Crotaline Envenomation Research Articles

Comparing the Use of Crotaline-Polyvalent Immune Fab (Ovine) Versus Observation in Children.

In the United States, studies are inconclusive regarding the indications for polyvalent antivenom administration for crotaline envenomation. We compared polyvalent antivenom administration versus observation used at 2 separate institutions. We hypothesized that deferring antivenom leads to increased hospital length of stay and surgical interventions. Retrospective chart review of children who presented to Le Bonheur Children's Hospital (LBCH) in Memphis, Tennessee, and Monroe Carell Jr Children's Hospital at Vanderbilt (MCJCHV) in Nashville, Tennessee, from 2009 to 2021. Patient demographics, treatment utilization, bite location, and outcomes from both sites were statistically examined. A total of 183 patients met the inclusion criteria (123 at LBCH, 60 at MCJCHV). At LBCH, mean age was 9.2 years, 54% were male, and 79% of known snakes identified as copperheads. At MCJCHV, mean age was 8.9 years, 65% were male, and 88% of known snakes identified as copperheads. The most commonly envenomated areas for both sites were the foot (42%), hand (27%), and ankle (26%). Patients at LBCH were managed with antivenom only 25% of the time, whereas 75% were observed; 82% of MCJCHV patients were managed with antivenom ( P < 0.001). There were no significant differences in length of stay (mean, 1.5 days at LBCH and 1.8 days at MCJCHV; P = 0.136) or surgical intervention (3.3% of LBCH encounters, 5.0% of MCJCHV encounters; P = 0.685). Secondary outcomes aside from coagulopathy and admission location (intensive care unit vs floor) were also not significant. The use of antivenom did not impact hospital length of stay or surgical interventions. Our results should be interpreted cautiously as our study reflects regional experiences with snake species in the Southeast United States and not North America as a whole. Other institutional differences in management and smaller n at MCJCHV may have contributed to different outcomes. Further study is needed to determine intermediate and long-term effects of deferring antivenom use.

ANAVIP® interaction with western pygmy rattlesnake venom: In vitro assesment of reactivity using SE-HPLC

Every year large numbers of venomous snake bites occur around the world, especially in tropical areas. The World Health Organization classifies venomous snake bites as one of their highest priority neglected tropical diseases, one of the reasons being the short supply of antivenom compared to the number of snake envenomations. The standard of care for snake envenomation is administration of antivenom. Many antivenoms are polyvalent, which are produced using venoms from multiple species of snakes. The polyvalent antivenoms can treat envenomation from snake venoms used in the production, but also show cross-reactivity against snake venoms with similar composition. Determining cross-reactivities of antivenoms could help improve the quality of treatment and provide a better understanding of venom-antivenom binding. One antivenom only has been available in the United States for treatment of North American Crotaline envenomation, with the recent introduction of an F(ab’)2 antivenom (ANAVIP®). Size-exclusion high performance liquid chromatography (SE-HPLC) was used to assess cross-reactivity of the western pygmy rattlesnake, Sistrurus miliarius streckeri (S. m. streckeri), against ANAVIP®. Estimates of venom-antivenom reactivity was measured in reaction mixtures based on the increase in elution profile area of higher molecular weight complexes (region 1) and on the decrease in elution profile area of reactants (region 2). Reaction mixtures contained ANAVIP® (1.0 mg/ml) and S. m. streckeri venom (0.125, 0.25, 0.5, or 1.0 mg/ml). Controls were ANAVIP® and S. m. streckeri (1.0 mg/ml). Mixtures were incubated at 37 °C for 30 min, then stored at 4 °C (5 min) prior to SE-HPLC. Relative binding, estimated from the increase in region 1 (immune complexes) and decrease in region 2 (reactants) region areas, suggested saturation of reactive antivenom binding sites at 0.125 (and above) mg venom/mg antivenom. SE-HPLC data indicate that binding of ANAVIP® to S. m. streckeri venom does occur, consistent with protective effects observed clinically. Further studies are needed to compare the binding of S. m. streckeri venom to other commercially available antivenoms, and the binding of ANAVIP® to other venoms of clinical significance.

Thromboelastography in the management of snakebite-induced coagulopathy: a case series and literature review.

