Factor XIII deficiency
Encyclopedia
Factor XIII
deficiency may occur very rarely, and can cause a severe bleeding tendency. Incidence is 1 in a million to 1 in 5 million people. Most are due to mutations in the A subunit. Administration of recombinant
A subunit improves clot stability and is becoming a therapeutic option for patients with this condition. This deficiency leads to defective cross-linking of fibrin
and vulnerability to late re-bleeds when the primary hemostatic
plug is overwhelmed. Bleeding tendencies similar to hemophiliacs develop such as hemarthroses and deep tissue bleeding.
’s rFXIII is not currently a marketed drug but just recently finished phase III clinical trials in Spring 2010. 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
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 pharmokinetics studies have reported no immunogenic response to rFXIII or associated yeast products.
Factor XIII
Factor XIII or fibrin stabilizing factor is an enzyme of the blood coagulation system that crosslinks fibrin.- Function :Factor XIII is a transglutaminase that circulates in the plasma as a heterotetramer of two catalytic A subunits and two carrier B subunits...
deficiency may occur very rarely, and can cause a severe bleeding tendency. Incidence is 1 in a million to 1 in 5 million people. Most are due to mutations in the A subunit. Administration of recombinant
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
A subunit improves clot stability and is becoming a therapeutic option for patients with this condition. This deficiency leads to defective cross-linking of fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
and vulnerability to late re-bleeds when the primary hemostatic
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
plug is overwhelmed. Bleeding tendencies similar to hemophiliacs develop such as hemarthroses and deep tissue bleeding.
Fresh frozen plasma and cryoprecipitate
Fresh frozen plasma and cryoprecipitate are the mainstay of therapy for Factor XIII deficiency, but carries risk related to transfusion.Factor XIII concentrates
Two commercially-produced factor XIII concentrates are currently available in Europe, one is manufactured by Bio Products Laboratory (BPL) and is only available in the United Kingdom, and the other called Fibrogammin-P and is produced by Beringwerke of Germany. FXIII concentrate is only available under IND or through clinical trial in the United States.Recombinant Factor XIII
Recombinant Factor XIII (rFXIII) is the only prospective drug alternative to receiving blood transfusions, the traditional treatment for Factor XIII deficiency. Novo NordiskNovo Nordisk
Novo Nordisk manufactures and markets pharmaceutical products and services. Created in 1989 through a merger of two Danish companies dating back to the 1920s, it has become one of the world's leading companies in diabetes care, where Novo Nordisk pursues research into pulmonary delivery systems;...
’s rFXIII is not currently a marketed drug but just recently finished phase III clinical trials in Spring 2010. 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
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
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 pharmokinetics studies have reported no immunogenic response to rFXIII or associated yeast products.