Glanzmann thrombasthenia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Glanzmann thrombasthenia is a bleeding disorder that is characterized by prolonged or spontaneous bleeding starting from birth. People with Glanzmann thrombasthenia tend to bruise easily, have frequent nosebleeds (epistaxis), and may bleed from the gums. They may also develop red or purple spots on the skin caused by bleeding underneath the skin (petechiae) or swelling caused by bleeding within tissues (hematoma). Glanzmann thrombasthenia can also cause prolonged bleeding following injury, trauma, or surgery (including dental work). Women with this condition can have prolonged and sometimes abnormally heavy menstrual bleeding. Affected women also have an increased risk of excessive blood loss during pregnancy and childbirth.

About a quarter of individuals with Glanzmann thrombasthenia have bleeding in the gastrointestinal tract, which often occurs later in life. Rarely, affected individuals have bleeding inside the skull (intracranial hemorrhage) or joints (hemarthrosis).

The severity and frequency of the bleeding episodes in Glanzmann thrombasthenia can vary greatly among affected individuals, even in the same family. Spontaneous bleeding tends to become less frequent with age.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the ITGA2B or ITGB3 gene cause Glanzmann thrombasthenia. These genes provide instructions for making the two parts (subunits) of a receptor protein called integrin alphaIIb/beta3 (αIIbβ3). This protein is abundant on the surface of platelets. Platelets are small cells that circulate in blood and are an essential component of blood clots. During clot formation, integrin αIIbβ3 helps platelets bind together. Blood clots protect the body after injury by sealing off damaged blood vessels and preventing further blood loss.

ITGA2B or ITGB3 gene mutations result in a shortage (deficiency) of functional integrin αIIbβ3. As a result, platelets cannot clump together to form a blood clot, leading to prolonged bleeding.

Three types of Glanzmann thrombasthenia have been classified according to the amount of integrin αIIbβ3 that is available. People with type I (the most common type) have less than 5 percent of normal integrin αIIbβ3 levels, people with type II have between 5 and 20 percent of normal integrin αIIbβ3 levels, and people with the variant type have adequate integrin αIIbβ3 levels but produce only nonfunctional integrin.

Some people with Glanzmann thrombasthenia do not have an identified mutation in either the ITGA2B or ITGB3 gene; the cause of the disorder in these individuals is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Glanzmann thrombasthenia is estimated to affect 1 in one million individuals worldwide, but may be more common in certain groups, including those of Romani ethnicity, particularly people within the French Manouche community.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Prolonged bleeding time · Very frequent (99-80%)

Prolongation of the time taken for a standardized skin cut of fixed depth and length to stop bleeding.

Spontaneous, recurrent epistaxis · Very frequent (99-80%)

Bruising susceptibility · Frequent (79-30%)

An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.

Gingival bleeding · Frequent (79-30%)

Hemorrhage affecting the gingiva.

Prolonged bleeding after surgery · Frequent (79-30%)

Bleeding that persists longer than the normal time following a surgical procedure.

Prolonged bleeding following circumcision · Frequent (79-30%)

Bleeding that persists for a longer than usual time following circumcision.

Ecchymosis · Occasional (29-5%)

A purpuric lesion that is larger than 1 cm in diameter.

Gastrointestinal hemorrhage · Occasional (29-5%)

Hemorrhage affecting the gastrointestinal tract.

Other findings in the same source

From: Orphanet

Additional reported features include Macroscopic hematuria (Occasional (29-5%)); Menometrorrhagia (Occasional (29-5%)); Menorrhagia (Occasional (29-5%)); Purpura (Occasional (29-5%)); Spontaneous hematomas (Occasional (29-5%)); Impaired ristocetin-induced platelet aggregation (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Glanzmann thrombasthenia is Haematology, with a haematologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

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.

• Which blood-cell, marrow, bleeding or clotting finding matters most?
• Does the diagnosis need confirmation or a more precise subtype?
• Which symptoms or laboratory changes should trigger earlier review?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Glanzmann thrombasthenia. 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.