Diagnosis: Heparin resistance
• Heparin acts as a cofactor for antithrombin (AT) and accelerates the ability for AT to inactivate factors such as factors IIa (thrombin), IXa, Xa, and XIa.
• The activated partial thromboplastin time (aPTT) is usually used to monitor unfractionated heparin (UFH) therapy. After a bolus dose and infusion, the aPTT is checked after 6 hours to determine whether the aPTT is in the therapeutic range. Depending on the aPTT, heparin can be adjusted to achieve the target based on being over, under, or at target.
• However, if heparin is administered and the aPTT does not increase, heparin resistance should be considered. Usually, if more than 25,000 to 35,000 IU of heparin is administered in a 24-hour period without achieving the therapeutic target (as measured by aPTT or activated clotting time) constitutes heparin resistance. Anti-Xa activity of the heparin can be determined. If the anti-Xa is elevated out of proportion to the measured aPTT, then heparin resistance should be considered.
• Common causes for heparin resistance are elevated factor VIII activity (acute phase reactant), congenital or acquired antithrombin deficiency, increased heparin clearance, and increased heparin-binding proteins.
• Treatment can consist of switching to an alternate anticoagulant such as argatroban. In addition, administering antithrombin through infusion of plasma or antithrombin concentrates may be useful. Monitoring with anti-Xa activity instead of aPTT may be useful.
