FACTOR XIII (Fibrin Stabilizing Factor) DEFICIENCY
Factor XIII (FXIII), or fibrin stabilizing factor, deficiency was first reported in the literature in 1960. It is the rarest factor deficiency, occurring in 1 per 5 million births. It is inherited in an autosomal recessive fashion, meaning that both parents must carry the gene to pass it on to their children; it affects men and women equally.
Symptoms
FXIII protein stabilizes the formation of a blood clot. Without it, a clot will still develop, but will then break down and cause recurrent bleeds. Umbilical cord bleeding is common in factor XIII deficiency, reported in almost 80% of cases. Up to 30% of patients sustain a spontaneous intracranial hemorrhage, a brain bleed, which is the leading cause of mortality. Other symptoms of FXIII deficiency include bruising, nose and mouth bleeds, muscle bleeds and delayed bleeding after surgery.
Women can experience menorrhagia, long, heavy menstrual periods, and repeat miscarriages. Men with FXIII deficiency may show signs of infertility.
Testing
Because patients with FXIII deficiency form a clot, clotting tests come back normal. Instead, diagnosis is made using FXIII assays and a clot solubility test.
Treatment
In February 2011, the US Food and Drug Administration (FDA) approved Corifact®, a product manufactured by CSL Behring to prevent bleeding in people with congenital FXIII deficiency. In 2013, the FDA expanded the use to include peri-operative management of surgical bleeding in adults and children. Corifact is given via intravenous infusion.
Corifact is made from the pooled plasma of healthy donors. It can be used for patients lacking FXIII or who have reduced levels of it. People receiving Corifact may develop antibodies against FXIII, making the product ineffective. If higher than recommended doses are given, there is a risk of clot formation.
In December 2013, the FDA approved Tretten®, 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; 95% of patients with FXIII deficiency have the A-subunit deficiency. Tretten is the only recombinant product approved to treat these patients. Common side effects include headache, and pain in the extremities and at the injection site.
Cryoprecipitate should not be used to treat patients with FXIII deficiency except in life- and limb-threatening emergencies when FXIII concentrate is not available.