Inhibitors of Factor XIII/13 in Older Patients

Akitada Ichinose; for the The Japanese Collaborative Research Group (JCRG) on AH13 Hemorrhagic Acquired Coagulopathies

doi:10.1055/s-0034-1390151

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2014; 40(06): 704-711
DOI: 10.1055/s-0034-1390151

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inhibitors of Factor XIII/13 in Older Patients

Authors

Akitada Ichinose

¹Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan

for the The Japanese Collaborative Research Group (JCRG) on AH13 Hemorrhagic Acquired Coagulopathies

Abstract

Factor XIII/13 (FXIII or F13) is a plasma protransglutaminase, which stabilizes fibrin clots, and thus plays an important role in hemostasis. Autoimmune hemo(rrha)philia due to anti-F13 autoantibodies (AH13) has been on the rise in Japan, which has become the leading superaging society in the 21st century. The mean age of Japanese AH13 cases has risen to 70.4 years. A total of 83 AH13 cases have been diagnosed in the world as of July 2014. To raise the awareness of AH13, the author and members of the Japanese Collaborative Research Group first proposed “Criterion and Algorithm of Laboratory Tests for anti F13” in February 2012. AH13 is not just an acquired isolated defect of F13 molecule itself but a disturbance caused by autoantibodies. Accordingly, AH13 cases are diagnosed in patients with otherwise unexplained hemorrhages by a combination of a severe deficiency of F13 activity and the presence of anti-F13 autoantibodies. As patients with this disease manifest life-threatening bleeding symptoms, prompt diagnosis and proper treatment are essential. Because AH13 tends to become chronic and intractable, affected patients must be closely followed for a prolonged period.

Keywords

anti-factor XIII/13 autoantibody - autoimmune hemorrhagic disease - chronic intractable disease - hemostatic therapy - immunosuppressive treatment

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References

References
1 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 (7) 1404-1406
2 Muszbek L, Bereczky Z, Bagoly Z, Komáromi I, Katona É. Factor XIII: a coagulation factor with multiple plasmatic and cellular functions. Physiol Rev 2011; 91 (3) 931-972
3 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 (4) 362-370
4 Ariëns RA, Kohler HP, Mansfield MW, Grant PJ. Subunit antigen and activity levels of blood coagulation factor XIII in healthy individuals. Relation to sex, age, smoking, and hypertension. Arterioscler Thromb Vasc Biol 1999; 19 (8) 2012-2016
5 Gemmati D, Serino ML, Ongaro A , et al. A common mutation in the gene for coagulation factor XIII-A (VAL34Leu): a risk factor for primary intracerebral hemorrhage is protective against atherothrombotic diseases. Am J Hematol 2001; 67 (3) 183-188
6 Egbring R, Kröniger A, Seitz R. Factor XIII deficiency: pathogenic mechanisms and clinical significance. Semin Thromb Hemost 1996; 22 (5) 419-425
7 Ichinose A, Souri M. Japanese collaborative research group on “Acquired haemorrha-philia due to factor XIII deficiency”. As many as 12 cases with haemorrhagic acquired factor XIII deficiency due to its inhibitors were recently found in Japan. Thromb Haemost 2011; 105 (5) 925-927
8 Ichinose A. Hemorrhagic acquired factor XIII (13) deficiency and acquired hemorrhaphilia 13 revisited. Semin Thromb Hemost 2011; 37 (4) 382-388
9 Lorand L, Acquired inhibitors of fibrin stabilization: a class of hemorrhagic disorders of diverse origins. In: Green D. ed. Anticoagulants Physiologic, Pathologic, and Pharmacologic. Boca Raton, FL: CRC Press 1994: 169-191
10 Egbring R, Kröniger A, Seitz R. Erworbene inhibitoren gegen Faktor XIII [German]. Hamostaseologie 1996; 16: 174-179
11 Boehlen F, Casini A, Chizzolini C , et al. Acquired factor XIII deficiency: a therapeutic challenge. Thromb Haemost 2013; 109 (3) 479-487
12 Ogawa Y, Mihara M, Souri M , et al. Complete remission achieved by steroid pulse therapy following rituximab treatment in a case with autoimmune haemorrhaphilia due to anti-factor XIII antibodies (ePub ahead of print). 2014; 112 (4) doi: 10.1160/TH14-04-0323
13 Sugiyama H, Uesugi H, Suzuki S, Tanaka K, Souri M, Ichinose A. Aggressive fatal case of autoimmune hemorrhaphilia resulting from anti-Factor XIII antibodies. Blood Coagul Fibrinolysis 2013; 24 (1) 85-89
14 Ichinose A. Japanese criterion 2012 for the diagnosis and treatment of acquired hemorrhaphilia XIII/13. In: 58th Annual Meeting of the Scientific and Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH), June 27–30, 2012 , ACC Liverpool (Liverpool, England); Ichinose A: An update on Japanese criterion 2012 for the diagnosis and treatment of autoimmune/acquired hemorrhaphilia XIII/13; a proposal of algorithm of laboratory tests and differential diagnosis. XXIV Congress of the International Society on Thrombosis and Haemostasis, 59th SSC Program, Subcommittee session; June 29–July 4, 2013; Amsterdam RAI (Amsterdam, The Netherlands)
15 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 (9) 2063-2065
16 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (4) 692-694
17 Baudo F, Collins P, Huth-Kühne A , et al; EACH2 registry contributors. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood 2012; 120 (1) 39-46
18 Ichinose A, Souri M. Reduced difference of α₂-plasmin inhibitor levels between plasma and serum in patients with severe factor XIII deficiency, including autoimmune hemorrhaphilia due to anti-factor XIII antibodies. Int J Hematol 2012; 95 (1) 47-50
19 Huth-Kühne A, Baudo F, Collins P , et al. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica 2009; 94 (4) 566-575
20 Muszbek L, Ariëns RA, Ichinose A. ISTH SSC SUBCOMMITTEE ON FACTOR XIII. Factor XIII: recommended terms and abbreviations. J Thromb Haemost 2007; 5 (1) 181-183