Skip to main content

Advertisement

SpringerLink
Log in

High frequency of decreased antithrombin level in pregnant women with thrombosis

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Venous thromboembolism (VTE) occurs frequently in pregnant women and is a significant cause of maternal death. Hemostatic abnormalities were examined in 18 pregnant women with thrombosis. We studied five families with congenital antithrombin (AT) deficiency, and two families with congenital protein C (PC) deficiency. One woman with PC deficiency showed protein S (PS) Tokushima. The AT activity levels were significantly lower at the onset of thrombosis in the pregnant women than during the stable state. The PS activity and antigen levels were also significantly lower at the onset of thrombosis. In the patients with congenital AT deficiency, AT activity was significantly low in the stable state and decreased further at the onset of thrombosis. Although AT levels were normal before pregnancy, they subsequently decreased and in two cases the patients required the administration of AT after pregnancy. Gene analysis revealed one family with AT Budapest, one family with AT Toyama, and three families with AT Glasgow. Additionally, there were one family with PC Tochigi and one family with combined heterozygous of PC deficiency and PS Tokushima. In conclusion, the deficiency of natural anticoagulants, especially AT, is an important cause of pregnancy-related VTE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Franchini M. Haemostasis and pregnancy. Thromb Haemost. 2006;95:401–13.

    CAS  PubMed  Google Scholar 

  2. Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol. 2003;16:153–68.

    Article  PubMed  Google Scholar 

  3. Creanga AA, Berg CJ, Syverson C, Seed K, Bruce FC, Callaghan WM. Pregnancy-related mortality in the United States, 2006–2010. Obstet Gynecol. 2015;125:5–12.

    Article  PubMed  Google Scholar 

  4. Martinelli I. Thromboembolism in women. Semin Thromb Hemost. 2006;32:709–15.

    Article  CAS  PubMed  Google Scholar 

  5. Jacobsen AF, Skjeldestad FE, Sandset PM. Incidence and risk patterns of venous thromboembolism in pregnancy and puerperium—a register-based case-control study. Am J Obstet Gynecol. 2008;198:233–7.

    Article  PubMed  Google Scholar 

  6. James AH. Venous thromboembolism in pregnancy. Arterioscler Thromb Vasc Biol. 2009;29:326–31.

    Article  CAS  PubMed  Google Scholar 

  7. Conard J, Horellou MH, van Dreden P, Lecompte T, Samama M. Thrombosis and pregnancy in congenital deficiencies in AT III, protein C or protein S: study of 78 women. Thromb Haemost. 1990;63:319–20.

    CAS  PubMed  Google Scholar 

  8. Pabinger I, Schneider B. Thrombotic risk in hereditary antithrombin III, protein C, or protein S deficiency. A cooperative, retrospective study. Gesellschaft fur Thrombose- und Hamostaseforschung (GTH) Study Group on Natural Inhibitors. Arterioscler Thromb Vasc Biol. 1996;16:742–8.

    Article  CAS  PubMed  Google Scholar 

  9. Friederich PW, Sanson BJ, Simioni P, Zanardi S, Hilsman MV, Girolami A, ten Cate JW, Prins MH. Frequency of pregnancy-related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis. Ann Intern Med. 1996;125:955–60.

    Article  CAS  PubMed  Google Scholar 

  10. Gerhardt A, Scharf RE, Beckmann MW, Struve S, Bender HG, Pillny M, Sandmann W, Zotz RB. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. N Engl J Med. 2000;342:374–80.

    Article  CAS  PubMed  Google Scholar 

  11. MacCallum P, Bowles L, Keeling D. Diagnosis and management of heritable thrombophilias. BMJ. 2014;17(349):g4387.

    Article  Google Scholar 

  12. Guimicheva B, Czuprynska J, Arya R. The prevention of pregnancy-related venous thromboembolism. Br J Haematol. 2015;168:163–74.

    Article  PubMed  Google Scholar 

  13. Nelson-Piercy C, MacCallum P, Mackillop L, on behalf of the Guidelines Committee of the Royal College of Obstetricians and Gynaecologists. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium. RCOG Green-top Guideline 2009; No. 37a. London: Royal College of Obstetricians and Gynaecologists; 2009.

  14. James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol. 2006;194:1311–5.

    Article  PubMed  Google Scholar 

  15. Liu S, Rouleau J, Joseph KS, Sauve R, Liston RM, Young D, Kramer MS. Epidemiology of pregnancy-associated venous thromboembolism: a population-based study in Canada. J Obstet Gynaecol Can. 2009;31:611–20.

    PubMed  Google Scholar 

  16. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86:1327–30.

    CAS  PubMed  Google Scholar 

  17. Ikejiri M, Shindo A, Ii Y, Tomimoto H, Yamada N, Matsumoto T, Abe Y, Nakatani K, Nobori T, Wada H. Frequent association of thrombophilia in cerebral venous sinus thrombosis. Int J Hematol. 2012;95:257–62.

    Article  PubMed  Google Scholar 

  18. Olds RJ, Lane DA, Caso R, Panico M, Morris HR, Sas G, Dawes J, Thein SL. Antithrombin III Budapest: a single amino acid substitution (429Pro to Leu) in a region highly conserved in the serpin family. Blood. 1992;79:1206–12.

    CAS  PubMed  Google Scholar 

  19. Sakuragawa N, Takahashi K, Kondo S, Koide T. Antithrombin III Toyama: a hereditary abnormal antithrombin III of a patient with recurrent thrombophlebitis. Thromb Res. 1983;31:305–17.

