Sunday April 4, 2010
On heparin resistance and antithrombin deficiency

Case: 64 year old male is admitted to ICU with atrial fibrillation associated with RVR (rapid ventricular response). Patient has previous history of stroke. With rate control management patient is started on heparin for anticoagulation purpose. Heparin drip is now at 2400 units/hour but PTT is still not therapeutic, You suspect Anti-Thombin deficiency and indeed its level is low. Unfortunately pharmacist reports to you that there is an Anti-Thrombin shortage and will not be available. What is your other option?


Answer: Heparin principally exerts its anticoagulant effect by activating Antithromin (AT); the heparin-antithrombin (H-AT) complex then inactivates thrombin, activated factor X (fXa) and other activated clotting factors.

Heparin resistance is defined as the need for more than 35 000 Units in 24 h to prolong the activated partial thromboplastin time (APTT) into the therapeutic range. In contrast, during cardiac bypass procedures, the definition of heparin resistance is based on the activated clotting time (ACT), with at least one ACT less than 400 s after heparinization and/or the need for exogenous antithrombin administration. Heparin therapy produces a decrease in circulating antithrombin that is independent of the initial dose, is detectable after 1 day, and peaks after 2–4 days.

In above case your salvage is in use of a direct antithrombin inhibitor like bivalirudin. An important advantage of using bivalirudin instead of heparin is that there is no need to monitor or supplement ATIII levels for therapeutic effect.