Hereditary antithrombin deficiency, also known as antithrombin III deficiency or AT III deficiency, is a disorder in which individuals are at increased risk for developing blood clots.
What are the risks of antithrombin deficiency?
People with antithrombin deficiency are at risk of developing a blood clot (thrombus) within a vein (thrombosis). The first episode of thrombosis typically occurs before the age of 40 years.
What does a low level of antithrombin mean?
A low blood level of antithrombin suggests that the patient may have antithrombin deficiency. However, it is important to keep in mind that many conditions can lower antithrombin levels (acute clots, heparin therapy, liver or kidney disease, etc.) without the patient having inherited antithrombin deficiency.
What is antithrombin III deficiency (ATIII deficiency)?
Antithrombin III deficiency (abbreviated ATIII deficiency) is a deficiency of antithrombin III. This deficiency may be inherited or acquired. It is a rare hereditary disorder that generally comes to light when a patient suffers recurrent venous thrombosis and pulmonary embolism, and repetitive intrauterine fetal death (IUFD).
What is the difference between congenital and acquired antithrombin deficiency?
The acquired form of antithrombin deficiency is more prevalent than the congenital form of the disorder. A low blood level of antithrombin suggests that the patient may have antithrombin deficiency.
How many people have antithrombin deficiency?
Type I antithrombin deficiency is the most common subtype and is thought to occur in about one in every 3,000 to 5,000 people in the United States and is not limited to any particular ethnic group. It is estimated that approximately 1 percent ...
Why is antithrombin not advisable?
Antithrombin concentrates are also used to prevent venous clots when blood thinners (such as heparin) are not advisable because they may lead to an increased risk of bleeding. This is especially true for neuro-surgery and in severe trauma or at the time of delivery.
What is the name of the disease that pulls blood away from the wall of a vein in the legs?
About 40 percent of people with antithrombin de ficiency develop a thrombus that pulls away from the wall of a vein in the legs or pelvis (deep vein thrombosis or DVT) and travels through the blood stream to the lungs (pulmonary embolism or PE). Pulmonary emboli are dangerous and hence DVT and PE must be treated quickly.
What is the risk of a blood clot in the leg?
People with antithrombin deficiency are at risk of developing a blood clot (thrombus) within a vein (thrombosis). The first episode of thrombosis typically occurs before the age of 40 years. A thrombus is a clump of blood cells (i.e., platelets, clotting factors, fibrin, etc.) that may become attached (adhere) to the interior wall of a blood vessel, usually a deep vein in the leg. This may be brought on by surgery, pregnancy, childbirth, trauma, or use of oral contraceptives. About 40 percent of people with antithrombin deficiency develop a thrombus that pulls away from the wall of a vein in the legs or pelvis (deep vein thrombosis or DVT) and travels through the blood stream to the lungs (pulmonary embolism or PE). Pulmonary emboli are dangerous and hence DVT and PE must be treated quickly. Thrombi also occur the superficial veins in the legs (superficial thrombophlebitis). Thrombi may also occur in the veins in the abdomen (mesenteric, portal, hepatic or splenic veins) or around the brain (sinus veins). Clots in the arteries of the heart may lead to heart attack (myocardial infarction) and clots in the arteries of the brain to stroke. However, arterial clots are rare in antithrombin deficiency.
What is the inherited tendency to clots in the veins?
An inherited tendency to thrombosis is known as thrombophilia . Antithrombin is a substance in the blood that limits the blood’s ability to clot (coagulation) and the primary inhibitor of thrombin, which is required for the development of blood clots; it also is the primary inhibitor of two clotting factors, factor Xa and factor IXa, that are required for the generation of thrombin. In people with congenital antithrombin deficiency, there is a reduced amount of this substance in the blood due to a genetic abnormality. Antithrombin deficiency may also be acquired; in such cases, the disorder may be reversible with resoluton/improvement in the disease process responsible for the deficiency.
What is acquired AT deficiency?
Acquired AT deficiency is the consequence of some other disorder, usually involving the liver, kidneys, or treatment of certain types of blood disorders, e.g., leukemias with a drug called L-asparaginase.
Can antithrombin be acquired?
In people with congenital antithrombin deficiency, there is a reduced amount of this substance in the blood due to a genetic abnormality. Antithrombin deficiency may also be acquired; in such cases, the disorder may be reversible with resoluton/improvement in the disease process responsible for the deficiency.
What is Antithrombin?
