Immune-Related and Non-Immune-Related Acquired Factor XIII Deficiency

Abstract

Coagulation factor XIII (FXIII) is an essential protein that stabilizes the hemostatic plug formed in the final stage of the coagulation reaction and controls its dissolution. In the blood, it exists as a heterotetramer consisting of A subunit dimers and B subunit dimers. Genetic defects in each subunit result in a congenital deficiency, which causes fatal or mild bleeding symptoms. Acquired FXIII deficiency can develop owing to reduced production or increased consumption of FXIII, and its severe form can cause various bleeding symptoms. In particular, autoimmune FXIII deficiency (AiF13D) causes fatal bleeding symptoms due to the suppression of FXIII activity by anti-FXIII autoantibodies and/or accelerated clearance of FXIII. AiF13D is characterized by extremely severe FXIII deficiency and severe bleeding symptoms. It is associated with the highest hemorrhagic mortality rate among autoimmune coagulation factor deficiencies, making it essential to differentiate it from other non-immune FXIII deficiencies (NiF13D), such as those arising from liver cirrhosis or leukemia. The probable and definitive diagnosis of AiF13D require the presence of FXIII inhibitors and anti-FXIII autoantibodies, respectively. FXIII inhibitors can be detected by a general FXIII activity assay in the mixed plasma of patients and healthy controls, and can be measured in a regular laboratory. In contrast, immunological assays are conducted in limited research facilities because they are not commercially available. NiF13D is usually treated by hemostatic therapy with FXIII concentrates, but AiF13D requires hemostatic therapy plus autoantibody eradication therapy with immunosuppressants. Since the disease often becomes resistant to treatment, long-term follow-up is strongly recommended.

Keywords

anti-factor XIII autoantibody - factor XIII inhibitor - hyper-clearance - hypo-production - hyper-consumption

Note

Core members of the Japanese Collaborative Research Group (JCRG) on autoimmune coagulation factor deficiencies (AiCFDs): A. Ichinose, T. Konta, M. Souri, T. Osaki, C. Yokoyama, M. Ieko, Y. Ogawa, H. Asakura, H. Wada, T. Hashiguchi, and I. Maruyama.

Author Contribution

A.I. initiated and designed the study, extracted data, wrote, edited, and proofread the manuscript.

Ethical Approval

The study protocol was reviewed and approved by the Ethics Committee of Yamagata University School of Medicine, Yamagata, Japan (approval number 2021–273). Written informed consent was obtained for participation in this study. All procedures were conducted in accordance with the Declaration of Helsinki.

