Optimal protamine‐to‐heparin dosing ratio for the prevention of bleeding complications in patients undergoing TAVR—A multicenter experience

Abstract

Background Despite major advances, transcatheter aortic valve replacement (TAVR) is still associated with procedure‐specific complications. Although previous studies reported lower bleeding rates in patients receiving protamine for heparin reversal, the optimal protamine‐to‐heparin dosing ratio is unknown. Hypothesis The aim of this study was a comparison of two different heparin antagonization regimens for the prevention of bleeding complications after TAVR. Methods The study included 1446 patients undergoing TAVR, of whom 623 received partial and 823 full heparin antagonization. The primary endpoint was a composite of 30‐day mortality, life‐threatening, and major bleeding. Safety endpoints included stroke and myocardial infarction at 30 days. Results Full antagonization of heparin resulted in lower rates of the primary endpoint as compared to partial heparin reversal (5.6% vs. 10.4%, p < .01), which was mainly driven by lower rates of life‐threatening (0.5% vs. 1.6%, p = .05) and major bleeding (3.2% vs. 7.5%, p < .01). Moreover, the incidence of major vascular complications was significantly lower in patients with full heparin reversal (3.5% vs. 7.5%, p < .01). The need for red‐blood‐cell transfusion was lower in patients receiving full as compared to partial heparin antagonization (10.4% vs. 15.9%, p < .01). No differences were observed in the incidence of stroke and myocardial infarction between patients with full and partial heparin reversal (2.2% vs. 2.6%, p = .73 and 0.2% vs. 0.4%, p = .64, respectively). Conclusions Full heparin antagonization resulted in significantly lower rates of life‐threatening and major bleeding after TAVR as compared to partial heparin reversal. The occurrence of stroke and myocardial infarction was low and comparable between both groups.

The contemporary role of protamine in the cardiac catheterization laboratory

“…Some authors have reported protamine dosing based on activated clotting time (ACT); for example, 10 mg protamine for ACT 201-250 s, 20 mg protamine for ACT 251-300 s, and 30 mg protamine for ACT > 300 s. 18 Protamine can also be used to partially reverse the effect of low molecular weight heparin, with dosing 1 mg of protamine per 1 mg of enoxaparin administered within 8 h, and 0.5 of mg protamine per 1 mg of enoxaparin administered within 8-12 h. 16,19 A recent observational study examined protamine dosing after TAVR, comparing partial heparin reversal (protamine-to-heparin ratio 0.4-0.6 mg for every 100 units heparin administered) versus full heparin reversal (protamine-to-heparin ratio 0.9-1.0). 20 Full heparin reversal was associated with significantly lower mortality and major bleeding (5.6% vs. 10.4%, p < 0.01), although these non-randomized results may be affected by different type of vascular closure device use between groups. 20 While these findings suggest that full heparin reversal dosing is safe and effective in the setting of TAVR, the timing of protamine with respect to heparin was not reported and may have impacted the findings.…”

“…Protamine can also be used to partially reverse the effect of low molecular weight heparin, with dosing 1 mg of protamine per 1 mg of enoxaparin administered within 8 h, and 0.5 of mg protamine per 1 mg of enoxaparin administered within 8–12 h 16,19 . A recent observational study examined protamine dosing after TAVR, comparing partial heparin reversal (protamine‐to‐heparin ratio 0.4–0.6 mg for every 100 units heparin administered) versus full heparin reversal (protamine‐to‐heparin ratio 0.9–1.0) 20 . Full heparin reversal was associated with significantly lower mortality and major bleeding (5.6% vs. 10.4%, p < 0.01), although these non‐randomized results may be affected by different type of vascular closure device use between groups 20 .…”

“…A recent observational study examined protamine dosing after TAVR, comparing partial heparin reversal (protamine‐to‐heparin ratio 0.4–0.6 mg for every 100 units heparin administered) versus full heparin reversal (protamine‐to‐heparin ratio 0.9–1.0) 20 . Full heparin reversal was associated with significantly lower mortality and major bleeding (5.6% vs. 10.4%, p < 0.01), although these non‐randomized results may be affected by different type of vascular closure device use between groups 20 . While these findings suggest that full heparin reversal dosing is safe and effective in the setting of TAVR, the timing of protamine with respect to heparin was not reported and may have impacted the findings.…”

“…However, the authors did not use a defined hemostasis protocol, and used a lower protamine dose (median 0.5 mg protamine per 100 U heparin, or 35 mg protamine) 5 . As mentioned previously, based on observational data, optimal dosing for hemostasis after TAVR appears to be full reversal, with 1 mg protamine per 100 U heparin 20 …”

Impact of transradial versus transfemoral access for preprocedural coronary angiography on TAVR-associated complications

“…Transcatheter aortic valve replacement (TAVR) has evolved as an alternative to surgery for the treatment of symptomatic severe aortic stenosis [1] . Since its introduction in 2002, major technical and clinical advances have been achieved, leading to continuous improvement of procedural outcomes [2] , [3] , [4] , [5] , [6] . Nevertheless, TAVR remain to be associated with several procedure-specific complications.…”