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Background: 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. Methods: 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. Results: 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%). Conclusion: 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.

BACKGROUND Venom-induced consumption coagulopathy (VICC) is characterized by coagulation dysfunction accompanied by decreased coagulation factor activity and fibrinogen (FBG) concentrations. We report a patient with VICC caused by snake bite who manifested persistent FBG deficiency without abnormal coagulation factor activity. This information may be helpful in diagnosing and treating VICC. CASE SUMMARY A 49-year-old man who had been bitten by a snake 13 h previously was admitted to the Emergency Department of our hospital with visible swelling of a finger and a bleeding puncture site. The provisional diagnosis was VICC, this being made based on persistent bleeding from the puncture site and subcutaneous hemorrhage. Laboratory evidence of coagulation abnormalities, including fibrinolysis, and findings on thromboelastography confirmed VICC. He had persistent afibrinogenemia requiring intravenous infusions of cryoprecipitate and fresh frozen plasma, together with continuous large doses of human FBG. After this treatment, the patient’s right upper limb swelling improved significantly and his subcutaneous hemorrhage resolved. All of his abnormal laboratory findings returned to normal by day 25. During 6 months’ of follow-up, the patient had no further hemorrhagic events. CONCLUSION Hemorrhagic snake venom can result in coagulation dysfunction characterized by persistent FBG deficiency without abnormal coagulation factor activity.

Snakebite envenoming is a serious and life-threatening but neglected problem in the tropics. The focus in the Indian subcontinent is usually on the Indian cobra (Naja naja), common krait (Bungarus caeruleus), Russell's viper (Daboia russelii), and Indian saw-scaled viper (Echis carinatus). The Indian polyvalent antivenom contains hyperimmunized horse antibodies against only these 4 species. However, regional intraspecific variations are important in viper envenomings, leading to marked differences in clinical presentation and response to the available polyvalent antivenom. Echis carinatus sochureki, a subspecies of Echis carinatus, has been linked to serious morbidity in the Thar Desert regions of Rajasthan, although consistent reports are lacking. We report a patient with prolonged venom-induced consumption coagulopathy owing to Echis carinatus sochureki envenoming who did not respond to Indian polyvalent antivenom in Jodhpur, India. Features of local and hemotoxic envenoming resolved after a week with supportive care. Echis sochureki venom has been shown to be different from Echis carinatus in terms of composition and in vitro neutralization by antivenom. Clinicians in the tropical desert regions must suspect Echis sochureki envenoming in the setting of nonresponsiveness to Indian polyvalent antivenom. This will help optimize antivenom use in these patients, preventing potentially life-threatening antivenom associated reactions. Because the usefulness of Indian polyvalent antivenom appears to be limited in this setting, there is an urgent need to advocate for region-specific antivenom or monovalent antivenom for this area.

Patient: Male, 62 Final Diagnosis: Splenic hemorrhage Symptoms: Hypotension • syncope Medication: — Clinical Procedure: Splenic artery angio-embolization Specialty: Critical Care Medicine Objective: Rare disease Background: Snakebite envenoming results from injection of a mixture different toxins following snakebite. Coagulopathy and life-threatening hemorrhage can occur, or venom-induced consumption coagulopathy (VICC). A rare case is presented of spontaneous splenic hemorrhage due to VICC that was successfully treated by non-surgical splenic artery embolization. Case Report: A 62-year-old man was admitted to the emergency department after an episode of dizziness and loss of consciousness following a snakebite. He was transferred to our hospital with hypotension and an abnormal blood coagulation test. On admission, he was hypotensive, with reduced hemoglobin and hematocrit levels, but did not complain of abdominal pain. The occult source of bleeding was identified by abdominal computed tomography (CT) as splenic hemorrhage. Treatment began with the administration of antivenom and blood transfusion. Splenic artery angio-embolization was performed to control the bleeding and was without complication. Conclusions: Snakebite envenoming associated with VICC is a serious and life-threatening condition. Because of the possibility of associated occult bleeding from internal organs or blood vessels, imaging studies should be performed as soon as possible. For patients who are hemodynamically stabilized and have atraumatic hemorrhage from the spleen, non-operative treatment using angio-embolization may be performed with intensive monitoring and follow-up.

