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Causative genetic mutations for antithrombin deficiency and their clinical background among Japanese patients

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Abstract

We summarize causative genetic mutations for antithrombin (AT) deficiency and their clinical background in Japanese patients. A total of 19 mutations, including seven novel mutations, were identified. We also summarize clinical symptoms of thrombosis, age at onset, family history, and contributing factors for thrombosis, and review the use of prophylactic anticoagulation in pregnant women with heterozygous type II heparin binding site defects (HBS) AT deficiency. The prevalence of thrombosis in probands with type I AT deficiency (88%) was double that observed in those with type II AT deficiency (50%). The prevalence of thrombotic episodes among family members was also higher for type I AT deficiency subjects (82%) than for those with type II AT deficiency (0%). The most common contributing factor for thrombosis among women with type I AT deficiency was pregnancy. Forty-five percent of women with type I AT deficiency developed thrombotic events before the 20th week of gestation. In contrast, women with type II (HBS) AT deficiency appear to be at a lower risk of thrombosis during pregnancy. In conclusion, thrombotic risk varies among different subtypes. Risk assessments based on genetic/clinical backgrounds may contribute to appropriate diagnosis, treatment, and prophylaxis for patients with AT deficiency.

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Acknowledgements

We sincerely thank the following clinicians who introduced the patients to us: Masahiro Ashizawa (Saitama Medical Center, Jichi Medical University), Chikara Fujita (Suzu General Hospital), Hidenori Imai (Juntendo University Urayasu Hospital), Shinsaku Imashuku (Takasago Seibu Hospital), Jin Iwasawa (Tsuchiura Kyodo General Hospital), Kazuo Kawasaki (Jundu Eye Clinic), Taizou Kimura (Tsukuba University Hospital), Mami Kobukata (JA Oita Koseiren Tsurumi Hospital), Kei Murao (Kyushu Rosai Hospital), Mayumi Nagasawa (Kanazawa Medical University), Tsuyoshi Nakamaki (Showa University), Tomonori Nakazato (Yokohama Municipal Citizen’s Hospital), Wataru Omi (Kanazawa Medical Center), Narihide Shinoda (Shinko Memorial Hospital), Moeko Shinohara (Ishikawa Prefectural Central Hospital), Sawako Takeuchi (Aiiku Hospital), Kohji Tanakaya (Iwakuni Medical Center), Sachie Tsuzura (Chikamori Hospital), Yoshiyuki Wakugawa (Kyushu Medical Center), Kouhei Yamaguchi (Aomori Prefectural Central Hospital). We also appreciate clinical advice from Tomoe Hayashi (Kanazawa City Hospital) and Yasuko Kadohira (Kanazawa University). This work was supported in part by grants-in-aid from the Ministry of Health, Labor and Welfare of Japan [Grant Number 26070201], Japan Society for the Promotion of Science [Grant Numbers 15K19176, 25462818, and 15K08643], and Hokkoku Cancer Fund.

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Authors and Affiliations

  1. Division of Health Sciences, Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan

    Akiko Sekiya, Sayaka Kamijima, Shonosuke Kaneko, Shiori Katsu, Miho Hanamura, Haruka Nakano, Shigeki Ohtake & Eriko Morishita

  2. Department of Central Clinical Laboratory, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan

    Fumina Taniguchi & Daisuke Yamaguchi

  3. Department of Central Clinical Pathology, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan

    Mao Takata

  4. Department of Internal Medicine (III), Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Hidesaku Asakura

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  1. Akiko Sekiya
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  2. Fumina Taniguchi
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  3. Daisuke Yamaguchi
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Correspondence to Eriko Morishita.

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Sekiya, A., Taniguchi, F., Yamaguchi, D. et al. Causative genetic mutations for antithrombin deficiency and their clinical background among Japanese patients. Int J Hematol 105, 287–294 (2017). https://doi.org/10.1007/s12185-016-2142-8

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  • DOI: https://doi.org/10.1007/s12185-016-2142-8

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