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PubMed1979

IgE antibodies to bee venom, phospholipase A, melittin and wasp venom.

Specific IgE antibodies against bee venom, phospholipase A, melittin and wasp venom have been examined in fifty patients with an unusually severe reaction after bee or wasp sting. Two thirds of the bee venom-sensitive patients also have detectable IgE antibodies to wasp venom. More than 50% of the wasp venom-sensitive patients are also allergic to bee venom. Phospholipase A and melittin IgE antibodies were found, respectively, in two thirds and one third of the bee venom-sensitive cases. Specific IgE antibody determinations by the Radioallergosorbent test play an essential role in the diagnostic work. After a reaction to hymenoptera stings both bee and wasp venom tests are necessary due to the high incidence of a false or incomplete identification of the stinging insect. Melittin, known for its potent pharmacological activity and possibly responsible for most of the side effects in bee venom immunotherapy, can probably not be excluded from therapeutic venom preparations since IgE antibodies to the melittin preparation were detected in one third of the cases.

Bee Venoms↗
PubMed2007

Flow-assisted quantification of in vitro activated basophils in the diagnosis of wasp venom allergy and follow-up of wasp venom immunotherapy.

BACKGROUND: Correct identification of the culprit venom is a prerequisite for specific venom immunotherapy (VIT). Despite the efficacy of VIT, issues as how to monitor treatment and when to discontinue maintenance therapy remain to be established. METHODS: To evaluate diagnostic performances of the basophil activation test (BAT) in wasp venom allergy, 80 patients with a definite history of wasp venom anaphylaxis (systemic reactors) and 14 wasp-stung asymptomatic controls (stung controls) were enrolled. Venom-induced basophil activation was analyzed flow cytometrically by double-labeling with anti-IgE and anti-CD63. Results were compared to wasp IgE levels and results of a venom skin test (VST). To establish whether the BAT constitutes a candidate marker to monitor VIT, the BAT was repeated in 22 patients on the 5th day of a build-up course and after 6 months of maintenance VIT. Whether the BAT could contribute in the decision of discontinuing VIT was assessed in a cross-sectional analysis in 30 patients receiving treatment for 3 years. RESULTS: Comparison between systemic reactors and stung controls revealed a sensitivity of 86.4% and specificity of 100% for venom IgE, and sensitivity of 81.8% for VST, respectively. In contrast to stung controls, patients demonstrated dose-dependent venom-induced basophil activation. The BAT attained a sensitivity of 83.8% and specificity of 100%. At the end of the build-up course, no effect of VIT on the BAT was demonstrable. When the BAT was repeated after 6 months of treatment, submaximal stimulation of the cells demonstrated a significant decreased CD63 expression (P < 0.04). Patients having VIT for 3 years also demonstrated significantly lower venom-induced CD63 expression (P < 0.001). After 3 years, 60% of the patients had a negative BAT for submaximal stimulation of the cells whereas only 17.9% of the patients had negativation of wasp IgE. CONCLUSIONS: The BAT is a reliable instrument for the diagnosis of wasp venom anaphylaxis and might constitute an instrument to monitor wasp VIT.

Adolescent↗
PubMed1990

Antigenic relationship between the venom of the night adder Causus maculatus and venoms of other viperids.

Monovalent antivenoms were raised in mice against the venoms of Causus maculatus, Vipera ammodytes, Echis carinatus, Cerastes cerastes, Bitis arietans, Agkistrodon rhodostoma and Bothrops atrox. These antivenoms as well as four commercially available antivenoms were tested against the venoms of 15 viperid species by means of immunoelectrophoresis and/or ELISA. Cross-reactive protein bands were determined by immunoblot. ELISA cross-reactions of C. maculatus antivenom were low with all heterologous venoms. When investigating the other viperine antivenoms in ELISA stronger cross-reactions were observed with several heterologous venoms. In immunoblot, two heterologous antivenoms cross-reacted with one or two protein bands of C. maculatus venom whereas there were at least four heterologous antivenoms cross-reacting with each of the other venoms. The findings indicate that there is little antigenic affinity between C. maculatus venom and the other venoms investigated. Broad in vitro cross-reactions between viperine antivenoms and Causus venom which were reported in literature seem to be attributable to the use of antivenoms of commercial grade. Specificity of commercially produced, mono- or polyvalent antivenoms may not be strictly limited to those venoms, against which potency is claimed on the label of the product.

