HDCN Article Review/Hyperlink

Martien JFM, Deegens JK, Kapinga TH, Beukhof JR, Huijgens PC, van Loenen AC, van der Meulen J

Citrate compared to low molecular weight heparin anticoagulation in chronic hemodialysis patients

Kidney Int (Mar) 49:806-813 1996

Regional anticoagulation with citrate has been developed for use as an alternative to unfractionated heparin, particularly in patients with a high risk of bleeding. Prolonged use of citrate anticoagulation is complicated by concerns with calcium homeostasis and the development of metabolic alkalosis. Low molecular weight heparins (LMWH) offer advantages over unfractionated heparin with regard to dosing schedules and antithrombotic activity.

This randomized cross-over study tested the hypothesis that anticoagulation with LMWH could provide comparable outcomes to regional anticoagulation citrate in chronic hemodialysis. Citrate anticoagulation was obtained by infusing citrate into the arterial blood line at a concentration of 0.34 mmol/100 ml/min of blood flow (minimum 0.68 mmol/min), using a calcium- and magnesium-free dialysate, and infusing calcium and magnesium into the venous line at a rate dependent on the blood flow rate. LMWH anticoagulation was obtained by administering a single pre-dialysis bolus dose of LMWH (nadroparin calcium) (60 to 80 IU/kg according to hematocrit and treatment length), except for treatments in excess of 5 hours, when 2/3 of the dose was given pre-dialysis and the remaining 1/3 after 2.5 hours of dialysis (7 of 21 patients). LMWHs produced systemic anticoagulation (increases in ACT, APTT, and anti-Xa activity), whereas, citrate did not. The increase in level of systemic anticoagulation with LMWH was greater in patients who were also receiving coumarins (6 of 21 patients). The plasma concentration of prothrombin fragments increased slightly during dialysis with citrate, but was unchanged with LMWH. Changes in serum calcium and magnesium were similar for citrate and LMWH. Also, removal of urea and creatinine was similar in both groups.

Comments: This study does not add greatly to our ability to choose an appropriate anticoagulation regimen for hemodialysis. The authors conclude that citrate is to be preferred in patients with active bleeding or with a high risk of bleeding, while LMWHs provide a simple means of anticoagulation in patients with no bleeding risk. However, their study is not designed to address either of these points. We are told nothing of the bleeding disposition of the patients and there are no measures of bleeding other than the time taken for bleeding to cease at the access site. Further, there was no unfractionated heparin arm to the study to serve as a comparison with use of LMWH in patients without a bleeding tendency.

Nevertheless, LMWHs are an attractive alternative to unfractionated heparin, if for no other reason than they may allow single bolus administration of the drug. Concerning their use in chronic hemodialysis, however, several of questions unanswered. For example, will the low molecular weight of LMWHs lead to their dialytic loss in high-flux dialysis, thereby requiring repeated drug dosing during this increasing popular form of dialysis? For nephrologists in the United States, the issue remains moot, since no LMWH has yet been approved by the FDA for use as an anticoagulant in hemodialysis. (Richard A. Ward, Ph.D., University of Louisville, KY)