Factor XIII Deficiency

 

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ABSTRACT

Factor XIII (FXIII) is a tetrameric zymogen (FXIII-A₂B₂) that is converted into an active transglutaminase (FXIIIa) by thrombin and Ca²⁺ in the terminal phase of the clotting cascade. By cross-linking fibrin chains and α₂ plasmin inhibitor to fibrin, FXIIIa mechanically stabilizes fibrin and protects it from fibrinolysis. Severe deficiency of the potentially active A subunit (FXIII-A) is a rare but severe hemorrhagic diathesis. Delayed umbilical stump bleeding is characteristic, and subcutaneous, intramuscular, and intracranial bleeding occurs with a relatively high frequency in nonsupplemented patients. In addition, impaired wound healing and spontaneous abortion in women are also features of FXIII deficiency. The extremely rare B subunit deficiency results in milder bleeding symptoms. FXIII concentrate is now available for on-demand treatment and primary prophylaxis. A quantitative FXIII activity assay is recommended as a screening test for the diagnosis of FXIII deficiency. For classification purposes, FXIII-A₂B₂ antigen in the plasma is first determined, and if decreased, further measurement of the individual subunits is recommended in the plasma and FXIII-A in platelet lysate. Analytical aspects of FXIII activity and antigen assays are discussed in this article. There are no hot-spot mutations in the F13A1 and F13B genes, and the majority of causative mutations are missense/nonsense point mutations.

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Mehran KarimiM.D. 

Professor of Pediatric Hematology-Oncology, Hematology Research Center

Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

Email: Karimim@sums.ac.ir