Background: Factor XIII (FXIII) deficiency is an extremely rare bleeding disorder with estimated incidence of one per two million. All routine coagulation tests are normal in FXIII deficiency (FXIIID), which complicates the diagnosis of this disorder. Precise diagnosis of FXIIID requires more specific tests, including qualitative tests as well as quantitative tests such as FXIII activity, antigen assays, and finally molecular studies to confirm FXIIID.
Objective: This study was conducted to present different quantitative and qualitative methods as well as molecular approaches for screening and diagnosis of FXIIID with advantages and disadvantages of each method.
Methods: All relevant English-language publications were searched in Medline (until 2015).
Results and discussion: Clot solubility assay is the most widely used method for detection of FXIIID but it is not standardized. The sensitivity of this method is dependent upon different factors mainly clotting factors and the solubilizing agents; therefore, FXIII activity assay is recommended for screening of FXIIID. Among FXIII activity assays, photometric assay is more common but FXIII activity is overestimated in this assay due to lack of sample blank in commercial assay, which can have fatal consequences in severe FXIIID, for which fluorometric assay is an appropriate alternative preventing the overestimation observed in photometric assay. There are different methods for measurement of FXIII-A2, FXIII-B2, and FXIII-A2B2 as well as detection and quantification of FXIII inhibitor, which are mentioned in detail in this review. There are no mutational hotspots in FXIII-A and FXIII-B genes with a few recurrent mutations in some populations; therefore, full sequencing of FXIII genes has remained a main molecular approach for confirmation of FXIIID.
Conclusion: Familiarity with different methods for diagnosis of FXIIID and their advantages and disadvantages can help in appropriate and timely diagnosis of this disorder to prevent misdiagnosis of FXIIID and its fatal consequences.
Keywords: Factor XIII deficiency; Laboratory diagnosis; Rare bleeding disorder.