Consumption of Serum Factors and Prothrombin During Intravascular Clotting in Rabbits

Abstract

We have studied the effect of experimental intravascular clotting upon Factors II, VII, IX, and X in rabbits. Animals were given sodium warfarin intravenously to block the synthesis of these factors and, 4 hours later, were infused with either dilute tissue thromboplastin or saline. The tissue thromboplastin induced intravascular clotting extensive enough to halve fibrinogen and platelet levels and to reduce markedly Factor V and Factor VIII levels. These changes resulted from a consumption during clotting of about 10 per cent of the available prothrombin. Each of the serum factors fell further during the infusion of tissue thromboplastin than during the infusion of saline; apparently, serum factors activated during clotting do not circulate in the rabbit. Net losses due to intravascular clotting equalled about 15 to 30 per cent of the Factors VII, IX, and X initially present. These data suggest that consumption during intravascular clotting may account for the low levels of Factors VII, IX, and X described in patients with diffuse intravascular clotting complicating septicaemia. The evidence of consumption of Factor IX raises the possibility that tissue thromboplastin may activate intrinsic clotting during hemostasis in vivo.

Do Platelets Enhance Thromboplastin —Induced Intravascular Clotting?

“…The observed decrease in factor IX activity during the infusion (Figure 3), which confirms the findings of Rapaport et al (1966), deserves a special comment. Factor IX is probably not activated by thrombin , neither is it con-…”

“…Previous studies have shown that Macrogol does not influence the platelet level or the clotting system ). The development of thrombocytopenia was followed closely by samples obtained from the ear vein as described by Rapaport et al (1966). At the time of maximal thrombocytopenia, i.e., 12-16 days after the injections, a cannula was inserted in the femoral artery of all animals (Evensen et al 1967), and blood samples were taken to check the preparatory treatment.…”

Pathophysiology of Generalized Intravascular Coagulation

“…The elevated concentrations of thromboplastin in leukemic cells may explain the high incidence of generalized intravascular coagulation observed in acute promyelocytic leukemia [55,85,254] and in the course of leukemic cell destruction consecutive to chemotherapy [102]. It is well documented that infusions of tissue thromboplastin cause generalized intravascular coagulation [78,195,208,229]. It is understandable that patients suffering from leukemia or cancer may develop generalized intravascular coagulation, especially when tumor cells break down or are destroyed.…”