Publikationsverlauf

Eingereicht: 01. März 2025

Angenommen: 11. Juni 2025

Accepted Manuscript online:
12. Juni 2025

Artikel online veröffentlicht:
09. Juli 2025

• References

• 1 Lorand JB, Urayama T, Lorand L. Transglutaminase as a blood clotting enzyme. Biochem Biophys Res Commun 1966; 23 (06) 828-834
• 2 Ichinose A. Physiopathology and regulation of factor XIII. Thromb Haemost 2001; 86 (01) 57-65
• 3 Lorand L. Factor XIII: structure, activation, and interactions with fibrinogen and fibrin. Ann N Y Acad Sci 2001; 936: 291-311
• 4 Lorand L, Dickenman RC. Assay method for the fibrin-stabilizing factor. Proc Soc Exp Biol Med 1955; 89 (01) 45-48
• 5 Laki K, Lóránd L. On the solubility of fibrin clots. Science 1948; 108 (2802): 280
• 6 Loewy AG, Edsall JT. Studies on the formation of urea-insoluble fibrin. J Biol Chem 1954; 211 (02) 829-838
• 7 Lorand L, Urayama T, De Kiewiet JW, Nossel HL. Diagnostic and genetic studies on fibrin-stabilizing factor with a new assay based on amine incorporation. J Clin Invest 1969; 48 (06) 1054-1064
• 8 Loewy AG, Dunathan K, Kriel R, Wolfinger Jr HL. Fibrinase. I. Purification of substrate and enzyme. J Biol Chem 1961; 236: 2625-2633
• 9 Muszbek L, Ariëns RA, Ichinose A. ISTH SSC Subcommittee on Factor XIII. Factor XIII: recommended terms and abbreviations. J Thromb Haemost 2007; 5 (01) 181-183
• 10 Schwartz ML, Pizzo SV, Hill RL, McKee PA. The subunit structures of human plasma and platelet factor XIII (fibrin-stabilizing factor). J Biol Chem 1971; 246 (18) 5851-5854
• 11 Souri M, Koseki-Kuno S, Takeda N, Degen JL, Ichinose A. Administration of factor XIII B subunit increased plasma factor XIII A subunit levels in factor XIII B subunit knock-out mice. Int J Hematol 2008; 87 (01) 60-68
• 12 Byrnes JR, Lee T, Sharaby S. et al. Reciprocal stabilization of coagulation factor XIII-A and -B subunits is a determinant of plasma FXIII concentration. Blood 2024; 143 (05) 444-455
• 13 Katona E, Pénzes K, Csapó A. et al. Interaction of factor XIII subunits. Blood 2014; 123 (11) 1757-1763
• 14 Ichinose A. Factor XIII is a key molecule at the intersection of coagulation and fibrinolysis as well as inflammation and infection control. Int J Hematol 2012; 95 (04) 362-370
• 15 Bagoly Z, Katona E, Muszbek L. Factor XIII and inflammatory cells. Thromb Res 2012; 129 (Suppl. 02) S77-S81
• 16 Ichinose A, McMullen BA, Fujikawa K, Davie EW. Amino acid sequence of the b subunit of human factor XIII, a protein composed of ten repetitive segments. Biochemistry 1986; 25 (16) 4633-4638
• 17 Ichinose A, Hendrickson LE, Fujikawa K, Davie EW. Amino acid sequence of the a subunit of human factor XIII. Biochemistry 1986; 25 (22) 6900-6906
• 18 Kaetsu H, Hashiguchi T, Foster D, Ichinose A. Expression and release of the a and b subunits for human coagulation factor XIII in baby hamster kidney (BHK) cells. J Biochem 1996; 119 (05) 961-969
• 19 Ichinose A. Extracellular transglutaminase: factor XIII. Prog Exp Tumor Res 2005; 38: 192-208
• 20 Ichinose A, Bottenus RE, Davie EW. Structure of transglutaminases. J Biol Chem 1990; 265 (23) 13411-13414
• 21 Yee VC, Pedersen LC, Le Trong I, Bishop PD, Stenkamp RE, Teller DC. Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII. Proc Natl Acad Sci U S A 1994; 91 (15) 7296-7300
• 22 Protopopova AD, Ramirez A, Klinov DV, Litvinov RI, Weisel JW. Factor XIII topology: organization of B subunits and changes with activation studied with single-molecule atomic force microscopy. J Thromb Haemost 2019; 17 (05) 737-748
• 23 Singh S, Hagelueken G, Ugurlar D. et al. Cryo-EM structure of the human native plasma coagulation factor XIII complex. Blood 2025; 145 (04) 438-449
• 24 Board PG, Webb GC, McKee J, Ichinose A. Localization of the coagulation factor XIII A subunit gene (F13A) to chromosome bands 6p24—-p25. Cytogenet Cell Genet 1988; 48 (01) 25-27
