Document Type

Article

Publication Date

4-1-2026

Abstract

Background/Introduction: Heparin intolerance, most notably heparin-induced thrombocytopenia (HIT), presents a major clinical challenge during cardiopulmonary bypass (CPB), where systemic anticoagulation is essential for safe circulation through the extracorporeal circuit. While several alternative anticoagulants have been described, there is limited consensus regarding their safety, dosing, and outcomes. The objective of this study was to map existing evidence describing alternative anticoagulation strategies for heparin-intolerant adult patients undergoing CPB and to summarize reported patient outcomes, dosing strategies, and intraoperative management considerations.

Methodology: This scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Statement. Eligible studies included adult patients who received an alternative anticoagulant to heparin during CPB. Pediatric, ventricular assist device (VAD), and review studies were excluded. Searches were performed on PubMed, CINAHL, and ScienceDirect on October 14, 2025, using Boolean and MeSH-based terms for heparin alternatives and CPB. Grey literature was excluded. Data were charted using a PRISMA-ScR data collection form, including study design, anticoagulant type, dosing, monitoring strategy, and outcomes.

Results: Forty-five studies met inclusion criteria. Most were single-patient case reports or small series. Bivalirudin was most frequently used (25 studies), followed by argatroban (6), recombinant hirudin (5), cangrelor (5), tirofiban (2), and single studies of therapeutic plasma exchange and nafamostat mesilate. Bivalirudin demonstrated reproducible dosing and monitoring practices, though bleeding and coagulopathy remained common. Cangrelor, used with heparin, showed encouraging results with minimal bleeding. Mortality was low across studies, and most complications were related to bleeding rather than thrombosis.

Discussion/Conclusions: Available evidence for heparin alternatives during CPB is limited and predominantly case-based. Bivalirudin remains the best-studied agent with predictable performance, while cangrelor shows promise as an emerging option. Future multicenter, prospective studies are needed to define standardized protocols and clarify comparative efficacy and safety profiles.

Keywords: heparin intolerance, heparin-induced thrombocytopenia, cardiopulmonary bypass, bivalirudin, argatroban, cangrelor, anticoagulation alternatives

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