Factor XIII Deficiency (Fibrin Stabilizing Factor Deficiency)
What is Factor XIII Deficiency?
Factor XIII Deficiency or Fibrin Stabilizing Factor Deficiency was first reported in the medical literature in 1960. It is a rare bleeding disorder and occurs in 1 per 5 million births. It affects men and women equally.
Factor XIII is a fibrin stabilizing factor. Though individuals with Factor XIII Deficiency form blood clots normally, these clots are unstable and break down easily, this leads to frequent bleeding episodes and problems with wound healing, internal bleeding and easy bruising.
The severity of the disease varies among individuals. Some individuals present with mild symptoms whereas other may present with life-threatening bleeds and intra cranial hemorrhage (bleeds).
Early diagnosis and proper regular treatment can help prevent fatal and serious bleeding episodes.
Patterns of Inheritance
The disease is caused by an inherited mutation and this results in deficiency of Factor XIII. The condition is inherited in an autosomal recessive manner which means both parents have to carry a copy of the mutated gene for the offspring to present with the disease. There is a 25% chance of every child presenting with the disease and a 50% chance that every child will be a carrier.
Factor XIII Deficiency caused by a mutation in the F13A1 gene is known as Factor XIIIA Deficiency or Factor XIII Deficiency type 2. Factor XIII Deficiency due to a mutation in the F13B gene is rare and less severe than Factor XIIIA. Factor XIIIB Deficiency is known as type 1.
FXIII has two subunits: subunit A and subunit B. Most FXIII Deficiencies are caused by mutations in subunit A and subunit B mutations are very rare.
Image source: Pixabay
Symptoms and Diagnosis
Symptoms
Factor XIII has an important role in the body’s wound healing, ability to carry pregnancy to full term and development of new blood vessels.
Symptoms vary vastly among individuals. Around 80% of babies born with FXIII Deficiency have uncontrolled bleeding from the umbilical cord stump. If the deficiency is moderate, individuals may experience frequent nosebleeds, bleeding from gums and hematomas during early childhood. Easy bruising is another common symptom.
Women with FXIII Deficiency may experience heavy, menstrual bleeding requiring clinical interventions. In women with homozygous FXIII Deficiency, recurrent miscarriages are common.
The risk of intercranial bleeding is more common in FXIII Deficiency as compared to the other bleeding disorders. Around 30% of affected individuals experience a sudden intra cranial bleed. Around 25% of affected individuals also experience slower wound healing due to repeated bleeds from the same wound. Abnormal, heavy bleeding after any trauma or surgery is common.
Image source: Pixabay
Diagnosis
Is based on symptoms, patient’s clinical history, family history and a combination of laboratory tests and genetic tests:
- Screening coagulation tests commonly done for a case of suspected bleeding disorder are activated partial thromboplastin time (aPTT) and prothrombin time (PT). These tests are normal and not affected by Factor XIII Deficiency.
- A clot solubility test is useful in individuals who have a very low level of FXIII. This test involves taking a sample of the patient’s plasma and mixing with calcium and thrombin to create a clot. In the presence of FXIII, the clot will be stable for 24 hours or more. If the patient does not have sufficient FXIII, the clot dissolves within a few minutes to a few hours.
- Factor XIII activity – some tests measure the FXIII activity in the blood. The test is useful only if the factor levels are above 10%.
- Molecular testing – involves genotyping to check for the mutations in the genes that code for the A-subunit or B-subunit of FXIII. This is the most accurate and useful test to plan future therapies and also screen for future pregnancies.
Image source: Pixabay
Current Management
Factor XIII Deficiency can be treated with Factor XIII concentrates. FXIII levels need to be just slightly elevated to prevent bleeding symptoms. FXIII concentrate is made from plasma extracted from the blood of several blood donors. These products undergo a process of viral inactivation to prevent any dangerous pathogen or viruses that can be present in blood.
Unfortunately, we do not have Factor XIII available in India and most patients get Fresh frozen plasma (FFP) or cryoprecipitate regularly once a month. This treatment involves a risk of viral infections and allergic reactions. Patients need to be tested for transfusion transmitted infections regularly- at least every six months.
Most individuals with moderate to severe FXIII Deficiency need to undergo prophylactic therapy with FFP/cryoprecipitate or FXIII concentrate at least once in 3-4 weeks to prevent serious bleeding events (especially intercranial bleeds).
Investigational Therapies
Factor XIII concentrate (Corifact) was approved by the US Food and Drug Administration (USFDA) in 2011 for prophylactic treatment for inherited FXIII Deficiency. This is a drug given through intravenous infusions.
In 2014, Coagulation Factor XIII A-Subunit, Recombinant (Tretten) was approved to prevent bleeding episodes in children and adults with Factor XIII A-subunit deficiency.
References
Description, Types, Causes, Diagnosis, Treatment
https://rarediseases.org/rare-diseases/factor-xiii-deficiency/
https://rarediseases.info.nih.gov/diseases/10766/factor-xiii-deficiency
Standard of care guidelines
https://www.uptodate.com/contents/factor-xi-eleven-deficiency
https://emedicine.medscape.com/article/209984-treatment
https://www.ahcdo.org.au/documents/item/70
https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.13058
https://www.rarebleedingdisorders.com/bleeding-disorders/factor-13.html
National Resources
Hemophilia Federation (India)
A-128, Mohammadpur (Behind Bhikaji Cama Place),
New Delhi - 110066
Email: support@hemophilia.in
Ph: +91-11-45034951/4972, +91-11-41552819
Contact Dr. Shashi Apte for any support – 098224 04983
The website of the HFI lists all the affiliated chapters according to country-wide zones: Northern Region, Western Region, Eastern Region and Southern Region. Look up the website to find your local city/town chapter.
Disease Videos
Factor XIII Deficiency (Fibrin Stabilizing Factor Defect)
Keywords
Factor XIII Deficiency, Clotting Factor XIII, Fibrin, Fibrin Stabilizing Factor, F13A1 Gene, F13B Gene, Haematoma, Intercranial Bleeds, Fresh Frozen Plasma, Cryoprecipitate, FXIII Concentrate