• 25 Ichinose A, Davie EW. Characterization of the gene for the a subunit of human factor XIII (plasma transglutaminase), a blood coagulation factor. Proc Natl Acad Sci U S A 1988; 85 (16) 5829-5833
• 26 Kida M, Souri M, Yamamoto M, Saito H, Ichinose A. Transcriptional regulation of cell type-specific expression of the TATA-less A subunit gene for human coagulation factor XIII. J Biol Chem 1999; 274 (10) 6138-6147
• 27 Izumi T, Nagaoka U, Saito T, Takamatsu J, Saito H, Ichinose A. Novel deletion and insertion mutations cause splicing defects, leading to severe reduction in mRNA levels of the A subunit in severe factor XIII deficiency. Thromb Haemost 1998; 79 (03) 479-485
• 28 Wang W, Huang L, Ma Q. et al. Homozygous intronic mutation leading to inefficient transcription combined with a novel frameshift mutation in F13A1 gene causes FXIII deficiency. J Hum Genet 2011; 56 (06) 460-463
• 29 Kaczmarek E, Liu Y, Berse B, Chen CS, McDonagh J. Biosynthesis of plasma factor XIII: evidence for transcription and translation in hepatoma cells. Biochim Biophys Acta 1995; 1247 (01) 127-134
• 30 Beckers CML, Simpson KR, Griffin KJ. et al. Cre/lox studies identify resident macrophages as the major source of circulating coagulation factor XIII-A. Arterioscler Thromb Vasc Biol 2017; 37 (08) 1494-1502
• 31 Webb GC, Coggan M, Ichinose A, Board PG. Localization of the coagulation factor XIII B subunit gene (F13B) to chromosome bands 1q31-32.1 and restriction fragment length polymorphism at the locus. Hum Genet 1989; 81 (02) 157-160
• 32 Rodriguez de Cordoba S, Rey-Campos J, Dykes DD, McAlpine PJ, Wong P, Rubinstein P. Coagulation factor XIII B subunit is encoded by a gene linked to the regulator of complement activation (RCA) gene cluster in man. Immunogenetics 1988; 28 (06) 452-454
• 33 Bottenus RE, Ichinose A, Davie EW. Nucleotide sequence of the gene for the b subunit of human factor XIII. Biochemistry 1990; 29 (51) 11195-11209
• 34 Inoue Y, Peters LL, Yim SH, Inoue J, Gonzalez FJ. Role of hepatocyte nuclear factor 4alpha in control of blood coagulation factor gene expression. J Mol Med (Berl) 2006; 84 (04) 334-344
• 35 Shirahata A, Nakamura T, Shiiki M. [Pathophysiology of coagulation in the newborn infant] [in Japanese]. Rinsho Ketsueki 1987; 28 (07) 1065-1074
• 36 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70 (01) 165-172
• 37 Hayano Y, Imai N, Karasawa T. [Studies on the physiological changes of blood coagulation factor XIII during pregnancy and their significance (author's transl)] [in Japanese]. Nippon Sanka Fujinka Gakkai Zasshi 1982; 34 (04) 469-477
• 38 The Human Gene Mutation Database. Institute of Medical Genetics in Cardiff. Accessed February 28, 2025 at: https://www.hgmd.cf.ac.uk/
• 39 Ichinose A, Izumi T, Hashiguchi T. The normal and abnormal genes of the a and b subunits in coagulation factor XIII. Semin Thromb Hemost 1996; 22 (05) 385-391
• 40 Duckert F, Jung E, Shmerling DH. A hitherto undescribed congenital haemorrhagic diathesis probably due to fibrin stabilizing factor deficiency. Thromb Diath Haemorrh 1960; 5: 179-186
• 41 Kohler HP, Ichinose A, Seitz R, Ariens RA, Muszbek L. Factor XIII and Fibrinogen SSC Subcommittee of the ISTH. Diagnosis and classification of factor XIII deficiencies. J Thromb Haemost 2011; 9 (07) 1404-1406
• 42 Saito M, Asakura H, Yoshida T. et al. A familial factor XIII subunit B deficiency. Br J Haematol 1990; 74 (03) 290-294
• 43 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 (13) 4410-4412
• 44 Kamura T, Okamura T, Murakawa M. et al. Deficiency of coagulation factor XIII A subunit caused by the dinucleotide deletion at the 5′ end of exon III. J Clin Invest 1992; 90 (02) 315-319
• 45 Hashiguchi T, Saito M, Morishita E, Matsuda T, Ichinose A. Two genetic defects in a patient with complete deficiency of the b-subunit for coagulation factor XIII. Blood 1993; 82 (01) 145-150
• 46 Schroeder V, Meili E, Cung T, Schmutz P, Kohler HP. Characterisation of six novel A-subunit mutations leading to congenital factor XIII deficiency and molecular analysis of the first diagnosed patient with this rare bleeding disorder. Thromb Haemost 2006; 95 (01) 77-84