: North American crotaline envenomations are a significant source of morbidity annually. Envenomation is marked by a constellation of effects that can include severe tissue damage, systemic effects such as anaphylaxis, and coagulopathy with bleeding. Traditionally, static plasma-derived tests such as protime and PTT are used to assess coagulation status. However, other tests are available that provide a whole blood assessment of all portions of coagulation including initiation, propagation, and clot maintenance. One such analytical test is TEG. Minimal data is available regarding the effect of snake venom on TEG results. We report on three cases of North American crotaline envenomation with subsequent TEG analysis. Our results show that TEG analysis does relate the same information as traditional monitoring parameters. Although only in an isolated case, the TEG analysis potentially revealed a fibrinolytic process prior to the same process being apparent with traditional monitoring. Future research is necessary to identify the role of TEG in crotaline snakebite management.

Ovine Crotalid Antivenin Improves Symptoms After Copperhead Snake Envenomation

Copperhead snake envenomation carries less morbidity than other crotaline envenomations, and there is uncertainty as to whether antivenin is indicated.

Coagulation parameters in copperhead compared to other Crotalinae envenomation: secondary analysis of the F(ab’)2 versus Fab antivenom trial

Context: Coagulation derangements in copperhead envenomation are considered less severe than other crotaline envenomations, resulting in recommendations to limit both coagulation testing and antivenom treatment. A prospective, blinded, multicenter, randomized clinical trial comparing the effectiveness of F(ab’)2 versus Fab antivenom in crotaline envenomation patients was completed in 2011. We determined the difference between coagulation parameters in copperhead compared to other crotaline envenomations.Methods: We performed a post hoc analysis comparing the coagulation parameters (platelets and fibrinogen) prospectively obtained in the aforementioned trial. All the patients received antivenom in one of three treatment arms [F(ab’)2 with maintenance, F(ab’)2 with placebo maintenance, or Fab with maintenance]. Coagulation parameters were measured at pretreatment baseline, during acute hospitalization, day 5, day 8, and day 15 post-envenomation. Mean platelet count and fibrinogen levels for the copperhead and other crotaline groups were compared. The platelet and fibrinogen point estimates with distribution are presented graphically over time. Results: 122 patients were enrolled in the study. There were 22 patients with copperhead envenomation, 93 with other crotaline envenomations, and 7 that could not be definitively determined. The mean age was 42 (SD 20) years. There was a minor pretreatment difference in mean baseline platelet count between the copperhead group (246 × 109/L 95% CI 215, 277) compared to other crotaline envenomation patients (184 × 109/L 95% CI 167, 202). There was a modest pretreatment difference in mean fibrinogen level between copperhead patients (345 mg/dL 95% CI 277, 415) and other crotaline patients (261mg/dL 95% CI 241, 281). Pretreatment coagulation parameter means were normal and converged post treatment.Conclusion: On average, copperhead envenomations have less severe initial coagulation derangements. However, in mild envenomations, differences in laboratory values are minimal and there is substantial variation in individual patients regardless of species. Species alone should not be used to determine the need for laboratory testing or treatment in crotaline snakebite.

A new F(abʹ)2 antivenom for the treatment of crotaline envenomation in children

Study objectiveTo evaluate the efficacy and safety of a new F(abʹ)2 antivenom preparation in the treatment of Crotalinae envenomation in children. MethodsWe present a case series of children younger than 16 years who suffered Crotalinae envenomation and were treated with a new F(abʹ)2 antivenom. Envenomated children treated with the new antivenom were assessed for efficacy of the product, defined as improvement of any hemotoxicity (hypofibrinogenemia, defined as fibrinogen <150 mg/dL, or thrombocytopenia, defined as platelets <150 000/mm3), and the cessation of the advancement of swelling. Safety was also evaluated by monitoring for adverse events. A secondary parameter assessed in these children was recurrent hemotoxicity after initial control of signs and symptoms with follow-up visits and laboratory testing on posttreatment days 5, 8, and 15. ResultsTwenty-one children received the F(abʹ)2 antivenom. Efficacy was achieved in all children receiving the product with initial control of swelling and improvement in those with hemotoxicity. No patients suffered anaphylaxis or any other serious adverse events from the F(abʹ)2 treatment. There were no cases of recurrent hemotoxicity recorded in the study between time of initial control and postinfusion day 15. ConclusionsIn this series of children, the F(abʹ)2 antivenom appeared to be both safe and effective in the treatment of hemotoxicity and local tissue toxicity (swelling) from Crotalinae envenomation.

