Factor XIII Deficiency
“In my case I’ve had one bleeding event that came on without obvious cause. I’m now on prophylaxis and try to stay positive, but learning to manage this rare condition and watching for head injury symptoms has been a huge part of daily life.”
A rare inherited coagulation disorder characterised by impaired fibrin stabilisation, leading to delayed and potentially severe bleeding despite normal routine coagulation tests.
Epidemiology
Factor XIII deficiency is an extremely rare disorder, with an estimated prevalence of approximately 1 per 1,000,000 to 3,000,000 individuals worldwide. Both sexes are equally affected. The condition is more frequently observed in populations with high rates of consanguinity.
Clinical description
Bleeding manifestations typically begin in the neonatal period or early childhood but may present later in life. A hallmark feature is delayed bleeding, often occurring hours to days after trauma or surgery.
Typical clinical features include:
– Prolonged bleeding from the umbilical stump in neonates
– Easy bruising and soft tissue bleeding
– Mucocutaneous bleeding (epistaxis, gingival bleeding)
– Menorrhagia in affected females
– Excessive or delayed bleeding following trauma, dental procedures, or surgery
– Intracranial haemorrhage (a major cause of morbidity and mortality – up to 30% incidence throughout life)
– Recurrent pregnancy loss in affected women
– Poor wound healing
– Joint bleeding is uncommon compared with haemophilia A or B.
Etiology
Factor XIII deficiency is caused by pathogenic variants affecting factor XIII, a transglutaminase essential for stabilising the fibrin clot by cross-linking fibrin strands.
Two distinct subtypes are recognised:
Type A – deficiency of the FXIII-A subunit (which is the functional subunit), caused by variants in the F13A1 gene
Accounts for the vast majority of cases
Typically associated with more severe bleeding
Type B – deficiency of the FXIII-B subunit (which is the subunit that carries the A subunit), caused by variants in the F13B gene
Much rarer
Often associated with milder or variable bleeding severity
Both subunits are required for normal FXIII activity; deficiency of either results in impaired clot stability.
Diagnostic methods
Diagnosis is often delayed because routine coagulation tests are normal.
Key diagnostic features include:
Normal prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time
Reduced or absent FXIII activity on specific functional assays
Abnormal clot solubility test (clot dissolves in urea or monochloroacetic acid)
FXIII antigen assays to distinguish Type A from Type B deficiency
Molecular genetic testing can confirm the diagnosis, identify the subtype, and support family studies.
Differential diagnosis
Differential diagnoses include:
Haemophilia A and B
von Willebrand disease
Other rare coagulation factor deficiencies
Acquired FXIII deficiency
The presence of normal routine coagulation tests with significant bleeding should prompt specific FXIII testing.
Genetic counseling
Inheritance is autosomal recessive. Genetic counselling is recommended for affected individuals and their families. Carrier parents have a 25% risk of having an affected child with each pregnancy. Prenatal diagnosis may be considered in families with severe disease.
Congenital factor XIII deficiency
Prevalence
<1 / 1,000,000
Management and treatment
There is no curative therapy, but effective prophylactic treatment is available.
Management strategies include:
Regular prophylactic replacement therapy with FXIII concentrate (plasma-derived or recombinant)
On-demand FXIII replacement for acute bleeding or surgery
Antifibrinolytic agents (e.g. tranexamic acid) as adjunctive therapy for mucosal bleeding
Because FXIII has a long half-life, prophylaxis is typically administered every 4–6 weeks. Lifelong prophylaxis is strongly recommended for individuals with severe deficiency, particularly to prevent intracranial haemorrhage.
Prognosis
With early diagnosis and appropriate prophylactic treatment, prognosis is excellent and life expectancy is usually normal. Without treatment, the risk of life-threatening bleeding, particularly intracranial haemorrhage, is significant.
Last update: July 2026
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