Unexpected Bleeding Normal Coagulation Tests: Congenital Factor XIII Deficiency

Congenital factor XIII deficiency is a very rare bleeding disorder, which affects one in 1-2 million patients globally and is a difficult disease to diagnose, because of the normality of routine coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen levels. This coagulopathy is either congenital or acquired, but most documented cases are congenital, being caused by the mutation of F13A1 gene which encodes the A subunit of the factor XIII heterotetramer (A2B2 complex). The clinical manifestations of factor XIII deficiency consist in uncontrolled bleeding, poor wound healing, even miscarriages in young women and intracranial bleeding. Management of this deficiency is based on replacement therapy, including factor XIII concentrates (both plasma-derived and recombinant), cryoprecipitate and fresh frozen plasma, each having specific indications and adverse reactions. The clinical case presented above illustrates a young female with a history of multiple episodes of spontaneous hemoperitoneum, a severe adverse reaction to fresh frozen plasma (TRALI) and a delayed factor XIII deficiency diagnosis.