• 47 Hashiguchi T, Ichinose A. Molecular and cellular basis of deficiency of the b subunit for factor XIII secondary to a Cys430-Phe mutation in the seventh Sushi domain. J Clin Invest 1995; 95 (03) 1002-1008
• 48 Koseki S, Souri M, Koga S. et al. Truncated mutant B subunit for factor XIII causes its deficiency due to impaired intracellular transportation. Blood 2001; 97 (09) 2667-2672
• 49 Zhang WG, Souri M, Ichinose A. Proteosomal degradation of naturally recurring R260C missense and exon-IV deletion mutants of factor XIII A-subunit expressed in mammalian cells. Haemophilia 2013; 19 (03) 415-419
• 50 Peyvandi F, Palla R, Menegatti M. et al; European Network of Rare Bleeding Disorders Group. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost 2012; 10 (04) 615-621
• 51 Menegatti M, Palla R, Boscarino M. et al; PRO-RBDD study group. Minimal factor XIII activity level to prevent major spontaneous bleeds. J Thromb Haemost 2017; 15 (09) 1728-1736
• 52 Seitz R, Duckert F, Lopaciuk S, Muszbek L, Rodeghiero F, Seligsohn U. Study Group. ETRO Working Party on Factor XIII questionnaire on congenital factor XIII deficiency in Europe: status and perspectives. Semin Thromb Hemost 1996; 22 (05) 415-418
• 53 Ivaskevicius V, Biswas A, Bevans C. et al. Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function. Haematologica 2010; 95 (06) 956-962
• 54 Dorgalaleh A. Novel insights into heterozygous factor XIII deficiency. Semin Thromb Hemost 2024; 50 (02) 200-212
• 55 Mannucci PM. Bleeding symptoms in heterozygous factor XIII [corrected] deficiency. Haematologica 2010; 95 (09) e6
• 56 Elbatarny M, Mollah S, Grabell J. et al; Zimmerman Program Investigators. Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from the merging project. Haemophilia 2014; 20 (06) 831-835
• 57 Singh S, Pezeshkpoor B, Jamil MA. et al. Heterozygosity in factor XIII genes and the manifestation of mild inherited factor XIII deficiency. J Thromb Haemost 2024; 22 (02) 379-393
• 58 Nussbaum M, Morse BS. Plasma fibrin stabilizing factor activity in various diseases. Blood 1964; 23: 669-678
• 59 Mandel EE, Gerhold WM. Plasma fibrin-stabilizing factor: acquired deficiency in various disorders. Am J Clin Pathol 1969; 52 (05) 547-556
• 60 Yan MTS, Rydz N, Goodyear D, Sholzberg M. Acquired factor XIII deficiency: a review. Transfus Apher Sci 2018; 57 (06) 724-730
• 61 Ichinose A. Hemorrhagic acquired factor XIII (13) deficiency and acquired hemorrhaphilia 13 revisited. Semin Thromb Hemost 2011; 37 (04) 382-388
• 62 Franchini M, Frattini F, Crestani S, Bonfanti C. Acquired FXIII inhibitors: a systematic review. J Thromb Thrombolysis 2013; 36 (01) 109-114
• 63 Ichinose A. Japanese Collaborative Research Group on AH13. Autoimmune acquired factor XIII deficiency due to anti-factor XIII/13 antibodies: a summary of 93 patients. Blood Rev 2017; 31 (01) 37-45
• 64 Ichinose A, Osaki T, Souri M. Diagnosis and treatment of autoimmune acquired coagulation factor deficiencies: an evidence-based review of Japanese practice. Semin Thromb Hemost 2025; 51 (05) 491-505
• 65 Souri M, Osaki T, Ichinose A. Anti-factor XIII A subunit (FXIII-A) autoantibodies block FXIII-A2 B2 assembly and steal FXIII-A from native FXIII-A2 B2. J Thromb Haemost 2015; 13 (05) 802-814
• 66 Smith J, Bodine JS, Cunningham MT. et al. Perioperative therapeutic plasma exchange in a patient with rare factor XIII inhibitor. Transfus Apher Sci 2023; 62 (03) 103654
• 67 Lee KN, Birckbichler PJ, Patterson Jr MK. Colorimetric assay of blood coagulation factor XIII in plasma. Clin Chem 1988; 34 (05) 906-910
• 68 Kohler HP, Ariëns RA, Whitaker P, Grant PJ. A common coding polymorphism in the FXIII A-subunit gene (FXIIIVal34Leu) affects cross-linking activity. Thromb Haemost 1998; 80 (04) 704
