Anticoagulacion En Dialisis

THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS

Anticoagulation for Continuous Renal Replacement Therapy
Ashita J. Tolwani* and Keith M. Wille†
*Division of Nephrology, University of Alabama at Birmingham, and †Division of Pulmonary, Allergy, and Critical Care, University of Alabama at Birmingham, Birmingham, Alabama

ABSTRACT Continuous renal replacement therapy (CRRT) has emerged as thepreferred dialysis modality for critically ill patients with acute kidney injury, particularly those with hemodynamic instability. Anticoagulation is necessary for effective delivery of CRRT, but this requirement can also present challenges, as many critically ill patients with sepsis and inflammation already have a higher risk of bleeding as well as clotting. Without anticoagulation, CRRT filterand circuit survival are diminished, and therapy becomes less helpful. Heparins are presently the most commonly used anticoagulants worldwide for CRRT. They are widely available and can be easily monitored, but disadvantages include risks of hemorrhage, heparin resistance, and heparin-induced thrombocytopenia (HIT). Because of the potential side effects of heparin, alternative methods ofanticoagulation have been investigated, including regional heparin ⁄ protamine, low molecular weight heparins, heparinoids, thrombin antagonists (hirudin and argatroban), regional citrate, and platelet inhibiting agents (prostacyclin and nafamostat). Each of these techniques has unique advantages and disadvantages, and anticoagulation for CRRT should be adapted to the patient’s characteristics andinstitution’s experience. Of the alternative methods, citrate anticoagulation is gaining wider acceptance with the development of simplified and safer protocols.

The primary disadvantage of continuous renal replacement therapy (CRRT) is the need for anticoagulation to prevent clotting of the extracorporeal circuit. Although nonrandomized studies have shown that CRRT without anticoagulation is feasible inpatients with coagulopathy, most patients require some form of anticoagulation. The ideal anticoagulant should provide optimal anti-thrombotic activity with minimal bleeding complications and negligible systemic effects. It should be inexpensive, have a short half-life, and be easily reversed. Moreover, monitoring methods of the anticoagulant effect should be simple and readily available. Theadvantages and disadvantages of various reported methods of systemic and regional anticoagulation for CRRT are reviewed in this manuscript. Unfractionated Heparin Unfractionated heparin (UFH), the most commonly used anticoagulant for CRRT, potentiates antithrombin III by a 1000-fold, resulting in inhibition of factors IIa
Address correspondence to: Ashita J. Tolwani, MD, MSe, ZRB 604, 1530 3rd Ave.S., Birmingham, AL 35294-0007, or e-mail: atolwani@uab.edu. Seminars in Dialysis—Vol 22, No 2 (March–April) 2009 pp. 141–145 DOI: 10.1111/j.1525-139X.2008.00545.x ª 2009 Wiley Periodicals, Inc. 141

(thrombin) and Xa. UFH is made up of heparin molecules of varied sizes (5–30 kDa). The larger fragments have predominantly anti-IIa activity and are cleared more rapidly than the smaller fragments.Anti-IIa activity is measured by the activated partial thromoboplastin time (APTT). The smaller fragments principally inhibit Xa and may result in an anticoagulant effect in the setting of a normal APTT because of its delayed clearance (1–3). UFH metabolites are eliminated by the kidneys. Plasma half-life is approximately 90 minutes but can increase up to 3 hours in the presence of renalinsufficiency. The advantages of UFH are that it is inexpensive, widely available and familiar to physicians, easy to administer, simple to monitor, and reversible with protamine. Disadvantages include the unpredictable and complex pharmacokinetics of UFH (resulting in dosing variability), the development of heparin-induced thrombocytopenia (HIT), heparin resistance because of low patient antithrombin...