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Review Article| Volume 57, ISSUE 6, P700-704, December 2018

State of the art in factor XIII laboratory assessment

  • Michael A. Durda
    Affiliations
    The Ohio State University College of Medicine, Columbus, OH, United States
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  • Alisa S. Wolberg
    Correspondence
    Corresponding author at: 819 Brinkhous-Bullitt Building, CB #7525, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7525, United States.
    Affiliations
    University of North Carolina at Chapel Hill, Department of Pathology and Laboratory Medicine, Chapel Hill, NC, United States
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  • Bryce A. Kerlin
    Affiliations
    Nationwide Children’s Hospital, Division of Hematology/Oncology/Blood and Marrow Transplantation, Columbus, OH, United States

    The Research Institute at Nationwide Children’s Hospital, Center for Clinical & Translational Research, Columbus, OH, United States

    The Ohio State University College of Medicine, Department of Pediatrics, Columbus, OH, United States
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      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.

      Abbreviations:

      FXIII (Factor XIII), pFXIII (Plasma Factor XIII), FXIIIa (activated form of blood coagulation FXIII), FXIII-A (Factor XIII A-subunit monomer), FXIII-A2 (Factor XIII A-subunit dimer), FXIII-B (Factor XIII B-subunit monomer), FXIII-B2 (Factor XIII B-subunit dimer), FXIII-A2B2 (subunit structure of plasma FXIII), FXIII-A2* (active A subunit dimer), α2-AP (α2-antiplasmin)