Objective This study aimed to determine the effect of repeated antivenom therapy compared with that of single antivenom therapy for treating snakebite-related systemic complications. Methods A retrospective medical record review from January 2008 to September 2016 was performed. Patients with snakebite injury who visited the Emergency Department in one tertiary center of Korea were included. The primary outcome was the survival rate. The secondary outcome was the effect of repeated antivenom therapy for treating snakebite-related systemic complications compared with that of single antivenom therapy on hospital length of stay. Results A total of 110 patients with snakebites were included. All patients survived to discharge. Twenty-nine (26.4%) patients had snakebite-related systemic complications. Of these, nine patients received repeated antivenom therapy and 20 patients received single antivenom therapy. The length of stay was significantly longer in those who received repeated antivenom therapy compared with those who received single antivenom therapy (10.0 [4.0–11.0] vs. 3.5 [0–7.0] days). Conclusion We were unable to demonstrate any superiority of repeated versus single antivenom therapy. However, repeated antivenom therapy is associated with a longer hospital stay. The reason for this finding is unknown.

Objective: Rhabdophis tigrinus (Yamakagashi in Japanese) is a venomous non-front-fanged colubroid snake capable of inflicting envenoming with life-threatening defibrinating coagulopathy. However, b...

Background Venom‐induced consumption coagulopathy is a common consequence of snake envenoming that can lead to life‐threatening hemorrhage, and is associated with microangiopathic hemolytic anemia (MAHA), acute kidney injury and thrombocytopenia. The role of microvesicles (MV) in snakebite patients has not been previously investigated. Objective To compare changes in subsets of circulating MV levels in snakebite patients with venom induced consumption coagulopathy and with or without microangiopathic hemolysis to those of healthy controls. Methods This study used samples from patients recruited to the Australian Snakebite Project (ASP) with snake envenoming, including bites by brown snakes, tiger snakes, and taipans. Citrated blood from envenomed patients was collected, processed, and stored according to a national standardized protocol. Full blood count and coagulation parameters were measured as per routine clinical care and blood films were examined for evidence of hemolysis. Baseline coagulation parameters were measured on a Behring Coagulation System. Flow cytometry was performed to detect CD41a (platelet), CD62e (endothelial), and glycophorin (red cell) MV. The results were analyzed using BD software and appropriate statistical tools. Results and Conclusions The red cell MV in snakebite patients with MAHA (n = 13) were significantly higher than those without MAHA (n = 17) while there was no significant difference in platelet MV levels between the snakebite patients with and without MAHA. Interestingly, the endothelial MV were reduced in all snakebite patient samples compared to the control samples. Measuring red cell MV at presentation could be useful as a predictive marker for MAHA in patients with snakebites.

A previously well man developed acute, marked tender bilateral gynaecomastia two months after confirmed taipan (Oxyuranus scutellatus) envenomation. He had had laboratory evidence of thrombotic microangiopathy (TMA) including microangiopathic haemolytic anaemia, thrombocytopenia and acute kidney injury. Scrotal ultrasound revealed bilateral testicular atrophy, his serum testosterone was repeatedly low, while his luteinising and follicle stimulating hormone were elevated. It is hypothesised that TMA-related testicular ischaemia was responsible for his primary gonadal failure and dramatic clinical presentation.

