HEMOSTATIC DISORDER OF UREMIA - THE PLATELET DEFECT, MAIN DETERMINANTOF THE PROLONGED BLEEDING-TIME, IS CORRELATED WITH INDEXES OF ACTIVATION OF COAGULATION AND FIBRINOLYSIS

Several parameters of primary hemostasis and markers of activation of coagulation and fibrinolysis were measured in 38 patients with severe (creatinine clearance <20 ml/min) chronic renal failure (CRF) without dialysis and diseases or drugs affecting hemostasis. Bleeding time (BT ) was prolonged in 25/48 patients, and was correlated with age of pati ents, severity of renal failure, hematocrit, impairment in platelet ag gregation-secretion and decrease in platelet ATP content. Defects in v on Willebrand factor played no role in the prolongation of the BT. Mul tivariate analysis showed that only platelet dysfunction and severity of renal disease were independent predictors of the BT in uremia. The platelet functional disorder was significantly correlated with a reduc tion in platelet ATP and ADP. High levels of plasma thrombin-antithrom bin complexes (TAT), prothrombin fragment F-1+2, fibrinogen and factor VIIc were observed in patients with CRF, as described in prethromboti c states. Plasmin-antiplasmin complexes (PAP), fibrinogen and fibrin d egradation products (FgDP, FnDP) were significantly increased, and the activity of plasminogen activator Inhibitor (PAI-I) was slightly redu ced, denoting an activation of fibrinolysis. A negative correlation wa s found between platelet levels of ATP and ADP with plasma TAT, F-1+2 and PAP. Furthermore, plasma PAI-1 activity was negatively correlated with the BT and was lower in patients with prolonged BT as compared wi th controls and patients with normal BT. These links between primary h emostasis and activation of coagulation and fibrinolysis suggest that increased intravascular generation of thrombin and/or plasmin is an im portant mediator of the defects in primary hemostasis, prolongation of the BT and, probably, bleeding in CRF.