Factor XIII Factor XIII or fibrin stabilizing factor is a zymogen found in blood of humans and some other animals. It is activated by thrombin to factor XIIIa. Factor XIIIa is an enzyme of the blood coagulation system that crosslinks fibrin. Deficiency of X ...

deficiency occurs exceedingly rarely, causing a severe bleeding tendency. The incidence is one in a million to one in five million people, with higher incidence in areas with consanguineous marriage such as Iran that has the highest global incidence of the disorder. Most are due to mutations in the A subunit gene (located on chromosome 6p25-p24). This mutation is inherited in an autosomal recessive fashion. Deficiency of Factor XIII leads to defective cross-linking of fibrin and vulnerability to late re-bleeds when the primary

hemostatic An antihemorrhagic (antihæmorrhagic) agent is a substance that promotes hemostasis (stops bleeding). It may also be known as a hemostatic (also spelled haemostatic) agent. Antihemorrhagic agents used in medicine have various mechanisms of action: ...

plug is overwhelmed. Bleeding tendencies similar to hemophiliacs develop, such as hemarthroses and deep tissue bleeding. As Factor XIII is composed of two subunit protein, A and B, for which the genes are located on different chromosomes, administration of recombinant A subunit improves clot stability and is becoming a therapeutic option for patients with this condition.

Signs and symptoms

Diagnosis

Bleeding manifestation with normal PT, aPTT, TT, BT, and CT is suspected as factor XIII Deficiency. Confirmatory test is urea lysis test. If clot is easily lysed in 5(M) urea solution then unstable clot and factor-XIII deficiency is confirmed.

Treatment

Fresh frozen plasma and cryoprecipitate

Fresh frozen plasma and cryoprecipitate are the mainstay of therapy for Factor XIII deficiency, but carry risk related to transfusion.

Factor XIII concentrates

Two commercially produced factor XIII concentrates are currently available in Europe, one manufactured by Bio Products Laboratory (BPL) and only available in the United Kingdom. The other, Fibrogammin-P, is produced by Beringwerke of Germany. In the U.S. FXIII concentrate is only available under the Federal Drug Administration's Investigational New Drug (IND) Program, or through clinical trial.

Recombinant factor XIII

Recombinant factor XIII (rFXIII) is the only drug alternative to receiving blood transfusions, the traditional treatment for factor XIII deficiency.

Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...

’s rFXIII, catridecacog, was approved by the

US Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

in 2014. Although it is a recombinant protein, rFXIII subunit A is identical in structure and function to the A subunit of factor XIII naturally produced in the body by healthy individuals. These patients need exogenous subunit A of factor XIII since they have a mutation which prevents production of the A subunit. However, since the B-subunit is located on a separate chromosome, factor XIII deficient patients actually produce the B-subunit normally. When these two subunits interact in the plasma, the enzyme is activated and can act within the clotting cascade. rFXIII acts by inhibiting

fibrinolysis Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other ...

factors which enzymatically cleave the fibrin matrix, leading to the ultimate formation of clots. rFXIII is synthetically bio-engineered through a yeast expression system and administered intravenously. In clinical trials, the drug was administered once every four weeks or administered on-demand in order to treat bleeding episodes. The introduction of rFXIII as a treatment for factor XIII deficiency eliminates the risk of pathogenic infection present in plasma-based treatments. rFXIII treatment would also not be dependent on blood donations, consequently increasing availability and product quality. One of the biggest fears in developing rFXIII was that the body would mount an immune-response to the protein; however, several safety and pharmacokinetics studies have reported no

immunogenic Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injectio ...

response to rFXIII or associated yeast products.

References

External links

{{Diseases of megakaryocytes, us=y Coagulopathies Haemophilia