Signs of crotaline envenomation (box 2) Approximately 80% of pit viper bites result in the injection of venom [17,18]. Pit viper venom is a complex mixture of proteins and other macromolecules, with more than 50 identified components. The clinical effects produced by envenomation can be broadly classified into three groups. Local tissue

Inhibitors,research,lifescience,medical effects include soft tissue necrosis and chemically mediated inflammation. A number of venom components, including myotoxic phospholipases A2 such as crotoxin, venom metalloproteinases that activate tumor necrosis factor-alpha (TNF-α), myotoxin a, hyaluronidase, phosphomonoesterase, phosphodiesterase, arginine ester hydrolase, and histamine- and bradykinin-like factors, cause direct tissue injury and produce a broad cytokine response in the victim [7,19-22]. Clinically, these effects are evident as pain, redness, swelling, tenderness, and myonecrosis that Inhibitors,research,lifescience,medical begin adjacent to the bite site and spread with movement of the venom through the lymphatic system. More than 90% of envenomated pit viper BAY 11-7082 mw victims develop Inhibitors,research,lifescience,medical local tissue effects [7]. Hematologic venom effects include fibrinogen degradation and platelet aggregation and destruction [23,24]. On a laboratory basis, these are manifest by decreased fibrinogen levels, elevated prothrombin time, and thrombocytopenia. Detection of fibrin split products may be an early sign

of a hematologic venom effect, and is a sensitive predictor of subsequent coagulopathy. In prospective studies, the presence of fibrin split products

within the first 12 hours of treatment Inhibitors,research,lifescience,medical predicted subsequent hypofibrinogenemia with 87% sensitivity and 69% specificity [25]. In some patients, elevated fibrin split products were the only early signs of developing hypofibrinogenemia. Clinically, oozing of blood from the bite site and ecchymosis of the surrounding tissue are common. Systemic bleeding Inhibitors,research,lifescience,medical may manifest as nuisance bleeding, such as gingival bleeding or haemolacria, or more serious bleeding, such as significant epistaxis, gastrointestinal bleeding, or intracranial hemorrhage. Even among the population with severe defibrination or thrombocytopenia, most patients do not develop medically significant bleeding signaling pathway [26]. However, severe and fatal bleeding complications have been reported [27-31]. Systemic venom effects include hypotension from direct cardiovascular toxicity, third-spacing and vasodilatation, nausea and vomiting, angioedema, and neurotoxicity. Many pit vipers envenomations can cause patients to experience a metallic taste and localized neuromuscular effects (fasciculation and myokymia). Severe systemic neurotoxicity induced by Mojave toxin A, including cranial neuropathy and flaccid paralysis, are frequent manifestations from Mojave rattlesnake (Crotalus scutulatus) and Southern Pacific rattlesnake (C.