• 69 Souri M, Osaki T, Ichinose A. Detection of factor XIII inhibitors in 33 patients with autoimmune factor XIII deficiency in Japan. Int J Hematol 2024; 120 (04) 472-481
• 70 Ichinose A, Tamaki T, Aoki N. Factor XIII-mediated cross-linking of NH2-terminal peptide of alpha 2-plasmin inhibitor to fibrin. FEBS Lett 1983; 153 (02) 369-371
• 71 Ichinose A, Aoki N. Reversible cross-linking of alpha 2-plasmin inhibitor to fibrinogen by fibrin-stabilizing factor. Biochim Biophys Acta 1982; 706 (02) 158-164
• 72 Leitner M, Büchold C, Pasternack R, Binder NB, Moore GW. Clinical validation of an automated fluorogenic factor XIII activity assay based on isopeptidase activity. Int J Mol Sci 2021; 22 (03) 1002
• 73 Chou SC, Lin CY, Yen CT. et al. Acquired FXIII inhibitor: patient characteristics and treatment outcome, a case series in Taiwan. J Formos Med Assoc 2021; 120 (1 Pt 2): 411-414
• 74 Pénzes K, Rázsó K, Katona É, Kerényi A, Kun M, Muszbek L. Neutralizing autoantibody against factor XIII A subunit resulted in severe bleeding diathesis with a fatal outcome—characterization of the antibody. J Thromb Haemost 2016; 14 (08) 1517-1520
• 75 Bovet J, Hurják B, De Maistre E, Katona É, Pénzes K, Muszbek L. Autoimmune factor XIII deficiency with unusual laboratory and clinical phenotype. J Thromb Haemost 2020; 18 (06) 1330-1334
• 76 Ichinose A, Osaki T, Souri M. Pathological coagulation parameters in as many as 54 patients with autoimmune acquired factor XIII deficiency due to anti-factor XIII autoantibodies. Haemophilia 2021; 27 (03) 454-462
• 77 Ajzner E, Schlammadinger A, Kerényi A. et al. Severe bleeding complications caused by an autoantibody against the B subunit of plasma factor XIII: a novel form of acquired factor XIII deficiency. Blood 2009; 113 (03) 723-725
• 78 Osaki T, Sugiyama D, Magari Y, Souri M, Ichinose A. Rapid immunochromatographic test for detection of anti-factor XIII A subunit antibodies can diagnose 90 % of cases with autoimmune haemorrhaphilia XIII/13. Thromb Haemost 2015; 113 (06) 1347-1356
• 79 Osaki T, Yokoyama C, Magari Y, Souri M, Ichinose A. Novel immunochromatographic test for anti-factor XIII B subunit autoantibodies to diagnose autoimmune acquired factor XIII deficiency. Thromb Haemost 2023; 123 (08) 793-803
• 80 Ichinose A, Kohler HP, Philippou H. Factor XIII and Fibrinogen SSC Subcommittee of the ISTH. Recommendation for ISTH/SSC Criterion 2015 for autoimmune acquired factor XIII/13 deficiency. Thromb Haemost 2016; 116 (04) 772-774
• 81 Boggio LN, Green D. Acquired hemophilia. Rev Clin Exp Hematol 2001; 5 (04) 389-404 , quiz 431
• 82 Franchini M, Lippi G, Favaloro EJ. Acquired inhibitors of coagulation factors: part II. Semin Thromb Hemost 2012; 38 (05) 447-453
• 83 Cugno M, Gualtierotti R, Tedeschi A, Meroni PL. Autoantibodies to coagulation factors: from pathophysiology to diagnosis and therapy. Autoimmun Rev 2014; 13 (01) 40-48 Erratum in: Autoimmun Rev. 2015;14:650
• 84 Lewis JH, Szeto IL, Ellis LD, Bayer WL. An acquired inhibitor to coagulation factor 13. Johns Hopkins Med J 1967; 120 (06) 401-407
• 85 Ichinose A, Osaki T, Souri M. Autoimmune acquired factor XIII deficiency in Japan 2021 update: focused on annual incidence and clinical features. Haemophilia 2022; 28 (05) e121-e124
• 86 Osaki T, Souri M, Ichinose A. Plasma proteomics associated with autoimmune coagulation factor deficiencies reveals the link between inflammation and autoantibody development. Int J Hematol 2022; 115 (05) 672-685
• 87 Shimoyama S, Kanisawa Y, Ono K, Souri M, Ichinose A. First and fatal case of autoimmune acquired factor XIII/13 deficiency after COVID-19/SARS-CoV-2 vaccination. Am J Hematol 2022; 97 (02) 243-245
• 88 Nakamura S, Sugasaki M, Souri M. et al. Autoimmune acquired factor XIII/13 deficiency after SARS-CoV-2 mRNA vaccination. Thromb Haemost 2022; 122 (10) 1837-1842
• 89 Osaki T, Souri M, Ichinose A. Important roles of the human leukocyte antigen class I and II molecules and their associated genes in the autoimmune coagulation factor XIII deficiency via whole-exome sequencing analysis. PLoS One 2021; 16 (09) e0257322