Rebound Coagulopathy in Patients With Snakebite Presenting With Marked Initial Coagulopathy

An estimated 70% of patients with pit viper snakebites require antivenom to treat serious complications such as coagulopathy. Evidence-based guidance is limited for the appropriate administration of Crotalinae Polyvalent Immune Fab (FabAV) and the duration of laboratory follow-up. The objective of our study was to assess the incidence of marked and recurrent envenomation coagulopathy at our trauma center and identify practice patterns that may prevent serious complications. A retrospective case review was conducted over a 3-year period on patients treated for symptomatic snakebite injury. Case records were reviewed for the inclusion criteria of international normalized ratio (INR) greater than 2.0. The exclusion criterion was limited to patients receiving anticoagulant therapy. In all, 61 patients were identified on retrospective chart review and 3 patients (4.9%) met inclusion criteria. Two of the 3 patients had marked rebound coagulopathy requiring readmission and additional treatment. In our small series, 2 patients presenting after crotaline envenomation with increased INR (>6.0), decreased fibrinogen (<60 mg/dL), and decreased platelet count (<100,000/mL) had recurrent coagulopathy and were asymptomatic, and recurrence was noted only with follow-up laboratory testing. All patients responded positively within a matter of hours to repeat FabAV administration, with resolution of rebound coagulopathy. We recommend periodic monitoring of patients with increased INR, decreased fibrinogen, and decreased platelet count. Patients should be monitored for 10 to 14 days after envenomation to identify asymptomatic rebound coagulopathy. Prompt readministration of FabAV appears to correct the coagulopathy.

Ethical considerations in design of a study to evaluate a US Food and Drug Administration-approved indication: antivenom versus placebo for copperhead envenomation.

In 2000, the US Food and Drug Administration approved CroFab(®) Crotalidae Polyvalent Immune Fab, ovine (FabAV), which had received orphan drug designation, for use in patients with minimal to moderate North American crotaline envenomations including copperhead snakes. As existing evidence on the effectiveness of FabAV for this indication is limited, wide practice variation in its use exists. In order to provide more definitive clinical evidence as to the role of this treatment, a new randomized, placebo-controlled trial of FabAV specifically for copperhead bites was initiated. In light of the existing US Food and Drug Administration approval, ethical considerations of participation in this trial have been raised. We discuss the ethical principles pertinent to this randomized, placebo-controlled trial with placebo arm. We apply an accepted framework for ethical research to this trial. Due to the evidence gap in the literature, wide-ranging treatment recommendations by medical experts, and broad practice variation, clinical equipoise exists in the treatment of copperhead envenomation with FabAV. The impact of this clinical equipoise on the value and scientific validity of the trial is discussed. The trial's risk-benefit ratio is also considered. Potential risks to the patients are minimized as the protocol includes a plan for rescue therapy in the event that patients progress to severe envenomation symptoms. Overall, risks are further minimized by the inclusion of an interim analysis with stopping rules based on demonstrated efficacy should the therapy clearly prove to be beneficial. Although a post-marketing clinical study of this nature is unusual for an approved indication, this trial adheres to all ethical preconditions found in existing guidelines for clinical research involving human subjects.

A Retrospective Review of Early Gastrointestinal Symptoms in the Prediction of Crotaline Envenomation Severity: Thornton SL, Nguyen KT, Shenn SK, Castillo EM, Clark RF, Cantrell FL. Wilderness Environ Med 2012;23:360–2.

A Retrospective Review of Early Gastrointestinal Symptoms in the Prediction of Crotaline Envenomation Severity: Thornton SL, Nguyen KT, Shenn SK, Castillo EM, Clark RF, Cantrell FL. Wilderness Environ Med 2012;23:360–2.

