Hematological, hemostatic and clinical chemistry disturbances induced by Crotalus durissus terrificus snake venom in dogs.

The aim of this study was to investigate the hematological, hemostatic and biochemical disturbances induced by the injection of Crotalus durissus terrificus venom in dogs under controlled conditions. For this purpose three groups of animals were used: an experimental group (E), which was injected i.m. with C. durissus terrificus venom (1 mg/kg); and two control groups--antivenom (AV) and control (C)--which were injected i.m. with 150 mM NaCl. Groups E and AV were treated i.v. with Crotalus antivenom 2 hours after the first injection. Serum levels of alkaline phosphatase and alanine aminotransferase were increased in groups E and AV at 24 and 48 hours after serumtherapy, respectively. The increased serum levels of myoglobin, creatine kinase and aspartate aminotransferase demonstrated that animals developed rhabdomyolysis. A persistent neutrophilic leukocytosis was already noticeable at 2 hours after envenomation and lasted even after serumtherapy. The animals of groups E and AV presented eosinopenia 24 hours after serumtherapy, and collagen-induced platelet hypoaggregation was observed without thrombocytopenia. Increased levels of fibrinogen/fibrin degradation products (FnDP/FgDP), hypofibrinogenemia, and alpha2-antiplasmin consumption were observed at 2 hours after envenomation, indicating secondary activation of fibrinolysis. Our data suggest that the biochemical and hemostatic disturbances induced by C. durissus terrificus venom in dogs are related to its myotoxic and thrombin-like activities.

Envenoming by Bothrops jararaca in Brazil: association between venom antigenaemia and severity at admission to hospital.

The association between the clinical severity of Bothrops jararaca envenoming at admission and serum venom and plasma fibrinogen concentrations before antivenom administration is reported in 137 patients admitted to Hospital Vital Brazil, Instituto Butantan, São Paulo, Brazil, between 1989 and 1990. Other variables such as age, gender, site of the bite, use of tourniquet and the time interval between the bite and start of antivenom therapy, spontaneous systemic bleeding, and the 20 minute whole blood clotting test (20WBCT) at admission showed no association with either severity or serum venom antigen concentration (SVAC). Mean SVAC in patients with mild envenoming was significantly lower than in the group with moderate envenoming (P = 0.0007). Patients with plasma fibrinogen concentrations > 1.5 g/L had a lower mean SVAC than patients with plasma fibrinogen concentrations < or = 1.5 g/L (P = 0.02). Those admitted with a tourniquet in place had significantly higher plasma fibrinogen concentrations than those without a tourniquet (P = 0.002). A multiple logistic regression model showed independent risk factors for severity: bites at sites other than legs or forearms, SVACs > or = 400 ng/mL, and the use of a tourniquet. Rapid quantification of SVAC before antivenom therapy might improve initial evaluation of severity in B. jararaca bites.

Coagulopathy following lethal and non-lethal envenoming of humans by the South American rattlesnake (Crotalus durissus) in Brazil.

The South American tropical rattlesnake (Crotalus durissus subspp) is responsible for approximately 10% of bites from venomous snakes in Brazil. We studied 24 victims of bites by this species over 3 years, in south-eastern Brazil, particularly investigating haemostatic alterations. Thirteen patients were defined as moderately envenomed and 11 as severe. There were two deaths, which were not attributed to venom-induced haemostatic disturbances. However, envenoming by C. durissus is frequently associated with haemostatic disorders, which are probably attributable mainly to the action of the thrombin-like enzyme, with possible additional effects secondary to the powerful myotoxic activity of the venom.

Snakebite by the bushmaster (Lachesis muta) in Brazil: case report and review of the literature.

