c. Consumption coagulopathyにおける凝血学的変化の成立機転について

抄録

Normal saline solution containing 2 units of thrombin per ml was infused intravenously to the rabbits, weighing 2∼3 kg, at a rate of 30 ml/kg/hour over 3—6 hours and changes in platelet counts and activities of various clotting factors in the rabbits were followed up till 5th day after the infusion. In some of the rabbits, ¹³¹I-labeled autologous fibrinogen was infused 44 hours prior to or 24 hours after the 3 hours' infusion of the thrombin solution. Tracer data of plasma fibrinogen fraction were analysed using the method described by Atencio. Production rate of plasma fibrinogen was estimated by ⁷⁵Se-methionine incorporation during and 2 hours after 3 hours, infusion of the thrombin solution. The results obtained were as follows: (1) Thrombin infusion over 6 hours resulted in marked reduction in platelet counts and plasma fibrinogen levels. Both prothrombin time and celite-activated PTT were much prolonged. Among various clotting factors, Factors II, V and VIII were decreased remarkably. Hemorrage was observed in these rabbits and most of them died in a short period of time. Autopsy revealed disseminated thrombi in renal and pulmonary vasclar tree. Similar but less severe changes were observed in the rabbits infused with the thrombin solution over 3 hours. In these animals, slight but significant increase was observed in fibrinolytic activity of plasma after the infusion. (2) The thrombin infusion resulted in 63% reduction of the radioactivity of plasma fibrinogen fraction, while plasma fibrinogen conentration decreased by 50%. The difference of these figures was interpreted as the result of the dilution by the cold fibrinogen newly synthesized. There was no substantial decrease in the radioactivity of plasma fibrinogen fraction during 24 hours after completion of the thrombin infusion. This may result from the influx of ¹³¹I-labeled fibrinogen in the interstitial pool into the plasma pool. As a specific activity, about 10 times of ⁷⁵Se-methionine were incorporated into plasma fibrinogen fraction either during or 2 hours after the thrombin infusion as compared with the normal control animals. (3) Both fibrinogen concentration and activities of various clotting factors began to increase 24 hours after the completion of the thrombin infusion. Rebound increase was marked in both fibrinogen and Factor VIII levels and attained to the peak level faster. Recovery of platelet counts was delayed. Acceleration in turnover rate of ¹³¹I-labeled autologous fibrinogen was observed in rebound hypercoagulable state followed by thrombin-induced consumption coagulopathy. (4) A case of megakaryocytic thrombocytopenia complicated with consumption coagulopathy was reported and the correlation of her clinical course to the changes in the clotting mechanism observed in the consumption coagulopathy induced by thrombin infusion in experimental rabbits was discussed.