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Epidemiology:
Prevalence of homozygous forms is estimated at around 1/2,000,000. Both sexes are equally affected.

Clinical description:
Congenital FXIII deficiency can manifest at any age, but diagnosis is often made during infancy. Umbilical stump bleeding manifests in up to 80% of patients. Other common signs include intracranial hemorrhage (25-30%), soft tissue bleeding, bruising, hemarthroses (20%), and recurrent spontaneous abortions. In most cases, hemorrhages are delayed (12-36hr) after trauma or surgery. Patients may have poor wound healing. Acquired forms of the disease have also been reported in association with hepatic failure, inflammatory bowel disease (see this term), and myeloid leukemia.

Etiology:
Congenital FXIII deficiency is usually caused by mutations in the F13A1 gene (6p24.2-p23) encoding the catalytic A subunit, but mutations have also been found in the F13B gene (1q31-q32.1) encoding the B subunit. Transmission is autosomal recessive. The phenotype is less severe when the F13B gene is mutated.

Diagnostic methods:
Diagnosis is based on quantitative FXIII activity measurement and antigen assays. Common clotting assays such as activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) are normal and cannot be used for the screening. The clot solubility test may also be used (clot is stable for more than 24 hours in case of FXIII deficiency). Molecular testing is available, but unnecessary for diagnosis.

Differential diagnosis:
Differential diagnoses mainly include the other congenital coagulation factor deficiencies: fibrinogen, factors II, V, VII, X, XI, VIII, IX (see these terms).

Antenatal diagnosis:
Antenatal diagnosis is possible if the causal mutations have previously been identified in the family.

Management and treatment:
Factor XIII concentrates or fresh frozen plasma (when FXIII concentrates are not available) is usually used for the treatment of bleedings. Prophylactic therapy with FXIII concentrate should be indicated to prevent recurrent bleedings such as intracranial hemorrhage.

Prognosis:
Intracranial hemorrhage can be life threatening, but prognosis is favorable if adequate treatment is provided.