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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое No intervention (observational study)
  This is a prospective observational study. No intervention is assigned as part of the study protocol. All patients receive standard clinical care. A preoperative blood sample is collected for measurement of antithrombin levels, and clinical data are recorded to assess the relationship between antithrombin levels and heparin resistance without influencing treatment.

Первичные конечные точки

• Heparin resistance [Срок оценки: Intraoperative (immediately after initial heparin administration)]

Вторичные конечные точки (3)

• Activated clotting time after initial heparin dose [Срок оценки: Intraoperative (after initial heparin administration)]
• Total heparin dose [Срок оценки: Intraoperative]
• Antithrombin supplementation [Срок оценки: Intraoperative]

Критерии участия

Критерии включения

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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Швеция · 1 центр

• Sahlgrenska University Hospital — Gothenburg

Публикации

• Chen Y, Phoon PHY, Hwang NC. Heparin Resistance During Cardiopulmonary Bypass in Adult Cardiac Surgery. J Cardiothorac Vasc Anesth. 2022 Nov;36(11):4150-4160. doi: 10.1053/j.jvca.2022.06.021. Epub 2022 Jun 24. PMID 35927191
• Levy JH, Sniecinski RM, Maier CL, Despotis GJ, Ghadimi K, Helms J, Ranucci M, Steiner ME, Tanaka KA, Connors JM. Finding a common definition of heparin resistance in adult cardiac surgery: communication from the ISTH SSC subcommittee on perioperative and critical care thrombosis and hemostasis. J Thromb Haemost. 2024 Apr;22(4):1249-1257. doi: 10.1016/j.jtha.2024.01.001. Epub 2024 Jan 11. PMID 38215912
• Rivera Jimenez KE, Mamani Ticona YM, Gutierrez-Chavez G, Astudillo CO, Calle E, Heredia GAT, Lopez Delgado DS, Rivera-Lozada O, Barboza JJ. Heparin Resistance in Cardiac Surgery with Cardiopulmonary Bypass: Mechanisms, Clinical Implications, and Evidence-Based Management. Medicina (Kaunas). 2025 Nov 23;61(12):2088. doi: 10.3390/medicina61122088. PMID 41470090

Идентификаторы

NCT: NCT07549568 · ANTITHROMBIN-HLM-2026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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