Bleeding Following Rattlesnake Envenomation in Patients With Preenvenomation Use of Antiplatelet or Anticoagulant Medications

Rattlesnake envenomations commonly produce coagulopathy and thrombocytopenia, yet clinically significant bleeding is uncommon. It is unknown if patients who use antiplatelet or anticoagulant medications prior to envenomation are at increased risk for bleeding after envenomation. This was a retrospective cohort study of patients age 14 years and older who were admitted to a single academic medical center for rattlesnake envenomation. Patients who reported use of antiplatelet or anticoagulant medications prior to envenomation were compared to patients not on those medications. Severity and timing of bleeding was compared between groups, as was a composite endpoint of major bleeding at any time, shock, readmission, or death. A total of 319 patients met inclusion criteria; 31 (9.7%) were documented to be taking antiplatelet or anticoagulant medications including aspirin, clopidogrel, and/or warfarin. Seventeen of the 319 patients developed bleeding associated with envenomation (major = 9; minor = 4; trivial = 4), with major bleeding occurring in five patients on antiplatelet or anticoagulant medications versus four patients not on antiplatelet or anticoagulant medications (p < 0.001). Seven of the 17 presented with early bleeding. This early bleeding occurred in three of 31 (9.7%) patients on antiplatelet or anticoagulant medications and four of 288 (1.4%) patients not on antiplatelet or anticoagulant medications (relative risk [RR] = 6.9; 95% confidence interval [CI] = 1.6 to 29.4; p = 0.022). Clinical outcome data were available for 300 of the 319 (94%) subjects following discharge. Late bleeding (bleeding after discharge from the index hospitalization) occurred in nine subjects, one of whom also had early bleeding (major = 2, minor = 3, trivial = 4). Three of these nine subjects with late bleeding were on antiplatelet or anticoagulant medications, compared with six not on antiplatelet or anticoagulant medications (p = 0.042). Both cases of late major bleeding occurred in patients on antiplatelet or anticoagulant medications. Therefore, among patients with follow-up data available, the overall rate of bleeding (early and late) was seven of 28 (25%) in patients taking antiplatelet or anticoagulant medications and 10 of 273 (3.7%) in patients not taking antiplatelet or anticoagulant medications (p < 0.001). The use of antiplatelet or anticoagulant medications was also associated with an increased risk of reaching the composite endpoint of major bleeding, shock, readmission, or death (6 of 31, or 19.4% vs. 14 of 288, or 4.9%; RR = 3.98; 95% CI = 1.65 to 9.62; p = 0.008). The risk of developing bleeding following rattlesnake envenomation is increased in patients who use antiplatelet or anticoagulant medications. This risk is greatest early after envenomation during the index hospitalization. However, risk of late, major bleeding appears also to be greatest in patients on antiplatelet or anticoagulant medications. Extra vigilance should be taken in patients on antiplatelet or anticoagulant medications and a careful risk/benefit analysis should be undertaken before continuing these medications in the weeks following the envenomation.

Medically Significant Late Bleeding After Treated Crotaline Envenomation: A Systematic Review

We estimate the proportion of patients with crotaline snake envenomation who are treated with Crotalidae polyvalent immune Fab (ovine) antivenom and who develop medically significant late bleeding. We performed a systematic review of all published cohort studies of North American crotaline snake envenomation patients treated with Fab antivenom. We searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to April 30, 2012. Data were extracted by 2 trained researchers. Late bleeding was defined as bleeding that began or recurred after initial control of the envenomation syndrome. Medically significant late bleeding was defined a priori as late bleeding treated with RBC transfusion, vasoactive drug infusion, surgery, or rehospitalization or associated with a hemoglobin decrease of greater than or equal to 3 g/dL, hematocrit decrease of greater than or equal to 8%, disability, or death. Summary incidence and 95% confidence intervals (CIs) were calculated with a random-effects Poisson regression model. Nineteen unique cohort studies were identified. Four studies collected data prospectively, and in 9 studies, patients were followed actively after hospital discharge. A total of 1,017 subjects were enrolled in these cohort studies. Late bleeding was reported in 9 subjects (0.9%; 95% CI 0.4% to 2.2%), of whom 5 subjects (0.5%; 95% CI 0.1% to 1.7%) had medically significant late bleeding. Three patients received RBC transfusion; no deaths or permanent sequelae were reported. Estimates of risk may be affected by underreporting. Medically significant late bleeding appears to be uncommon in snakebite victims treated with Fab antivenom.

