Preview

Obstetrics, Gynecology and Reproduction

Advanced search

Management of antithrombin III deficiency in pregnancy: a representative case and a literature review

https://doi.org/10.17749/2313-7347/ob.gyn.rep.2021.230

Full Text:

Abstract

The work is aimed at discussing pregnancy management for the most thrombogenic genetic thrombophilia - antithrombin III (AT-III) deficiency. A detailed analysis of the literature and clinical case of pregnancy management in a patient with AT-III deficiency, pulmonary embolism and habitual history of miscarriage has been performed and presented. Patients with AT-III deficiency are at high risk for developing thrombotic and obstetric complications even despite using therapeutic doses of anticoagulants. Indications for use and modes of administration of AT-III concentrate have not been currently defined clearly. Monitoring therapy with low molecular weight heparin is largely complicated because a test for determining anti-Xa activity is AT-III-dependent. In addition to standard methods for controlling antithrombotic therapy, we used tests characterizing the dynamic blood clot parameters: thromboelastography and thrombin generation test. The peak risk resulting in both thrombotic and hemorrhagic complications in such patients occurs during period of labor and the postpartum period, when a change in the regimen of anticoagulant therapy is required with its temporary withdrawal and additional administration of AT-III concentrate.

About the Authors

S. V. Akinshina
«Medical Centre for Women» LLC
Russian Federation

Svetlana V. Akinshina - MD, PhD, Obstetrician-Gynecologist, Hematologist, «Medical Centre for Women» LLC.

62 Str. Zemlyanoi Val, Moscow 109004.



P. K. Genina
Sechenov University
Russian Federation

Polina K. Genina - 6th year Student, Department of General Medicine, Sechenov University.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991.



V. O. Bitsadze
Sechenov University
Russian Federation

Victoria O. Bitsadze - MD, Dr Sci Med, Professor of RAS, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991.

Scopus Author ID: 6506003478.

Researcher ID: F-8409-2017.



J. Kh. Khizroeva
Sechenov University
Russian Federation

Jamilya Kh. Khizroeva - MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991.

Scopus Author ID: 57194547147.

Researcher ID: F-8384-2017.



V. I. Tsibizova
Almazov National Medical Research Centre, Health Ministry of Russian Federation
Russian Federation

Valentina I. Tsibizova - MD, PhD, Obstetrician-Gynecologist, Research Laboratory of Operative Gynecology, Institute of Perinatology and Pediatrics; Physician, Department of Functional and Ultrasound Diagnostics, Almazov National Medical Research Centre.

2 Akkuratova Str., Saint Petersburg 197341.



A. D. Makatsariya
Sechenov University
Russian Federation

Alexander D. Makatsariya - MD, Dr Sci Med, Professor, Academician of RAS, Head of the Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991.

Scopus Author ID: 57222220144.

Researcher ID: M-5660-2016.



References

1. Di Minno M.N., Ambrosino P., Ageno W. et al. Natural anticoagulants deficiency and the risk of venous thromboembolism: a meta-analysis of observational studies. Thromb Res. 2015;135(5):923-32. https://doi.org/10.1016/j.thromres.2015.03.010.

2. Vossen C.Y., Conard J., Fontcuberta J. et al. Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT). J Thromb Haemost. 2005;3(3):459-64. https://doi.org/10.1111/j.1538-7836.2005.01197.x.

3. Lim W., Eikelboom J.W., Ginsberg J.S. Inherited thrombophilia and pregnancy associated venous thromboembolism. BMJ. 2007;334(7607):1318-21. https://doi.org/10.1136/bmj.39205.484572.55.

4. Wickstrom K., Edelstam G., Lowbeer C.H. et al. Reference intervals for plasma levels of fibronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy. Scand J Clin Lab Invest. 2004;64(1):31-40. https://doi.org/10.1080/00365510410003859.

5. James A.H., Bates S.M., Bauer K.A. et al. Management of hereditary antithrombin deficiency in pregnancy. Thromb Res. 2017;157:41-5. https://doi.org/10.1016/j.thromres.2017.05.017.

6. Franchi F., Biguzzi E., Martinelli I. et al. Normal reference ranges of antithrombin, protein C and protein S: effect of sex, age and hormonal status. Thromb Res. 2013;132(2):e152-7. https://doi.org/10.1016/j.thromres.2013.07.003.

7. Folkeringa N., Brouwer J.L., Korteweg F.J. et al. Reduction of high fetal loss rate by anticoagulant treatment during pregnancy in antithrombin, protein C or protein S deficient women. Br J Haematol. 2007;136(4):656-61. https://doi.org/10.1111/j.1365-2141.2006.06480.x.

