J Extra Corpor Technol 2024 , 56 , 136 – 144 Ó The Author ( s ), published by EDP Sciences , 2024 https :// doi . org / 10.1051 / ject / 2024015
Available online at : ject . edpsciences . org
REVIEW ARTICLE
Heparin resistance management during cardiac surgery : a literature review and future directions
Salman Pervaiz Butt ( MBA , MSc , MPHYS , ACCP , FCCP , CES-A ) 1 ,* , Vivek Kakar 2 , 3 , Arun Kumar ( MD ) 4 , Nabeel Razzaq ( ACP , MSc ) 5 , Yasir Saleem ( MSc ) 6 , Babar Ali 7 , Nuno Raposo ( ECCP ) 5 , Fazil Ashiq ( MD ) 4 , Arshad Ghori ( MD ) 4 , Philip Anderson ( MD ) 4 , Nilesh Srivatav ( MD ) 5 , Yazan Aljabery ( MD ) 5 , Salman Abdulaziz ( MBBS , FRCP ) 8 , Umer Darr ( MD ) 5 , and Gopal Bhatnagar ( MD ) 5
1 Perfusion Services , Heart Vascular and Thoracic Institute , Cleveland Clinic , PO BOX 112412 , Abu Dhabi , United Arab Emirates 2 Critical Care Institute , Cleveland Clinic , PO BOX 112412 , Abu Dhabi , United Arab Emirates 3 Cleveland Clinic Lerner College of Medicine , Western Reserve University , 44195 Ohio , USA 4 Anesthesiology Institute , Cleveland Clinic , PO BOX 112412 , Abu Dhabi , United Arab Emirates 5 Cardiothoracic Surgery Department Heart and Vascular Institute , Cleveland Clinic , PO BOX 112412 , Abu Dhabi , United Arab Emirates 6 All India Institute of Medical Sciences , 110029 New Delhi , India 7 Department of Cardiac Perfusion Technology , Khyber Medical University , 25100 Peshawar , Pakistan 8 ECMO Task Force , Department of Health , PO BOX 5674 , 20224 Abu Dhabi , United Arab Emirates
Received 9 April 2024 , Accepted 18 June 2024
Abstract – Introduction : Heparin , a commonly used anticoagulant in cardiac surgery , binds to antithrombin III ( ATIII ) to prevent clot formation . However , heparin resistance ( HR ) can complicate surgical procedures , leading to increased thromboembolic risks and bleeding complications . Proper diagnosis and management of HR are essential for optimizing surgical outcomes . Methodology : Diagnosis of HR involves assessing activated clotting time ( ACT ) and HR assays . Management strategies were identified through a comprehensive review of the literature , including studies exploring heparin dosage adjustments , antithrombin supplementation , and alternative anticoagulants in cardiac surgery patients with HR . A thorough search of relevant studies on HR was conducted using multiple scholarly databases and relevant keywords , resulting in 59 studies that met the inclusion criteria . Discussion : HR occurs when patients do not respond adequately to heparin therapy , requiring higher doses or alternative anticoagulants . Mechanisms of HR include AT III deficiency , PF4 interference , and accelerated heparin clearance . Diagnosis involves assessing ACT and HR assays . HR in cardiac surgery can lead to thromboembolic events , increased bleeding , prolonged hospital stays , and elevated healthcare costs . Management strategies include adjusting heparin dosage , supplementing antithrombin levels , and considering alternative anticoagulants . Multidisciplinary management of HR involves collaboration among various specialities . Strategies include additional heparin doses , fresh frozen plasma ( FFP ) administration , and antithrombin concentrate supplementation . Emerging alternatives to heparin , such as direct thrombin inhibitors and nafamostat mesilate , are also being explored . Conclusion : Optimizing the management of HR is crucial for improving surgical outcomes and reducing complications in cardiac surgery patients . Multidisciplinary approaches and emerging anticoagulation strategies hold promise for addressing this challenge effectively .
Key words : Anticoagulation , Cardiac surgery , Heparin resistance , Activated clotting time , Anti-thrombin .
Introduction
Antithrombin III ( ATIII ) is a serine protease inhibitor that inhibits thrombin amongst other factors . Heparin is the most negative biological material known and it is because of this strong negative charge that it exerts its therapeutic effect by
* Corresponding author : buttsab9 @ hotmail . com binding and activating ATIII through electrostatic interactions , increasing the ATIII-Thrombin reaction by 1000-fold , inhibiting the coagulation cascade [ 1 , 2 ]. Unfractionated Heparin ( UFH ) is a commonly used medication for preventing blood clot formation during cardiac surgery , and extracorporeal circulation . Heparin binds to several proteins , but it is the binding to ATIII that is important , as this inactivates thrombin . Binding to ATIII blocks several different clotting factors ,
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