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

Abstract

IntroductionThere 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.MethodsWe 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.ResultsIn 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.ConclusionsIn 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.

Enoxaparin versus unfractionated heparin for venous thromboembolism prophylaxis in renally impaired ICU patients

“…Despite the increased bleeding risk with enoxaparin, there was no observed decrease in VTE. Our findings are unique as the majority of our patients experienced AKI, which is in contrast to the current literature that enrolled mostly patients with chronic renal disease 11‐13 . However, this makes our findings less generalizable to other types of renal impairment.…”

“…The study demonstrated less major bleeding with UFH post‐intervention with no difference in the rate of VTE. Conversely, a subgroup analysis of the PROTECT study compared the efficacy and safety of prophylactic LMWH versus UFH in patients with severe or end‐stage renal disease 12 . The subgroup analysis found no difference in major bleeding or thromboembolic events between UFH and LMWH.…”

Thromboprophylaxis in Intensive Care Unit Patients: A Literature Review

“…When dalteparin 5000 IU daily was compared with UFH 5000 IU twice daily in patients with renal insufficiency or end-stage renal disease (ESRD), there was no significant difference in the incidence of VTE or major bleeding. Patients with severe renal dysfunction who were on dalteparin did have a greater incidence of proximal DVTs compared to those on UFH; there was no greater risk of VTE or major bleeding [ 40 ].…”

Venous thromboembolism risk factors and prophylaxis of elderly intensive care unit patients in a Chinese general hospital

“…For patients with high risk of bleeding, graduated compression stockings (GCS) and (or) intermittent pneumatic compression (IPC) were used to prevent thrombosis until the risk of bleeding was reduced, and then chemoprophylaxis should be prescribed or both were used in combination. ICU patients should be evaluated dynamically according to the development of the disease (26). García-Olivares and other researchers discovered that establishing a prophylaxis protocol in the ICU can reduce the incidence of VTE from 11.9% to 4.5% (27,28).…”