Antithrombin III deficiency (abbreviated ATIII deficiency) is a deficiency of

antithrombin III Antithrombin (AT) is a small glycoprotein that inactivates several enzymes of the coagulation system. It is a 432-amino-acid protein produced by the liver. It contains three disulfide bonds and a total of four possible glycosylation sites. α-Ant ...

. This deficiency may be inherited or acquired. It is a rare

hereditary disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

that generally comes to light when a patient suffers recurrent venous

thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (th ...

and

pulmonary embolism Pulmonary embolism (PE) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream ( embolism). Symptoms of a PE may include shortness of breath, chest pain particularly upon breathin ...

, and repetitive intrauterine fetal death (IUFD). Hereditary antithrombin deficiency results in a state of increased coagulation which may lead to

venous thrombosis Venous thrombosis is blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off (embolizes) and flows to the lungs t ...

. Inheritance is usually

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosom ...

dominant, though a few

recessive In genetics, dominance is the phenomenon of one variant ( allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant an ...

cases have been noted. The disorder was first described by Egeberg in 1965. The causes of acquired antithrombin deficiency are easier to find than the hereditary deficiency. The prevalence of antithrombin deficiency is estimated at ~0.02 to 0.2% of the general population, and 1-5% of patients with venous thromboembolism. There is an elevated risk of thrombosis, whereby 50% patients with AT deficiency were found to have venous thromboembolism by age 50.

Cause

Diagnosis

A clinical suspicion for antithrombin deficiency can be made in patients with: 1. recurrent venous thromboembolic disease, 2. childhood thrombosis, 3. thrombosis in pregnancy. Testing for antithrombin activity can confirm deficiency if the levels are less than 70%. Deficiency can result from genetic predisposition or from acquired causes such as: acute thrombosis, disseminated intravascular coagulopathy, liver disease, nephrotic syndrome, asparaginase deficiency, oral contraception/estrogens. Genetic testing for abnormalities of the ''SERPINC1'' gene can be done to evaluate further.

Management

In patients with antithrombin deficiency, they may develop resistance to unfractionated heparin, especially with continuous infusions. If large quantities of unfractionated heparin are required e.g. greater than 35000 units per day, this would point towards resistance. Antithrombin concentrates have been used, though with risk of bleeding at large doses of unfractionated heparin. Low molecular weight heparin at full weight based dosing is effective; however, measurements of peak anti-Xa levels may not reflect anticoagulant effect. Vitamin K antagonists, and direct oral anticoagulants, including anti-Xa inhibitors and thrombin inhibitors have also been used, though data is limited.

References

External links

{{Disorders of globin and globulin proteins Serpinopathies Rare diseases Coagulopathies

Cause

Diagnosis

Management

See also

References

External links