|Protein C Deficiency
|Protein S Deficiency
|Prothrombin 20210A mutation
|Factor V Leiden Deficiency
|Antithrombin III deficiency (AT3)
|Cerebral Venous Sinus thrombosis
- Autosomal dominant loss of Antithrombin leads to a procoagulant state
- 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.
- 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
|Factor V Leiden mutation||3-7%|
|Prothrombin gene mutation||1-2%|
|Protein C deficiency||0.3%|
|Protein S deficiency||0.1%|
- Thrombophilia screen in those under 40 with venous thrombosis
- Factor Xa inhibition assay
- There is no clear evidence of increased arterial disease in antithrombin deficiency.
- 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