The term heparin resistance is likely best defined as the failure of an appropriate dose of unfractionated heparin (UFH) to achieve a predetermined level of anticoagulation. Unfortunately, and despite many prior reports, there is no established consensus as to what either the appropriate dose or the predetermined level should be. Traditionally, assays used to monitor anticoagulation with UFH have been clot based, including the activated partial thromboplastin time, used for patients on the ward or intensive care unit, and the activated clotting time, used for patients undergoing vascular interventions and cardiopulmonary bypass. Unfortunately, these tests may be highly influenced by other factors occurring in many patients, especially those with inflammation or acute infection, as noted during the COVID-19 pandemic. Many hospitals have thus moved to anti-Xa testing for heparin monitoring. Another important factor in defining heparin resistance includes dosing, whether weight-based or total daily dosing is used, as initial reports of heparin resistance described daily doses independent of body weight. Multiple causes of apparent heparin resistance include hypercoagulability, antithrombin deficiency, andexanet alfa used for direct oral anticoagulant reversal, thrombocytosis, and antiphospholipid antibody syndromes. Treatment options for managing patients with heparin resistance include weight-based dosing and administration of additional UFH, antithrombin supplementation, or the use of an alternative anticoagulant such as the direct thrombin inhibitors bivalirudin or argatroban.
