Thrombogenic Activity of Leukocytes

Peritoneal leukocytes from rabbits that had been pretreated with endotoxin have a considerable procoagulant activity in vitro. To determine whether these leukocytes were thrombogenic, the leukocytes were infused into normal rabbits. When the leukocytes were infused intravenously, pulmonary emboli and death occurred. When similar numbers of leukocytes derived from control rabbits were infused, no thrombi were found. To investigate the effect of an infusion of leukocytes into the arterial circulation leukocytes were infused into the aorta. When leukocytes from control rabbits were infused, minimal renal cortical necrosis was observed in two out of nine cases; no other thrombi were found, and coagulation changes were minimal. When peritoneal leukocytes derived from endotoxin-primed rabbits were infused into the aorta, renal cortical necrosis occurred in six out of ten cases, and infarction or thrombosis occurred in the lung, liver, spleen, and myocardium. Coagulation test showed changes compatible with the defibrination syndrome, including a fall in the platelet count, fibrinogen level, and levels of factor V and factor VIII, and prolongation of the prothrombin time and partial thromboplastin time. Very high doses of heparin were required to prevent the thrombogenic effect of leukocytes. The relative ineffectiveness of heparin is attributed to an antiheparin effect of the leukocyte. Infusion of rabbit brain thromboplastin extract, which had a tissue factor activity similar to that of infused leukocytes from endotoxin-treated rabbits, caused renal cortical necrosis in 9 out of 15 cases, but the coagulation changes were slight.