Skip to main content

Advertisement

SpringerLink
Log in

The challenging follow-up of pregnancy in women with known thrombotic thrombocytopenic purpura: a single-center experience of a preemptive management protocol

  • original Article
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Background

Although thrombotic thrombocytopenic purpura frequently affects women of childbearing age, there is no clear recommendation for the management of subsequent pregnancies in women with established thrombotic thrombocytopenic purpura.

Methods

This single-center, retrospective, observational study included all women with hereditary thrombotic thrombocytopenic purpura or immune thrombotic thrombocytopenic purpura who had had at least one subsequent pregnancy after thrombotic thrombocytopenic purpura diagnosis between 2003 and 2022. The strategy comprised weekly surveillance of platelet count during pregnancy (and quarterly monitoring of ADAMTS13 activity) for women with immune thrombotic thrombocytopenic purpura, without any routine prophylactic treatment. In case of thrombocytopenia < 150,000/mm3 (with or without hemolysis relapse), women with hereditary thrombotic thrombocytopenic purpura systematically received plasma infusions twice weekly until platelet count normalized.

Results

A total of 13 patients were included (7 with hereditary thrombotic thrombocytopenic purpura and 6 with immune thrombotic thrombocytopenic purpura, with 20 planned pregnancies (11 and 9, respectively). All pregnancies resulted in live births, and all mothers survived. There was a marked improvement in pregnancy terms in the hereditary thrombotic thrombocytopenic purpura group compared to index pregnancies (37 [35;39] versus 31 [24;38] weeks, p = 0.037) and birth weights (3265 [3029;3410] versus 2160 [1240;2705] grams, p = 0.016), with need for plasma support mostly starting during the third trimester (5/7 patients, 7/11 pregnancies). A single hereditary thrombotic thrombocytopenic purpura relapse occurred, with rapid resolution after plasma support intensification. There were no relapses in the immune thrombotic thrombocytopenic purpura group, with ADAMTS13 activity systematically above 40% during all monitored pregnancies.

Conclusion

These real-life data support the feasibility of a preemptive approach to pregnancy monitoring in women with known thrombotic thrombocytopenic purpura who undergo active surveillance within a multidisciplinary network.

Graphical abstract

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

All data are available upon reason request for the corresponding author.

References

  1. George JN, Al-Nouri ZL (2012) Diagnostic and therapeutic challenges in the thrombotic thrombocytopenic purpura and hemolytic uremic syndromes. Hematol Am Soc Hematol Educ Program 2012:604–609. https://doi.org/10.1182/asheducation-2012.1.604

    Article  Google Scholar 

  2. Mariotte E, Azoulay E, Galicier L et al (2016) Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy. Lancet Haematol 3(5):e237–e245. https://doi.org/10.1016/S2352-3026(16)30018-7

    Article  PubMed  Google Scholar 

  3. Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K (2017) Thrombotic thrombocytopenic purpura. Nat Rev Dis Primer 3(1):1–17. https://doi.org/10.1038/nrdp.2017.20

    Article  Google Scholar 

  4. Tsai HM, Lian EC (1998) Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 339(22):1585–1594. https://doi.org/10.1056/NEJM199811263392203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Furlan M, Robles R, Galbusera M et al (1998) von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 339(22):1578–1584. https://doi.org/10.1056/NEJM199811263392202

    Article  CAS  PubMed  Google Scholar 

  6. Scully M, Cataland S, Coppo P et al (2017) Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost 15(2):312–322. https://doi.org/10.1111/jth.13571

    Article  CAS  PubMed  Google Scholar 

  7. Scully M, Yarranton H, Liesner R et al (2008) Regional UK TTP Registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br J Haematol 142(5):819–826. https://doi.org/10.1111/j.1365-2141.2008.07276.x

    Article  PubMed  Google Scholar 

  8. Coppo P, Veyradier A (2020) TTP in the setting of pregnancy: the story still has to be written. J Thromb Haemost 18(10):2775–2777. https://doi.org/10.1111/jth.15030

    Article  PubMed  Google Scholar 

  9. Moatti-Cohen M, Garrec C, Wolf M et al (2012) Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura. Blood 119(24):5888–5897. https://doi.org/10.1182/blood-2012-02-408914

    Article  CAS  PubMed  Google Scholar 

  10. Scully M, Starke R, Lee R, Mackie I, Machin S, Cohen H (2006) Successful management of pregnancy in women with a history of thrombotic thrombocytopaenic purpura. Blood Coagul Fibrinolysis Int J Haemost Thromb 17(6):459–463. https://doi.org/10.1097/01.mbc.0000240918.65306.20