Animals↗
PubMed2005

Mitochondrial DNA sequences from dried snake venom: a DNA barcoding approach to the identification of venom samples.

Outdated nomenclature and incorrect taxonomic characterisation of snake venoms in the current toxinological literature have serious implications for the replicability of results from snake venom toxin research. The situation has not improved, despite attempts to supply toxinologists with regular updates on snake systematics. Here, we demonstrate the successful extraction of DNA, and subsequent sequencing of the mitochondrial 12S gene, from dried snake venoms. This approach offers a new and potentially straightforward method for accurate species identification. Mitochondrial DNA (mtDNA) sequences isolated from snake venom can be used to clarify or validate snake species identification through comparison against existing sequences in the GenBank database, and through phylogenetic analyses with other sequences. Pooled venoms can also be screened a priori for the presence of multiple species, and the species names on the labels of commercial venoms verified. Moreover, if the species from which the venom sample has been taken is known, and the specimen is available as a voucher, the mtDNA sequence of the haplotype isolated from that species venom sample could serve as a sequence standard (or 'DNA barcode') for that species. Our new method of DNA barcoding venoms ensures the identification of venoms even after future taxonomic changes.

Animals↗
PubMed2002

Neutralization of a snake venom hemorrhagic metalloproteinase prevents coagulopathy after subcutaneous injection of Bothrops jararaca venom in rats.

Coagulopathy is one of the major complications following envenomations by crotalid and viperid snakes. The present study was undertaken to examine the effect of a hemorrhagic metalloproteinase in Bothrops jararaca venom, jararafibrase I (JF I), on the development of coagulopathy using rat snakebite model. Coagulation parameters were monitored after subcutaneous injection of B. jararaca crude venom, JF I-neutralized venom and purified JF I in rats. Crude venom induced unclottable blood and fibrinogen consumption, while JF I-neutralized venom and purified JF I did not induce coagulopathy. Plasma venom antigen level of rats given JF I-neutralized venom was lower than that of rats given crude venom. We conclude that venom hemorrhagic metalloproteinases play an important role in the development of coagulopathy through rapid spreading of venom coagulation components from the injected area into systemic circulation.

Animals↗
PubMed2003

Inhibition of hemorrhagic and edematogenic activities of snake venoms by a broad-spectrum protease inhibitor, murinoglobulin; the effect on venoms from five different genera in Viperidae family.

In order to obtain basic data on the effect of broad-spectrum protease inhibitor against local symptoms of Viperidae snake envenomation, inhibitory capacity of rat murinoglobulin on local hemorrhagic and edematogenic activities of venoms from Crotalus atrox, Bothrops jararaca, Lachesis muta muta, Trimeresurus flavoviridis and Echis carinatus sochureki were examined. Murinoglobulin, pre-incubated with the crude venoms at 37 degrees C for 15 min, inhibited hemorrhagic activity of all five venoms to various extents. The activity of C. atrox was almost completely inhibited at the murinoglobulin/venom ratio (w/w) of 20. The activity of B. jararaca, Lachesis muta muta and T. flavoviridis venoms was considerably inhibited at the ratio of 20 (77.2, 80.0 and 86.2% inhibition, respectively), however some of the activity still remained even at the ratio of 40 (84.2, 79.8 and 86.2% inhibition, respectively). Among the five venoms, E. c. sochureki venom is quite resistant to murinoglobulin treatment and statistically significant inhibition was only found at the ratio of 40 (64.1% inhibition). Fibrinolytic and gelatinase activities were more susceptible to murinoglobulin inhibition. The treatment at the ratios of 10 and 20 almost completely inhibited respectively the fibrinolytic and the gelatinase activities of all the venoms. Murinoglobulin treatment also significantly inhibited the edematogenic activity of L. muta muta, T. flavoviridis and Echis carinatus sochureki. The treatment of murinoglobulin at the ratio of 40 considerably suppressed the swelling up to 60 min after subcutaneous injection of L. muta muta and E. c. sochureki venoms, and up to 30 min after T. flavoviridis venom injection. Murinoglobulin is a potent inhibitor against local effects of multiple snake venoms in Viperidae family.

Animals↗
PubMed1999

Tests for detection of snake venoms, toxins and venom antibodies: review on recent trends (1987-1997).