• 90 Souri M, Ozawa T, Osaki T, Koyama T, Muraguchi A, Ichinose A. Cloning of human anti-factor XIII monoclonal antibody dissects mechanisms of polyclonal antibodies in a single patient. J Thromb Haemost 2023; 21 (02) 255-268
• 91 Osaki T, Souri M, Ozawa T, Muraguchi A, Ichinose A. Epitope analysis of human monoclonal antibodies from a patient with autoimmune factor XIII deficiency reveals their inhibitory mechanisms. FEBS Lett 2023; 597 (09) 1275-1289
• 92 Tsunemine H, Souri M, Kumode W, Arima N, Ichinose A. A case of autoimmune factor XIII deficiency due to clearance-accelerating and inhibitory anti-FXIII autoantibodies. Int J Hematol 2025; 121 (02) 257-264
• 93 Rodeghiero F, Tosetto A, Abshire T. et al; ISTH/SSC Joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010; 8 (09) 2063-2065
• 94 Ichinose A. Japanese Collaborative Research Group (JCRG) on AH13 Hemorrhagic Acquired Coagulopathies. Inhibitors of factor XIII/13 in older patients. Semin Thromb Hemost 2014; 40 (06) 704-711
• 95 Lawrie AS, Green L, Mackie IJ, Liesner R, Machin SJ, Peyvandi F. Factor XIII—an under diagnosed deficiency—are we using the right assays?. J Thromb Haemost 2010; 8 (11) 2478-2482
• 96 Schmitt FCF, von der Forst M, Miesbach W, Casu S, Weigand MA, Alesci S. Mild acquired factor XIII deficiency and clinical relevance at the ICU—a retrospective analysis. Clin Appl Thromb Hemost 2021; 27: 10 760296211024741
• 97 Blasi A, Patel VC, Spanke ENHE. et al. Fibrin clot quality in acutely ill cirrhosis patients: relation with outcome and improvement with coagulation factor concentrates. Liver Int 2022; 42 (02) 435-443
• 98 Ballerini G, Guerra S, Rodeghiero F, Castaman G. A contribution to the pathology of acquired plasma factor XIII deficiency. Semin Thromb Hemost 1985; 11 (04) 357-361
• 99 Kłoczko J, Wereszczyńska U, Wojtukiewicz M, Gybryelewicz A, Bielawiec M. Fibrin stabilization, factor XIII transamidase activity and subunits “A” and “B” concentration in plasma of patients with liver cirrhosis. Folia Haematol Int Mag Klin Morphol Blutforsch 1986; 113 (04) 539-544
• 100 Strilchuk AW, Meixner SC, Leung J. et al. Sustained depletion of FXIII-A by inducing acquired FXIII-B deficiency. Blood 2020; 136 (25) 2946-2954
• 101 Biland L, Duckert F, Prisender S, Nyman D. Quantitative estimation of coagulation factors in liver disease. The diagnostic and prognostic value of factor XIII, factor V and plasminogen. Thromb Haemost 1978; 39 (03) 646-656
• 102 Tacke F, Fiedler K, von Depka M. et al. Clinical and prognostic role of plasma coagulation factor XIII activity for bleeding disorders and 6-year survival in patients with chronic liver disease. Liver Int 2006; 26 (02) 173-181
• 103 Born P, Lippl F, Ulm K. et al. Reduced levels of coagulation factor XIII in patients with advanced tumor disease. Hepatogastroenterology 2000; 47 (31) 194-198
• 104 Carmassi F, Mariani G, Palla R. et al. Coagulation factor XIII in patients with acute and chronic renal disease. Nephron J 1980; 25 (04) 179-183
• 105 Intagliata NM, Davis JPE, Lafond J. et al. Acute kidney injury is associated with low factor XIII in decompensated cirrhosis. Dig Liver Dis 2019; 51 (10) 1409-1415
• 106 Zanetto A, Rinder HM, Campello E. et al. Acute kidney injury in decompensated cirrhosis is associated with both hypo-coagulable and hyper-coagulable features. Hepatology 2020; 72 (04) 1327-1340
• 107 Lv XY, Li ZJ. Reduced plasma coagulation factor XIII in patients with acute leukemia in remission during consolidation chemotherapy cycles. Ann Hematol 2023; 102 (07) 1739-1744
• 108 Zuch A, Kloczko J, Bielawiec M, Myśliwiec M, Grabowski R, Buluk K. Fibrin stabilizing factor (factor XIII) consumption as an indicator of disseminated intravascular coagulation (DIC). Folia Haematol Int Mag Klin Morphol Blutforsch 1977; 104 (06) 874-878
