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Factor XIII deficiency
This condition makes it difficult for blood clots to form effectively, leading to prolonged bleeding after injury or surgery. It is a lifelong disorder affecting individuals from birth.
Overview
Factor XIII deficiency is a rare genetic bleeding disorder where the body either produces insufficient amounts of Factor XIII or the Factor XIII produced does not work correctly. Factor XIII plays a crucial role in stabilising blood clots once they have formed. Without enough functional Factor XIII, clots are weak and break down too easily, leading to prolonged bleeding [PMID:33679844]. This condition affects both males and females equally and is typically identified early in life due to bleeding symptoms.
Symptoms & clinical features
Individuals with Factor XIII deficiency often experience a range of bleeding symptoms. Common signs include bleeding from the umbilical cord stump shortly after birth, which is a hallmark symptom. Other symptoms can include easy bruising, prolonged bleeding after cuts or surgery, nosebleeds, and heavy menstrual periods in women [PMID:35773295]. Internal bleeding, such as into joints (haemarthrosis) or muscles, can also occur, and in rare cases, bleeding into the brain (intracranial haemorrhage) may happen, which can be life-threatening.
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Affected organs
Factor XIII deficiency primarily affects the body's haemostatic system, meaning the ability to stop bleeding. Therefore, nearly all organs and tissues can be affected by bleeding complications. The skin, mucous membranes (like those lining the nose and mouth), muscles, and joints are common sites for bleeding. The brain is also a critical organ to be aware of because intracranial haemorrhage, though rare, can have severe consequences.
Risks & severity
The severity of Factor XIII deficiency can vary, but generally, individuals with significantly reduced Factor XIII activity tend to experience more severe bleeding episodes. The condition is present from birth, and symptoms often appear in infancy or early childhood. Without appropriate management, there is a risk of significant bleeding complications, including life-threatening haemorrhages, particularly into the central nervous system. Precise prevalence is estimated at approximately 1 in 2 million individuals globally, making it a very rare disorder.
Genetic causes
Factor XIII deficiency is caused by changes (variants) in either the F13A1 gene or the F13B gene. These genes provide instructions for making the two subunits, A and B, that form the active Factor XIII protein. The F13A1 gene is located on chromosome 6 and gives rise to the A-subunit, while the F13B gene is found on chromosome 1 and produces the B-subunit [PMID:33679844]. When variants in these genes lead to a non-functional or absent protein, the complete Factor XIII complex cannot be formed or cannot function correctly, impairing blood clot stability.
- F13A1 coagulation factor XIII A chain
- F13B coagulation factor XIII B chain
Inheritance pattern
Factor XIII deficiency is inherited in an autosomal recessive pattern. This means that an individual must inherit two altered copies of either the F13A1 or F13B gene - one from each parent - to develop the condition. If a person inherits only one altered copy and one normal copy, they are considered a carrier and typically do not show symptoms of the disorder. Carriers have a 50% chance of passing the altered gene to each of their children. If two carriers have a child together, there is a 25% chance with each pregnancy that the child will inherit two altered copies and develop Factor XIII deficiency.
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 Factor XIII deficiency typically involves a combination of clinical assessment and specialised blood tests. Standard coagulation tests, like prothrombin time (PT) and activated partial thromboplastin time (aPTT), are often normal, which can sometimes delay diagnosis. A specific test to measure Factor XIII activity in the blood is necessary for confirmation [PMID:35773295]. Genetic testing, often guided by an NHS clinical genetics service, can then identify the specific variants in the F13A1 or F13B genes. This can help confirm the diagnosis and inform family planning. Genomic testing for Factor XIII deficiency in the UK can be requested by clinicians through the NHS Genomic Medicine Service, typically via the R-code R115 Hereditary coagulation disorder.
Management & lifestyle
Management of Factor XIII deficiency primarily focuses on preventing and treating bleeding episodes. This often involves regular infusions of Factor XIII concentrate, which replaces the missing or deficient protein, especially before surgeries or in response to bleeding [PMID:33679844]. Antifibrinolytic agents, which help prevent clot breakdown, may also be used. Individuals with Factor XIII deficiency are typically managed by a specialist haematologist within an NHS Haemophilia Centre, which can provide comprehensive care, including genetic counselling. Close monitoring and a personalised management plan are crucial to minimise bleeding risks and ensure a good quality of life. Patients are advised to discuss all treatment options and lifestyle considerations with their healthcare team.
UK care pathway
In the UK, individuals suspected of having Factor XIII deficiency will typically be referred to an NHS Haemophilia Centre or a specialist haematology service. If a genetic cause is suspected, a referral to an NHS clinical genetics specialist can be made. Genetic counsellors are available through these services to provide information and support regarding inheritance patterns and family planning. Genomic testing for Factor XIII deficiency can be accessed through the NHS Genomic Medicine Service under R-code R115, 'Hereditary coagulation disorder,' following a clinical assessment.
Frequently asked questions
What is Factor XIII and why is it important?
Factor XIII is a protein in the blood that is essential for stabilising blood clots. When you get a cut, other factors form a blood clot, but Factor XIII makes the clot strong and durable, preventing it from breaking down too quickly and allowing the wound to heal.
How is Factor XIII deficiency diagnosed?
Diagnosis involves specific blood tests that measure the level and activity of Factor XIII. Standard blood clotting tests are often normal. Genetic testing can also be used to identify changes in the F13A1 or F13B genes that cause the condition.
Can Factor XIII deficiency be treated?
Yes, Factor XIII deficiency can be managed. Treatment often involves infusions of Factor XIII concentrate to replace the missing protein, particularly to prevent or stop bleeding episodes. Management plans are individualised and overseen by specialist doctors.
What should I do if I think I or my child might have Factor XIII deficiency?
If you suspect Factor XIII deficiency due to unusual bleeding or a family history, it is important to speak to your GP. They can refer you to a haematologist or a specialist centre for further assessment and testing.
Is Factor XIII deficiency always severe?
The severity can vary. Some individuals may experience more frequent and severe bleeding episodes, including internal bleeding, while others might have milder symptoms. The level of Factor XIII activity in the blood often correlates with the severity of the condition.
References
- Hsieh L, Nugent D. Factor XIII deficiency. Haemophilia : the official journal of the World Federation of Hemophilia. 2008. PMID: 19141159
- Karimi M, Bereczky Z, Cohan N. Factor XIII Deficiency. Seminars in thrombosis and hemostasis. 2009. PMID: 19598071
- Mangla A, Killeen RB, Kumar A. Factor XIII Deficiency. 2026. PMID: 32491399
- Kumar R, Vidaurre J, Gedela S. Valproic Acid-Induced Coagulopathy. Pediatric neurology. 2019. PMID: 31201069
- Karimi M, Peyvandi F, Naderi M. Factor XIII deficiency diagnosis: Challenges and tools. International journal of laboratory hematology. 2018. PMID: 29027765
- Hayward CPM, Mathews N. Factor XIII Deficiency and Measurement. Clinics in laboratory medicine. 2026. PMID: 42140679
- Anwar R, Miloszewski KJ. Factor XIII deficiency. British journal of haematology. 1999. PMID: 10583246
- Yan MTS, Rydz N, Goodyear D. Acquired factor XIII deficiency: A review. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2018. PMID: 30446212