Hereditary antithrombin deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Hereditary antithrombin deficiency is a disorder of blood clotting. People with this condition are at higher than average risk for developing abnormal blood clots, particularly a type of clot that occurs in the deep veins of the legs. This type of clot is called a deep vein thrombosis (DVT). Affected individuals also have an increased risk of developing a pulmonary embolism (PE), which is a clot that travels through the bloodstream and lodges in the lungs. In hereditary antithrombin deficiency, abnormal blood clots usually form only in veins, although they may rarely occur in arteries.

About half of people with hereditary antithrombin deficiency will develop at least one abnormal blood clot during their lifetime. These clots usually develop after adolescence.

Other factors can increase the risk of abnormal blood clots in people with hereditary antithrombin deficiency. These factors include increasing age, surgery, or immobility. The combination of hereditary antithrombin deficiency and other inherited disorders of blood clotting can also influence risk. Women with hereditary antithrombin deficiency are at increased risk of developing an abnormal blood clot during pregnancy or soon after delivery. They also may have an increased risk for pregnancy loss (miscarriage) or stillbirth.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Hereditary antithrombin deficiency is caused by mutations in the SERPINC1 gene. This gene provides instructions for producing a protein called antithrombin (previously known as antithrombin III). This protein is found in the bloodstream and is important for controlling blood clotting. Antithrombin blocks the activity of proteins that promote blood clotting, especially a protein called thrombin.

Most of the mutations that cause hereditary antithrombin deficiency change single protein building blocks (amino acids) in antithrombin, which disrupts its ability to control blood clotting. Individuals with this condition do not have enough functional antithrombin to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Hereditary antithrombin deficiency is typically inherited in an autosomal dominant pattern, which means one altered copy of the SERPINC1 gene in each cell is sufficient to cause the disorder. Inheriting two altered copies of this gene in each cell is usually incompatible with life; however, a few severely affected individuals have been reported with mutations in both copies of the SERPINC1 gene in each cell.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Hereditary antithrombin deficiency is estimated to occur in about 1 in 2,000 to 3,000 individuals. Of people who have experienced an abnormal blood clot, about 1 in 20 to 200 have hereditary antithrombin deficiency.

Understanding terms used in the source

These definitions explain medical words used above. A definition is not evidence that another condition is present, and it does not predict how a symptom will develop. Ask the clinician which terms apply to the actual examination or test result.

Pulmonary embolism

An embolus (that is, an abnormal particle circulating in the blood) located in the pulmonary artery and thereby blocking blood circulation to the lung. Usually the embolus is a blood clot that has developed in an extremity (for instance, a deep venous thrombosis), detached, and traveled through the circulation before becoming trapped in the pulmonary artery.

Miscarriage

A pregnancy that ends at a stage in which the fetus is incapable of surviving on its own, defined as the spontaneous loss of a fetus before the 22th week of pregnancy.

Stillbirth

Death of the fetus in utero after at least 22 weeks of gestation.

Affected

This term applies to a family member who is diagnosed with the same condition as the individual who is the primary focus of investigation (the proband).

Which doctor should you see?

The suggested department for discussing Hereditary antithrombin deficiency is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Hereditary antithrombin deficiency. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.