvalent antivenom (PAV) raised against the ‘Big Four’ venomous snakes of India (Naja naja, Daboia russelli, Echis carinatus, and Bungarus caeraleus) is the only choice of treatment. The WHO has recommended the evaluation of quality and safety of commercial antivenom by in vitro laboratory tests prior to their pre-clinical evaluation in animal model and therapeutic use. Therefore, in this study an attempt has been made to evaluate the quality of commercial polyvalent antivenom produced in India by simple, and affordable laboratory tests. Proteomic analysis revealed that PAVs contained 78.7–94.8% IgG/F(ab’)2 and small quantities of plasma proteins. The PAVs showed batch-to-batch variations with varying amounts of undigested IgG and its aggregates, and moderate complement activation. However, absence of IgE, negligible endotoxin contamination, and recommended limit of preservative (cresol) in PAVs were observed. The PAVs contain varying proportions and least amount of venom-specific antibodies against venoms of the ‘Big Four’ snakes from different locales of India, and against eastern India N. kaouthia venom, respectively. The importance of independent in vitro laboratory tests for the quality control and safety assessment for improving the quality of Indian commercial PAV is reinforced.

The study of coagulation profile in relation to anti snake venom administration among patients with snake bite in a tertiary care hospital

The study of coagulation profile in relation to anti snake venom administration among patients with snake bite in a tertiary care hospital