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Antithrombin III deficiency
Last reviewed: 05.07.2025
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Antithrombin III is a natural anticoagulant, accounting for 75% of all plasma anticoagulant activity, a glycoprotein with a molecular weight of 58,200 and a plasma content of 125–150 mg/ml. The primary structure of antithrombin III consists of 432 amino acids. It blocks prothrombinase - inactivates factors XIIa, XIa, Xa, IXa, VIIIa, kallikrein and thrombin.
In the presence of heparin, the activity of antithrombin III increases more than 2000 times. Deficiency of antithrombin III is inherited autosomal dominantly. Most carriers of this pathology are heterozygotes, homozygotes die very early from thromboembolic complications.
Currently, up to 80 mutations of the gene located on the long arm of chromosome 1 have been described. The incidence of this pathology varies greatly among different ethnic groups.
[ Causes antithrombin III deficiency
The incidence of hereditary AT III deficiency is relatively rare (1:10,000). [ 9 ] Acquired AT III deficiency is more common. Transmission of AT III deficiency occurs in an autosomal dominant pattern with a variable protective factor. Homozygosity is incompatible with life (death immediately after birth). Thrombosis appears at about the age of twenty years, and in the 4th-5th decades of life, symptoms are observed in 2/3 of patients. Trauma, surgery, estrogen therapy, provoked thrombotic complications. Risk factors are obesity and dyslipidemic syndrome. In these patients, thrombosis affects the venous system. Arterial thromboses are less common. The most common localizations are: veins of the legs, mesenteric veins, cavernous veins, superficial periombilic veins.
Pathogenesis
Antithrombin III (AT III) is a plasma α-glycoprotein formed by a single peptide chain. AT III inhibits thrombin (the primary target) and free plasma factors Xa, IXa, VIIa. In plasma, AT III is found in two forms: α-antithrombin and β-antithrombin. AT III deficiency is a risk factor for thromboembolic diseases. Both quantitative and qualitative deficiencies of AT III are known.
Forms
Hereditary antithrombin III deficiency can be of 2 types:
- Type I - decreased synthesis of antithrombin III as a result of gene mutation;
- Type II - decreased functional activity of antithrombin III with its normal production.
Clinical manifestations of hereditary antithrombin III deficiency:
- deep vein thrombosis of the legs, ileofemoral thrombosis (arterial thrombosis is not typical for this pathology);
- habitual miscarriage;
- antenatal fetal death;
- thrombophilic complications after taking oral contraceptives.
The functional activity of antithrombin III is determined by the ability of a plasma sample to inhibit a known amount of thrombin or factor Xa added to the sample in the presence or absence of heparin.
With low antithrombin III activity, the main coagulation tests are not changed, fibrinolysis tests and bleeding time are normal, platelet aggregation is within normal limits. With heparin therapy, there is no characteristic adequate increase in APTT.
What tests are needed?
Treatment antithrombin III deficiency
Normally, the antithrombin level is 85–110%. During pregnancy, it is slightly reduced and is 75–100%. The lower limit of antithrombin III concentration is variable, so it is necessary to take into account not only the level, but also the clinical situation. However, when the antithrombin III level decreases below 30% of patients die from thrombosis.
The basis of treatment of antithrombin III deficiency is antithrombotic agents. In the presence of thrombophilia symptoms, treatment is necessary, and this is not debated. For these purposes, fresh frozen plasma (as a source of antithrombin III), low molecular weight heparins (enoxaparin sodium, nadroparin calcium, dalteparin sodium) are used.
If the level of antithrombin III is low, sodium heparin is not used, since heparin resistance and heparin-induced thrombosis are possible.
During pregnancy, the drugs of choice are low-molecular heparins, their doses are selected individually under the control of a hemostasiogram. The II and III trimesters of pregnancy are considered critical, when the coagulation potential of the blood increases, and the level of antithrombin III decreases.
Outside of pregnancy, patients may be advised to take vitamin K antagonists (warfarin) long-term.