Makindo Medical Notes

🧬 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)

🧪 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.