Various methods developed for the detection of snake venoms, toxins and venom antibodies, during the last decade is reviewed. Radioimmunoassay, agglutination assay, enzyme-linked immunosorbent assay (ELISA), fluorescence immunoassay etc. have been used for detection of venoms and toxins. Important contributions have been made to improve the specificity, sensitivity, rapidity and simplicity of the ELISA method. Monoclonal antibodies and affinity-purified venom-specific antibodies were used to achieve species specificity of ELISA and the latter seems to be the ideal for venom detection. Incorporation of avidin-biotin system as well as the fluorogenic substrate in the enzyme immunoassay sufficiently increased the sensitivity of the assay to detect venom concentrations to picogram levels. The ability to use undiluted blood and other whole biological fluids reduce the assay time considerably. Although there have been several reports were on venom detection, so far only a few field kits have been developed. This implies that the experiments and design were only at the laboratory levels and still more work has to be carried out before it could be used in the field. Concerning the venom antibody detection, ELISA has been used extensively and the humoral response of patients envenomed by snake has been investigated in detail. Non-specific reactivity along with cross-reactivity still limits the use of ELISA for species identification in epidemiological studies. Overall, ELISA remains the suitable method for the detection of snake venoms, toxins and venom antibodies in body fluids. The possible use of a biosensor approach to solve some of the problems associated with the ELISA method are also discussed.

Agglutination Tests↗
PubMed2003

Allergen-specific immunosuppression by mucosal treatment with recombinant Ves v 5, a major allergen of Vespula vulgaris venom, in a murine model of wasp venom allergy.

Up to 5% of the population suffer from systemic, 19% from local allergic hypersensitivity reactions to stinging insects. Even though specific immunotherapy is very effective in treating allergy to insect venom, new concepts of treatment strategies with only the disease eliciting allergen in recombinant form, along with antigen application via a less invasive route might be suggested for enhanced treatment efficacy and compliance. In the present study we aimed (i) to establish a mouse model of wasp venom allergy, mimicking the natural mode of sensitization, and (ii) to develop a prophylactic treatment strategy based on mucosal tolerance induction, using one major wasp venom allergen in recombinant form, i.e. recombinant (r)Ves v 5. Immunization with wasp venom--with or without the use of the adjuvant aluminium hydroxide--led to comparable T helper 2-like immune responses in vivo and in vitro. Intranasal administration of rVes v 5 prior to sensitization with wasp venom resulted in a significant reduction of wasp venom-specific antibody levels (immunoglobulin E (IgE)/IgG2a), type I hypersensitivity reactions in vivo and cytokine production in vitro. Pretreatment with the whole venom was less effective and caused toxic side reactions in higher concentrations, suggesting a favourable use of the recombinant venom allergen for mucosal application. Increased mRNA levels of transforming growth factor-beta and interleukin-10, along with adoptive cell transfer experiments indicated that the immunosuppression after intranasal rVes v 5-application has been mediated by regulatory mechanisms. This is further supported by the fact that the immunosuppression to rVes v 5 was associated with a bystander suppression to the unrelated aero-allergen Bet v 1. In conclusion, we demonstrated that the intranasal application of recombinant Ves v 5 prevented subsequent allergic sensitization to all components of the whole wasp venom. As allergy to insect venom develops in dependence of the frequency of insect stings, a prophylactic treatment based on mucosal tolerance induction with recombinant allergens might be of interest for people at high risk to frequent exposure to the stinging insects.

Allergens↗
PubMed2006

Venom evolution widespread in fishes: a phylogenetic road map for the bioprospecting of piscine venoms.

Knowledge of evolutionary relationships or phylogeny allows for effective predictions about the unstudied characteristics of species. These include the presence and biological activity of an organism's venoms. To date, most venom bioprospecting has focused on snakes, resulting in six stroke and cancer treatment drugs that are nearing U.S. Food and Drug Administration review. Fishes, however, with thousands of venoms, represent an untapped resource of natural products. The first step involved in the efficient bioprospecting of these compounds is a phylogeny of venomous fishes. Here, we show the results of such an analysis and provide the first explicit suborder-level phylogeny for spiny-rayed fishes. The results, based on approximately 1.1 million aligned base pairs, suggest that, in contrast to previous estimates of 200 venomous fishes, >1,200 fishes in 12 clades should be presumed venomous. This assertion was corroborated by a detailed anatomical study examining potentially venomous structures in >100 species. The results of these studies not only alter our view of the diversity of venomous fishes, now representing >50% of venomous vertebrates, but also provide the predictive phylogeny or "road map" for the efficient search for potential pharmacological agents or physiological tools from the unexplored fish venoms.

