title: Diagnosis of factor XIII deficiency.
abstract: 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).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Hematology and Blood Transfusion, School of Allied Medical Sciences , Iran University of Medical Sciences , Tehran , Iran.
authors.forename: Akbar
authors.initials: A
authors.lastname: Dorgalaleh
authors.affiliation: b Department of Hematology and Blood Transfusion, School of Allied Medical Sciences , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Shadi
authors.initials: S
authors.lastname: Tabibian
authors.affiliation: b Department of Hematology and Blood Transfusion, School of Allied Medical Sciences , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Maryam Sadat
authors.initials: MS
authors.lastname: Hosseini
authors.affiliation: b Department of Hematology and Blood Transfusion, School of Allied Medical Sciences , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Yadolla
authors.initials: Y
authors.lastname: Farshi
authors.affiliation: b Department of Hematology and Blood Transfusion, School of Allied Medical Sciences , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Fateme
authors.initials: F
authors.lastname: Roshanzamir
authors.affiliation: c Department of Pediatrics Hematology & Oncology , Ali Ebn-e Abitaleb Hospital Research Center for Children and Adolescents Health [RCCAH], Zahedan University of Medical Sciences , Zahedan , Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Naderi
authors.affiliation: a Department of Hematology and Blood Transfusion, School of Allied Medical Sciences , Iran University of Medical Sciences , Tehran , Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Kazemi
authors.affiliation: d Cellular and Molecular Research Center, Iran University of Medical Sciences , Tehran , Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Zaker
authors.affiliation: b Department of Hematology and Blood Transfusion, School of Allied Medical Sciences , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Ali Noroozi
authors.initials: AN
authors.lastname: Aghideh
authors.affiliation: e School of Nursing and Midwifery , Shahroud University of Medical Sciences , Shahroud , Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Shamsizadeh
mesh_terms: D005177:Factor XIII Deficiency / Q000175:diagnosis*; D006801:Humans
keywords: Factor XIII deficiency; Laboratory diagnosis; Rare bleeding disorder