The bushmaster (Lachesis muta) of Central and South America, the world's longest pit viper, is capable of injecting a large dose of potent venom when it bites. A 28-year-old man, bitten by a 1.82 m long L. m. muta in Brazil, developed pain and oedema at the bite site, nausea, vomiting, diarrhoea and sweating. There was peripheral neutrophil leucocytosis and evidence of fibrinogen consumption with secondary activation of the fibrinolytic system. Two hours after the bite, eight ampoules of Instituto Butantan Lachesis antivenom was administered, and haemostasis was normal 24 hr later. A review of reports of 20 cases of bites in humans reliably attributed to this snake in Costa Rica, French Guiana, Brazil, Colombia and Venezuela confirms a syndrome of nausea, vomiting, abdominal colic, diarrhoea, sweating, hypotension, bradycardia and shock, possibly autopharmacological or autonomic in origin, not seen in victims of other American crotaline snakes. These, and other symptoms of bushmaster envenoming, are explained by haemorrhagic, coagulant and neurotoxic venom activities. The therapeutic efficacy of non-specific Bothrops/Crotalus polyvalent antivenoms in these cases has been unimpressive. For the treatment of bites by a snake which potentially injects a large dose (> 300 mg dry weight) of venom with a range of life-threatening activities, there is an urgent need to develop more potent specific antivenoms and to treat the dramatic and life-threatening cardiovascular symptoms.

Hematological changes induced by Bothrops jararaca venom in dogs.

The mechanism of consumption coagulopathy observed in cases of human envenomation by Bothrops jararaca is well established. However, this mechanism may vary according to the animal species studied. In order to study both the clinical and laboratory aspects of bothropic envenomation in dogs, a sublethal defibrinating dose of venom (100 micrograms/kg) was given intravenously. A coagulopathy similar to that observed in humans - including fibrinogen depletion, consumption of factors II, X, V and antithrombin III, and moderate thrombocytopenia - was observed. The presence of circulating activated platelets was also noted. Neutrophilic leukocytosis, lymphopenia, and monocytosis occurred at different times. Erythrocytic values remained normal in dogs treated with B. jararaca venom compared with those treated with saline alone. The erythrocyte sedimentation rate fell rapidly after venom administration and this fall was correlated logarithmically with fibrinogen concentration. Since the effects of envenomation in dogs is similar to that in humans, it was concluded that the dog can be used as a good animal model for studying human venom-induced coagulopathy.

Hematological changes induced by Bothrops jararaca venom in dogs

The mechanism of consumption coagulopathy observed in cases of human envenomation by Bothrops jararaca is well established. However, this mechanism may vary according to the animal species studied. In order to study both the clinical and laboratory aspcts of bothropic envenomation in dogs, a sublethal defibrinating dose of venom (100 µg/kg) was given intravenously. A coagulopathy similar to that observed in humans - including fibronogen depletion, consumption of factors II, X, V and antithrombin III, and moderate thrombocytopenia -was observed. The presence of circulatin activated platelets was also noted. Neutrophilic leukocytosis, lymphopenia, and monocytosis occurred at different times. Erythrocytic values remained normal in dogs treated with B. jararaca venom compared with those treated with saline alone. The erythrocyte sedimentation rate fell rapidly after venom administration and this fall was correlated logarithmically with fibrinogen concentration. Since the effect of envenomation in dogs is similar to that in humans, it was concluded that the dog can be used as a good animal model for studying human venom-induced coagulopathy

Reliability of the simple 20 minute whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes. Butantan Institute Antivenom Study Group.

Reliability of the simple 20 minute whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes. Toxicon 32, 1045-1050, 1994.--A simple whole blood clotting test (WBCT20) was assessed for its efficacy in determination of severe defibrinogenation in patients envenomed by Bothrops snakes in Brazil. There was a close relationship between the results of the WBCT20 and plasma fibrinogen levels in 69 moderately envenomed patients. The advantage of the WBCT20 over estimation of plasma fibrinogen concentrations in patients is that it is a simpler, faster and more reliable test. It is also of use in assessing the effectiveness of antivenom therapy in relation to the restoration of blood coagulability.

Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in São Paulo, Brazil.