Animals↗
PubMed1998

Allergy to bumblebee venom. II. IgE cross-reactivity between bumblebee and honeybee venom.

To obtain more information on IgE cross-reactivity between bumblebee venom and honeybee venom, we tested sera from venom-sensitized patients for specific IgE against venoms from the European bumblebee (Bombus terrestris), the North American bumblebee (Megabombus pennsylvanicus), and the honeybee (Apis mellifera). RAST, RAST-inhibition, and immunoblotting experiments indicate that bumblebee venom and honeybee venom contain venom-specific IgE-binding epitopes. These results suggest that immunotherapy using honeybee venom may not be effective in all bumblebee venom-allergic patients. Our experiments also revealed differences in IgE binding for venom from European and American bumblebees.

Animals↗
PubMed1995

Bee venom hypersensitivity and its management: patients perception of venom desensitisation.

The objectives of the study were to review bee venom immunotherapy from the patient's perspective: in particular its benefits and its problems, and to investigate any genetic tendency for bee venom hypersensitivity. A self administered, 9 item questionnaire was sent to 219 patients who had undergone either inpatient or outpatient bee venom immunotherapy at Flinders Medical Center. The clinic records of these patients were also reviewed. The controls for the genetic study were sought from patients, staff and students at Flinders University and Flinders Medical Centre. One hundred and forty-six questionnaires (some incomplete and anonymous) were received. The female to male ratio was 1:2.5. The age at the time of the initial anaphylactic reaction to a bee sting ranged between 2 to 59 years, with 67% of patients being less then 20 years old. Forty percent of patients underwent venom immunotherapy for a period less than 2 years with only 11% maintaining therapy for the recommended period of 5 years or more. Thirty three percent of patients stopped their therapy on their own accord. Bee stings occurring during bee venom immunotherapy (n = 56) were generally well tolerated except in 8 subjects, 7 of whom had not reached the maintenance dose. The reduction in systemic reactions to subsequent bee stings was significantly better in the study group receiving bee venom than in an historic control group treated with whole bee extract (p = 0.03). Fear of bee stings and restricted life styles were improved during or after venom immunotherapy. The frequency of a positive family history of systemic reactions to bee stings in the patient cohort was 31%, whereas in controls it was 15% (p = 0.013). Bee venom immunotherapy has dual benefits: patients are protected from subsequent sting anaphylaxis and there is reduced psychological morbidity. However, to be effective, venom immunotherapy requires a prolonged period of carefully supervised treatment and each venom injection can cause local and systemic side effects. Genetic factors appear to be present in those patients who develop immediate hypersensitivity to be stings.

Adolescent↗
PubMed2002

Unmasking venom gland transcriptomes in reptile venoms.

While structural studies of reptile venom toxins can be achieved using lyophilized venom samples, until now the cloning of precursor cDNAs required sacrifice of the specimen for dissection of the venom glands. Here we describe a simple and rapid technique that unmasks venom protein mRNAs present in lyophilized venom samples. To illustrate the technique we have RT-PCR-amplified a range of venom protein transcripts from cDNA libraries derived from the venoms of a hemotoxic snake, the Chinese copperhead (Deinagkistrodon acutus), a neurotoxic snake, the black mamba (Dendroaspis polylepis), and a venomous lizard, the Gila monster (Heloderma suspectum). These include a metalloproteinase and phospholipase A2 from D. acutus, a potassium channel blocker, dendrotoxin K, from D. polylepis, and exendin-4 from H. suspectum. These findings imply that the apparent absence and/or lability of mRNA in complex biological matrices is not always real and paves the way for accelerated acquisition of molecular genetic data on venom toxins for scientific and potential therapeutic purposes without sacrifice of endangered herpetofauna.

Animals↗
PubMed1996

Immunoreactivity and pharmacokinetics of horse anti-scorpion venom F(ab')2-scorpion venom interactions.

