Citrate Anticoagulation in Hemodialysis

In hemodialysis, the patient’s blood is flown through an extracorporeal circuit containing a hemodialyzer. This process stimulates coagulation for several reasons, most notably the blood’s contact with the artificial surfaces of the tubing and dialyzer membrane and with air in the venous bubble trap, turbulent and stagnant blood flow, shear stress and hemoconcentration during the treatment [1]. Technological advances, e.g., the development of air-free blood circuits and more biocompatible materials for both tubing and dialyzer membranes, may eventually help reduce thrombogenicity of the extracorporeal circuit but are unlikely to eliminate this problem anytime soon. As a result, anticoagulation is (and will be, for the years to come) generally required for hemodialysis in the vast majority of patients. In most cases in the United States, unfractionated heparin is the agent of choice to provide dialysis anticoagulation. While this is usually well-tolerated and relatively safe, there are significant drawbacks. The most obvious of these is that the anticoagulation is systemic in nature, which translates into an increased bleeding risk. This is certainly undesirable in endstage renal disease patients, who are already afflicted with uremic thrombocytopathy, and it is particularly dangerous for patients with additionally increased bleeding risk, e.g., patients after surgery or trauma, and patients with active (e.g., gastro-intestinal) bleeding. Another possible complication related to heparin use, albeit rare in dialysis patients, is heparininduced thrombocytopenia (HIT) type II [2], a potentially life-threatening condition associated with a mortality rate of 8 to 20 percent. Other possible side-effects of heparin use include osteoporosis, hair loss, and hyperlipidemia. Starting in late 2007, a series of severe anaphylactoid reactions had caused serious injuries and deaths. These reactions were later linked to heparin contaminated with oversulfated chondroitin sulfate [3, 4]. Several alternatives to heparin anticoagulation are potentially available, each of them accompanied by specific disadvantages. Intermittent saline flushes, i.e., flushing of the extracorporeal circuit with 25 to 50 mL of 0.9% sodium chloride solution every 15 to 30 minutes, is often used during acute dialysis in patients with increased bleeding risk or in patients with HIT type II. Since the procedure, surprisingly, is not automated, it is very laborious. Furthermore, its capacity to prevent clotting is rather limited, with partial clotting occurring in approximately 20 percent, and complete clotting of the extracorporeal circuit in about 7 percent of treatments [1]. Clotting of the extracorporeal system, of course, is associated with blood loss to the patient, and even with partial clotting, solute clearances will be impaired. Other agents used for systemic anticoagulation in hemodialysis are fondaparinux, danaparoid, and direct thrombin inhibitors. These have other downsides,