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Factor XIII

Factor XIII is a coagulation factor that is also called fibrin stabilizing factor. Factor XIII is a transglutaminase that catalyzes the cross-linking of glutamyl and lysyl groups on fibrin monomers, stabilizing clots.Clots formed in the absence of activated Factor XIII lack stability and are easily lysed by proteolytic enzymes.

Factor XIII consists of two catalytic a subunits and two noncatalytic b subunits. The a subunits are encoded by the F13A1 gene and synthesized primarily by megakaryocytes, monocytes and macrophages. The b subunits are encoded by the F13B gene and are synthesized by hepatocytes.

Factor XIII deficiency can present with umbilical cord bleeding after birth, intracranial hemorrhage, or delayed bleeding and wound healing after trauma. A factor XIII concentrate is now available for prophylaxis.

Factor XIII deficiency is a rare disorder affecting 1 in 2 million people worldwide. Congenital factor XIII deficiency is inherited in an autosomal recessive pattern of inheritence. FXIII deficiency is usually caused by mutations in the F13A1 gene, but mutations have also been found in the F13B gene. Homozygous individuals have mutations in both copies of either the F13A1 or F13B gene.

Signs and symptoms of inherited factor XIII deficiency begin soon after birth, usually with abnormal bleeding from the umbilical cord. If the condition is not treated, affected individuals may have episodes of excessive and prolonged bleeding that can be life-threatening. Abnormal bleeding can occur after surgery or minor trauma. The condition can also cause spontaneous bleeding into the joints or muscles. Women with inherited factor XIII deficiency tend to have menorrhagia and may experience recurrent pregnancy losses miscarriages. Other signs and symptoms of inherited factor XIII deficiency include nosebleeds, bleeding of the gums, easy bruising, delayed wound healing, and abnormal scar formation. Inherited factor XIII deficiency also increases the risk of intracranial hemorrhage, which is the leading cause of death in people with this condition.

Some people, including parents of individuals with factor XIII deficiency, carry a single mutated copy of the F13A1 or F13B gene in each cell. Carriers usually have 20 to 60 percent of the normal amount of circulating Factor XIII. The majority of carriers do not have abnormal bleeding episodes under normal circumstances and are never diagnosed. However, others may experience abnormal bleeding after surgery, dental work, or major trauma.

Acquired deficiencies of factor XIII become apparent later in life and have been described in association with drugs, chronic renal failure, hepatic cirrhosis, inflammatory bowel disease, myeloid leukemia, and lymphoproliferative disorders. In most cases these acquired deficiencies are partial and do not lead to significant bleeding. The development of inhibitors to factor XIII is a rare cause of depressed factor XIII activity.

Normal clots do not dissolve in less than 24 hours. A level of less than 1‑2% Factor XIII will produce a clot which dissolves in concentrated urea or weak acid. A positive test (dissolution of the clot in < 24 hours) indicates severe Factor XIII deficiency (the homozygous state). Clinically, patients with homozygous Factor XIII deficiency present with soft tissue bleeding, postoperative bleeding, umbilical cord hemorrhage in neonates, and delayed wound healing.

The reference interval for Factor XIII activity using a chromogenic assay is 69-143%.Specimen requirement for testing is one light blue top (sodium citrate) tube of blood.

In February 2011, the US Food and Drug Administration approved Corifact, a product manufactured by CSL Behring of Marburg, Germany, to prevent bleeding in people with congenital Factor XIII deficiency. In 2013, the FDA expanded the use to include perioperative management of surgical bleeding in adults and children. Corifact is made from the pooled plasma of healthy donors and is given by intravenous infusion. Factor XIII has a half-life of approximately 10 days, and only a 5% nadir level is needed for replacement.

In December 2013, the FDA approved Tretten®, a recombinant protein manufactured by Novo Nordisk, for routine prophylaxis in people with congenital FXIII A subunit deficiency. It is an intravenous infusion product for children and adults.

Current guidelines recommend that cryoprecipitate only be used to treat patients with FXIII patients with life- and limb-threatening emergencies when FXIII concentrate is not available.


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