The immunoreactivity and pharmacokinetics of a new horse F(ab')2 scorpion antivenom and its effect on Buthus occitanus mardochei venom plasma disposition in the rabbit were studied. The scorpion venom-specific F(ab')2 affinity constant determined by immunoradiometric assay was 1.6 +/- 0.6 10(8) M-1. One group received a F(ab')2 bolus dose of 9.57 mg.kg-1 i.v. bolus or i.m.. The plasma F(ab')2 concentration followed a biexponential decline after i.v. administration with distribution and elimination half-lives of 2.54 +/- 0.36 and 49.52 +/- 3.07 hr, respectively. The total volume of distribution (Vdss or Vd beta) was between 230 and 255 ml.kg-1. Total body clearance was 3.56 +/- 0.34 ml.kg-1.hr-1. After intramuscular administration, Tmax was 48 hr and the absolute bioavailability was 36%. Two other groups of rabbits received i.v.60 micrograms.kg-1 B. occitanus mardochei venom either alone (control group) or followed by 3 mg.kg-1 scorpion venom-specific F(ab')2 administered by intravenous infusion 1.75 hr later. In the rabbits treated with horse F(ab')2 antivenom the venom concentration profile was initially identical to that observed in the control group which received venom alone before F(ab')2 administration. Subsequent infusion of antivenom induced a 1.5-fold elevation of the plasma venom concentration with a Tmax 0.5 hr after F(ab')2 administration. The AUC was 10-fold higher in the F(ab')2-treated group than in the control group in the post-F(ab')2 infusion period. Twelve hours after F(ab')2 administration the venom disposition declined with a terminal half-life equal to that of F(ab')2 (49.49 +/- 7.53 hr). These data show the ability of F(ab')2 to alter venom pharmacokinetics and demonstrate that the scorpion toxins adopt the F(ab')2 elimination properties.

Animals↗
PubMed2006

Extraction and protein component analysis of venom from the dissected venom glands of Latrodectus tredecimguttatus.

Black widow spiders (genus Latrodectus) have attracted increasing attention due to frequently reported human injuries caused by them and the potential applications of biologically active components in their venoms. Although a number of studies have described the biological properties and structures of several venomous proteins such as latrotoxins, a comprehensive analysis of protein component of the venom from the spider is not available. We used combinative proteomic strategies to assess the protein components of the crude venom collected from Latrodectus tredecimguttatus by extracting the dissected venom glands. The experiments demonstrated that the crude venom of L. tredecimguttatus has a high abundance of acidic proteins with molecular masses greater than 15 kDa, and the content of proteins and peptides of below 15 kDa is low. 86 unique proteins were identified, part of which were contaminations of cellular components during the extraction, determined in comparison with venom obtained by electrostimulation. Except for members of latrotoxin family that were commonly considered as the primary toxic components of the venom, several other special enzymes and proteins were detected such as protease, phosphatase, lysozyme, inhibitory protein, and so on. These protein components, particularly the proteases, were speculated to play important roles in the action of L. tredecimguttatus venom.

Animals↗
PubMed2000

Characterization of beta-adrenoceptors responsible for venom production in the venom gland of the snake Bothrops jararaca.

We have shown that the stimulation of beta-adrenoceptors is an important step in venom production in the Bothrops jararaca venom gland. In the present study, the pharmacological profile of the beta-adrenoceptor present in Bothrops jararaca venom gland was characterized by radioligand binding assay and by the ability of isoprenaline to promote accumulation of cyclic AMP in dispersed secretory cells. In both cases, the venom glands were obtained from non-extracted snakes (quiescent stage) or from snakes which venom was extracted 4 days before sacrifice (venom production stimulated stage). [125I]-iodocyanopindolol ([125I]-ICYP) bound to extracted gland membranes in a concentration-dependent and saturable manner, but with low affinity. Propranolol, beta1- or beta2-selective adrenoceptors ligands displaced the [125I]-ICYP binding with low affinity, while selective beta3-adrenoceptor ligands did not displace the [125I]-ICYP binding. The displacement of [125I]-ICYP by propranolol was similar in non-extracted and extracted glands, showing the presence of beta-adrenoceptors in both stages. In dispersed secretory cells of non-extracted glands, isoprenaline (1 microM) increased the cyclic AMP production and propranolol (10 microM) was able to block this effect. On the other hand, in extracted glands, isoprenaline had no effect. The results suggest that the beta-adrenoceptors present in the Bothrops jararaca venom glands are different from those (beta1, beta2 or beta3) described in mammals, but are coupled to the Gs protein, like the known beta-adrenoceptor subtypes. Moreover, previous in vivo stimulation of venom production desensitizes the beta-adrenoceptors system and, although the receptors could be detected by binding studies, they are not coupled to the Gs protein, indicating that beta-adrenoceptors stimulation contributes to the initial steps of venom synthesis.

Adrenergic beta-1 Receptor Agonists↗
PubMed2001

Lachesis muta muta venom: immunological differences compared with Bothrops atrox venom and importance of specific antivenom therapy.