• 109 Ichinose A, Maruyama I, Imaguma M, Synmyozu K, Igata A. [Disseminated intravascular coagulation (DIC); findings in 40 patients (author's transl)] [in Japanese]. Nihon Naika Gakkai Zasshi 1981; 70 (11) 1531-1536
• 110 Hayakawa K, Tamura S, Gima H. et al. [Successful treatment of chronic disseminated intravascular coagulation using recombinant human soluble thrombomodulin in a dialysis patient with dissecting aortic aneurysm] [in Japanese]. Rinsho Ketsueki 2014; 55 (11) 2300-2305
• 111 Kawano H, Yamamoto D, Uchihashi Y. et al. Severe inhibitor-negative acquired factor XIII/13 deficiency with aggressive subdural haemorrhage. Blood Coagul Fibrinolysis 2013; 24 (06) 638-641
• 112 Janning M, Holstein K, Spath B. et al. Relevant bleeding diathesis due to acquired factor XIII deficiency. Hamostaseologie 2013; 33 (Suppl. 01) S50-S54
• 113 Henriksson P, Hedner U, Nilsson IM. Factor XIII (fibrin stabilising factor) in Henoch-Schönlein's purpura. Acta Paediatr Scand 1977; 66 (03) 273-277
• 114 Kamitsuji H, Tani K, Yasui M. et al. Activity of blood coagulation factor XIII as a prognostic indicator in patients with Henoch-Schönlein purpura. Efficacy of factor XIII substitution. Eur J Pediatr 1987; 146 (05) 519-523
• 115 Egbring R, Kröniger A, Seitz R. Factor XIII deficiency: pathogenic mechanisms and clinical significance. Semin Thromb Hemost 1996; 22 (05) 419-425
• 116 Galloway MJ, Mackie MJ, McVerry BA. Reduced levels of factor XIII in patients with chronic inflammatory bowel disease. Clin Lab Haematol 1983; 5 (04) 427-428
• 117 Van Bodegraven AA, Tuynman HA, Schoorl M, Kruishoop AM, Bartels PC. Fibrinolytic split products, fibrinolysis, and factor XIII activity in inflammatory bowel disease. Scand J Gastroenterol 1995; 30 (06) 580-585
• 118 Hayat M, Ariëns RA, Moayyedi P, Grant PJ, O'Mahony S. Coagulation factor XIII and markers of thrombin generation and fibrinolysis in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2002; 14 (03) 249-256
• 119 D'Argenio G, Cosenza V, Riegler G, Della Valle N, Deritis F, Mazzacca G. Gruppo Italiano per lo Studio del Colon e del Retto (GISC). Serum transglutaminase correlates with endoscopic and histopathologic grading in patients with ulcerative colitis. Dig Dis Sci 2001; 46 (03) 649-657
• 120 Stadnicki A, Kloczko J, Nowak A, Sierka E, Sliwiński Z. Factor XIII subunits in relation to some other hemostatic parameters in ulcerative colitis. Am J Gastroenterol 1991; 86 (06) 690-693
• 121 Hudson M, Wakefield AJ, Hutton RA. et al. Factor XIIIA subunit and Crohn's disease. Gut 1993; 34 (01) 75-79
• 122 Seitz R, Leugner F, Katschinski M. et al. Ulcerative colitis and Crohn's disease: factor XIII, inflammation and haemostasis. Digestion 1994; 55 (06) 361-367
• 123 Kopeć M, Latallo ZS, Stahl M, Wegrzynowicz Z. The effect of proteolytic enzymes on fibrin stabilizing factor. Biochim Biophys Acta 1969; 181 (02) 437-445
• 124 Bagoly Z, Haramura G, Muszbek L. Down-regulation of activated factor XIII by polymorphonuclear granulocyte proteases within fibrin clot. Thromb Haemost 2007; 98 (02) 359-367
• 125 Suzuki R, Toda H, Takamura Y. Dynamics of blood coagulation factor XIII in ulcerative colitis and preliminary study of the factor XIII concentrate. Blut 1989; 59 (02) 162-164
• 126 Lorenz R, Olbert P, Born P. Factor XIII in chronic inflammatory bowel diseases. Semin Thromb Hemost 1996; 22 (05) 451-455
• 127 Gerlach R, Raabe A, Zimmermann M, Siegemund A, Seifert V. Factor XIII deficiency and postoperative hemorrhage after neurosurgical procedures. Surg Neurol 2000; 54 (03) 260-264 , discussion 264–265
• 128 Haas T, Korte W, Spielmann N. et al. Perioperative course of FXIII in children undergoing major surgery. Paediatr Anaesth 2012; 22 (07) 641-646
• 129 Chuliber FA, Schutz NP, Viñuales ES. et al. Nonimmune-acquired factor XIII deficiency: a cause of high volume and delayed postoperative hemorrhage. Blood Coagul Fibrinolysis 2020; 31 (08) 511-516