    Article  Google Scholar 

  11. Kremer Hovinga JA, George JN (2019) Hereditary thrombotic thrombocytopenic purpura. N Engl J Med. 381(17):1653–1662. https://doi.org/10.1056/NEJMra1813013

    Article  PubMed  Google Scholar 

  12. van Dorland HA, Taleghani MM, Sakai K et al (2019) The international hereditary thrombotic thrombocytopenic purpura registry: key findings at enrollment until 2017. Haematologica 104(10):2107–2115. https://doi.org/10.3324/haematol.2019.216796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Alwan F, Vendramin C, Liesner R et al (2019) Characterization and treatment of congenital thrombotic thrombocytopenic purpura. Blood 133(15):1644–1651. https://doi.org/10.1182/blood-2018-11-884700

    Article  CAS  PubMed  Google Scholar 

  14. Zheng XL, Vesely SK, Cataland SR et al (2020) ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost JTH 18(10):2496–2502. https://doi.org/10.1111/jth.15010

    Article  PubMed  Google Scholar 

  15. Fakhouri F, Scully M, Provôt F et al (2020) Management of thrombotic microangiopathy in pregnancy and postpartum: report from an international working group. Blood 136(19):2103–2117. https://doi.org/10.1182/blood.2020005221

    Article  CAS  PubMed  Google Scholar 

  16. Zheng XL, Vesely SK, Cataland SR et al (2020) Good practice statements (GPS) for the clinical care of patients with thrombotic thrombocytopenic purpura. J Thromb Haemost JTH 18(10):2503–2512. https://doi.org/10.1111/jth.15009

    Article  Google Scholar 

  17. Wind M, Gaasbeek AGA, Oosten LEM et al (2021) Therapeutic plasma exchange in pregnancy: a literature review. Eur J Obstet Gynecol Reprod Biol 260:29–36. https://doi.org/10.1016/j.ejogrb.2021.02.027

    Article  CAS  PubMed  Google Scholar 

  18. Sakai K, Fujimura Y, Nagata Y et al (2020) Success and limitations of plasma treatment in pregnant women with congenital thrombotic thrombocytopenic purpura. J Thromb Haemost 18(11):2929–2941. https://doi.org/10.1111/jth.15064

    Article  CAS  PubMed  Google Scholar 

  19. Khaskheli Nissa M, Baloch S, Sheeba A (2014) Iatrogenic risks and maternal health: issues and outcomes. Pak J Med Sci. 30(1):111–115. https://doi.org/10.12669/pjms.301.4062

    Article  Google Scholar 

  20. Pandey S, Vyas GN (2012) Adverse Effects of Plasma Transfusion. Transfusion (Paris) 52(Suppl 1):65S-79S. https://doi.org/10.1111/j.1537-2995.2012.03663.x

    Article  CAS  Google Scholar 

  21. Narick C, Triulzi DJ, Yazer MH (2012) Transfusion-associated circulatory overload after plasma transfusion. Transfusion (Paris) 52(1):160–165. https://doi.org/10.1111/j.1537-2995.2011.03247.x

    Article  Google Scholar 

  22. Zheng XL, Vesely SK, Cataland SR et al (2020) ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost JTH 18(10):2486–2495. https://doi.org/10.1111/jth.15006

    Article  PubMed  Google Scholar 

  23. Nakashima MO, Zhang X, Rogers HJ et al (2016) Validation of a panel of ADAMTS13 assays for diagnosis of thrombotic thrombocytopenic purpura: activity, functional inhibitor, and autoantibody test. Int J Lab Hematol 38(5):550–559. https://doi.org/10.1111/ijlh.12542

    Article  CAS  PubMed  Google Scholar 

  24. Mancini I, Valsecchi C, Palla R, Lotta LA, Peyvandi F (2012) Measurement of anti-ADAMTS13 neutralizing autoantibodies: a comparison between CBA and FRET assays. J Thromb Haemost JTH 10(7):1439–1442. https://doi.org/10.1111/j.1538-7836.2012.04744.x

    Article  CAS  PubMed  Google Scholar 

  25. Sinkovits G, Szilágyi Á, Farkas P et al (2018) Concentration and subclass distribution of anti-ADAMTS13 IgG autoantibodies in different stages of acquired idiopathic thrombotic thrombocytopenic purpura. Front Immunol 9:1646. https://doi.org/10.3389/fimmu.2018.01646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hamroun A, Prouteau C, Provôt F (2020) Hereditary thrombotic thrombocytopenic purpura. N Engl J Med 382(4):392–393. https://doi.org/10.1056/NEJMc1915670

    Article  PubMed  Google Scholar 

  27. Scully M, Thomas M, Underwood M et al (2014) Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood 124(2):211–219. https://doi.org/10.1182/blood-2014-02-553131