Snakebite Survivors Club: Retrospective review of rattlesnake bites in Central California

ObjectiveWe investigated clinical patterns of crotaline envenomation presenting to a tertiary-care academic hospital in Central California over a 10-year period. MethodsAn IRB-approved, retrospective chart review was conducted on all patients diagnosed with snakebite from December 2000 to December 2010. Data abstracted: demographics, anatomic location of bite, comorbid conditions and intoxicants, length of stay, antivenom dose, laboratory results, and complications or procedures. ResultsThere were 46 snakebite cases admitted over the study period. Five were “dry bites”; the remaining cases (41/46) received antivenom. There was a male predominance (83% male victims). Upper extremity bites were more common (32/41 upper vs 10/42 lower extremity). One victim sustained bilateral bites to the hands. Thirty-five patients (85%) were admitted, with an average length of stay 2.12 days. The longest hospitalization was 15 days. There were no fatalities. The average time from bite to ED presentation was 2 h 44 min. Bites occurred during every month except November, with the majority occurring during spring and summer months and peaking in June (12/42 cases). Most bites occurred in the hours between noon and 8 pm. The amount of antivenom given ranged from 2 to 35 vials (average, 9 vials). Interfacility transfers were common in our study population: thirteen (32%) patients were transferred into our emergency department for a higher level of care, and 3 (7%) were transferred out (two because of insurance requirements, and one for higher level of Pediatric ICU care). There were no surgical interventions in our study group. Intoxication did not appear to play a major role in this population as only 3 patients (7%) were found to be acutely intoxicated: one with cannabis and amphetamines, 1 with alcohol, and 1 with opioids. ConclusionsIn Central California, crotaline envenomations occurred mainly in adult males. Dry bites, or bites not requiring antivenom administration, were uncommon, comprising only 10% of bites in this study population. Contrary to popular and clinical beliefs, substance abuse and/or alcohol intoxication did not appear to play a role in the majority of patients in this study. Care providers and snakebite specialists should be aware that snakebite patients are often transferred between facilities, a finding that may be useful in designing future first aid protocols and research. We hope these findings add concrete data and help correct some common misconceptions about snakebites in Central California.

Crotalidae Polyvalent Immune Fab: A Guide to Its Use in North American Crotaline Envenomation

Intravenous crotalidae polyvalent immune Fab (CroFab(®)) is effective in patients with minimal, moderate or severe crotaline envenomation, halting the progression of local venom effects and ameliorating haematological and other systemic abnormalities of envenomation. Despite treatment, patients may experience delayed-onset or recurrent venom effects (e.g. coagulopathy). Intravenous crotalidae polyvalent immune Fab is generally well tolerated, with acute hypersensitivity reactions being the most commonly occurring adverse event.

A Retrospective Review of Early Gastrointestinal Symptoms in the Prediction of Crotaline Envenomation Severity

Rattlesnake envenomations are cited to cause gastrointestinal (GI) symptoms, which may be indicators of systemic envenomation. We sought to identify whether the presence of early GI symptoms, defined as occurring within 4 hours of the bite, could be used to predict antivenom use or bite severity. We performed a retrospective review of a statewide poison system's database for all cases of rattlesnake envenomation from January 2000 to December 2009. Data collected included presence of GI symptoms and antivenom use. The GI symptoms were further classified as early (within 4 hours) or late. Bite severity was determined using the minimal to moderate to severe scoring system from collected data. Data were then analyzed with a χ(2) test and Fisher's exact test to evaluate for association between early GI symptoms and either antivenom use or bite severity. There were 2570 reported rattlesnake exposures in the database. Sixty-one (2.4%) of these had GI symptoms reported. Of these, 36 (59%) had symptoms develop within 4 hours of envenomation. A total of 49 patients (80%) received antivenom. Early GI symptoms were seen in 31 (63%) of patients receiving antivenom versus 5 (42%) of patients not receiving antivenom (P = .20). Early GI symptoms were seen in 4 of 6 (66%) of the severe group, 19 of 29 (66%) of the moderate group, and 13 of 26 (50%) of the minimal group (P = .47). Gastrointestinal symptoms after rattlesnake envenomations were rarely reported in this poison center study, and the presence of early GI symptoms did not predict bite severity or the use of antivenom.