    Article  CAS  PubMed  Google Scholar 

  20. Thein SL, Lane DA. Use of synthetic oligonucleotides in the characterization of antithrombin III Northwick Park (393 CGT—TGT) and antithrombin III Glasgow (393 CGT—CAT). Blood. 1988;72:1817–21.

    CAS  PubMed  Google Scholar 

  21. Miyata T, Zheng YZ, Sakata T, Tsushima N, Kato H. Three missense mutations in the protein C heavy chain causing type I and type II protein C deficiency. Thromb Haemost. 1994;71:32–7.

  22. Miyata T, Sakata T, Zheng YZ, Tsukamoto H, Umeyama H, Uchiyama S, Ikusaka M, Yoshioka A, Imanaka Y, Fujimura H, Kambayashi J, Kato H. Genetic characterization of protein C deficiency in Japanese subjects using a rapid and nonradioactive method for single-stand conformational polymorphism analysis and a model building. Thromb Haemost. 1996;76:302–11.

    CAS  PubMed  Google Scholar 

  23. Hayashi T, Nishioka J, Shigekiyo T, Saito S, Suzuki K. Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S. Blood. 1994;83:683–90.

    CAS  PubMed  Google Scholar 

  24. Galambosi PJ, Ulander VM, Kaaja RJ. The incidence and risk factors of recurrent venous thromboembolism during pregnancy. Thromb Res. 2014;134:240–5.

    Article  CAS  PubMed  Google Scholar 

  25. Tanaka H, Katsuragi S, Osato K, Hasegawa J, Nakata M, Murakoshi T, Yoshimatsu J, Sekizawa A, Kanayama N, Ishiwata I, Ikeda T. Increase in maternal death-related venous thromboembolism during pregnancy in Japan (2010–2013). Circ J. 2015;79:1357–62.

    Article  PubMed  Google Scholar 

  26. Shindo A, Wada H, Ishikawa H, Ito A, Asahi M, Ii Y, Ikejiri M, Tomimoto H. Clinical features and underlying causes of cerebral venous thrombosis in Japanese patients. Int J Hematol. 2014;99:437–40.

    Article  PubMed  Google Scholar 

  27. Terni E, Giannini N, Chiti A, Gialdini G, Orlandi G, Montano V, Orsucci D, Brondi M, Bonuccelli U, Mancuso M. Cerebral sinus venous thrombosis: clinical and pathogenetic perspectives from Tuscany. Blood Coagul Fibrinolysis. 2015 [Epub ahead of print].

  28. Hasegawa M, Wada H, Wakabayashi H, Yoshida K, Miyamoto N, Asanuma K, Matsumoto T, Ohishi K, Shimokariya Y, Yamada N, Uchida A, Sudo A. The relationships among hemostatic markers, the withdrawal of fondaparinux due to a reduction in hemoglobin and deep vein thrombosis in Japanese patients undergoing major orthopedic surgery. Clin Chim Acta. 2013;425:109–13.

    Article  CAS  PubMed  Google Scholar 

  29. Jiang Y, McIntosh JJ, Reese JA, Deford CC, Kremer Hovinga JA, Lämmle B, Terrell DR, Vesely SK, Knudtson EJ, George JN. Pregnancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura. Blood. 2014;123:1674–80.

  30. Suzuki A, Sanda N, Miyawaki Y, Fujimori Y, Yamada T, Takagi A, Murate T, Saito H, Kojima T. Down-regulation of PROS1 gene expression by 17beta-estradiol via estrogen receptor alpha (ERalpha)-Sp1 interaction recruiting receptor-interacting protein 140 and the corepressor-HDAC3 complex. J Biol Chem. 2010;285:13444–53.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Habe K, Wada H, Ito-Habe N, Suzuki H, Nobori T, Mizutani H. Two patients with antiphospholipid antibody developed disseminated intravascular coagulation. Intern Med. 2013;52:269–72.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by a Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan for Blood Coagulation Abnormalities and the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Mie, Japan

    Yuki Kamimoto, Kazuhiro Osato, Nao Murabayashi & Tomoaki Ikeda

  2. Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Hideo Wada & Kaname Nakatani

  3. Central Laboratory, Mie University Hospital, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Makoto Ikejiri

  4. Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Takashi Sugiyama

  5. Department of Cardiology, Mie University Graduate School of Medicine, Tsu, Mie, Japan

    Norikazu Yamada & Masaaki Ito

  6. Blood Transfusion Service, Mie University Graduate School of Medicine, Tsu, Mie, Japan

    Takeshi Matsumoto & Kohshi Ohishi

  7. Department of Neurology, Mie University Graduate School of Medicine, Tsu, Mie, Japan

    Hidehiro Ishikawa & Hidekazu Tomimoto

Authors
  1. Yuki Kamimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hideo Wada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Makoto Ikejiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kaname Nakatani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takashi Sugiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kazuhiro Osato
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nao Murabayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Norikazu Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Takeshi Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kohshi Ohishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hidehiro Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hidekazu Tomimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Masaaki Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Tomoaki Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hideo Wada.

Ethics declarations

Conflict of interest

There are no conflicts of interest for any of the authors in association with this study.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kamimoto, Y., Wada, H., Ikejiri, M. et al. High frequency of decreased antithrombin level in pregnant women with thrombosis. Int J Hematol 102, 253–258 (2015). https://doi.org/10.1007/s12185-015-1822-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-015-1822-0

Keywords

Search

Navigation