Abstract

The hypothesis that the administration of fibrinogen concentrate enables restoration of impaired clot formation and increased bleeding in severe thrombocytopenia was tested. Thirty pigs were anesthetized, instrumented for blood sampling (routine coagulation tests, modified thrombelastography ROTEM, hemodynamic monitoring and platelet apheresis to a target below 30 x 10(9) L(-1) after splenectomy. Thereafter 10 each of the animals randomly received two apheresis platelet concentrates, 250 mg kg(-1) fibrinogen concentrate or normal saline solution. A standardized liver injury was subsequently inflicted to induce uncontrolled hemorrhage. Median (Q1, Q3) clot firmness increased significantly more in thrombocytopenic pigs after fibrinogen administration (42 mm (41, 43) to 60 mm (57, 63)) than following platelet transfusion (40 mm (37, 45) to 52 mm (48, 55), P = 0.0004) or placebo (45 mm (41, 48) to 45 mm (43, 46), P = 0.0002). Median blood loss velocity after liver injury was significantly less with fibrinogen (33 mL min(-1), P = 0.005) than with platelets (62 mL min(-1), P = 0.037) or saline (84 mL min(-1), P = 0.005), and median survival time after liver injury was 55 min in the fibrinogen, 26 min in the platelet (P = 0.035) and 19 min in the saline group (P = < 0.0001). These data show for the first time that impaired clot formation during thrombocytopenia improves with administration of fibrinogen concentrate, which results in a slowdown of blood loss and prolonged survival.

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