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ANTICOAGULATION

Low-Molecular-Weight Heparins in Renal Impairment and Obesity: Available Evidence and Clinical Practice Recommendations Across Medical and Surgical Settings

Clinical Associate Professor; Director, Antithrombosis Center, Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago

Sarah A Spinler, PharmD FCCP BCPS (AQ Cardiology)

Professor of Clinical Pharmacy, Department of Pharmacy Practice, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, PA

Ann Wittkowsky, PharmD CACP FASHP FCCP

Clinical Professor of Pharmacy, School of Pharmacy, University of Washington, Seattle, WA

William E Dager, PharmD FCSHP

Pharmacist Specialist, University of California Davis Medical Center, Sacramento, CA

Reprints: Dr. Nutescu, Department of Pharmacy Practice, College of Pharmacy, The University of Illinois at Chicago, 833 S. Wood St., MC 886, Rm. 164, Chicago, IL 60612, fax 312/413 4805, enutescu{at}uic.edu

OBJECTIVE: To develop practical recommendations for the use of low-molecular-weight heparins (LMWHs) as prophylaxis and treatment of venous thromboembolism and acute coronary syndromes in patients with impaired renal function or obesity.

DATA SOURCES: Multiple MEDLINE searches were performed (November 2008) to identify studies for inclusion, using a comprehensive list of search terms including, but not limited to, LMWH, enoxaparin, dalteparin, tinzaparin, obesity, weight, renal, kidney, elderly, monitoring, and anti-Xa.

STUDY SELECTION AND DATA EXTRACTION: Only articles published in English that were relevant for this review were included.

DATA SYNTHESIS: In the majority of patients, standardized prophylaxis or treatment doses of LMWHs can be used without the need for monitoring and adjusting regimens. For patients with severe renal impairment (estimated creatinine clearance [CrCl] <30 mL/min), doses of some LMWHs should be adjusted or unfractionated heparin should be used instead. CrCl should be estimated using the Cockcroft-Gault method. Differences are noted in the degree of accumulation of various LMWHs in patients with moderate-to-severe renal impairment, and thus, the degree of dose adjustment may differ among the various LMWHs. Increasing the prophylactic doses of LMWH may be appropriate in morbidly obese patients (body mass index 40 kg/m²). The use of total body weight is appropriate for therapeutic doses of LMWH in obese patients. Laboratory monitoring of the anticoagulation effect of LMWHs is generally not necessary, but should be considered in patients with morbid obesity (weight >190 kg), those with severe renal impairment, and those with moderate renal impairment with prolonged (>10 days) LMWH use. When anti-Xa activity is monitored, it should be determined using a chromogenic method and a calibration curve based on the LMWH used.

CONCLUSIONS: Additional data are needed for specific dose guiding in obese and renally impaired patients, who are often excluded from larger clinical trials. Practice recommendations are made based on available evidence and authors' clinical opinions.

Key Words: anti-Factor Xa activity, chronic kidney disease, dalteparin, dosing, enoxaparin, low-molecular-weight heparin, monitoring, obesity, practice recommendations, renal impairment, tinzaparin

Published Online, May 19, 2009. www.theannals.com, DOI 10.1345/aph.1L194

THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE UNIVERSAL PROGRAM NUMBER: 407-000-09-008-H01-P