Background Venom-induced consumption coagulopathy (VICC) from tiger snake (Notechis scutatus) envenomation results in a dose-dependent coagulopathy that is detectable on coagulometry. However, individual coagulation factor activities in dogs with tiger snake envenomation have not been determined. This study aimed to characterise VICC and the time course of recovery in tiger snake envenomed dogs and to investigate an association between tiger snake venom (TSV) concentrations and factor activity. Methods This was a prospective, observational, cohort study. The study cohort was 11 dogs of any age, breed, sex, body weight >10 kg, confirmed serum TSV on ELISA and treated with antivenom. Blood was collected at enrolment before antivenom administration, then at 3, 12 and 24 h after antivenom administration. Tiger snake venom concentrations were detected with a sandwich ELISA. Fibrinogen was measured using a modified Clauss method, and coagulation factors (F) II, V, VII, VIII and X were measured with factor-deficient human plasma using a modified prothrombin (PT) and activated partial thromboplastin (aPTT) method. Linear mixed models, with multiple imputations of censored observations, were used to determine the effect of time and TSV concentration on the coagulation times and factor activity. This cohort was compared to 20 healthy controls. Results At enrolment, there were severe deficiencies in fibrinogen, FV and FVIII, with predicted recovery by 10.86, 11.75 and 13.14 h after antivenom, respectively. There were modest deficiencies in FX and FII, with predicted recovery by 20.57 and 32.49 h after antivenom, respectively. No changes were detected in FVII. Prothrombin time and aPTT were markedly prolonged with predicted recovery of aPTT by 12.58 h. Higher serum TSV concentrations were associated with greater deficiencies in FII, FV and FVIII, and greater prolongations in coagulation times. The median (range) serum TSV concentration was 57 (6–2295) ng/mL. Conclusions In tiger snake envenomed dogs, we detected a profound, TSV-concentration-related consumption of select coagulation factors, that rapidly recovered toward normal. These findings allowed further insight into tiger snake VICC in dogs.

Objective Viperidae snakes are responsible for 95 % of the bites caused by exotic-bred snakes in our country. Their envenoming may be associated with a severe acute coagulation disorder - venom-induced consumption coagulopathy (VICC). Thus, its early prediction is vital for an adequate therapy including antivenom delivery. Material and methods Laboratory coagulation tests of 14 patients suffering from VICC were processed and statistically analyzed to evaluate the importance of individual parameters in the time after the bite. Results The pathological values of D-dimer (D-dim) and fibrinogen (FBG) were found to be the first indicators of VICC development, with a median time of 4.55 hours since the bite, while median values for prothrombin time and international normalized ratio (PT/INR), activated partial thromboplastin time (APTT), and thrombin time (TT) were 5.9 h, 8.15 h, and 5.5 h, respectively. In the first samples, the values of D-dim were found to be pathologically increased in all 14 patients, while pathological levels of FBG were seen only in 11 cases. PT/INR and APTT were prolonged in 8 and 6 cases, respectively. Conclusion An increase in D-dim values was found to be the first parameter signaling developing VICC in all analyzed cases (Tab. 2, Ref. 12).

Russell's viper bite is an important public health problem of tropical countries including Thailand. Common manifestations after Russell's viper bite are local tissue swelling, coagulopathy, and ne...

Snake venoms are mixtures of numerous proteinacious components that exert diverse functional activities on a variety of physiological targets. Because the toxic constituents found in venom vary from species to species, snakebite victims can present with a variety of life-threatening pathologies related to the neurotoxic, cytotoxic and haemotoxic effects of venom. Of the 1·8 million people envenomed by snakes every year, up to 125 000 die, while hundreds of thousands survive only to suffer with life-changing long-term morbidity. Consequently, snakebite is one of the world's most severe neglected tropical diseases. Many snake venoms exhibit strong haemotoxic properties by interfering with blood pressure, clotting factors and platelets, and by directly causing haemorrhage. In this review we provide an overview of the functional activities of haemotoxic venom proteins, the pathologies they cause in snakebite victims and how their exquisite selectivity and potency make them amenable for use as therapeutic and diagnostic tools relevant for human medicine.

