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An HD patient discusses discovering, learning about,
and living with hereditary antithrombin deficiency.
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Disease Profile

Patients with HD have a significantly increased risk of venous thrombosis and pulmonary embolism.   Characteristic features of HD are venous thromboembolic events presenting at an early age, an absence of predisposing factors, a strong family history, frequent recurrence of thrombosis, and unusual (for example cerebral or mesenteric veins) or widespread location of thrombi.

The most common sites for thrombosis are the deep and superficial veins of the leg, as well as the iliac and femoral veins.  Other commonly encountered sites of thrombosis include the pelvic veins, inferior vena cava, mesenteric vessels, hepatic, portal, renal, axillary, brachial, cerebral and retinal veins.

The majority of patients with HD Type I experience at least one thrombotic episode between 10 and 35 years of age, usually triggered by high risk situations such as surgery, delivery, pregnancy, trauma or severe infection.  Thrombotic events in HD patients are uncommon prior to puberty but increase after age 14, particularly during periods of high risk, such as pregnancy, surgery, or pro-longed bed rest.   Asymptomatic HD patients do not require anticoagulant prophylaxis, except in settings of increased risk.   However, HD individuals with a history of thrombosis may require prophylaxis, even outside of high-risk settings.

Oral anticoagulants are highly effective in the management of HD. Warfarin is often administered indefinitely in patients with recurrent venous thrombosis.  Asymptomatic HD individuals from a family with a history of thrombophilia are not generally anticoagulated prophylactically unless they are exposed to situations that predispose them to developing thrombosis (pregnancy, surgery, prolonged immobilization).

Currently, plasma derived human AT concentrates are used for the prevention of thromboembolic complications in patients with HD who are undergoing a high-risk event such as surgery or delivery.   Human plasma-derived AT has been approved for these indications for more than 10 years in the United States and in several European countries.

Surgery is a risk because it typically causes a decrease in AT levels, with greater decreases occurring in procedures associated with more extensive tissue damage and hemorrhage.  Accordingly, antithrombotic prophylaxis is commonly used perioperatively, particularly in patients with known HD deficiency.

Pregnancy is also a risk factor because it can produce a physiologic increase in coagulation factors, and a decrease in fibrinolytic activity.  Pregnant women with Type 1 HD have an exceedingly high risk of thrombosis both during pregnancy and after delivery.  Published literature indicates that the incidence of thrombosis in this genetic subtype can range from 37% to 70%.  Therefore, pregnant women with HD are often given anticoagulant prophylaxis including administration of AT.

Warfarin is usually avoided during the first 3 months of pregnancy due to teratogenic potential, and during the last week of pregnancy due to bleeding risk for the fetus.  Heparin is often the anticoagulant of choice, as it does not cross the placenta. However, when heparin is used in AT deficient patients, heparin resistance may occur.  This may be managed by using high doses of heparin or by supplementing heparin administration with AT concentrates.

What assays are used to measure AT levels and diagnose the disease?

Divider Imagery

References

Bauer, K. A. (1995) Natural anticoagulants and the prethrombotic state
In Blood: Principles and Practice of Hematology, edited by R. I. Hardin,
S. E. Lux, T. P. Stossel; J. P. Lippincott Company, Phildadelphia.
Pp 1319-1339.

Conard, J., Horellou, M. H., van Dreden, P. Lecompte, T. Samama,
M. (1990) Thrombosis and pregnancy in congenital deficiencies in AT III, protein C or
protein S: study of 78 women. Thromb Haemost 63:319-320.

De Stefano, V., Leone, G., Mastrangelo, S., Tripod, A., Rodeghiero,
F., Castaman, G., Barbui, T., Finazzi, G., Bizzi, B., Manucci, P. M. (1994) Thrombosis
during pregnancy and surgery in patients with congenital deficiency of antithrombin III,
protein C, protein S. Thromb Haemost 71:799-800.

Hellgren, M., Tengborn L., Abildgaard, U. (1982). Pregnancy in women with congenital
antithrombin III deficiency: experience of treatment with heparin and antithrombin.
Gynecol Obstect Invest. 14:127-141.

Pabinger, I., Schneider, B. (1996). Thrombotic risk in hereditary antithrombin III,
protein C, or protein S deficiency. A cooperative, retrospective study. Gesellschaft
fur Thrombose- und Hamostaseforschung (GTH) Study Group on Natural Inhibitors. 16:742-748.

van Boven, H.H., and Lane, D. A. (1997) Antithrombin and its inherited deficiency states.
Seminars in Hematology 34:188-204.