Heparin is a highly sulfated glycosaminoglycan which is widely used as an injectable anticoagulant. Heparin binds to antithrombin III causing a conformational change that results in its activation through an increase in the flexibility of its reactive site loop. The activated antithrombin III then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa.
Thus, since heparin requires antithrombin III to function, heparin “resistance” is most commonly the result of inadequate antithrombin III. This can be treated with either fresh frozen plasma or recombinant human antithrombin III.