Physiologic Inhibitors of Coagulation in Patients on Chronic Hemodialysis

Patients on hemodialysis are at increased risk for bleeding and thromboses. The intriguing balance between these risks is more complex than once thought, as endogenous clotting factors and their regulators come into contact with bioincompatible dialyzer membranes, in the setting of an extracorporeal circuit of blood flow, in the face of the uremic state. In this review, we summarize the current data on the interaction between the physiologic inhibitors of coagulation and hemodialysis. Data sources and study selection were obtained from research and review articles related to the endogenous anticoagulation pathway published in English on MEDLINE from 1972 to 2002. While protein C activity and protein S antigen concentrations are increased, there is no change in antithrombin III levels during hemodialysis in relation to predialysis levels. Plasma protein Z, which has only recently been studied in uremic subjects, is increased as well. In addition, hemodialysis leads to elevated tissue factor plasminogen inhibitor, thrombomodulin, tissue plasminogen activator, and plasminogen activator inhibitor-1 activities. The potential functional significance of these observations is discussed. Finally, as erythropoietin is commonly prescribed to uremic patients and is recognized to be prothrombotic, an appraisal of its interaction with the naturally occurring anticoagulants is presented. It is apparent that we are only beginning to realize the complexity of the interplay between this myriad of serum factors and hemodialysis. Further research is needed to shed light on this underexplored area of hemodialysis.