Lachesis muta muta and Bothrops atrox snakes are responsible for most accidents occurring in the Amazon. The clinical features of the accidents are similar; however, there are still controversies about the efficacy of Bothrops antivenoms for treating L. m. muta accidents. In this work, we evaluated the antigenic cross-reactivity between these venoms using polyclonal and monoclonal antibodies and the efficacy of B. atrox and L. m. muta experimental antivenoms in cross-neutralizing the main toxic activities of each venom. Electrophoretic patterns differed consistently between the species. However, antigenic cross-reactivity was extensive except for a few bands. Several species-specific monoclonal antibodies were obtained by immunization of Balb/c mice with L. m. muta whole venom or B. atrox and L. m. muta specific antigens. The monoclonal antibodies specific to L. m. muta recognized different bands of this venom and the antibodies specific to B. atrox recognized a complex pattern on whole venom by Western blotting. These antibodies are important tools for developing an immunoassay able to discriminate patients bitten by these snakes. The experiments involving cross-neutralization of the main activities of the venoms showed that hemorrhage and blood incoagulability induced by B. atrox venom were similarly neutralized by both B. atrox and L. m. muta antivenoms. However, B. atrox antivenom partially neutralized the hemorrhage and completely failed in neutralizing coagulopathy induced by L. m. muta venom. Therefore, antigenic variation between B. atrox and L. m. muta venoms does occur and the use of specific antivenom is suggested for patients bitten by Lachesis snakes.

Animals↗
PubMed1996

Allergens in Hymenoptera venom. XXVII: bumblebee venom allergy and allergens.

BACKGROUND: Allergic reactions to bumblebee stings are much less common than allergic reactions to honeybee stings. Preliminary studies suggest that there may be a high degree of cross-reactivity between honeybee and bumblebee venoms. OBJECTIVE: This study was done to determine the immunochemical and structural relationships between bumblebee and honeybee venom allergens. METHODS: Allergens were purified from bumblebee venom and compared immunochemically with sera from patients with allergy and hyperimmunized rabbits. The purified proteins were characterized, enzyme activities were measured, and the complete amino acid sequences of two proteins were determined. RESULTS: The venoms wer highly cross-reactive, consistent with the degree of structural similarity in the phospholipases. Hyaluronidases and acid phosphatases were also similar. Bumblebee venom contained several proteins not found in honeybee venom, including an interesting tryptic amidase related to clotting enzymes and acrosin. CONCLUSION: Skin testing with honeybee venom will detect almost all cases of bumblebee venom allergy, however; RAST with bumblebee venom can detect some additional cases.

Allergens↗
PubMed1997

Relationship of venom effects to venom antigen and antivenom serum concentrations in a patient with Crotalus atrox envenomation treated with a Fab antivenom.

STUDY OBJECTIVE: To describe the association among venom antigenemia, serum antivenom concentrations, and venom effects in a 53-year-old woman who was bitten by a Western Diamondback rattlesnake (Crotalus atrox). METHODS: The patient was enrolled in a multicenter trial of an investigational Fab antivenom. Her clinical condition and coagulation parameters were monitored for 2 weeks after the bite. RESULTS: After antivenom administration, the progression of the venom's effects was arrested. The antivenom reversed some local venom effects, caused venom antigens to disappear from the blood, and resolved the patient's profound thrombocytopenia (before antivenom, 12,000/mm3; 1 hour after antivenom, 227,000/mm3). Local venom effects recurred twice in the 24 hours after antivenom administration but were easily managed with additional Fab antivenom. Venom antigenemia was detected on days 5 and 8 after the initial treatment and was accompanied in one instance by the new onset of hypofibrinogenemia (119 mg/L) that resolved spontaneously and in both instances by renewed profound thrombocytopenia. Repeat Fab antivenom does no days 6 and 9 were followed by increases in platelet count (from 16,000 to 40,000/mm3 and from 11,000 to 20,000/mm3, respectively) and by the reduction or disappearance of venom antigenemia. The patient sustained no significant bleeding complications, and all laboratory values had returned to normal 2 weeks after the bite. CONCLUSION: Initial control of local symptoms and coagulopathy was prompt after the administration of Fab antivenom. Repeat doses during the 24 to 36 hours after a bite may be necessary for local control. Recrudescence of coagulopathy was likely due in part to renewed venom antigenemia after clearance of Fab antivenom. The role of Fab antivenom in the treatment of recurrent coagulopathy requires further study.

Adolescent↗