Essentials Russell's viper envenoming is a major health issue in South Asia and causes coagulopathy. We studied the effect of fresh frozen plasma and two antivenom doses on correcting coagulopathy. Fresh frozen plasma did not hasten recovery of coagulopathy. Low-dose antivenom did not worsen coagulopathy. SUMMARY: Background Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom-induced consumption coagulopathy (VICC). Objectives To investigate the effects of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. Methods We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1 : 1) to high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4 U of FFP. The primary outcome was the proportion of patients with an International Normalized Ratio (INR) of < 2 at 6 h after antivenom administration. Secondary outcomes included anaphylaxis, major hemorrhage, death, and clotting factor recovery. Results From 214 eligible patients, 141 were randomized: 71 to high-dose antivenom, and 70 to low-dose antivenom/FFP; five had no post-antivenom blood tests. The groups were similar except for a delay of 1 h in antivenom administration for FFP patients. Six hours after antivenom administration, 23 of 69 (33%) patients allocated to high-dose antivenom had an INR of < 2, as compared with 28 of 67 (42%) allocated to low-dose antivenom/FFP (absolute difference 8%; 95% confidence interval - 8% to 25%). Fifteen patients allocated to FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion-related acute lung injury. Three deaths occurred in low-dose antivenom/FFP patients, including one intracranial hemorrhage. There was no difference in recovery rates of INR or fibrinogen, but there was more rapid initial recovery of factor V and FX in FFP patients. Conclusion FFP after antivenom administration in patients with Russell's viper bites did not hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting that low-dose antivenom is sufficient. NHMRC. Grant Numbers: 631073, 1061041, 1059542

SummaryThe 20-minute whole blood clotting test (WBCT20) is used as a bed-side diagnostic test for coagulopathic snake envenoming. We aimed to assess the performance of the WBCT20 in diagnosis of venom induced consumption coagulopathy (VICC) in Russell’s viper envenoming. Adult patients admitted with suspected snake bites were recruited from two hospitals. WBCT20 and prothrombin time (PT) test were performed on admission. WBCT20 was done by trained clinical research assistants using 1 ml whole blood in a 5 ml borosilicate glass tube with a 10 mm internal diameter. The PT was measured by a semi-automated coagulation system and international normalised ratio (INR) calculated. VICC was defined as present if the INR was >1.4. The diagnostic utility of WBCT20 was determined by calculating the sensitivity and specificity of the WBCT20 on admission for detecting VICC. There were 987 snake bites where both WBCT20 and PT were done on admission samples. This included 79 patients (8 %) with VICC. The WBCT20 was positive in 65/79 patients with VICC (sensitivity 82 %; 95 % confidence interval [CI]: 72–90 %) and was falsely positive in 13/908 with no coagulopathy. The WBCT20 was negative in 895/908 snake bites with no coagulopathy (specificity: 98 % 95 % CI: 97–99 %) and was falsely negative in 14/79 with VICC. Using trained clinical staff, the WBCT20 test had a relatively good sensitivity for the detection of VICC, but still missed almost one fifth of cases where antivenom was potentially indicated.Supplementary Material to this article is available online at www.thrombosis-online.com.

Taipans (Oxyuranus spp.) are medically important venomous snakes from Australia and Papua New Guinea. The objective of this study was to describe taipan envenoming in Australian and its response to antivenom.Confirmed taipan bites were recruited from the Australian Snakebite Project. Data were collected prospectively on all snakebites, including patient demographics, bite circumstances, clinical effects, laboratory results, complications and treatment. Blood samples were taken and analysed by venom specific immunoassay to confirm snake species and measure venom concentration pre- and post-antivenom.There were 40 confirmed taipan bites: median age 41 years (2-85 years), 34 were males and 21 were snake handlers. Systemic envenoming occurred in 33 patients with neurotoxicity (26), complete venom induced consumption coagulopathy (VICC) (16), partial VICC (15), acute kidney injury (13), myotoxicity (11) and thrombocytopenia (7). Venom allergy occurred in seven patients, three of which had no evidence of envenoming and one died. Antivenom was given to 34 patients with a median initial dose of one vial (range 1-4), and a median total dose of two vials (range 1-9). A greater total antivenom dose was associated with VICC, neurotoxicity and acute kidney injury. Early antivenom administration was associated with a decreased frequency of neurotoxicity, acute kidney injury, myotoxicity and intubation. There was a shorter median time to discharge of 51 h (19-432 h) in patients given antivenom 4 h post-bite, compared to 175 h (27-1104 h) in those given antivenom 4 h. Median peak venom concentration in 25 patients with systemic envenoming and a sample available was 8.4 ng/L (1-3212 ng/L). No venom was detected in post-antivenom samples, including 20 patients given one vial initially and five patients bitten by inland taipans.Australian taipan envenoming is characterised by neurotoxicity, myotoxicity, coagulopathy, acute kidney injury and thrombocytopenia. One vial of antivenom binds all measurable venom and early antivenom was associated with a favourable outcome.