237. Snakebite Survivors Club: Ten-year, retrospective review of Crotaline envenomations in Central California

237. Snakebite Survivors Club: Ten-year, retrospective review of Crotaline envenomations in Central California

253. Medically Significant Late Bleeding Following Treated Crotaline Envenomation: A Structured Topic Review

253. Medically Significant Late Bleeding Following Treated Crotaline Envenomation: A Structured Topic Review

Incidence of Immediate Hypersensitivity Reaction and Serum Sickness Following Administration of Crotalidae Polyvalent Immune Fab Antivenom: A Meta‐analysis

Crotalidae polyvalent immune Fab (ovine) (FabAV) is commonly used in the treatment of symptomatic North American crotaline snake envenomation. When approved by the U.S. Food and Drug Administration in 2000, the incidences of immediate hypersensitivity reactions and serum sickness were reported as 0.14 and 0.18, respectively. The objective of this meta-analysis was to evaluate the incidence of immediate hypersensitivity reactions and serum sickness reported in studies of patients treated with FabAV therapy after North American crotaline envenomation. The authors searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to September 20, 2010, for English-language medical literature and cross-referenced bibliographies of reviewed articles. The published abstracts of the major toxicology conferences were also searched. All prospective and retrospective cohort studies with patients receiving FabAV therapy for North American crotaline envenomations were eligible for data abstraction. Two content experts reviewed full-text articles and extracted relevant study design and outcome data. Proportions of immediate hypersensitivity and serum sickness for each study were analyzed in a random-effects model to produce an overall estimate of immediate hypersensitivity and serum sickness incidence associated with FabAV administration. The literature search revealed 11 unique studies of patients who received FabAV that contained information on immediate hypersensitivity reactions and serum sickness. The meta-analysis produced a combined estimate of the incidence of immediate hypersensitivity of 0.08 (95% confidence interval [CI] = 0.05 to 0.11) and a combined estimate of the incidence of serum sickness of 0.13 (95% CI = 0.07 to 0.21). In this systematic literature review and meta-analysis, the combined estimates of the incidence of immediate hypersensitivity reactions and serum sickness from FabAV in the treatment of symptomatic North American crotaline envenomations appear to be lower than previously reported, at 0.08 and 0.13, respectively.

Crotalidae Polyvalent Immune Fab

Crotalidae polyvalent immune Fab is an antivenom comprising purified, sheep-derived, Fab IgG fragments and is indicated for use in patients with North American crotaline envenomation. Crotalidae polyvalent immune Fab is produced using four North American snake venoms: Crotalus atrox, Crotalus adamanteus, Crotalus scutulatus, and Agkistrodon piscivorus. Intravenous crotalidae polyvalent immune Fab was effective in patients aged ≥10 years who had minimal or moderate envenomation by a North American crotaline, who presented within 6 hours of the snakebite, and who had progression of the envenomation syndrome, according to the results of two prospective trials. One trial was a noncomparative, multicenter pilot study and the other trial was a randomized, open-label, multicenter trial in which patients received scheduled or 'as needed' administration of crotalidae polyvalent immune Fab after initial control had been achieved. A prospective, postmarketing trial demonstrated the efficacy of crotalidae polyvalent immune Fab in confirmed Crotalus viridis helleri envenomation (indicating cross-protection against a venom not used in its production). Results of these prospective trials are supported by the findings of additional (mainly retrospective) studies demonstrating the efficacy of crotalidae polyvalent immune Fab in patients with crotaline envenomation, including patients with severe envenomation, pediatric patients, and patients with symptoms of neurotoxicity. Despite treatment with crotalidae polyvalent immune Fab, patients may experience delayed-onset or recurrent venom effects (e.g. coagulopathy). Intravenous crotalidae polyvalent immune Fab was generally well tolerated; acute hypersensitivity reactions (e.g. urticaria, rash, pruritus) were the most commonly occurring adverse event.

