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Article Review/Hyperlink
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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)
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