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Glanzmann thrombasthenia
This condition causes symptoms such as easy bruising, nosebleeds, and prolonged bleeding after injury or surgery. It affects individuals from birth and is due to changes in genes crucial for platelet aggregation.
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Overview
Glanzmann thrombasthenia is a rare genetic disorder that impacts how blood clots. Individuals with this condition have platelets that do not aggregate (stick together) properly [PMID:33678082]. Platelets are small, disc-shaped cells in the blood that are essential for stopping bleeding by forming a clot at the site of injury. In Glanzmann thrombasthenia, the platelets are present in normal numbers and look normal, but they cannot perform their crucial function of aggregating, which is necessary for effective clot formation.
Symptoms & clinical features
The primary symptom of Glanzmann thrombasthenia is bleeding, which can range from mild to severe, and its severity can vary significantly even within the same family. Common signs of the condition include easy bruising, frequent or prolonged nosebleeds (epistaxis), bleeding from the gums, and heavy or prolonged menstrual periods (menorrhagia) in women [PMID:33678082]. Individuals may also experience excessive bleeding after minor injuries, dental procedures, or surgery (haematomas). Less commonly, gastrointestinal bleeding or bleeding into joints can occur. The bleeding typically starts in infancy or early childhood.
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Affected organs
Glanzmann thrombasthenia primarily affects the blood and blood vessels. The disorder impacts platelets, which are produced in the bone marrow and circulate in the bloodstream. Consequently, symptoms are evident wherever blood vessels are present, especially in areas prone to injury or where bleeding can easily manifest, such as the skin, mucous membranes (nose, mouth, gastrointestinal tract), and the reproductive system in females.
Risks & severity
The severity of Glanzmann thrombasthenia can be variable, with some individuals experiencing only mild bleeding episodes and others facing life-threatening haemorrhages. The main risks are related to uncontrolled bleeding, particularly following trauma, surgery, or childbirth. Anaemia can develop due to chronic blood loss [PMID:33678082]. While the condition causes significant bleeding tendencies, typical life expectancy is often unaffected by Glanzmann thrombasthenia if appropriately managed.
Genetic causes
Glanzmann thrombasthenia is caused by pathogenic variants in either the ITGA2B gene or the ITGB3 gene. These genes provide instructions for making components of a specific protein complex called integrin αIIbβ3 (also known as glycoprotein IIb/IIIa). This integrin is found on the surface of platelets and is vital for their ability to stick together (aggregate) to form a clot. The ITGA2B gene provides the blueprint for the alphaIIb subunit, while the ITGB3 gene provides the code for the beta3 subunit [PMID:20301389]. When these genes have alterations, the integrin αIIbβ3 complex either isn't produced correctly, is dysfunctional, or is absent from the platelet surface. This impaired function leads to platelets being unable to aggregate effectively, resulting in the bleeding symptoms characteristic of Glanzmann thrombasthenia.
- ITGA2B integrin subunit alpha 2bThe ITGA2B gene encodes a crucial subunit of a protein complex vital for platelet aggregation and proper blood clot formation, with variants linked to inherited bleeding disorders.
- ITGB3 integrin subunit beta 3The *ITGB3* gene provides instructions for producing the beta-3 subunit of integrin αIIbβ3, a protein essential for platelet aggregation and blood clot formation.
Inheritance pattern
Glanzmann thrombasthenia is inherited in an autosomal recessive pattern. This means that an individual must inherit two altered copies of the same gene - one from each parent - to develop the condition. People who have only one altered copy of the gene are called carriers. Carriers typically do not show symptoms of Glanzmann thrombasthenia because their one working copy of the gene is sufficient for normal platelet function. When two carriers have children, there is a 25% chance with each pregnancy that their child will inherit two altered copies and develop Glanzmann thrombasthenia, a 50% chance the child will be a carrier like the parents, and a 25% chance the child will inherit two working copies of the gene and not be affected or a carrier.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of Glanzmann thrombasthenia is typically suspected based on a history of abnormal bleeding and is confirmed through specific laboratory tests. Initial blood tests will often show normal platelet count and size. However, specialised platelet function tests, such as light transmission aggregometry (LTA), will reveal a characteristic pattern of absent or severely reduced platelet aggregation in response to various chemical stimuli [PMID:33678082]. Genetic testing, which involves analysing the ITGA2B and ITGB3 genes, confirms the diagnosis by identifying pathogenic variants. In the UK, genetic testing for inherited bleeding disorders falls under the NHS Genomic Medicine Service and is typically accessed via an R-code (e.g., R15), usually initiated by haematologists or clinical geneticists.
