Paradoxic changes in chronic intravascular coagulation

Paradoxic changes in platelet and fibrinogen levels were found in chronic intravascular coagulation induced in dogs. After pre-experiment base-line values were obtained with saline alone, thrombaplastin (acetone-dried dog-brain emulsion in saline, clarified by centrifugation) was given by continuous intravenous infusion at 2.5 ml/hr for 5 to 7 days. With undiluted thromboplastin, fibrinogen and platelet levels steadily fell and then stabilized at 50–100 mg/100 ml of plasma for fibrinogen and 5-10 × 103/mm3 for platelets. Fibrinogen decreased more rapidly than platelets. Infusion of a 10-fold dilution of thromboplastin paradoxically increased fibrinogen to 550–650 mg/100 ml but with contemporaneous decrease of platelets to 20–40 × 103/mm5. With 100-fold dilution of thromboplatin the fibrinogen also increased, to more than 500 mg/100 ml, while the platelets remianed in the normal range. Whenever the thromboplastin infusion was stopped, platelets and fibrinogen levels increased, exceeding the preinfusion level and remaining high for 2 to 3 weeks. These data suggest that, in chronic intravascular coagulation in the dog, the liver is better able to compensate in the synthesis of fibrinogen than the marrow can in the synthesis of platelets. When intravascular coagulation is not too profound, fibrinogen or platelets may be normal or increased, as we have found in some patients who had evidence of intravascular coagulation without hypofibrinogenemia and thrombocytopenia.