Studies on possibility of surgery during defibrination therapy

Abstract

Defibrase is one of the thrombin like enzyme from bothrops atrox venom which couse fibrin formation by splitting off only fibrinopeptide A from fibrinogen. Defibrination therapy with this enzyme is expected to be a new type of anticoagulant therapy for thrombotic disorders.In this paper, following investigations were carried out to study the possibility of surgery durling defibrination therapy with Defibrase;1. Changes of coagulation and fibrinolysis systems effected by Defibrase.Twenty one mongrel dogs were used. Eleven dogs were given 50μl/kg of Defibrase (Bothrops atrox marajoensis) diluted in 100ml saline intravenously for 1 hour. Another 10 dogs were given 100μl/kg of Defibrase in a similar manner. Blood samples were obtained by venous puncture before and after infusion, and following blood examinations were carried out; red blood cell, hematcrit, platelet count, fibrinogen level, prothrombin time, activated partial thromboplastin time, coagulation factors (II, V, VII-X, VIII, IX), fibrin and fibrinogen degradiation products (FDP), plasminogen, plasmin, anti-plasmin and protamin sulfate test.2. Fibrinogen levels that prevent thrombosis on experimental model of thrombus formation.Twenty mongrel dogs were used. In a series of 10 dogs, endotheriums of femoral arteries were injured by 5% sulfulic acid for thrombus formation as control. In another series of 10 dogs, Defibrase therapy was done for 6 hours to 3 days before the experiment to achieve a low fibrinogen concentration, and thrombus formation was investigated after that.3. Hemorrhagic tendency.Observation for hemorrhagic tendency following surgery under the defibrination therapy was done. Plasma fibrinogen concentration was markedly decreased without any change of RBC, Ht and platelet count after infusion of Defibrase. Coagulation factor II and IX were slightly increased. Factor V, VII-X and VIII were decreased but they recovered after 24 hours. Prothrombin time and activated partial thromboplastin time were prolonged at fibrinogen levels of below 100mg/dl. FDP was increased markedly for 4 to 6 hours after infnsion, though changes of plasminogen levels which supported increase of FDP were not observed.Olsson pointed out that the hemorrhagic tendency durling defibrination therapy was not due to the lack of fibrinogen, but to the anticoagulant effect of FDP, and hemorrhage did not occur when FDP had fallen to low concentration. In our experiments, however, bleeding was durable in many cases when fibrinogen level was under 50mg/dl inspite of FDP was in normal limit. For hemostasis, some levels of fibrinogen is needed besides FDP. The level of fibrinogen for certain hemostasis and effective anticoagulant therapy was 50 to 100mg/dl.