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PubMed · 9360849

Defibrinogenating enzymes.

W R Bell
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Abstract

The venoms from 3 snakes have been shown to induce defibrinogenation: ancrod from the venom of Calloselasma rhodostoma (formerly known as Agkistrodon rhodostoma), batroxobin from the venom of Bothrops atrox moojeni, and crotalase from the venom of Crotalus adamanteus. The purified fractions of ancrod, batroxobin, and crotalase possess coagulant, proteolytic and esterolytic properties, although their primary mechanism of action is a proteolytic effect on circulating fibrinogen. Ancrod cleaves only the A-fibrinopeptides, but not the B-fibrinopeptides, from fibrinogen; this contrasts with thrombin, batroxobin and crotalase, which cleave both fibrinopeptides A and B. Within minutes of administration of ancrod or batroxobin, there is a significant reduction in plasma fibrinogen levels, and these remain exceedingly low with repeated administration (once or twice daily). The rapid fall in plasma fibrinogen levels is accompanied by a slightly delayed but marked rise in the level of fibrinogen-fibrin degradation products. Plasminogen levels are decreased and blood viscosity is reduced, but formed elements in the circulating blood remain unaltered. Ancrod and batroxobin have been investigated in patients with stroke, deep-vein thrombosis, myocardial infarction, peripheral arterial thrombosis, priapism, and sickle-cell crisis; crotalase has not been administered to humans. However, results have been difficult to interpret, and additional well designed trials are needed to better define the optimum role of ancrod and batroxobin in the management of these conditions. Overall, treatment is well tolerated and serious adverse events are infrequent. In the coagulation laboratory, ancrod, batroxobin and crotalase may be used as reagents to perform coagulation studies on specimens of blood that contain heparin. These venom fractions can be substituted for thrombin in performing the thrombin time and in removing fibrinogen from plasma for accurate determination of fibrinogen-fibrin degradation products.

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AncrodAnimalsBatroxobinBlood CoagulationCardiovascular DiseasesCerebrovascular DisordersFibrinogenFibrinolytic AgentsHumansSerine EndopeptidasesSnakesJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Review

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W R Bell. 1997. Defibrinogenating enzymes.. https://doi.org/10.2165/00003495-199700543-00005

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Tumour necrosis factor (TNF) is known to have procoagulant activity, and platelet depletion is a feature of TNF-mediated systemic inflammatory responses. The aim of this study was to investigate the role of fibrinogen consumption in the development of TNF-mediated systemic inflammatory responses and in the associated depletion of platelets. Three murine models of TNF-mediated systemic inflammatory responses were examined: the systemic toxicity reactions (STR) induced by TNF or lipopolysaccharide (LPS) and severe malaria (SM), a prominently neurological complication of Plasmodium berghei ANKA infection in susceptible mice. There was an acceleration in the consumption of fibrinogen during TNF-STR but not during LPS-STR or SM. However, a concomitant reduction in platelet count was found in all conditions. Mice preliminarily depleted in fibrinogen by treatment with ancrod, an enzyme that specifically degrades fibrinogen, showed no protection against mortality during TNF- or LPS-STR or SM, although they were protected against tissue damage during a modification of the classical local Shwartzman reaction. During TNF- and LPS-STR platelets were even lower in ancrod-treated than control mice and during SM they were not significantly different. This study shows that fibrinogen consumption, although accelerated by the direct injection of TNF, is not necessary for the development of TNF-mediated systemic inflammatory responses in mice, at variance with local pathology, and does not contribute to the associated depletion of platelets.

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