RELATIONSHIP OF PLATELETS, BLOOD COAGULATION, AND FIBRINOLYSIS TO HYPERACUTE REJECTION OF RENAL XENOGRAFTS

Hyperacute rejection of some renal allografts, and most xenografts, is thought to result from the interaction of preformed humoral antibodies in the recipient with antigens in the donor kidney. These studies were undertaken to determine the pathophysiological mechanisms triggered by this violent immunological rejection reaction. Seven pig kidneys were transplanted into 7 dogs. The entire venous effluent was collected over timed intervals. Rejection of the transplant proceeded rapidly and was complete within 7 min. Biopsies were obtained 3 and 7 min after transplantation. They revealed platelet aggregates in the small arteries, arterioles, and glomeruli. Platelets in renal vein blood fell precipitously within the 1st min after reestablishing renal circulation; the mean platelet count fell from a control level of 134,000/mm to 33,000/mm. By 7 min, the platelet count fell to 700/mm. There was also a significant prolongation of the partial thromboplastin time and a consumption of fibrinogen, prothrombin, and factors V and VIII in renal vein blood (P< 0.05). The concentration of fibrinogen split products in renal vein blood increased while the whole blood lysis time decreased. A simultaneous decrease in renal blood flow and increase in arterial resistance occurred. It is concluded that the pathophysiological basis of hyperacute rejection of the pig to dog renal xenograft is the induction of platelet aggregation, leading to the formation of platelet plugs and activation of the clotting and fibrinolytic system. The end result is progressive intrarenal intravascular coagulation of the cortical vessels and cortical necrosis. © 1969 by The Williams and Wilkins Co.