Antithrombin is a protein in our blood stream, which functions as a naturally occurring mild blood thinner. It is like a police protein that prevents us from clotting too much. It blocks our blood clotting mechanism by inactivating the major clotting protein “thrombin.” It is, therefore, called “anti-thrombin.” While antithrombin III was the original name given to this protein, the correct name now is just antithrombin, with the “III” dropped. Common names and abbreviations for the same protein are antithrombin, antithrombin III, AT, ATIII, and heparin cofactor I.
What is the abbreviation for antithrombin?
While antithrombin III was the original name given to this protein, the correct name now is just antithrombin, with the “III” dropped. Common names and abbreviations for the same protein are antithrombin, antithrombin III, AT, ATIII, and heparin cofactor I.
What is the normal antithrombin level?
Activity and antigen levels are typically expressed in “percent.” Normal ranges differ from lab to lab, but typically are approximately 80% – 120 %. Healthy newborns have only half the antithrombin levels of adults, but gradually reach the adult levels by 6 months of age. This is important to keep in mind when interpreting the tests of newborn children. Being on birth control pills, hormone replacement therapy, or being pregnant does not change antithrombin test results significantly and results are, thus, reliable. However, being on warfarin (coumadin®, Jantoven®) can increase antithrombin levels; therefore, a normal level while a person is on warfarin does not absolutely rule out the presence of AT deficiency. Once a patient is off warfarin the antithrombin activity test should be repeated. There are many different mutations in the antithrombin gene that can lead to inherited AT deficiency. Genetic testing is, therefore, not possible in routine clinical practice. It is reserved for research studies. Patients with inherited AT deficiency typically have levels in the 40% – 60 % range. It is not well established whether the degree of AT decrease correlates with the risk of thrombosis, i.e. whether patients with lower values have a higher risk for thrombosis.
What is the antithrombin activity test?
The antithrombin activity test determines whether the antithrombin that is present actually works. There are 2 main types of antithrombin deficiency (AT deficiency), depending on which of these two tests results is low. They are referred to as “type 1” and “type 2” deficiency. Activity and antigen levels are typically expressed in “percent.”.
How many people with AT deficiency develop blood clots?
In general, approximately 50% of individuals with AT deficiency will develop a blood clot during their life. A significant number of individuals develop clots before they are 30 years old; however, quite a few people also reach old age without ever developing a clot.
What are the risk factors for blood clots?
A person’s risk for blood clots depends on a number of factors, such as the degree and type of deficiency, the family history of clots , and other risk factors for clots (such as pregnancy or estrogen therapy, surgery or immobility, obesity, smoking and others). Inherited AT deficiency is an uncommon genetic disorder.
Why are blood clots uncommon in children with AT deficiency?
Blood clots are uncommon in children with AT deficiency, probably because another naturally occurring blood thinner (α2-macroglobulin) is higher during the first two decades of life, protecting most children from blood clots.
How long does it take for antithrombin III to normalize?
12 Because the anticoagulant effect of heparin is mediated by antithrombin III activity, heparin resistance is a clue to potential antithrombin III deficiency. Antithrombin III levels usually normalize within 48 to 72 hours after cessation of heparin treatment. 12
What is AT deficiency?
AT deficiency is associated almost exclusively with venous thrombosis. It usually manifests as deep venous thrombosis (DVT) of the extremities and PE but can also occur in unusual sites, such as cerebral sinuses and mesenteric, portal, and renal veins.
What percentage of thrombotic disease is caused by protein C?
Protein C, protein S, and antithrombin III deficiencies account for 14 to 25 percent of cases of familial thrombotic disease (including systemic thrombosis), although the majority tend to be venous rather than arterial. 2 Hematologic disorders may account for as many as 8 percent of all ischemic strokes. 3 How- ever, the combined prevalence of these disorders is 1 percent or less in the general population. 4 Deficiencies occur in either the amount (quantitative deficiency) or the molecular function (qualitative deficiency) of these coagulant proteins.
What is the normal range for thrombotic thrombosis?
In affected individuals AT levels are about 40–60% (normal range, 80–120%).
What is the prevalence of ATIII deficiency?
The prevalence of ATIII deficiency is estimated to be 0.02% to 0.2%. 141-144
What is the antigenic level of heterozygotes?
Heterozygotes usually have antigenic levels less than 60%. 12 Acquired deficiency may also result from liver disease, disseminated intravascular coagulation, and nephrotic syndrome. Protein S deficiency accounts for 2% to 3% of venous thromboses and clinically presents and behaves like protein C deficiency.