In São Paulo City, Brazil, 121 patients with moderately severe envenoming by Bothrops snakes (principally B. jararaca) were randomized for treatment with Brazilian polyspecific Bothrops antivenoms: Instituto Butantan (39 patients), Instituto Vital Brazil (41), Fundação Ezequiel Dias (FUNED) (41). The initial dose was four ampoules (40 ml) in 89 patients with less severe envenoming and eight ampoules (80 ml) in 32 patients with more severe envenoming. A second dose of four ampoules was required in 20 patients. Patients receiving the three antivenoms were comparable in all respects before treatment. There were no deaths. The majority showed rapid clinical improvement, resolution of local envenoming, cessation of bleeding and restoration of blood coagulability. No differences in the efficacy of the three antivenoms were revealed by clinical or laboratory observations, including measures of haematological, haemostatic and biochemical abnormalities. Twelve patients developed abscesses (Butantan 1, Vital Brazil 6, FUNED 5) and seven developed local necrosis (3,1,3). Of 88 patients followed up 20-30 days after the bite 33 (37.5%) still had symptoms or signs of local envenoming, especially swelling. Early (anaphylactic) reactions were unexpectedly frequent after all three antivenoms but were significantly more frequent with Butantan (87%) than with Vital Brazil (37%) or FUNED (56%) antivenoms (p < 0.001). A possible explanation was the higher total protein content and percentage immunoglobulin of Butantan antivenom. The doses of antivenom recommended in Brazil and used in this study may be unnecessarily high, resulting in an unacceptably high incidence of reactions. Results of the study should prompt a critical re-evaluation of antivenom production techniques and dosage recommendations in Brazil.

Prothrombin and factor X activating properties of Bothrops erythromelas venom.

The enzymatic properties of Factor II (FII) and Factor X (FX) activators from Bothrops erythromelas venom were investigated. Both activators were inhibited by ethylenediaminetetraacetate (EDTA) and 1,10-phenanthroline, and are thought to be metalloproteinases with molecular weights of 90 kDa and 70-90 kDa, respectively. The activity of the FII activator in the crude venom was about 30 times greater than that in Oxyuranus scutellatus venom and the level of FX activator activity, which was CA2+ ion dependent, was similar to that in Daboia russelli venom. The venom also had two haemorrhagic factors (58 and 105 kDa) and two fibrinolytic enzymes (18 and 58 kDa).

Studies on blood coagulation and fibrinolysis in patients bitten by Bothrops jararaca (jararaca).

The blood coagulation and the fibrinolytic systems of nine patients envenomed by Bothrops jararaca in São Paulo (Brazil) were studied. Five of the accidents were caused by young snakes (less than 50 cm). On admission, four patients had non-clotting and three partially-clotting blood. Fibrinogen levels were decreased due to the thrombin-like activity of the venom as expected. Consequent secondary activation of the fibrinolytic system was evident from the low levels of alpha-2-antiplasmin and the high titres of fibrin(ogen) degradation products. High titres of cross-linked fibrin fragment D (D-dimer) in seven patients together with decreased platelet counts and/or factor V, and/or factor VIII in some, suggests intrinsic thrombin formation as these factors are not consumed in the defibrinogenation induced by venom thrombin-like fractions such as Ancrod and Batroxobin. However, normal or increased levels of antithrombin III in all and normal levels of factor II in eight patients do not support this interpretation. The existence of variable concentrations of other proteins in the venom of B. jararaca such as botrocetin and thrombocytin isolated from B. jararaca and B. atrox or crotalocytin from Crotalus horridus venom should be considered. Such proteins are known to activate factors V, VIII, XIII, and platelets without affecting prothrombin (factor II) and antithrombin III. Slower recovery of the haemostatic disturbances after antivenom administration to patients bitten by young snakes suggests a more severe coagulopathy in such accidents. This is supported by clinical observations.

An investigation of the coagulant activity of the venom of the saw-scaled viper (Echis carinatus) from Saudi Arabia.

Unlike the venom of Echis carinatus from India, Pakistan, Nigeria, Kenya, Iran and Oman, Saudi Arabian E. carinatus venom is a poor activator of prothrombin. However, it possesses similar defibrinogenating activity to the other venoms. This is because the venom from Saudi Arabian snakes contains a calcium-dependent factor X activator. It is suggested that in future studies of the coagulant activity of venoms, the determination of plasma coagulant activity should be carried out in the presence of added calcium ions. This applies particularly to those venoms which do not act on plasma or fibrinogen, but which do cause in vivo defibrinogenation.