Antithrombin as a Predictor of Heparin Resistance in Cardiac Surgery With Cardiopulmonary Bypass

This prospective observational cohort study aims to evaluate whether preoperative antithrombin (AT) levels can predict heparin resistance in adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) at Sahlgrenska University Hospital, Sweden.

Heparin is routinely administered during CPB to prevent thrombus formation in the extracorporeal circuit. Its anticoagulant effect depends on the presence of antithrombin, a key endogenous inhibitor of coagulation. Reduced levels of antithrombin are known to impair the anticoagulant response to heparin and may result in heparin resistance. Clinically, this can lead to repeated heparin dosing, delays in achieving adequate anticoagulation, and increased use of antithrombin supplementation. However, there is currently no well-established threshold for antithrombin levels that can reliably identify patients at risk prior to heparin administration.

The study is designed as a non-interventional investigation in which all patients are managed according to standard clinical practice. A single additional blood sample for measurement of antithrombin will be obtained after induction of anesthesia and prior to administration of heparin. This timing is chosen to ensure standardized conditions and to minimize the influence of hemodilution and perioperative physiological changes.

Clinical and perioperative data will be collected from routine medical records, including anesthesia records, perfusion protocols, and laboratory systems. These data will be used to assess the relationship between preoperative antithrombin levels and the anticoagulant response to heparin during CPB, as well as associated perioperative outcomes.

The primary objective is to determine whether antithrombin levels can serve as a clinically useful predictor of heparin resistance. The analysis will focus on evaluating the discriminative ability of antithrombin and identifying a threshold value that may be useful for clinical decision-making. Secondary analyses will explore the association between antithrombin levels, heparin dosing requirements, and perioperative outcomes.

As an observational study, no changes are made to patient management. The study is expected to provide clinically relevant information that may support more individualized anticoagulation strategies and reduce unnecessary use of antithrombin supplementation in the future.

Inclusion criteria

• Age ≥18 years
• Planned cardiac surgery with cardiopulmonary bypass
• Ability to provide informed consent

Exclusion criteria

• Emergency cardiac surgery
• Ongoing antithrombin supplementation prior to surgery
• Known severe congenital coagulation disorder affecting interpretation of outcomes
• Severe liver failure
• Missing key data required to define heparin resistance (e.g., missing heparin dose or ACT values)