• 130 Hetz M, Juratli T, Tiebel O. et al. Acquired factor XIII deficiency in patients with multiple trauma. Injury 2023; 54 (05) 1257-1264
• 131 Yamada Y, Abe T, Tanohata R, Ochiai H. Changes in coagulation factor XIII activity during resuscitation for hemorrhagic shock. J Rural Med 2024; 19 (02) 76-82
• 132 Chuliber FA, Penchasky D, Santoro DM. et al. Acquired factor XIII deficiency in patients under therapeutic plasma exchange: a poorly explored etiology. J Clin Apher 2021; 36 (01) 59-66
• 133 Hanafusa N, Hamasaki Y, Kawarasaki H. et al. The effect of different apheresis modalities on coagulation factor XIII level during antibody removal in ABO-blood type incompatible living related renal transplantation. Transfus Apher Sci 2013; 49 (02) 254-258
• 134 Shainoff JR, Estafanous FG, Yared JP, DiBello PM, Kottke-Marchant K, Loop FD. Low factor XIIIA levels are associated with increased blood loss after coronary artery bypass grafting. J Thorac Cardiovasc Surg 1994; 108 (03) 437-445
• 135 Noitz M, Brooks R, Szasz J. et al. Acquired factor XIII deficiency is common during ECMO therapy and associated with major bleeding events and transfusion requirements. J Clin Med 2023; 12 (12) 4115
• 136 Moerer O, Huber-Petersen JF, Schaeper J, Binder C, Wand S. Factor XIII activity might already be impaired before veno-venous ECMO in ARDS patients: a prospective, observational single-center cohort study. J Clin Med 2021; 10 (06) 1203
• 137 Burkhardt H, Zellner PR, Möller I. [Factor XIII deficiency in burns]. Chirurg 1977; 48 (08) 520-523
• 138 Guilabert P, Abarca L, Usúa G. et al. Factor XIII in major burns coagulation. Burns 2024; 50 (07) 1769-1778
• 139 Matsuoka M, Majima T, Onodera T. et al. Hemorrhagic-acquired factor XIII deficiency associated with tocilizumab for treatment of rheumatoid arthritis. Int J Hematol 2012; 96 (06) 781-785
• 140 Mokuda S, Murata Y, Sawada N. et al. Tocilizumab induced acquired factor XIII deficiency in patients with rheumatoid arthritis. PLoS One 2013; 8 (08) e69944
• 141 Souri M, Mokuda S, Inanami H, Osaki T, Takasugi K, Ichinose A. Non-autoimmune combined factor XIII A and B subunit deficiencies in rheumatoid arthritis patients treated with anti-interleukin-6 receptor monoclonal antibody (tocilizumab). Thromb Res 2016; 140: 100-105
• 142 Kumar R, Vidaurre J, Gedela S. Valproic acid-induced coagulopathy. Pediatr Neurol 2019; 98: 25-30
• 143 Pohlmann-Eden B, Peters CN, Wennberg R, Dempfle CE. Valproate induces reversible factor XIII deficiency with risk of perioperative bleeding. Acta Neurol Scand 2003; 108 (02) 142-145
• 144 Teich M, Longin E, Dempfle CE, König S. Factor XIII deficiency associated with valproate treatment. Epilepsia 2004; 45 (02) 187-189
• 145 Koenig S, Gerstner T, Keller A, Teich M, Longin E, Dempfle CE. High incidence of vaproate-induced coagulation disorders in children receiving valproic acid: a prospective study. Blood Coagul Fibrinolysis 2008; 19 (05) 375-382
• 146 Ferretti A, Baldacci E, Fazio F. et al. Acquired FXIII deficiency and AL amyloidosis: a case of a rare association. Transfus Apher Sci 2020; 59 (06) 102903
• 147 Trabelsi B, Baccouche H, Eddhib J, Chakroun A, Sonia M. Acquired factor XIII deficiency and its unprecedented association with multiple myeloma: case report and literature review. Blood Coagul Fibrinolysis 2024; 35 (05) 293-295
• 148 Ghansah H, Orbán-Kálmándi R, Debreceni IB. et al. Low factor XIII levels and altered fibrinolysis in patients with multiple myeloma. Thromb Res 2024; 234: 12-20
• 149 von Meijenfeldt FA, Havervall S, Adelmeijer J. et al. COVID-19 is associated with an acquired factor XIII deficiency. Thromb Haemost 2021; 121 (12) 1668-1669
• 150 Souri M, Kaetsu H, Ichinose A. Sushi domains in the B subunit of factor XIII responsible for oligomer assembly. Biochemistry 2008; 47 (33) 8656-8664
• 151 Ichinose A, Sugiura M, Rodeghiero F, Tosetto A, James P. Jap J Thromb Hemost 2014; 25 (02) 275 [abstract]