This study aims to investigate whether the level of antithrombin (AT) in the blood before cardiac surgery can predict how well patients respond to heparin, a medication used to prevent blood clotting during surgery with a heart-lung machine (cardiopulmonary bypass).

Heparin requires antithrombin to work effectively. Some patients have lower levels of antithrombin, which may result in reduced response to heparin, a condition known as heparin resistance. This can lead to difficulties achieving adequate anticoagulation during surgery and may require additional medication or adjustments in treatment.

In this study, an additional blood sample will be taken after anesthesia induction but before the administration of heparin. No changes will be made to the patient's treatment or care. Clinical data, including laboratory values, heparin dosing, and surgical outcomes, will be collected from routine medical records.

The goal is to identify a clinically useful antithrombin threshold that can help detect patients at risk of heparin resistance. This may improve patient safety, optimize treatment strategies, and reduce unnecessary use of antithrombin therapy in the future.

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)

Adult patients undergoing elective or sub-acute cardiac surgery with cardiopulmonary bypass at Sahlgrenska University Hospital, Sweden. Patients are consecutively included to reflect routine clinical practice and minimize selection bias.

De-identified individual participant data underlying the results reported in this study (including demographic, clinical, laboratory, and perioperative variables) will be made available. Data will be stored and managed through DORIS, a secure research data repository at the University of Gothenburg, in accordance with Swedish data protection legislation and the General Data Protection Regulation (GDPR, EU 2016/679).

Access to data will be provided upon reasonable request from qualified researchers, subject to ethical approval and data access agreements. A persistent digital object identifier (DOI) will be assigned to the dataset. Data access will be granted following review and approval of a methodologically sound research proposal, ensuring compliance with applicable legal and ethical requirements.

Data will be available beginning 6 months following publication of the primary results and will remain available for at least 5 years thereafter.

Access to de-identified individual participant data and supporting documentation (study protocol, statistical analysis plan, and analytic code) will be granted to qualified researchers upon reasonable request. Requests must include a methodologically sound research proposal and, where applicable, approval from a relevant ethics committee.

Data will be made available following approval of a data access agreement, in compliance with applicable legal and ethical requirements, including the General Data Protection Regulation (GDPR, EU 2016/679) and Swedish data protection legislation.

Data and analytic code will be accessed through DORIS, a secure research data repository at the University of Gothenburg, and will not be publicly downloadable.