Here we review recent developments concerning the diagnosis, classification and treatment of factor XIII (FXIII) deficiency and new findings related to the pathogenesis of the disease.
Most recently, the International Society on Thrombosis and Haemostasis, Scientific and Standardization Committee published a guideline for the diagnosis and classification of FXIII deficiencies. Since 2009, three novel mutations causing severe bleeding diathesis were discovered in the FXIII-A gene and one in the FXIII-B gene. A newly described FXIII-A deficiency was of the extremely rare qualitative type II deficiency. The first well established founder effect was reported for a causative FXIII-A mutation. More than a quarter of all FXIII-A deficiencies are due to autoantibody, among them the first case of deficiency caused by anti-FXIII-B autoantibody was reported in the last 2 years. The safety and effectiveness of plasma FXIII concentrate for prophylaxis and treatment is now well established. The new recombinant FXIII product is currently in phase III clinical trial and the preliminary data are promising.
FXIII deficiency is considered the most underdiagnosed bleeding diathesis. The recommended algorithm for its diagnosis and classification could improve the diagnostic efficiency. The preferred choice for substitution therapy is FXIII concentrate (plasma-derived or, in the future, recombinant).
aClinical Research Center, University of Debrecen, Medical and Health Science Center
bThrombosis, Hemostasis and Vascular Biology Research Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary
cOUS Dipartimentale per la Diagnosi e Terapia delle Coagulopatie, A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano and Luigi Villa Foundation, Milan, Italy
Correspondence to Flora Peyvandi, MD, PhD, Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, Via Pace, 9-20122 Milan, Italy. Fax: +39 02 54100125; e-mail: email@example.com