Home Topics Hypercoagulation Dis...Antithrombin Deficiency

Antithrombin III Deficiency

Antithrombin III (AT III) is a type of anticoagulant protein (produced by the liver) that prevents the blood from excessively and unnecessarily clotting. Along with other anticoagulants, antithrombin III prevents the complex clotting procedure, known as the coagulation cascade, from occurring when the body doesn’t need it.

As a result, people with insufficient levels of antithrombin III suffer from a condition known as antithrombin III deficiency, rare blood coagulation disorder that puts people at a far greater risk of developing dangerous blood clots, also referred to as thrombosis.

Because blood clots can break free and roam about the body, they obstruct blood flow, putting people at risk for a number of potentially fatal conditions, including:

pulmonary embolisms (clots that block the lungs’ airways)
stroke
venous thrombosis (clots that obstruct the body’s veins).

Causes of Antithrombin III Deficiency

Antithrombin III deficiency is a hereditary disorder, meaning the disease runs in families. If a member of your immediate family has an antithrombin III deficiency, the rest of the family is at risk and, therefore, should be screened for this blood disorder as well.

Antithrombin III deficiency may also develop due to a genetic defect that occurs during fetal development. Genetic anomalies may result in insufficient or abnormally functioning antithrombin III.

In rare cases, patients may develop antithrombin III deficiency as the result of some more serious underlying health condition, including:

atrial septal defect
cancers
kidney failure
liver disease
nephrotic syndrome
physical trauma
systemic erythromatosus lupus
trunucs arteriosus
ventriculoseptal defect.

Medications and treatments for severe medical conditions may also contribute to the development of antithrombin III deficiency. Some of these include:

bone marrow transplants
chemotherapy
medication that increases coagulation activity
medication that inhibits protein development.

This blood clotting disorder occurs at roughly equal rates in men and women, affecting about one in every 2,000 to 5,000 people.

Types of Antithrombin III Deficiencies

Here are the two types of hereditary antithrombin III deficiency:

Congenital antithrombin III deficiency occurs when a person inherits defective genes from only one parent. With this type of antithrombin III deficiency, the anticoagulant protein levels are 40 percent to 60 percent lower than they are for normal for people with congenital antithrombin III deficiency. However, patients with congenital antithrombin III deficiency may lead normal childhoods.

This condition is often not diagnosed until the first thrombolytic event, which may not occur until the individual reaches early adulthood. While early adulthood is the most common for antithrombin III deficiency symptoms to arise, a blood clot caused by antithrombin deficiency can occur at any age.

For example, although some people with antithrombin III deficiency don't develop blood clots until well into middle age, others may have congential antithrombin III deficiency complications that start during childhood.
Severe antithrombin III deficiency occurs when both parents pass the antithrombin deficiency on to their child. Severe antithrombin III deficiency has a very poor prognosis, with serious thrombolytic activity (clotting complications) occurring early in infancy.

Antithrombin III Deficiency Risk Factors

The only true risk for hereditary antithrombin III deficiency is a family history of this condition, specifically in either or both parents. Keep in mind that, as of yet, researchers haven’t found a link between antithrombin III deficiency and ethnicity or gender.

Antithrombin III Deficiency Symptoms

Unless anticoagulation III deficiency causes a thrombolytic event, the condition typically does not cause apparent symptoms. In fact, a person with congenital antithrombin III deficiency can live for decades without any thrombolytic (abnormal clotting) activity.

However, when patients do exhibit symptoms, they tend to experience the effects of blood clot obstructions in the legs and/or lungs. While leg clots point to venous thrombosis (also known as deep vein thrombosis, DVT), clots in the lungs cause pulmonary embolism. Because both can be fatal and require immediate medical attention, being familiar with the following symptoms is essential:

chest pain
coughing
leg pain
swelling
tenderness.

Keep in mind that pregnancy and the use of oral contraceptives (birth control pills) can exacerbate symptoms and, therefore, increase the possibility of developing DVT and pulmonary embolism.

As a result, women with an antithrombin III deficiency should be monitored carefully during pregnancy. Because pregnancy changes the body’s levels of all coagulation factors, it can put these women at an even higher risk of developing blood clots, which is ultimately linked to a higher risk of spontaneous abortions and miscarriages.

Diagnosing Antithrombin Deficiency

Because congenital antithrombin III deficiency runs in families, people with the hetrozygote strain (the type of antithrombin III deficiency inherited from only one parent) are usually diagnosed when a family member develops a blood clot. Once tests reveal the presence of antithrombin three deficiency in one family member, other family members are usually screened as well.

Failing this, diagnosis of antithrombin III deficiency may not occur until a blood clot develops. The chance that a blood clot will develop is quite high. While 50 percent of people with an antithrombin III deficiency develop a blood clot at least once in their life, 80 percent of all cases will have experienced a blood clot by age 60.

Blood clots may develop spontaneously or may appear into response to trauma or a "thrombolytic challenge." The insertion of a catheter into a blood vessel, for instance, may be sufficient to trigger a blood clot in someone with antithrombin III deficiency.

Antithrombin III Deficiency Treatment: Heparin

Because no treatment for antithrombin III deficiency exists, treatments revolve around preventing abnormal clotting. Typical treatments include transfusions of antithrombin III (gathered from donor plasma) and the use of anticoagulant medications.

In general, doctors only recommend taking anticoagulants, such as heparin and warfarin, for antithrombin III therapy when a blood clot has already developed. Initial treatment with warfarin and heparin aims to dissolve existing blood clots and prevent recurrence. This course of treatment tends to last for six months after the initial clot diagnosis.

Should a second blood clot occur, the risk of life-threatening clots in the lungs or other organs increases dramatically. In such cases, long-term use of warfarin and heparin is often recommended.

To avoid potential complications with these medications, be sure to inform your doctor of other medications you may be taking or other medical conditions from which you may be suffering. For example, pregnant women should be aware that both warfarin and antithrombin III infusions have been linked to fetal damage, especially in the early stages of pregnancy. As a result, balance the benefits of antithrombin III deficiency treatment versus the risks placed on the fetus with your doctor.

Keep in mind that the presence of antithrombin III deficiency does not automatically indicate a need for treatment, as the condition may be asymptomatic for decades.

Diagnosing severe antithrombin III deficiency, also known as homozygote antithrombin III deficiency, is typically easier, as these patients who have inherited the defective genes from both parents typically display symptoms of the condition during infancy. For example, diagnosis may be made if the child is born with purpura fulminans, or widespread clotting throughout the body.

If either type of antithrombin III deficiency is suspected, blood tests and other coagulation tests are generally sufficient to diagnose this condition.

Resources

GTC-Biotherapeutics (n.d.). What is Hereditary Antithrombin Deficiency? Retrieved September 21, 2007, from the atiii.com Web site: www.atiii.com/overview_intro.htm.

Harper, J. (2007). Antithrombin III Deficiency. Retrieved September 21, 2007, from the eMendicine Web site: www.emedicine.com/ped/topic119.htm.

U.S. National Library of Medicine (2007). Congenital Antithrombin III Deficiency. Retrieved September 21, 2007, from the MedlinePlus Web site: www.nlm.nih.gov/medlineplus/ency/article/000558.htm.