Platelet dysfunction in Uremia

Abstract

Bleeding diathesis and thrombotic tendencies are characteristic findings in patients with end-stage renal disease. The pathogenesis of uremic bleeding tendency is related to multiple dysfunctions of the platelets. The platelet numbers may be reduced slightly, while platelet turnover is increased. The reduced adhesion of platelets to the vascular subendothelial wall is due to reduction of GPIb and altered conformational changes of GPIIb/IIIa receptors. Alterations of platelet adhesion and aggregation are caused by uremic toxins, increased platelet production of NO, PGI(2), calcium and cAMP as well as renal anemia. Correction of uremic bleeding is caused by treatment of renal anemia with recombinant human erythropoietin or darbepoetin alpha, adequate dialysis, desmopressin, cryoprecipitate, tranexamic acid, or conjugated estrogens. Thrombotic complications in uremia are caused by increased platelet aggregation and hypercoagulability. Erythrocyte-platelet-aggregates, leukocyte-platelet-aggregates and platelet microparticles are found in higher percentage in uremic patients as compared to healthy individuals. The increased expression of platelet phosphatidylserine initiates phagocytosis and coagulation. Therapy with antiplatelet drugs does not reduce vascular access thrombosis but increases bleeding complications in endstage renal disease patients. Heparin-induced thrombocytopenia (HIT type II) may develop in 0-12 % of hemodialysis patients. HIT antibody positive uremic patients mostly develop only mild thrombocytopenia and only very few thrombotic complications. Substitution of heparin by hirudin, danaparoid or regional citrate anticoagulation should be decided based on each single case.