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

Abstract

PurposeAlthough 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.MethodsA 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.ResultsFor 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.ConclusionsIn 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-015-1880-5) contains supplementary material, which is available to authorized users.

The effect of bemiparin on neointimal hyperplasia and endothelial cell proliferation in a rabbit carotid artery model

“…In addition, LMWHs are successful in the prevention and treatment of thromboembolism. [6,[13][14][15][16][17][18][19][20][21][22][23][24][25] They are more effective than UFH in venous thromboembolism (VTE) and non-Q wave myocardial infarction. Routine heparin therapy in this setting is still under debate.…”

“…[16][17][18][19][20][21] Da Pozzo et al [3] reported that bemiparin provided a significant decrease, as shown by the reduction of endothelial cell tubule network, while both fondaparinux and UFH did not show any significant effect on in vitro angiogenesis. One major finding of this study is that bemiparin was the only drug to show inhibited angiogenesis in vitro experiments.…”

“…[4,5] It is effective as warfarin in VTE cases for three months and replaces in many cases oral antiocoagulants in clinical practice. [4][5][6] In another study, Ferdows et al [21] suggested dose reduction for prophylactic use of enoxaparin, bemiparin, and certoparin in patients with a creatinine clearance value below 30 mL/min. In addition, they suggested that prophylactic doses of tinzaparin and dalteparin were likely to be safe in patients with renal insufficiency and these patients do not need dose reduction.…”

“…In previous studies, LMWHs with the lowest molecular weight (enoxaparin, bemiparin, certoparin, and nadroparin) all showed accumulation in a therapeutic and prophylactic dose. [17][18][19][20][21] In addition, Da Pozzo et al [3] reported that each LMWH was a pleiotropic biological agent with its own chemical, biochemical, biophysical, and biological characteristics, displaying a unique pharmacodynamic and pharmacokinetic profile. According to this study, the safety and efficacy of bemiparin, endowed of the highest anti-FXa/anti-FIIa activity ratio of any second-generation LMWH, were demonstrated.…”

Perioperative Prophylaxis of Venous Thromboembolism in Routine Oncosurgery

“…Применение далтепарина натрия не сопровождается биоаккумуляцией и не требует коррекции профилактиче-ской дозы [18,19].…”