A systematic review on the accumulation of prophylactic dosages of low-molecular-weight heparins (LMWHs) in patients with renal insufficiency

Ferdows Atiq, Patricia M.L.A. van den Bemt, Frank W.G. Leebeek, Teun van Gelder, Jorie Versmissen

Although therapeutic dosages of most low-molecular-weight heparins (LMWHs) are known to accumulate in patients with renal insufficiency, for the lower prophylactic dosages this has not been clearly proven. Nevertheless, dose reduction is often recommended. We conducted a systematic review to investigate whether prophylactic dosages of LMWH accumulate in renal insufficient patients. A comprehensive search was conducted on 17 February 2015 using Embase, Medline, Web of Science, Scopus, Cochrane, PubMed publisher, and Google scholar. The syntax emphasized for LMWHs, impaired renal function, and pharmacokinetics. The search yielded 674 publications. After exclusion by reading the titles, abstracts, and if necessary the full paper, 11 publications remained. For dalteparin and tinzaparin, no accumulation was observed. Enoxaparin, on the other hand, did lead to accumulation in patients with renal insufficiency, although not in patients undergoing renal replacement therapy. Bemiparin and certoparin also did show accumulation. No data were available for nadroparin. In this systematic review, we show that prophylactic dosages of tinzaparin and dalteparin are likely to be safe in patients with renal insufficiency and do not need dose reduction based on the absence of accumulation. However, prophylactic dosages of enoxaparin, bemiparin, and certoparin did show accumulation in patients with a creatinine clearance (CrCl) below 30 ml/min, and therefore, dose reduction is required. The differences in occurrence of accumulation seem to depend on the mean molecular weight of LMWHs.