A modified stasis thrombosis model to study the antithrombotic actions of heparin and its fractions

The original stasis thrombosis model of Wessler has been modified. Numerous thrombogenic agents were evaluated for their pathophysiologic effects and were classified in terms of stasis clot in the jugular vein. Alterations produced in coagulation parameters, such as the PT, APTT, thrombin time, activated recalcification time (Hemachron), and thrombelastographic pattern were recorded. Since the pathophysiologic activation of the hemostatic system varies considerably in different diseases, a proper animal model along with a proper type of thrombogenic trigger should be carefully selected to produce pathogenesis and to study the therapeutic responses of heparin and its derivatives. In the modified stasis thrombosis model, besides monitoring the formation of the jugular vein stasis clot, it is proposed that the following tests may be useful to establish hypercoagulable states: Functional levels of various coagulation factors, platelet counts, fibrinogen levels, and whole blood activated clotting times. The nature of activation processes in each thrombogenic challenge should be carefully analyzed in terms of pathways involved; for example, the administration of heterologous serum (such as human, monkey) to rabbits produces anaphylactoid reactions, including hemolysis, thrombocytopenia, clinical chemistry abnormalities (enzymes), and many problems that may involve the complement and immune systems. All previous data obtained using heterologous sera as a thrombogenic trigger are of questionable value as to the efficacy of some of the antithrombotic agents tested against it. In addition to the species and the thrombogenic challenge, the following factors may contribute significantly to the pathophysiologic response and its alteration by various agents: (1) Composition of the thrombogenic agent; (2) effect of preparatory drugs, such as anesthetics, on the hemostatic parameters; (3) alterations on injection time, volume, osmolarity, and temperature; (4) variations in the circulation time of the thrombogenic agent and stasis time of the ligated jugular vein stasis segment; and (5) blood sample collection and handling. Since the kallikrein-kinin cascade is closely associated with the coagulation and the fibrinolytic network, a systemic monitoring of blood pressure may provide information on the effect of thrombogenic agents on hemodynamics.(ABSTRACT TRUNCATED AT 400 WORDS)