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.

The clinical signs, biochemical changes and serum and urine venom concentrations for a series of nine cases of Red bellied black snake [RBBS] (Pseudechis porphyriacus) envenomation in eight dogs seen in a regional Australian veterinary hospital are described. Although the resulting envenomation syndrome was, in most cases, relatively mild and responded rapidly to intravenous administration of a novel bivalent caprylic acid purified whole IgG equine antivenom for tiger (Notechis scutatus) and brown snake (Pseudonaja textilis), one fatality prior to antivenom treatment was recorded. The latter case occurred within 1 h of envenomation prior to receiving antivenom treatment. Intravascular haemolysis, pigmenturia, bite site swelling, lethargy, and generally mild coagulopathy were present in most cases. Detectable RBBS venom specific components were found in serum, bite site swab or urine using a standard sandwich ELISA approach. Serum levels fell within the range previously reported for human RBBS envenomation cases (6-79 ng/ml) whilst bite site and urine samples varied more markedly (8.2 to >5000 ng/ml and 2.2-1300 ng/ml respectively). No venom was detected from serum after antivenom treatment. The envenomation syndrome in dogs is similar to what is described for humans, with the exception of the presence of potentially severe venom induced consumption coagulopathy in one case (aPTT > 300 s and fibrinogen

Venom-induced consumption coagulopathy is the most important systemic effect of snake envenoming. Coagulation tests are helpful to accurately and promptly diagnose venom-induced consumption coagulopathy and administer antivenom, which is the only specific treatment available. However, bedside clotting tests play a major role in diagnosing coagulopathy in low-income settings, where the majority of snakebites occur. We conducted a literature search in MEDLINE® from 1946 to 30 November 2019, looking for research articles describing clinical studies on bedside coagulation tests in snakebite patients. Out of 442 articles identified, 147 articles describing bedside clotting assays were included in the review. Three main bedside clotting tests were identified, namely the Lee–White clotting test, 20-min whole blood clotting time and venous clotting time. Although the original Lee–White clotting test has never been validated for snake envenoming, a recently validated version has been used in some South American countries. The 20-min whole blood clotting time test is the most commonly used test in a wide range of settings and for taxonomically diverse snake species. Venous clotting time is almost exclusively used in Thailand. Many validation studies have methodological limitations, including small sample size, lack of case-authentication, the inclusion of a heterogeneous mix of snakebites and inappropriate uses of gold standard tests. The observation times for bedside clotting tests were arbitrary, without proper scientific justification. Future research needs to focus on improving the existing 20-min whole blood clotting test, and also on looking for alternative bedside coagulation tests which are cheap, reliable and quicker.