What is the role of protein C in coagulation?
Protein C is a vitamin K–dependent factor converted to an active protease by thrombin. 52 Once in active form, it limits coagulation by proteolysis of clotting factors Va and VIIIa. Protein S acts as a cofactor for activated protein C. 52 Antithrombin III acts as a protease inhibitor of most of the clotting factors in the coagulation cascade, except for factors Va and VIIIa, which are regulated by proteins C and S. 51 Combined, these factors serve to maintain the delicate balance between vascular hemostasis and fibrinolysis.
How many people have antithrombin 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.
What is a rare hereditary disorder that generally comes to light when a patient suffers recurrent?
It is a rare hereditary disorder that generally comes to light when a patient suffers recurrent venous thrombosis and pulmonary embolism, and repetitive intrauterine fetal death (IUFD). Hereditary antithrombin deficiency results in a state of increased coagulation which may lead to venous thrombosis.
Can antithrombin be deficient?
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.
What is the definition of a deficiency in antithrombin?
Deficiency of antithrombin (AT; antithrombin III) can be inherited or acquired; it is defined as an AT activity level that is consistently less than 80 percent of normal (or the lower limit of the assay's reference range). In some patients, AT deficiency can be associated with an increased risk of thromboembolism.
Is Edoxaban effective for thromboembolism?
Kawano H, Maemura K. Edoxaban Was Effective for the Treatment of Deep Vein Thrombosis and Pulmonary Thromboembolism in a Cancer Patient with Antithrombin III Deficiency. Intern Med 2016; 55:3285.
What causes antithrombin deficiency?
The first mechanism is increased excretion which may occur with renal failure associated with proteinuria nephrotic syndrome. The second mechanism results from decreased production as seen in liver failure or cirrhosis or an immature liver secondary to premature birth. The third mechanism results from accelerated consumption which is most pronounced as consequence of severe injury trauma but also may be seen on a lesser scale as a result of interventions such as major surgery or cardiopulmonary bypass.
What is the incidence of inherited antithrombin deficiency?
The incidence of inherited antithrombin deficiency has been estimated at between 1:2000 and 1:5000 in the normal population, with the first family suffering from inherited antithrombin deficiency being described in 1965. Subsequently, it was proposed that the classification of inherited antithrombin deficiency be designated as either type I or type II, based upon functional and immunochemical antithrombin analyses. Maintenance of an adequate level of antithrombin activity, which is at least 70% that of a normal functional level, is essential to ensure effective inhibition of blood coagulation proteases. Typically as a result of type I or type II antithrombin deficiency, functional antithrombin levels are reduced to below 50% of normal.
What is a type 1 heparin deficiency?
Type I antithrombin deficiency is characterized by a decrease in both antithrombin activity and antithrombin concentration in the blood of affected individuals. Type I deficiency was originally further divided into two subgroups, Ia and Ib, based upon heparin affinity. The antithrombin of subgroup Ia individuals showed a normal affinity for heparin while the antithrombin of subgroup Ib individuals showed a reduced affinity for heparin. Subsequent functional analysis of a group of 1b cases found them not only to have reduced heparin affinity but multiple or 'pleiotrophic' abnormalities affecting the reactive site, the heparin binding site and antithrombin blood concentration. In a revised system of classification adopted by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis, type Ib cases are now designated as type II PE, Pleiotrophic effect.
How to convert antithrombin to latent antithrombin?
Native antithrombin can be converted to latent antithrombin (L-antithrombin) by heating alone or heating in the presence of citrate. However, without extreme heating and at 37 °C (body temperature) 10% of all antithrombin circulating in the blood is converted to the L-antithrombin over a 24-hour period.
What is the P' region of antithrombin?
The P' region of antithrombin is unusually long relative to the P' region of other serpins and in un-activated or heparin activated antithrombin structures forms a tightly hydrogen bonded β-turn. P' elongation occurs through the breaking of all hydrogen bonds involved in the β-turn.
How long does it take for antithrombin to decay?
Antithrombin begins in its native state, which has a higher free energy compared to the latent state, which it decays to on average after 3 days. The latent state has the same form as the activated state - that is, when it is inhibiting thrombin.
What is the reactive bond of antithrombin?
The reactive bond is indicated by an arrow. Antithrombin is a serpin (serine protease inhibitor) and is thus similar in structure to most other plasma protease inhibitors, such as alpha 1-antichymotrypsin, alpha 2-antiplasmin and Heparin cofactor II .
