| Antithrombin III (Human); THROMBATE III®; Bayer Corp., Pharmaceutical Div. |
| Supplied: 500 IU & 1000 IU |
Clinical Pharmacology Antithrombin III (AT-III) |
| Antithrombin III is an alpha2-glycoprotein of MW 58000, and is normally present in the human plasma at a concentration of approx. 12.5 mg/dl. It is the major inhibitor of thrombin. Inactivation of thrombin by AT-III occurs by formation of a covalent bond resulting in an inactive 1:1 stoichiometric complex between the two. AT-III is also capable of inactivating other components of the coagulation cascade including factors IXa, Xa, XIa, and XIIa, as well as plasmin. The neutralization rate of serine proteases by AT-III is greately accelerated by the presence of heparin. |
AT-III Deficiency |
| The prevalence of the hereditary deficiency of AT-III is estimated to be one per 2000 to 5000 in the general population. The pattern of inheritance is autosomal dominant. In affected individuals, spontaneous episodes of thrombosis and pulmonary embolism may be associated with AT-III levels of 40%-60% of normal. The episodes usually appear after the age of 20, the risk increasing with age and in association with surgery, pregnancy and delivery. The frequency of thromboembolic events in hereditary AT-III deficiency during pregnancy has been reported to be 70%. Several studies of the beneficial use of (human) AT-III concentrates during pregnancy in women with hereditary deficiency have been reported. Greater than 85% of individuals with hereditary AT-III deficiency have had at least one thrombotic episode by the age of 50 years. 60% of patients show recurrent thrombosis. Clinical signs of pulmonary embolic events occur in 40% of affected individuals. |
| Indications and Usage |
| Antithrombin III is indicated for the
treatemtn of patients with hereditary AT-III deficiency
in connection with surgical or obstetrical procedures or
when they suffer from thromboembolism. The diagnosis of
AT-III hereditary deficiency should be based on a clear
family history of venous thrombosis as well as decreased
plasma AT-III levels, and the exclusion of acquired
deficiency. AT-III in plasma may be measured by amidolytic assays, clotting assays, or by immunoassays. The latter does not detect all hereditary AT-III deficiencies. AT-III levels in neonates of parents with hereditary AT-III deficiency should be measured immediately after birth. (Fatal neonatal thromboembolism, such as arotic thrombi in children of women with hereditary antithrombin III deficiency, has been reported.) |
Contraindications: NONE |
Dosage and Administration |
| Functional Activity is stated in
International Units (IU), potentcy is calibrated against
a WHO antithrombin III reference preparation. Dosage should be determined on an individual basis based on the pre-therapy plasma AT-III level, in order to increase plasma AT-III levels to the level found in normal plasma (100%). It can be calculated using this formula: units required (IU) = [(desired - baseline AT-III level in %)][weight in kg] / 1.4 The above formula is based on an espected incremental invivo recovery above baseline levels for AT-III of 1.4% per IU per kg administered. Thus, if a 70 kg individual has a baselin AT-III level of 57%, in order to increase AT-III to 120%, the initial AT-III dose would be [(120-57)] [70] / 1.4 = 3150 IU total. |