Management & lifestyle
Management of Glanzmann thrombasthenia focuses on preventing and treating bleeding episodes. Regular monitoring by a haematologist is crucial. Treatment for bleeding may involve local measures like pressure or nasal packing for nosebleeds. For more severe bleeding or before surgical procedures, interventions may include platelet transfusions, or infusions of recombinant activated factor VIIa (rFVIIa), which helps promote clotting through a different pathway [PMID:33678082]. Women with heavy menstrual bleeding may be offered hormonal therapy. Antifibrinolytic medications, such as tranexamic acid, can also be used to stabilise clots and reduce bleeding. It is important for individuals with Glanzmann thrombasthenia to avoid medications that interfere with platelet function, such as aspirin and non-steroidal anti-inflammatory drugs (NSAIDs). Genetic counselling is recommended to discuss the inheritance pattern and implications for family planning.
UK care pathway
In the UK, individuals suspected of having Glanzmann thrombasthenia would typically be referred to a haematologist. If an inherited bleeding disorder like Glanzmann thrombasthenia is suspected, an R-code under the NHS Genomic Medicine Service (e.g., R15 for inherited bleeding, clotting and platelet disorders) would guide genetic testing. Referrals to clinical genetics services can provide further support, including access to genetic counsellors who can help families understand the condition, its inheritance, and implications for relatives.
Frequently asked questions
Can Glanzmann thrombasthenia be cured?
Currently, there is no cure for Glanzmann thrombasthenia. Management focuses on preventing and treating bleeding episodes effectively. Research into new treatments, including gene therapy, is ongoing.
Is Glanzmann thrombasthenia related to haemophilia?
Both Glanzmann thrombasthenia and haemophilia are inherited bleeding disorders, but they affect different parts of the clotting process. Haemophilia involves deficiencies in specific clotting factors, while Glanzmann thrombasthenia results from platelets being unable to aggregate properly.
What should I avoid if I have Glanzmann thrombasthenia?
You should generally avoid medications that interfere with platelet function, such as aspirin and some pain relievers (NSAIDs). It's also important to avoid activities that carry a high risk of injury without appropriate precautions. Always discuss any medications or activities with your haematologist.
How does Glanzmann thrombasthenia affect pregnancy?
Pregnancy in women with Glanzmann thrombasthenia requires careful management by a specialist obstetric and haematology team due to the increased risk of bleeding during delivery and postpartum. Close monitoring and specific interventions may be necessary to ensure a safe outcome for both mother and baby.
Can carriers of Glanzmann thrombasthenia have symptoms?
Individuals who are carriers for Glanzmann thrombasthenia (meaning they have one altered gene copy) typically do not experience symptoms of the condition. They have enough normal protein function to maintain effective blood clotting.
References
- Nurden AT, Pillois X. ITGA2B and ITGB3 gene mutations associated with Glanzmann thrombasthenia. Platelets. 2018. PMID: 29125375
- Sandrock-Lang K, Wentzell R, Santoso S. Inherited platelet disorders. Hamostaseologie. 2016. PMID: 25707719
- Krause KA, Graham BC. Glanzmann Thrombasthenia. 2026. PMID: 30855858
- Kosaka Y, Lopez B, Kishimoto N. Functional classification of platelet gene variants using CRISPR HDR in CD34(+) cell-derived megakaryocytes. American journal of human genetics. 2025. PMID: 41349512
- Nurden AT, Freson K, Seligsohn U. Inherited platelet disorders. Haemophilia : the official journal of the World Federation of Hemophilia. 2012. PMID: 22726100
- Nurden AT. Glanzmann thrombasthenia. Orphanet journal of rare diseases. 2006. PMID: 16722529