State of the art in factor XIII laboratory assessment

Abstract

Factor XIII, a heterotetrameric proenzyme, is converted to an activated transglutaminase by thrombin and calcium in the final phases of coagulation. Factor XIII catalyzes the formation of crosslinks between fibrin monomers and between α2-antiplasmin and fibrin. These crosslinks mechanically stabilize fibrin against shear stress, enable red cell retention within the clot, and protect the clot from premature degradation. Congenital factor XIII deficiency is caused by autosomal recessive mutations, presenting early in life with a severe bleeding diathesis. Acquired deficiency may be caused by autoimmunity. Currently available assays for laboratory diagnosis of factor XIII deficiency include clot solubility assays, quantitative factor XIII activity assays, factor XIII antigen assays, and genetic testing. The International Society on Thrombosis and Haemostasis Scientific and Standardization Committee has recommended an algorithm for the laboratory diagnosis and differentiation of the different forms of factor XIII deficiency. However, implementation of this algorithm has been limited by technical and budgetary challenges associated with the currently available factor XIII-specific assays. The purpose of this review is to discuss the advantages and limitations of the currently available assays employed for the laboratory diagnosis of factor XIII deficiency.

Keywords: Amine incorporation; Ammonia release; Assays; Clot solubility; ELISA; Factor XIII deficiency; Isopeptidase; Rare bleeding disorder.