Antithrombin III human

Summary

Antithrombin III human (AT-III) is a plasma-derived or recombinant glycoprotein used to treat hereditary antithrombin deficiency, particularly in settings of high thrombotic risk such as surgery, obstetric procedures, or thromboembolic events. It is the primary physiological inhibitor of coagulation and is approved for prophylaxis and treatment of thromboembolic episodes in AT-III-deficient patients.

Mechanism of Action

Antithrombin III (AT-III) is a natural serine protease inhibitor that irreversibly inactivates thrombin (factor IIa), factor Xa, and other coagulation proteases (IXa, XIa, XIIa) by forming stable 1:1 stoichiometric complexes. Heparin accelerates this inhibition by inducing a conformational change in AT-III that dramatically increases its affinity for target proteases.

Routes of Administration

Goals & Uses

• DIC (disseminated intravascular coagulation) managementOff Label / InvestigationalLow
• Perioperative thromboprophylaxis in AT-III-deficient patientsSurgical Risk ManagementHigh
• Prevention of thromboembolic events in hereditary AT-III deficiencyAnticoagulation / Thrombosis ProphylaxisHigh
• Treatment of acute thromboembolism in hereditary AT-III deficiencyAnticoagulation / Thrombosis TreatmentHigh
• Obstetric thromboprophylaxis in AT-III-deficient patientsObstetric ManagementModerate

Contraindications

• Acquired AT-III deficiency without concurrent heparin resistanceClinical Indication MismatchModerate
• Hypersensitivity to human plasma-derived productsAllergy / ImmunologicHigh
• Hypersensitivity to goat milk or goat milk proteins (ATryn only)Allergy / ImmunologicHigh

Adverse Effects

• Hypersensitivity / anaphylaxisImmunologicalRare
• Dizziness / lightheadednessNeurologicUncommon
• Theoretical viral / prion transmission (plasma-derived only)InfectiousRare
• Chest tightness / dyspneaRespiratory / CardiovascularRare
• BleedingHematologicUncommonAbnormal bleeding or hemorrhage
• Infusion-site reactionsLocal / AdministrationUncommon

Drug Interactions

• Direct oral anticoagulants (rivaroxaban, apixaban, dabigatran)Moderate
• Warfarin / vitamin K antagonistsModerate
• Thrombolytics (alteplase, streptokinase)High
• Heparin (unfractionated or LMWH)High

Population Constraints

• PregnancyReproductive SafetyRelative
• Hepatic impairmentOrgan FunctionRelative
• Patients with known coagulopathy beyond AT-III deficiencyHematologic ComorbidityRelative
• Pediatric patientsAgeRelative

Regulatory Status

• European UnionApprovedApproved: Treatment and prevention of thromboembolic events in adults and children with hereditary antithrombin deficiency, Treatment and prevention of thromboembolic events in neonates with hereditary antithrombin deficiency (selected products)Multiple plasma-derived products approved by EMA; ATryn approved by EMA in 2006 (first approved recombinant product from transgenic animals in EU).
• United StatesApprovedApproved: Prophylaxis and treatment of thromboembolic events in patients with hereditary antithrombin deficiency in connection with surgical or obstetrical procedures or when they suffer from thromboembolism (Thrombate III), Prevention of peri-operative and peri-partum thromboembolic events in hereditary antithrombin deficient patients (ATryn)Thrombate III approved 1991; ATryn approved 2009 as first recombinant human protein from transgenic animals approved by FDA.
• United KingdomApprovedApproved: Treatment and prophylaxis of thromboembolic events in hereditary antithrombin deficiencyRecognized post-Brexit; plasma-derived and recombinant formulations available under MHRA authorization.

FDA-approved (Thrombate III and ATryn). Thrombate III is plasma-derived; ATryn is a recombinant product expressed in transgenic goat milk. EMA has also approved both formulations. Indicated specifically for hereditary antithrombin deficiency; not approved for general anticoagulation.

Evidence & Sources

No sources recorded yet.