    Article  CAS  PubMed  Google Scholar 

  28. Ducloy-Bouthors AS, Caron C, Subtil D et al (2003) Thrombotic thrombocytopenic purpura: medical and biological monitoring of six pregnancies. Eur J Obstet Gynecol Reprod Biol 111(2):146–152. https://doi.org/10.1016/S0301-2115(03)00199-4

    Article  PubMed  Google Scholar 

  29. Dennis AT, Solnordal CB (2012) Acute pulmonary oedema in pregnant women. Anaesthesia 67(6):646–659. https://doi.org/10.1111/j.1365-2044.2012.07055.x

    Article  CAS  PubMed  Google Scholar 

  30. Asmis LM, Serra A, Krafft A et al (2022) Recombinant ADAMTS13 for hereditary thrombotic thrombocytopenic purpura. N Engl J Med 387(25):2356–2361. https://doi.org/10.1056/NEJMoa2211113

    Article  CAS  PubMed  Google Scholar 

  31. Jiang Y, McIntosh JJ, Reese JA et al (2014) Pregnancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura. Blood 123(11):1674–1680. https://doi.org/10.1182/blood-2013-11-538900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Thanks to Felicity Kay for providing drafts and editorial assistance to the authors during preparation of this manuscript.

Funding

This study did not receive any grant from any funding agency in the public, commercial or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Nephrology, Dialysis, Transplantation, and Apheresis, Lille University, Lille University Hospital Center of Lille, 59000, Lille, France

    Aghiles Hamroun, Camille Prouteau, Rémi Lenain, Camille Roger, Arnaud Lionet, Mehdi Maanaoui, Marc Hazzan & François Provôt

  2. UMR1167 RID-AGE, Inserm, Institut Pasteur de Lille, Lille University, 59000, Lille, France

    Aghiles Hamroun

  3. Department of Hematology and Transfusion, Pôle de Biologie Pathologie Génétique, CHU Lille, Lille University, Lille, France

    Anne Bauters & Christophe Zawadzki

  4. CHU Lille, Hôpital Jeanne de Flandre, Lille University, 59000, Lille, France

    Damien Subtil

  5. Regional and University Hospital Center of Lille, Department of Pathology, Pathology Institute, Lille University, 59037, Lille, France

    Jean-Baptiste Gibier & Morgane Stichelbout

  6. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France

    Paul Coppo

  7. Inserm, CHU Lille, Institut Pasteur Lille, Lille University, U1190, EGID, F-59000, Lille, France

    Mehdi Maanaoui

  8. Lille University, EA 2694 Santé Publique, Épidémiologie Et Qualité Des Soins, F-59000, Lille, France

    Damien Subtil

  9. Hematology Department, Saint-Antoine Hospital, Paris, France

    Paul Coppo

  10. Sorbonne University, Paris, France

    Paul Coppo

Authors
  1. Aghiles Hamroun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Camille Prouteau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rémi Lenain
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Camille Roger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne Bauters
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christophe Zawadzki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Damien Subtil
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jean-Baptiste Gibier
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Morgane Stichelbout
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Paul Coppo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Arnaud Lionet
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mehdi Maanaoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Marc Hazzan
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. François Provôt
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study concept and design: AH, CP, FP; data acquisition and management: CP, FP, AB, CZ, J-BG, MS; statistical analyses: AH; drafting of the manuscript: AH, CP, FP; critical revisions: AH, CP, RL, CR, AB, CZ, DS, J-BG, MS, PC, AL, MM, MH, and FP; all authors approved the final version of the manuscript.

Corresponding author

Correspondence to François Provôt.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest regarding the content of this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 12 KB)

Supplementary file2 (DOCX 13 KB)

Supplementary Supplementary Figure 1. Study flowchart file3 (JPG 250 KB)

40620_2023_1790_MOESM4_ESM.jpg

Supplementary Supplementary Figure 2. Placental histology in index and first subsequent pregnancies (patient #3). Index pregnancy (intrauterine death at 26 weeks’ gestation): syncytial nuclear aggregates and placental villous hypermaturation (a, hematoxylin and eosin x4); perivillous trophoblast necrosis and recent placental infarction (b, hematoxylin and eosin x4). First subsequent pregnancy under monitoring (live birth delivery at 35 weeks’ gestation): normal placental histology without any evidence of villous hypermaturation or infarction (c, d, hematoxylin and eosin x4) file4 (JPG 1202 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hamroun, A., Prouteau, C., Lenain, R. et al. The challenging follow-up of pregnancy in women with known thrombotic thrombocytopenic purpura: a single-center experience of a preemptive management protocol. J Nephrol 36, 2519–2529 (2023). https://doi.org/10.1007/s40620-023-01790-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40620-023-01790-x

Keywords

Search

Navigation