Background The whole blood clotting test (WBCT) is a simple test of coagulation that is often used in the assessment, diagnosis, and therapeutic monitoring of snakebite patients in sub-Saharan Africa. WBCT requires only a clean glass tube and several milliliters of venous blood and is ideal for use in poorly equipped health centers throughout the rural areas where 95% of snakebites occur. However, questions surrounding the accuracy and reliability of the test remain unanswered due to variations in testing conditions and a lack of comparative research with which to validate them. This is the first study to evaluate WBCT results at both 20-min (WBCT20) and 30-min (WBCT30) reading times in the same group of snakebite patients. Methods In order to define the best reading time, the authors compared the results of serial WBCT evaluation at both 20 and 30 min after collection in 23 patients treated for snake envenomation in Bembèrèkè, northern Benin. Results WBCT results were identical at both reading times in patients without coagulopathy or when coagulation was restored permanently following a single dose of antivenom. Out of 17 patients with coagulopathy, 14 showed discrepancies between WBCT20 and WBCT30 results in at least one pair of serial evaluations. These could be completely contradictory results (e.g. normal clot at WBCT20 and no clot at WBCT30) or a marked difference in the quality of the clot (e.g. no clotting activity at WBCT20 and an unstable partial clot at WBCT30). WBCT discrepancies were encountered most frequently in three situations: initial normalization of hemostasis following antivenom therapy, detection of a secondary resumption of coagulopathy, or final restoration of hemostasis after a secondary resumption had occurred. Conclusions This study suggests that the WBCT is robust and that a sequential reading should improve the diagnosis and monitoring of venom-induced coagulopathies. It also indicates the possibility of discrepancies in the sensitivity of WBCT20 and WBCT30 for detecting the resolution or reoccurrence of coagulopathy and identifies how these findings, if confirmed, may be used to increase the efficacy and efficiency of antivenom treatment in the field.

This case report documents envenomation by an arboreal white-lipped green pit viper (Trimeresurus albolabris), a species found in South and Southeast Asia that causes the majority of venomous snakebites among Southeast Asian pit vipers. Clinical features vary from asymptomatic to serious coagulopathy that may progress into life-threatening or fatal hemorrhage. The proven life-threatening cases described in published literature, however, are sparse. Practically, no specific antivenom targeted to pit viper bites is available in Nepal. We report a case (managed with several non-evidence-based interventions) of noticeable coagulopathic envenomation due to confirmed T albolabris bite in Nepal. This is the first known reported case of such a bite in Nepal. This case highlights the urgent need to improve diagnosis, monitoring, and supportive care for bite victims and to study the effectiveness of Thai pit viper antivenoms for the treatment of T albolabris envenomations.

Background: The whole blood clotting test (WBCT) is a simple test of coagulation that is often used in the assessment, diagnosis, and therapeutic monitoring of snakebite patients in sub-Saharan Africa. WBCT requires only a clean glass tube and several milliliters of venous blood and is ideal for use in poorly equipped health centers throughout the rural areas where 95% of snakebites occur. However, questions surrounding the accuracy and reliability of the test remain unanswered due to variations in testing conditions and a lack of comparative research with which to validate them. This is the first study to evaluate WBCT results at both 20-min (WBCT20) and 30-min (WBCT30) reading times in the same group of snakebite patients. Methods: In order to define the best reading time, the authors compared the results of serial WBCT evaluation at both 20 and 30 min after collection in 23 patients treated for snake envenomation in Bembereke, northern Benin. Results: WBCT results were identical at both reading times in patients without coagulopathy or when coagulation was restored permanently following a single dose of antivenom. Out of 17 patients with coagulopathy, 14 showed discrepancies between WBCT20 and WBCT30 results in at least one pair of serial evaluations. These could be completely contradictory results (e.g. normal clot at WBCT20 and no clot at WBCT30) or a marked difference in the quality of the clot (e.g. no clotting activity at WBCT20 and an unstable partial clot at WBCT30). WBCT discrepancies were encountered most frequently in three situations: initial normalization of hemostasis following antivenom therapy, detection of a secondary resumption of coagulopathy, or final restoration of hemostasis after a secondary resumption had occurred. Conclusions: This study suggests that the WBCT is robust and that a sequential reading should improve the diagnosis and monitoring of venom-induced coagulopathies. It also indicates the possibility of discrepancies in the sensitivity of WBCT20 and WBCT30 for detecting the resolution or reoccurrence of coagulopathy and identifies how these findings, if confirmed, may be used to increase the efficacy and efficiency of antivenom treatment in the field.

