Hemostasis and fibrinolysis in renal transplantation

Results of histologic, biochemical, and immunologic studies suggest that coagulation and fibrinolysis are possibly important in kidney graft rejection, but there is no information about how or why they are involved. The touchstones of their importance are histologic reports of platelet-fibrin thrombi in glomerular vessels of rejecting kidneys. Most of the nonhistologic studies have made use of functional assays aimed at measuring coagulation changes in blood. Little use has been made of immunoassays, and there are almost no studies of recently described anticoagulant systems, such as the protein C pathway. Endothelial cells form the interface between donor and recipient tissues. Antibody or thrombin-stimulated endothelium produces PAF, and thrombin-stimulated endothelium produces both plasminogen activators and plasminogen-activator inhibitors. As important as these reactions might be, information about them has been obtained with the use of either in vitro experiments or artificial systems, and there is no direct evidence that they are relevant to transplantation. However, these observations do show that tissue factor, PAF and fibrinolytic activities can be immunologically triggered. This opens the possibility that allogeneic recognition may initiate the triggering process. The clotting and fibrinolytic phenomena discussed in this overview were consequences of allogeneic recognition. Such recognition reactions cause monocytes and macrophages to produce tissue factor, which is a potent initiator of coagulation. Endothelial cells also can be stimulated to elaborate tissue factor by immune complexes, interleukin-1, or endotoxin. These observations give cause to speculate that the link between immunity and coagulation in kidney transplantation could be products of allogeneic recognition that activate Factor VII and lead to fibrin deposition. If true, this suggests new approaches to the old problems of diagnosis and treatment of rejection reactions in organ transplantation.