Factor VIII complex in uraemia and effects of haemodialysis.

Abstract

Levels of the factor VII complex were found to be raised in patients with chronic renal failure and further raised by regular dialysis. Increased fibrinogen concentrations were also found. These results suggest the existence of a prothrombotic state in uraemia that is exacerbated by haemodialysis. Ristocetin-induced platelet agglutination, however, was depressed in uraemia and worsened by dialysis. This defect may be transferred to normal platelets from dialysed uraemic plasma, suggesting the existence of an inhibitor of the interaction between factor VIII and platelet glycoprotein.These results may help to explain the anomaly of a prolonged bleeding time together with accelerated atherogenesis that is found in patients with uraemia receiving dialysis.

Further Investigations of the Defective Protein C in Hemodialysis, Hemofiltration and Continuous Ambulatory Peritoneal Dialysis

“…In uremia, a paradoxical association of both bleeding tendency and thrombotic epi sodes is described [1,2]. Earlier we reported decreased protein C activity but normal pro tein C antigen level in hemodialysis patients and suggested that this could contribute to the thromboembolic complications observed in uremia [3].…”

“…The reason for this defective protein C is not clear but it could be due to the presence of a hitherto unknown dialyzable inhibitor of protein C in uremic plasma or a defect in the dicarboxylation of protein C. In order to further elucidate this we have determined protein C activity in patients with terminal renal failure treated in three different ways: intermittent hemodialysis, intermittent hemofiltration and continuous ambulatory peritoneal dialysis (CAPD). Fur thermore, we have examined the existence of an unknown inhibitor of protein C by deter mination of protein C coagulant activity during a series of in vitro experiments: (1) in vitro dialysis of uremic plasma against nor mal plasma: (2) in vitro dialysis of normal plasma against uremic plasma; (3) inhibition of normal plasma protein C activity with increasing amounts of ultrafiltrates obtained from hemofiltration patients.…”

Effects of Long-Term Treatment with Recombinant Human Erythropoietin on Physiologic Inhibitors of Coagulation

“…They found that total and free protein S antigens were in the upper end of the normal range prior to rHu-EPO therapy. This observation remains unexplained, but the high baseline levels of total and free protein S antigens might be neces sary to counterbalance a hypercoagulable state that has been reported in hemodialysis patients [31,32], hence helping to maintain a physiological anticoagulation state. We found a significant decrease in free protein S antigen Effects o f Erythropoietin on Physiologic Inhibitors of Coagulation during the first 6 months of rHu-EPO therapy, an obser vation in contrast with data recently reported by Clyne et al [33], These authors did not observe any change in eith er total or free protein S antigen levels measured by ELISA in patients treated with rHu-EPO.…”

Enhanced Coagulation and Fibrinolysis during Treatment with Recombinant Human Erythropoietin in Patients Undergoing Chronic Hemodialysis

“…Discussion rhEPO has recently been made available for clinical use, and many studies have shown that it can almost fully correct anemia in patients on dialysis treatment [1, 2], How ever, some adverse effects accompanied by treatment with rhEPO, such as headaches, chills, hypertension, and thrombotic events, have been reported [1-4], Hypercoagulability [13,14] and platelet hyperaggregability [15][16][17] have been described in dialysis patients. It has been reported that treatment with rhEPO increases platelet adhesion and shortens bleeding time in uremic patients [5,18].…”