CASE REPORTS Serious Adverse Incidents With the Usage of Low Molecular Weight Heparins in Patients With Chronic Kidney Disease Vasim Farooq, MBChB, Janet Hegarty, MBChB, Thangavelu Chandrasekar, MD(India), Elizabeth H. Lamerton, BScHons (Pharm), Sandip Mitra, MD, John B. Houghton, FRCP, Philip A. Kalra, FRCP, Stephen Waldek, FRCP, Donal J. O’Donoghue, FRCP, and Grahame N. Wood, MD ● Background: The aim of the study is to describe serious adverse events in patients with renal insufficiency administered low molecular weight heparins (LMWHs). Methods: Systematic case note review from July 2002 to March 2003, Hope Hospital, Salford, UK, was used. Results: Ten patients experienced an adverse incident on LMWH therapy. Five patients were on maintenance hemodialysis therapy, and 1 patient was on continuous ambulatory peritoneal dialysis therapy. Three patients had calculated creatinine clearances of 5, 11, and 33 mL/min (0.08, 0.18, and 0.55 mL/s), and 1 patient had an estimated glomerular filtration rate of 12 mL/min. Age range was 45 to 89 years. Indications for anticoagulation were suspected pulmonary embolism (1 patient), acute coronary syndrome (7 patients), severe nephrotic syndrome (1 patient), and postoperative venous thromboembolic prophylaxis (1 patient). Three patients also were administered aspirin; 1 patient, clopidogrel; and 3 patients, aspirin and clopidogrel. LMWHs used were enoxaparin (6 patients), tinzaparin (3 patients), and dalteparin sodium (1 patient). Bleeding sources were retroperitoneal (1 patient), spontaneous soft tissue (3 patients), gastrointestinal (2 patients), dialysis catheter and cannula sites (2 patients), hemorrhagic pericardial effusion (1 patient), and intracranial (1 patient). Activated partial thromboplastin time was prolonged in 7 of 10 patients, with no other identifiable cause found. Three patients died despite aggressive resuscitation, including packed red blood cell infusions and protamine sulfate administration. Eight of the 10 prescriptions for LMWHs were either started or continued within our directorate, giving an approximate incidence of major hemorrhagic events in patients with chronic kidney disease of 7.8%. Conclusion: LMWHs administered at fixed-weight doses and without monitoring show unpredict- able anticoagulant effects in patients with chronic kidney disease stages 4 and 5, leading to serious and even fatal adverse incidents. Am J Kidney Dis 43:531-537. © 2004 by the National Kidney Foundation, Inc. INDEX WORDS: Chronic kidney disease (CKD); hemorrhage; low molecular weight heparin (LMWH). L OW MOLECULAR weight heparins (LMWHs) are now the antithrombotic drug of choice in venous thromboembolic (VTE) dis- ease and acute coronary syndromes (ACSs), with up to a 20% reduction in clinical events in patients with ACS and/or non–ST-elevation myo- cardial infarction compared with standard unfrac- tionated heparin (UFH) treatment. 1 There have been numerous trials of efficacy and safety com- pared with UFH when administered in fixed weight-dependent doses and without the need for laboratory monitoring. 2,3 However, most clinical trials excluded subjects at most risk for unpredict- able control, such as children, pregnant women, the morbidly obese, the elderly, and those with chronic kidney disease (CKD) stages 4 and 5. Patients with impaired renal function adminis- tered multiple doses of LMWH had greater anti-Xa levels, reduced drug clearances, and pro- longed drug half-lives compared with patients with normal renal function. 4-8 Clear guidelines on dose reduction and/or monitoring for LMWHs administered to patients with CKD stages 4 and 5 have not been published. After an adverse incident involving LMWH in a patient with CKD, we undertook a systematic review of all suspected adverse incidents related to LMWHs at our institution during a 9-month period. INDEX CASE A 57-year-old obese woman with a background of insulin- treated type 2 diabetes, hypertension, atrial fibrillation, and a failing cadaveric renal allograft was admitted for establish- ment on maintenance hemodialysis therapy. She was admin- From the Departments of Renal Medicine; Pharmacy; and Haematology, Hope Hospital, Salford, UK. Received August 4, 2003; accepted in revised form Novem- ber 10, 2003. Address reprint requests to Grahame N. Wood, MD, Department of Renal Medicine, Hope Hospital, Stott Ln, Salford M6 8HD, UK. E-mail: grahame.wood@srht.nhs.uk © 2004 by the National Kidney Foundation, Inc. 0272-6386/04/4303-0015$30.00/0 doi:10.1053/j.ajkd.2003.11.012 American Journal of Kidney Diseases, Vol 43, No 3 (March), 2004: pp 531-537 531