Antithrombin III Deficiency (AT III)

Heparin resistance - This is the headline. Heparin has no direct anticoagulant action; it works by activating antithrombin, so with low antithrombin the ACT won't move on standard dosing. Expect it on bypass and on ECMO circuits, where ongoing consumption drops antithrombin further and heparin responsiveness falls with it.

Confirm which type before you plan - Send antithrombin activity and antithrombin antigen. Both low means type I; low activity with near-normal antigen means type II, and in type II the site of the mutation (reactive site vs heparin-binding site) determines how badly heparin will underperform.

Direct thrombin inhibitor as the workaround - Argatroban binds thrombin's active site directly and needs no antithrombin, which is why it is used as an alternative anticoagulant in heparin resistance and for extracorporeal circuit anticoagulation in patients with congenital antithrombin deficiency or low antithrombin concentrations. Reported starting range in the ECMO setting is 0.2 to 0.5 mcg/kg/min — institution-dependent, so confirm against your protocol. Bivalirudin, another direct thrombin inhibitor, has been used successfully in the same circuits.

Don't trust the ACT alone - ACT accuracy shifts with hemodilution, hypothermia, platelet dysfunction, coagulopathy, and the antithrombin level itself. A heparin concentration assay is less sensitive to those swings and is the better number when the ACT and the clinical picture disagree.

Chronic anticoagulation is the norm - Acute thrombosis in these patients is treated with heparin and maintained on an oral anticoagulant, often indefinitely. ⚠ Perioperative hold, bridge, and restart intervals are a volatile guideline call — pull them from your current institutional or ASRA guidance rather than from memory.

Regional anesthesia - The limiter is the anticoagulant on board, not the deficiency itself. ⚠ Verify neuraxial timing against current ASRA guidance for the specific agent and last dose; do not work from a remembered interval.

Keep blood moving - Virchow's triad still governs: stasis behind venous valves plus surgical trauma is what converts a hypercoagulable baseline into a clot. Avoid positions that obstruct venous return, keep the patient euvolemic, and don't let the case run longer than it needs to.

A falling level in sepsis is a severity marker - Antithrombin below 50% to 60% in sepsis tracks with worse outcomes and below 20% correlates with fatal ones, driven by increased plasma turnover and downregulated production. Read a dropping antithrombin as the illness getting worse, not just a lab drifting.

Antithrombin is a liver-synthesized serine protease inhibitor that inactivates thrombin, factor Xa, and factor IXa. It supplies up to 80% of the body's inhibition of thrombin generation, and heparin binding accelerates that reaction up to 1000-fold — which is the whole reason heparin works.

Hereditary deficiency runs about 1 in 2,000 to 1 in 5,000. Type I is a quantitative defect (heterozygotes carry roughly 50% of normal activity); type II is qualitative, with near-normal antigen but a defective reactive site, heparin-binding site, or both. It carries the highest thrombotic risk of the inherited thrombophilias, with first events peaking between ages 15 and 40 and clot appearing in unusual beds such as cerebral and mesenteric veins. Acquired deficiency follows liver failure, cirrhosis, nephrotic syndrome, DIC, sepsis, burns, trauma, and cardiopulmonary bypass.