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Factor XIII is a key molecule at the intersection of coagulation and fibrinolysis as well as inflammation and infection control

  • Progress in Hematology
  • Current understanding of thrombosis and hemostasis—from bench to bedside
  • Published:
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Abstract

Factor XIII (FXIII) is a transglutaminase consisting of two catalytic A subunits (FXIII-A) and two non-catalytic B subunits (FXIII-B) in plasma. FXIII-B protects FXIII-A from its clearance. FXIII-A is also present as a homodimer inside megakaryocytes/platelets and monocytes/macrophages. Although possible functions of intracellular FXIII-A have been proposed, these remain to be established. Intra- and extra-cellular FXIIIs support platelet adhesion and spreading as well as clot retraction, suggesting that FXIII is important for the stabilization of platelet–fibrin clots. Intra- and extra-cellular FXIIIs also support immobilization and killing of bacteria as well as phagocytosis by macrophages. Thus, FXIII may function in innate immunity. Congenital FXIII deficiency due to defective F13-A genes manifests as a life-long bleeding tendency, abnormal wound healing, and recurrent miscarriage. Although congenital FXIII-B deficiency used to be thought rare, reports of such cases have increased recently. As the bleeding tendency is often mild, patients with FXIII-B deficiency may be overlooked by physicians. Patients with acquired FXIII deficiency, in particular those with autoimmune hemorrhaphilia due to anti-FXIII antibodies, are on the increase, at least in Japan. It is important to diagnose such cases as early as possible, and to treat them with immunosuppression in combination with FXIII replacement therapy as their bleeding symptoms can be life-threatening.

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Notes

  1. Occurring frequently in clinical fields and less commonly in scientific fields, even in the official journal of the International Society of Thrombosis and Haemostasis as well as in PubMed.

  2. Acquired h(a)emophilia is a tentative, working name for this category of diseases, but remains unofficial as it is not included in the current version of the WHO ICD (2007). “Acquired h(a)emorrhaphilia” seems to be a more logical and proper appellation, because the term hemorrhaphilia stands for “love of bleeding/hemorrhage” while the word hemophilia literally means “love of blood” [29]. Thus, the author uses the term hemorrhaphilia for a bleeding disorder caused by anti-FXIII/13 inhibitors.

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Acknowledgments

We thank Dr. N. Hosono of Fukui Medical School, Prof. L. Muszbek of Debrecen University, Dr. V. Schroeder of Bern University, and Dr. M. Saito of Kanazawa University for communicating unpublished scientific or clinical data. This study was supported by a research grant from The Japanese Ministry of Health, Welfare, and Labor, and by a Grant-in-Aid for Scientific Research from Yamagata University, and was presented in part at the 23th ISTH meeting in Kyoto, Japan, in July 2011 and at the 73rd Annual Meeting of The Japanese Society of Hematology in Nagoya, Japan, in October 2011.

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  1. Department of Molecular Patho-Biochemistry & -Biology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan

    Akitada Ichinose

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Appendix

Appendix

Members of the Japanese collaborative research group on acquired/autoimmune hemorrhaphilia due to factor XIII/13 deficiency include: Ichinose A, Souri M, Iwata H, Sakata Y, Yatomi Y, Maruyama I, Kawamae K, Shigematsu H, Kobayashi T, Murata K, Ikeda M, Yukawa M, Sugita K, Maeda M, Kawasugi, K, Ishida F, Matsushita T, Shima M, Shirahata A, Madoiwa S, Fukutake K, Kitajima I, Takamatsu J, Miyata S, Fujii T, Takano K, Nakao A, Eguchi Y, Sakon K, Ojiro M, Ieko M, Tamai Y, Matsuura Y, Taki M, Wada H, Higasa S, and Nishikawa T.

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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 95, 362–370 (2012). https://doi.org/10.1007/s12185-012-1064-3

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