Hematologic Abnormalities Following Crotaline Snakebites In South Carolina

AbstractAbstract 4753 Background:Pit viper envenomation causes local tissue edema, pain, and ecchymosis. In certain geographical areas of the United States thrombocytopenia, hypofibrinogenemia and coagulopathy are common hematological abnormalities, and ones that dictate both a reason for treatment with antivenom as well as an important monitor of therapeutic efficacy. Data on the frequency and severity of hematological abnormalities following envenomation by crotaline species in South Carolina has not been reported. We evaluated clinical and hematologic laboratory findings and treatment course following copperhead and rattlesnake bites in South Carolina. Method:We conducted a retrospective evaluation of all copperhead and rattlesnake bites reported to the Palmetto Poison Center from April 2005 through June 2010. Severity of the snakebite and development of hematologic toxicity associated with envenomation cases were documented before and after crotaline Fab antivenom (CroFab®) administration. Adverse events associated with antivenom therapy, recurrence phenomena, delayed onset of symptoms, and performance of fasciotomy were also recorded. Results:Overall, 194 crotaline snakebites were identified- 156 copperhead bites and 38 rattlesnake bites. Males accounted for 75% of copperhead bite patients (median age, 36 years; 51% with bites on upper extremities) and 82% of rattlesnake bite patients (median age, 42.5 years; 76% on upper extremities). All patients except one were treated at a healthcare facility with > 80% arriving within 6 hours following the bite. Over 60% of patients received crotaline Fab antivenom; no patients received the older Antivenin Crotalidae Polyvalent. Severity of the envenomation for copperheads and rattlesnakes was classified as dry (7.74%, 13.16%), mild (68.39%, 73.68%), moderate (22.58%, 10.53%), and severe (1.39%, 2.63%), respectively. Seventeen of 156 patients (10.89%) developed abnormal hematologic laboratory results following copperhead bites and two of 38 (5.26%) patients developed abnormal hematologic laboratory parameters with rattlesnake bites. Of these, the most common abnormality was coagulopathy (16/17 = 94.11%; 2/2 = 100%), followed by hypofibrinogenemia (5/17 = 29.41%; 0/0 = 0.00%) and thrombocytopenia (2/17 = 11.76%; 0/0 = 0.00%) for copperheads and rattlesnakes respectively. Recurrence phenomena was observed in 4 patients with copperhead bites and 2 patients with rattlesnake bites, while delayed onset of symptoms were seen in 12 patients and 5 patients, respectively. Among those experiencing recurrence, 75% of patients bitten by copperheads experienced local effects including pain and swelling and 25% experienced coagulopathy, while a 100% of the patients bitten by rattlesnakes experienced recurrent local effects. Among those experiencing a delayed onset of symptoms, 90% of the patients with copperhead bites experienced coagulopathy while 10% had local effects and 100% of the patients bitten by rattlesnakes experienced coagulopathy. Reaction to the antivenom developed in three patients. Three patients underwent a fasciotomy. Conclusions:Antivenom therapy is typically administered to halt the progression of local envenomation effects and improve abnormal hematologic parameters towards normal. In South Carolina, the primary indication for antivenom treatment is most commonly to treat local clinical findings. Our poison center experience suggests coagulopathy is the most common hematologic laboratory abnormality following crotaline envenomation in addition to a low rate of thrombocytopenia in our geographic location. Other geographic areas of the United States are recognized to have more frequent and severe hematologic complications following crotaline bites. Disclosures:Bennett:Pfizer: Consultancy.

Recurrent Coagulopathy and Thrombocytopenia in Children Treated With Crotalidae Polyvalent Immune Fab

Recurrent signs and symptoms after initial treatment and control of coagulopathy and thrombocytopenia after American pit viper (crotaline) envenomations have been previously described in patients treated with Crotalidae polyvalent immune Fab antivenom (FabAV). The significance and necessity of treatment of these recurrent abnormalities are uncertain. Our goal was to further characterize recurrent coagulopathy or thrombocytopenia in pediatric patients. All cases presenting to our Toxicology Consult Service, which covers 6 hospitals in a metropolitan area, from May 2007 to April 2008 with recurrent coagulopathy after initial control with FabAV were included and retrospectively reviewed. Four cases of pediatric patients are presented who presented with recurrent coagulopathy and/or thrombocytopenia after initial control with FabAV. The patients were all treated with delayed administration of FabAV with variable results. Blood products administered without concurrent FabAV were of limited use. The laboratory abnormalities took up to 18 days to resolve in one case. One patient developed hemodynamically significant spontaneous bleeding. The cases presented here suggest administration of FabAV may correct delayed coagulopathy associated with crotaline envenomations. The first 3 cases illustrate that in the face of severe derangements in laboratory values, most envenomated patients treated with FabAV do not develop significant bleeding. These cases may respond to additional antivenom alone. However, case 4 illustrates that hemodynamically significant spontaneous bleeding can occur. Until more data are available, readministration of FabAV is a reasonable first-line therapy for delayed coagulopathy associated with crotaline envenomations.