      Keywords

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      References

        • Karimi M.
        • Bereczky Z.
        • Cohan N.
        • Muszbek L.
        Factor XIII deficiency.
        Semin Thromb Hemost. 2009; 35: 426-438
        • Muszbek L.
        • Ariens R.A.
        • Ichinose A.
        Isth Ssc subcommittee on factor X. factor XIII: recommended terms and abbreviations.
        J Thromb Haemost JTH. 2007; 5: 181-183
        • Hsu P.
        • Zantek N.D.
        • Meijer P.
        • Hayward C.P.
        • Brody J.
        • Zhang X.
        • et al.
        Factor XIII assays and associated problems for laboratory diagnosis of factor XIII deficiency: an analysis of international proficiency testing results.
        Semin Thromb Hemost. 2014; 40: 232-238
        • Lorand L.
        Factor XIII: structure, activation, and interactions with fibrinogen and fibrin.
        Ann NY Acad Sci. 2001; 936: 291-311
        • Kimura S.
        • Aoki N.
        Cross-linking site in fibrinogen for alpha 2-plasmin inhibitor.
        J Boil Chem. 1986; 261: 15591-15595
        • Sakata Y.
        • Aoki N.
        Cross-linking of alpha 2-plasmin inhibitor to fibrin by fibrin-stabilizing factor.
        J Clin Investig. 1980; 65: 290-297
        • Byrnes J.R.
        • Wilson C.
        • Boutelle A.M.
        • Brandner C.B.
        • Flick M.J.
        • Philippou H.
        • et al.
        The interaction between fibrinogen and zymogen FXIII-A2B2 is mediated by fibrinogen residues gamma390-396 and the FXIII-B subunits.
        Blood. 2016; 128: 1969-1978
        • Muszbek L.
        • Bagoly Z.
        • Bereczky Z.
        • Katona E.
        The involvement of blood coagulation factor XIII in fibrinolysis and thrombosis.
        Cardiovasc Hematol Agents Med Chem. 2008; 6: 190-205
        • Fraser S.R.
        • Booth N.A.
        • Mutch N.J.
        The antifibrinolytic function of factor XIII is exclusively expressed through alpha(2)-antiplasmin cross-linking.
        Blood. 2011; 117: 6371-6374
        • Duckert F.
        • Jung E.
        • Shmerling D.H.
        A hitherto undescribed congenital haemorrhagic diathesis probably due to fibrin stabilizing factor deficiency.
        Thrombosis et diathesis haemorrhagica. 1960; 5: 179-186
        • Seitz R.
        • Duckert F.
        • Lopaciuk S.
        • Muszbek L.
        • Rodeghiero F.
        • Seligsohn U.
        ETRO working party on factor XIII questionnaire on congenital factor XIII deficiency in Europe: status and perspectives. Study group.
        Semin Thromb Hemost. 1996; 22: 415-418
        • Inbal A.
        • Lubetsky A.
        • Krapp T.
        • Castel D.
        • Shaish A.
        • Dickneitte G.
        • et al.
        Impaired wound healing in factor XIII deficient mice.
        Thromb Haemost. 2005; 94: 432-437
        • Dardik R.
        • Loscalzo J.
        • Inbal A.
        Factor XIII (FXIII) and angiogenesis.
        J Thromb Haemost JTH. 2006; 4: 19-25
        • Inbal A.
        • Muszbek L.
        Coagulation factor deficiencies and pregnancy loss.
        Semin Thromb Hemost. 2003; 29: 171-174
        • Koseki-Kuno S.
        • Yamakawa M.
        • Dickneite G.
        • Ichinose A.
        Factor XIII a subunit-deficient mice developed severe uterine bleeding events and subsequent spontaneous miscarriages.
        Blood. 2003; 102: 4410-4412
        • Menegatti M.
        • Palla R.
        • Boscarino M.
        • Bucciarelli P.
        • Muszbek L.
        • Katona E.
        • et al.
        Minimal factor XIII activity level to prevent major spontaneous bleeds.
        J Thromb Haemost JTH. 2017;
        • Peyvandi F.
        • Palla R.
        • Menegatti M.
        • Siboni S.M.
        • Halimeh S.
        • Faeser B.
        • et al.
        Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European network of rare bleeding disorders.
        J Thromb Haemost JTH. 2012; 10: 615-621
        • Ichinose A.
        • Japanese Collaborative Research Group on AH
        Autoimmune acquired factor XIII deficiency due to anti-factor XIII/13 antibodies: a summary of 93 patients.
        Blood Rev. 2017; 31: 37-45
        • Biswas A.
        • Ivaskevicius V.
        • Thomas A.
        • Oldenburg J.
        Coagulation factor XIII deficiency. Diagnosis, prevalence and management of inherited and acquired forms.
        Hamostaseologie. 2014; 34: 160-166
        • Kohler H.P.
        • Ichinose A.
        • Seitz R.
        • Ariens R.A.
        • Muszbek L.
        • Factor X.
        • et al.
        Diagnosis and classification of factor XIII deficiencies.
        J Thromb Haemost JTH. 2011; 9: 1404-1406
        • Jennings I.
        • Kitchen S.
        • Woods T.A.
        • Preston F.E.
        • Uk N.
        Problems relating to the laboratory diagnosis of factor XIII deficiency: a UK NEQAS study.
        J Thromb Haemost JTH. 2003; 1: 2603-2608
        • Jennings I.
        • Kitchen S.
        • Menegatti M.
        • Palla R.
        • Walker I.
        • Makris M.
        • et al.
        Detection of factor XIII deficiency: data from multicentre exercises amongst UK NEQAS and PRO-RBDD project laboratories.
        Int J Lab Hematol. 2017; 39: 350-358
        • Ajzner E.
        • Muszbek L.
        Kinetic spectrophotometric factor XIII activity assays: the subtraction of plasma blank is not omissible [corrected].
        J Thromb Haemost JTH. 2004; 2: 2075-2077
        • Parameswaran K.N.
        • Cheng X.F.
        • Chen E.C.
        • Velasco P.T.
        • Wilson J.H.
        • Lorand L.
        Hydrolysis of gamma:epsilon isopeptides by cytosolic transglutaminases and by coagulation factor XIIIa.
        J Boil Chem. 1997; 272: 10311-10317
        • Oertel K.
        • Hunfeld A.
        • Specker E.
        • Reiff C.
        • Seitz R.
        • Pasternack R.
        • et al.
        A highly sensitive fluorometric assay for determination of human coagulation factor XIII in plasma.
        Anal Biochem. 2007; 367: 152-158
      1. TECHNOCHROM® FXIII package insert.
        diapharma, 2018
      2. Berichrom factor XIII chromogenic package insert.
        Siemens Healthineers, 2018 (Available from:)
        • Lawrie A.S.
        • Green L.
        • Mackie I.J.
        • Liesner R.
        • Machin S.J.
        • Peyvandi F.
        Factor XIII--an under diagnosed deficiency--are we using the right assays?.
        J Thromb Haemost JTH. 2010; 8: 2478-2482
        • Song Y.C.
        • Sheng D.
        • Taubenfeld S.M.
        • Matsueda G.R.
        A microtiter assay for factor XIII using fibrinogen and biotinylcadaverine as substrates.
        Anal Biochem. 1994; 223: 88-92
        • Wilmer M.
        • Rudin K.
        • Kolde H.
        • Poetzsch B.
        • Lenz W.
        • Moessmer G.
        • et al.
        Evaluation of a sensitive colorimetric FXIII incorporation assay. Effects of FXIII Val34Leu, plasma fibrinogen concentration and congenital FXIII deficiency.
        Thromb Res. 2001; 102: 81-91
        • Rijken D.C.
        • Abdul S.
        • Malfliet J.J.
        • Leebeek F.W.
        • Uitte de Willige S.
        Compaction of fibrin clots reveals the antifibrinolytic effect of factor XIII.
        J Thromb Haemost JTH. 2016; 14: 1453-1461
        • Kohler H.P.
        • Ariens R.A.
        • Whitaker P.
        • Grant P.J.
        A common coding polymorphism in the FXIII a-subunit gene (FXIIIVal34Leu) affects cross-linking activity.
        Thromb Haemost. 1998; 80: 704
        • Katona E.
        • Haramura G.
        • Karpati L.
        • Fachet J.
        • Muszbek L.
        A simple, quick one-step ELISA assay for the determination of complex plasma factor XIII (A2B2).
        Thromb Haemost. 2000; 83: 268-273
        • Kerlin B.
        • Brand B.
        • Inbal A.
        • Halimeh S.
        • Nugent D.
        • Lundblad M.
        • et al.
        Pharmacokinetics of recombinant factor XIII at steady state in patients with congenital factor XIII a-subunit deficiency.
        J Thromb Haemost JTH. 2014; 12: 2038-2043
      3. World Federation of hemophilia report on the Annual Global Survey 2012.
        2013 (Montreal, QC, Canada)
        • Biswas A.
        • Ivaskevicius V.
        • Seitz R.
        • Thomas A.
        • Oldenburg J.
        An update of the mutation profile of factor 13 A and B genes.
        Blood Rev. 2011; 25: 193-204
        • Karimi M.
        • Peyvandi F.
        • Naderi M.
        • Shapiro A.
        Factor XIII deficiency diagnosis: challenges and tools.
        Int J Lab Hematol. 2018; 40: 3-11
        • Dorgalaleh A.
        • Assadollahi V.
        • Tabibian S.
        • Shamsizadeh M.
        Molecular basis of congenital factor XIII deficiency in Iran.
        Clin Appl Thromb/Hemost. 2016; (1076029616680473)
        • Eshghi P.
        • Cohan N.
        • Lak M.
        • Naderi M.
        • Peyvandi F.
        • Menegatti M.
        • et al.
        Arg77His and Trp187Arg are the most common mutations causing FXIII deficiency in Iran.
        Clin Appl Thromb/Hemost. 2012; 18: 100-103