8. Mahmoodi B.K., Brouwer J.L., Ten Kate M.K. et al. A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin. J Thromb Haemost. 2010;8(6):1193-200. https://doi.org/10.1111/j.1538-7836.2010.03840.x.

9. Sabadell J., Casellas M., Alijotas-Reig J. et al. Inherited antithrombin deficiency and pregnancy: maternal and fetal outcomes. Eur J Obstet Gynecol Reprod Biol. 2010;149(1):47-51. https://doi.org/10.1016/j.ejogrb.2009.12.004.

10. James A.H., Jamison M.G., Brancazio L.R., Myers E.R. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol. 2006;194(5):1311-5. https://doi.org/10.1016/j.ajog.2005.11.008.

11. James A.H., Konkle B.A., Bauer K.A. Prevention and treatment of venous thromboembolism in pregnancy in patients with hereditary antithrombin deficiency. Int J Womens Health. 2013;5:233-41. https://doi.org/10.2147/IJWH.S43190.

12. Holbrook A., Schulman S., Witt D.M. et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians EvidenceBased Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e152S-e184S. https://doi.org/10.1378/chest.11-2295.

13. Bates S.M., Greer I.A., Middeldorp S. et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e691S-e736S. https://doi.org/10.1378/chest.11-2300.

14. Kearon C., Akl E.A., Ornelas J. et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-52. https://doi.org/10.1016/j.chest.2015.11.026.

15. Tiede A., Tait R.C., Shaffer D.W. et al. Antithrombin alfa in hereditary antithrombin deficient patients: A phase 3 study of prophylactic intravenous administration in high risk situations. Thromb Haemost. 2008;99(3):616-22. https://doi.org/10.1160/TH07-08-0489.

16. Rheaume M., Weber F., Durand M., Mahone M. Pregnancy-related venous thromboembolism risk in asymptomatic women with antithrombin deficiency: a systematic review. Obstet Gynecol. 2016;127(4):649-56. https://doi.org/10.1097/AOG.0000000000001347.

17. Pascual C., Munoz C., Huerta A.R. et al. A new case of successful outcome of pregnancy in a carrier of homozygous type II (L99F) antithrombin deficiency. Blood Coagul Fibrinolysis. 2014;25(1):74-6. https://doi.org/10.1097/MBC.0b013e3283646620.

18. Reducing the risk of venous thromboembolism during pregnancy and the puerperium. Green-top Guideline No. 37a. Royal College of Obstetricians and Gynaecologists, 2015. 40 p. Available at: https://www.rcog.org.uk/globalassets/documents/guidelines/gtg-37a.pdf.

19. ACOG Practice Bulletin No. 197: Inherited Thrombophilias in Pregnancy. Obstet Gynecol. 2018;132(1):e18-e34. https://doi.org/10.1097/AOG.0000000000002703.

20. ACOG Practice Bulletin No. 196: Thromboembolism in Pregnancy. Obstet Gynecol. 2018;132(1):e1-e17. https://doi.org/10.1097/AOG.0000000000002706.

21. Bates S.M., Rajasekhar A., Middeldorp S. et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv. 201827;2(22):3317-59. https://doi.org/10.1182/bloodadvances.2018024802.

22. Rogenhofer N., Bohlmann M.K., Beuter-Winkler P. et al. Prevention, management and extent of adverse pregnancy outcomes in women with hereditary antithrombin deficiency. Ann Hematol. 2014;93(3):385-92. https://doi.org/10.1007/s00277-013-1892-0.

23. Refaei M., Xing L., Lim W. et al. Management of venous thromboembolism in patients with hereditary antithrombin deficiency and pregnancy: case report and review of the literature. Case Rep Hematol. 2017;2017:9261351. https://doi.org/10.1155/2017/9261351.

24. Skelley J.W., White C.W., Thomason A.R. The use of direct oral anticoagulants in inherited thrombophilia. J Thromb Thrombolysis. 2017;43(1):24-30. https://doi.org/10.1007/s11239-016-1428-2.

25. Serrao A., Lucani B., Mansour D. et al. Direct oral anticoagulants in patients affected by major congenital thrombophilia. Mediterr J Hematol Infect Dis. 2019;11(1):e2019044. https://doi.org/10.4084/MJHID.2019.044.


Review

For citations:


Akinshina S.V., Genina P.K., Bitsadze V.O., Khizroeva J.K., Tsibizova V.I., Makatsariya A.D. Management of antithrombin III deficiency in pregnancy: a representative case and a literature review. Obstetrics, Gynecology and Reproduction. 2021;15(4):441-450. https://doi.org/10.17749/2313-7347/ob.gyn.rep.2021.230

Views: 387


ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)