Intracranial haemorrhage (ICH) is a rare life-threatening consequence of venom induced consumption coagulopathy in snake-bite. It is unclear why certain patients haemorrhage. We aimed to investigate ICH in snake envenoming. Cases of venom-induced consumption coagulopathy from July 2005–June 2014 were identified from the Australian Snakebite Project, a prospective multicentre cohort of snake-bites. Cases with venom-induced consumption coagulopathy were extracted with data on the snake-bite, clinical effects, laboratory investigations, treatment and outcomes. 552 cases had venom-induced consumption coagulopathy; median age, 40 y (2–87 y), 417 (76%) males, 253 (46%) from brown snakes and 17 died (3%). There were 6/552 (1%) cases of ICH; median age, 71 y (59–80 y), three males and five from brown snakes. All received antivenom and five died. All six had a history of hypertension. Time to onset of clinical effects consistent with ICH was 8–12 h in four cases, and within 3 h in two. Difficult to manage hypertension and vomiting were common. One patient had a normal cerebral CT on presentation and after the onset of focal neurological effects a repeat CT showed an ICH. ICH is rare in snake-bite with only 1% of patients with coagulopathy developing one. Older age and hypertension were associated with ICH.

Hump-nosed viper bite is the commonest venomous snakebite in Sri Lanka. Acute kidney injury (AKI) in association with coagulopathy is an important cause of mortality. Immunomodulating effects of fresh frozen plasma (FFP) could block the nephrotoxic effects of venom; and by replenishing depleted clotting factors resulting from venom induced consumption coagulopathy could offer an additional benefit in offsetting renal injury triggered by haematological disturbances. In a non-randomised observational study carried out from 2005 to 2008 in adults at the National hospital of Sri Lanka, the mean time for resolution of coagulopathy among 42 patients treated with FFP at the inception of coagulopathy was 4.7 hours compared to 18 patients treated with isotonic Saline among whom the mean time for normalisation of coagulopathy was 6.2 hours. None of these 60 patients developed acute renal failure. A separate cohort of 32 patients with coagulopathy after hump-nosed viper bite who had not received FFP during this study period developed acute renal failure and required haemodialysis. In the absence of safe and effective antivenom for hump-nosed viper in Sri Lanka, FFP may be a therapeutic option. FFP if given early to selected patients at inception of coagulopathy may prevent AKI and serve to save lives after hump-nosed viper bites.

The most common coagulopathy associated with snake envenoming worldwide is venom-induced consumption coagulopathy (VICC), which results from activation of the coagulation pathway by snake toxins including thrombin-like enzymes, prothrombin activators, and factor X activators. VICC has often been likened to disseminated intravascular coagulation (DIC) because of the elevated D-dimer, prolonged prothrombin time, and low fibrinogen. However, VICC is not characterized by other important features of DIC, such as evidence of systemic microthrombi and end-organ failure. In addition, the time course of VICC differs with rapid onset and resolution, and the mechanism of initiation of coagulation activation differs because thrombin generation in DIC is mediated by the tissue factor/factor VIIa pathway. In a proportion of patients with VICC, a clinical syndrome consistent with thrombotic microangiopathy has been reported and is characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. This thrombotic microangiopathy appears to only occur in conjunction with VICC but in several different snakes worldwide including vipers and elapids. Consistent with thrombotic microangiopathy, it progresses despite the resolution of the coagulopathy, suggesting a distinct but related process. The existence of the overlapping clinical syndromes of VICC and thrombotic microangiopathy in snake envenoming is the likely reason for the mistaken idea that snakebite causes DIC.

