Related Subjects: Thrombophilia testing
|Antiphospholipid syndrome
|Protein C Deficiency
|Protein S Deficiency
|Prothrombin 20210A mutation
|Factor V Leiden Deficiency
|Antithrombin III deficiency (AT3)
|Cerebral Venous Sinus thrombosis
|Budd-Chiari syndrome
🧬 Antithrombin Deficiency is an inherited thrombophilia that predisposes to venous thromboembolism.
It is most often inherited in an autosomal dominant manner, and loss of antithrombin’s natural anticoagulant function results in a procoagulant state.
📖 About
- Autosomal dominant loss of Antithrombin leads to increased risk of clot formation (procoagulant state).
⚗️ Aetiology
- Antithrombin is a small glycoprotein produced in the liver.
- It inhibits thrombin (IIa) and other serine proteases including Xa, IXa, XIa.
- Acts as an endogenous anticoagulant.
- Deficiency → unopposed clotting factor activity → hypercoagulable state.
- Inherited in an autosomal dominant fashion – family history of VTE or pulmonary embolism is common.
- Heparin/LMWH act via antithrombin; their effect is greatly reduced in deficiency → “Heparin resistance”.
🩺 Clinical Features
- Marked predisposition to venous thromboembolism.
- Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), Budd-Chiari syndrome.
- Arterial thrombosis is not typical.
- Heparin resistance in treatment due to lack of antithrombin activity.
- Risk further increased in pregnancy.
🔍 Differential Diagnoses (Hereditary Thrombophilias)
| Name | Frequency |
|---|
| Factor V Leiden mutation | 3–7% |
| Prothrombin gene mutation | 1–2% |
| Antithrombin deficiency | ~0.3% |
| Protein C deficiency | 0.3% |
| Protein S deficiency | 0.1% |
🧪 Investigations
- Thrombophilia screen in patients <40 years with unprovoked venous thrombosis.
- Factor Xa inhibition assay – functional test for antithrombin activity.
💊 Management
- No clear association with arterial disease.
- Standard anticoagulation (warfarin or DOACs) is effective for VTE prevention.
- LMWH may be less effective due to heparin resistance – higher doses or alternatives may be required.
- Lifelong anticoagulation may be indicated in recurrent or severe cases.
📝 Notes
- Antithrombin III has been trialled as therapy in critically ill patients.
- Meta-analyses show no survival benefit and increased bleeding risk.
- In nephrotic syndrome, urinary loss of antithrombin is thought to contribute to thrombosis risk, but evidence is limited.
