Because antithrombin inhibits thrombin and factors Xa, IXa, and XIa, deficiency of antithrombin predisposes to venous thrombosis.
(See also Overview of Thrombotic Disorders.)
Antithrombin is a plasma protein that inhibits thrombin and factors Xa, IXa, and XIa, thereby inhibiting thrombosis.
Heterozygous deficiency of antithrombin has a prevalence of about 0.02 to 0.2% (1); about half of people affected develop venous thromboses. Homozygous deficiency is probably lethal to the fetus in utero.
Acquired deficiencies occur in patients with disseminated intravascular coagulation, liver disease, or nephrotic syndromeHeparin exerts its anticoagulant effect by activating antithrombin.
General reference
1. Pabinger I, Thaler J. How I treat patients with hereditary antithrombin deficiency. Blood 2019;134(26):2346-2353. doi:10.1182/blood.2019002927
Diagnosis of Antithrombin Deficiency
Laboratory testing is done for patients with an unexplained blood clot and involves quantification of the capacity of patient plasma to inhibit thrombin in the presence of heparin. Heparin normally inhibits coagulation by accelerating inactivation of thrombin by antithrombin. In patients with antithrombin deficiency, inactivation of thrombin is reduced. The residual thrombin in the test mixture is inversely proportional to the functional antithrombin concentration in the patient's plasma. Antithrombin protein levels also can be measured with immunologic assays, but these tests only measure the amount of antithrombin protein in the sample and cannot assess the function of this protein. Since rare patients with antithrombin deficiency express dysfunctional antithrombin proteins, activity assays are favored over antigen assays for the diagnosis of antithrombin deficiency.
Treatment of Antithrombin Deficiency
Anticoagulation
1, 2).
Treatment references
1. Campello E, Spiezia L, Simion C, et al. Direct Oral Anticoagulants in Patients With Inherited Thrombophilia and Venous Thromboembolism: A Prospective Cohort Study. J Am Heart Assoc 2020;9(23):e018917. doi:10.1161/JAHA.120.018917
2. Pabinger I, Thaler J. How I treat patients with hereditary antithrombin deficiency. Blood 2019;134(26):2346-2353. doi:10.1182/blood.2019002927