Procoagulant toxins are important hemotoxins that have been investigated both as laboratory reagents and potential therapeutic agents. In human envenomation by some elapid and many viperid snakes, these toxins result in venom-induced consumption coagulopathy. Overall, the coagulant activity of the various venoms is difficult to characterize, and many studies simply characterize toxin conversion of isolated substrates, such as the effect of a snake toxin on purified fibrinogen, or on multiple single substrates. As the full effects of toxins on the coagulation pathway are rarely examined, even in vitro, our understanding of the pathophysiology of envenoming is limited. Although prothrombin activators cause a single effect in vitro, there may be complete consumption of fibrinogen, factor V, and factor VIII in vivo due to the downstream effects of the thrombin that is formed. Laboratory diagnosis is a key part of the treatment of snakebite coagulopathy. Assessing which assays are the most informative in snake envenoming, based on the pathophysiology of snakebite coagulopathy, will optimize diagnosis and timing of appropriate coagulation tests. A better understanding of the coagulation effects arising from human envenoming will also improve treatment with antivenom and define the role of adjuvant therapies such as factor replacement.

Background Snake venom induced consumption coagulopathy is a major systemic effect of envenoming. Observational studies suggest that antivenom improves outcomes for venom induced consumption coagulopathy in some snakebites and not others. However, the effectiveness of snake antivenom in all cases of venom induced consumption coagulopathy is controversial. Objectives To assess the effect of snake antivenom as a treatment for venom induced consumption coagulopathy in people with snake bite. Search methods The search was done on 30 January 2015. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (OvidSP), three other sources, clinical trials registers, and we also screened reference lists. Selection criteria All completed, published or unpublished, randomised, controlled trials with a placebo or no treatment arm, where snake antivenom was administered for venom induced consumption coagulopathy in humans with snake bites. Data collection and analysis Two authors reviewed the identified trials and independently applied the selection criteria. Main results No studies met the inclusion criteria for this review. Authors' conclusions Randomised placebo-controlled trials are required to investigate the effectiveness of snake antivenom for clinically relevant outcomes in patients with venom induced consumption coagulopathy resulting from snake bite. Although ethically difficult, the routine administration of a treatment that has a significant risk of anaphylaxis cannot continue without strong evidence of benefit.

Venomous snakebite is considered the single most important cause of human injury from venomous animals worldwide. Coagulopathy is one of the commonest important systemic clinical syndromes and can be complicated by serious and life-threatening haemorrhage. Venom-induced consumption coagulopathy (VICC) is the commonest coagulopathy resulting from snakebite and occurs in envenoming by Viperid snakes, certain elapids, including Australian elapids, and a few Colubrid (rear fang) snakes. Procoagulant toxins activate the clotting pathway, causing a broad range of factor deficiencies depending on the particular procoagulant toxin in the snake venom. Diagnosis and monitoring of coagulopathy is problematic, particularly in resource-poor countries where further research is required to develop more reliable, cheap clotting tests. MEDLINE and EMBASE up to September 2013 were searched to identify clinical studies of snake envenoming with VICC. The UniPort database was searched for coagulant snake toxins. Despite preclinical studies demonstrating antivenom binding toxins (efficacy), there was less evidence to support clinical effectiveness of antivenom for VICC. There were no placebo-controlled trials of antivenom for VICC. There were 25 randomised comparative trials of antivenom for VICC, which compared two different antivenoms (ten studies), three different antivenoms (four), two or three different doses or repeat doses of antivenom (five), heparin treatment and antivenom (five), and intravenous immunoglobulin treatment and antivenom (one). There were 13 studies that compared two groups in which there was no randomisation, including studies with historical controls. There have been numerous observational studies of antivenom in VICC but with no comparison group. Most of the controlled trials were small, did not use the same method for assessing coagulopathy, varied the dose of antivenom, and did not provide complete details of the study design (primary outcomes, randomisation, and allocation concealment). Non-randomised trials including comparison groups without antivenom showed that antivenom was effective for some snakes (e.g., Echis), but not others (e.g., Australasian elapids). Antivenom is the major treatment for VICC, but there is currently little high-quality evidence to support effectiveness. Antivenom is not risk free, and adverse reactions can be quite common and potentially severe. Studies of heparin did not demonstrate it improved outcomes in VICC. Fresh frozen plasma appeared to speed the recovery of coagulopathy and should be considered in bleeding patients.