Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction: A subgroup analysis of the PROTECT trial

Menaka Pai, Neill K.J. Adhikari, Marlies Ostermann, Diane Heels-Ansdell, James D. Douketis, Yoanna Skrobik, Ismael Qushmaq, Maureen Meade, Gordon Guyatt, William Geerts, Michael W. Walsh, Mark A. Crowther, Jan O. Friedrich, Lisa Burry, Rinaldo Bellomo, Nilton Brandão da Silva, Rubens Costa Filho, Michael J. Cox, Suzana Alves Silva, Deborah J. Cookon behalf of the PROTECT (Prophylaxis for Thromboembolism in Critical Care Trial) Investigators

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Introduction There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial. Methods We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance [CrCl] <30 ml/min; post hoc subgroup; n = 590). We compared dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios [HR] were calculated using Cox regression.

Results In patients with ESRD, there was no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and dalteparin. In patients with severe renal dysfunction, there was no significant difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were non-significant. Conclusions In critically ill patients with ESRD, or severe renal dysfunction, there was no significant difference in any VTE or major bleeding between UFH and dalteparin. Patients with severe renal dysfunction who received dalteparin had more proximal DVTs than those on UFH; this finding did not hold in patients with ESRD alone.

Original languageEnglish
Article numbere0198285
Number of pages15
JournalPLoS ONE
Issue number6
Publication statusPublished - 1 Jun 2018

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