Pathogenesis of Fibrinolysis in Defibrination Syndrome: Effect of Heparin Administration.

CUTE HYPOFIBRINOGENEMIA may result from systemic intravascular coagulation ( defibrination ),or from spontaneous pathologic fibninolysis, or both. The pathogenesis of these conditions has been ascribed to the local release of thromboplastic substances,1’2 or fibrinolytic substances34 or a cornbination of these.5’6’7 Since either thromboplastic or fibrinolytic substances may reduce the level of certain plasma components such as Factor V, anti-hernophilic factor (AHF) and fibrinogen, it may be difficult, on occasion, to determine the primary pathogenetic mechanism. The studies to be reported in this paper were made in a patient with hypofibrinogenernia secondary to disseminated colonic cancer. Evidence will be presented that systemic defibrination occurred and that locally induced fibrinolysis co-existed. The evidence for defibrination consisted of reduced levels of coagulation factors (AHF, Factor V, prothrombin and blood platelets). Fibninolysis was evidenced by reduced plasminogen levels and streptokinase (SK) and urokinase (UK) inhibitors, together with a prolonged thrombin clotting time. Additional laboratory evidence of fibrinolysis was obtained by the immuno-electrophoretic demonstration of fibrinolytic breakdown products in the plasma and serum. Clinical evidence of fibrinolysis was provided by the rapid disappearance of a large thrombus from a leg vein. Finally, parenteral administration of the anti-coagulant, heparin, sequentially corrected defibrination and secondary fibrinolysis; discontinuation of heparin resulted in the recurrence of intravascular coagulation and reactivation of the fibrinolytic process. These observations suggested that disseminated local thromboses were associated with both defibrination and fibrinolysis. The data further suggested that thrombosis and defibrination was primary, that fibrinolysis was secondary, and that local thrombosis initiated fibrinolysis.