Makindo Medical Notes

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

About

• Autosomal dominant loss of Antithrombin leads to a procoagulant state

Aetiology

• Antithrombin is a small glycoprotein molecule that inhibits thrombin and other serine protease produced by the liver
• It acts as an endogenous anticoagulant inactivating clotting factors such as IIa (thrombin), IVa, Xa, Xia
• Loss leads to a procoagulant state
• Deficiency is inherited as an autosomal dominant so a family history may be obtainable of venous thromboembolism and Pulmonary embolism.
• The effect of Antithrombin is greatly enhanced by Heparin and this is one of the ways that Heparin/LMWH work to induce anticoagulation.

Clinical

• Significant predisposition to venous thromboembolism
• Deep vein thrombosis, Pulmonary embolism, Budd-Chiari syndrome
• Arterial thromboses are not typical, Heparin resistance (works through AT)
• Increased thrombotic risk in pregnancy

Differential

Investigations

• Thrombophilia screen in those under 40 with venous thrombosis
• Factor Xa inhibition assay

Management

• There is no clear evidence of increased arterial disease in antithrombin deficiency.

Notes

• Antithrombin III has been used as a therapeutic agent in critically ill patients.
• Recent meta-analysis of the trials has suggested that it does not improve outcomes and only increases the risk of bleeding.
• It is thought that the procoagulant state in nephrotic syndrome may be in part to renal loss of Antithrombin but the evidence for this is poor