Deficiency of antithrombin III: causes, symptoms, diagnosis, treatment

Antithrombin III is a natural anticoagulant that accounts for 75% of all anticoagulant plasma 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.

At present, up to 80 mutations of a gene located on the long arm of chromosome 1 are described. The occurrence of this pathology varies greatly among different ethnic groups.

[1], [2], [3], [4], [5]

Epidemiology

Epidemiology of the deficiency of antithrombin III

In the European population, the incidence of antithrombin III deficiency is 1: 2000-1: 5000. According to some data - 0.3% in the population. Among patients with thromboembolic complications, the incidence of antithrombin III deficiency is 3-8%.

Hereditary deficiency of antithrombin III can be of 2 types:

• I type - a decrease in the synthesis of antithrombin III as a consequence of gene mutation;
• II type - a decrease in the functional activity of antithrombin III in its normal production.

Clinical manifestations of hereditary deficiency of antithrombin III:

• thrombosis of the deep veins of the legs, ileofemoral thrombosis (arterial thrombosis is not characteristic for this pathology);
• habitual miscarriage of pregnancy;
• antenatal fetal death;
• thrombophilic complications after taking oral contraceptives.

The functional activity of antithrombin III is determined from the ability of the plasma sample to inhibit a known amount of thrombin or factor Xa added to the sample in the presence or absence of heparin.

With a low activity of antithrombin III, the main coagulation tests are not changed, tests for fibrinolysis and bleeding time are normal, platelet aggregation is within normal limits. With heparin therapy, there is no characteristic adequate increase in APTT.

[6], [7], [8], [9], [10], [11], [12]

Treatment of the deficiency of antithrombin III

Treatment of a deficiency of antithrombin III

Normally, the level of antithrombin is 85-110%. At pregnancy it is a little lowered and makes 75-100%. The lower limit of the concentration of antithrombin III is variable, therefore it is necessary to take into account not only the level, but also the clinical situation. However, with a decrease in the level of antithrombin III below 30% of patients die from thrombosis.

The basis for treating the deficit of antithrombin III is antithrombotic agents. If there are symptoms of thrombophilia, treatment is necessary, and this is not debated. For these purposes, fresh frozen plasma (as a source of antithrombin III), low molecular weight heparins (sodium enoxaparin, calcium supraparin, dalteparin sodium) are used.

At a low level of antithrombin III, sodium heparin is not used, since heparin resistance and heparin-induced thromboses are possible.

When pregnancy drugs of choice are low molecular weight heparins, their doses are selected individually under the control of the hemostasiogram. Critical recognize the II and III trimesters of pregnancy, when the coagulation potential of blood increases, and the level of antithrombin III decreases.

Beyond pregnancy, patients may be recommended a long-term intake of vitamin K antagonists (warfarin).