Immune Thrombocytopenic Purpura Refractory to Corticosteroid Therapy in pregnant women: A literature review
DOI:
https://doi.org/10.33448/rsd-v14i1.48075Keywords:
Idiopathic thrombocytopenic purpura, Pregnancy, Thrombocytopenia.Abstract
Introduction: Immune Thrombocytopenic Purpura is defined as a platelet count below 100x109/L marked by signs of spontaneous bleeding. It is a pathology frequently observed in pregnant women. The pathophysiology is a reaction of autoantibodies that bind to platelet membrane proteins. The diagnosis is made by exclusion and confirmed by the response to therapy. It presents as a challenge during prenatal care and current guidelines present treatment protocols based on expert opinions and results of retrospective studies. Method: Narrative review of literature based on the data platforms: Scielo and PubMed. Inclusion and exclusion criteria were applied, totaling 34 articles discussed here. Results and Discussion: The management of Immune Thrombocytopenic Purpura is quite complex, with oral corticosteroids and immunoglobulins as the first line. Patients who are refractory to first-line treatment may use TPO receptor agonists, which have shown good results in published case reports, retrospective studies, and experimental studies in animals. Splenectomy is also a second-line therapeutic option but presents greater risks when performed in pregnant women. Conclusion: Immune Thrombocytopenic Purpura may present resistance to first-line treatment, and treatment protocols for resistant pregnant women are scarce. Among the second-line therapeutic options, the use of Thrombopoietin Receptor Agonists stands out, and the less recommended, splenectomy. Clinical trials with second-line therapies and treatment protocols for corticosteroid-resistant pregnant women are recommended.
Downloads
References
ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. (2019). Obstetrics and gynecology, 133(1), 1. https://doi.org/10.1097/AOG.0000000000003018
Al-Samkari, H., & Kuter, D. J. (2019). Optimal use of thrombopoietin receptor agonists in immune thrombocytopenia. Therapeutic advances in hematology, 10, 2040620719841735. https://doi.org/10.1177/2040620719841735
Amgen Inc Nplate (romiplostim) [informações de prescrição. (2008). Thousand Oaks: Califórnia: Amgen Inc.
Batra, A., Agarwal, S., Dewan, R., & Minocha, B. (2005). Idiopathic thrombocytopenic purpura complicating pregnancy. Journal of the Indian Medical Association, 103(10), 545–546.
Binder, T., Biolek, J., Srbová, A., Procházková, D., Vašková, A., Fadi, F., & Pánek, M. (2019). Acute immune trobocytopenic purpura in pregnant adolescent. Těžká akutní forma imunitní trombocytopenické purpury u nezletilé těhotné. Ceska gynekologie, 84(6), 443–449.
Bleau, N., Czuzoj-Shulman, N., Spence, A. R., & Abenhaim, H. A. (2017). Safety of splenectomy during pregnancy. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 30(14), 1671–1675. https://doi.org/10.1080/14767058.2016.1222365
Bussel, J. B., Hsieh, L., Buchanan, G. R., Stine, K., Kalpatthi, R., Gnarra, D. J., Ho, R. H., Nie, K., & Eisen, M. (2015). Long-term use of the thrombopoietin-mimetic romiplostim in children with severe chronic immune thrombocytopenia (ITP). Pediatric blood & cancer, 62(2), 208–213. https://doi.org/10.1002/pbc.25136
Bussel, J. B., Cooper, N., Lawrence, T., Michel, M., Vander Haar, E., Wang, K., Wang, H., & Saad, H. (2023). Romiplostim use in pregnant women with immune thrombocytopenia. American journal of hematology, 98(1), 31–40. https://doi.org/10.1002/ajh.26743
Bussel, J. B., & Knightly, K. A. (2024). Immune thrombocytopenia (ITP) in pregnancy. British journal of haematology, 204(4), 1176–1177. https://doi.org/10.1111/bjh.19230
Care, A., Pavord, S., Knight, M., & Alfirevic, Z. (2018). Severe primary autoimmune thrombocytopenia in pregnancy: a national cohort study. BJOG : an international journal of obstetrics and gynaecology, 125(5), 604–612. https://doi.org/10.1111/1471-0528.14697
Chua, S. J., Morton, M. R., Svigos, J., Ross, D. M., & Kane, S. (2020). Use of romiplostim in pregnancy for refractory idiopathic thrombocytopenic purpura: Two case reports with maternal and fetal outcomes and literature review. Obstetric medicine, 13(1), 45–50. https://doi.org/10.1177/1753495X18773960
DeCS 2024. (2024). São Paulo: BIREME / PAHO / WHO. https://decs.bvsalud.org/en/
Ferreira, I. J. M. C. F., Sousa, F., Vasco, E. M., Areia, A. L. F. A., Moura, J. P. A. S., Carda, J., & Ribeiro, L. (2018). Severe immune thrombocytopenia in pregnancy treated with Eltrombopag - A case report. Journal of gynecology obstetrics and human reproduction, 47(8), 405–408. https://doi.org/10.1016/j.jogoh.2018.06.010
Fujita, A., Sakai, R., Matsuura, S., Yamamoto, W., Ohshima, R., Kuwabara, H., Okuda, M., Takahashi, T., Ishigatsubo, Y., & Fujisawa, S. (2010). A retrospective analysis of obstetric patients with idiopathic thrombocytopenic purpura: a single center study. International journal of hematology, 92(3), 463–467. https://doi.org/10.1007/s12185-010-0684-8
Guillet, S., Loustau, V., Boutin, E., Zarour, A., Comont, T., Souchaud-Debouverie, O., Costedoat Chalumeau, N., Pan-Petesch, B., Gobert, D., Cheze, S., Viallard, J. F., Morin, A. S., Sauvetre, G., Cliquennois, M., Royer, B., Masseau, A., Terriou, L., Fieschi, C., Lambotte, O., Girault, S., … Godeau, B. (2023). Immune thrombocytopenia and pregnancy: an exposed/nonexposed cohort study. Blood, 141(1), 11–21. https://doi.org/10.1182/blood.2022017277
Koche, J.C. (2011). Fundamentos de metologia científica. Petrópolis: Vozes.
Kong, Z., Qin, P., Xiao, S., Zhou, H., Li, H., Yang, R., Liu, X., Luo, J., Li, Z., Ji, G., Cui, Z., Bai, Y., Wu, Y., Shao, L., Peng, J., Ma, J., & Hou, M. (2017). A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy. Blood, 130(9), 1097–1103. https://doi.org/10.1182/blood-2017-01-761262
Liu, Y., Wang, R., Han, P., Zhao, Y., Li, G., Li, G., Nie, M., Wang, L., Chen, J., Liu, X., & Hou, M. (2019). Effect of recombinant human thrombopoietin on immune thrombocytopenia in pregnancy in a murine model. International immunopharmacology, 67, 287–293. https://doi.org/10.1016/j.intimp.2018.12.032
Loustau, V., Debouverie, O., Canoui-Poitrine, F., Baili, L., Khellaf, M., Touboul, C., Languille, L., Loustau, M., Bierling, P., Haddad, B., Godeau, B., Pourrat, O., & Michel, M. (2014). Effect of pregnancy on the course of immune thrombocytopenia: a retrospective study of 118 pregnancies in 82 women. British journal of haematology, 166(6), 929–935. https://doi.org/10.1111/bjh.12976
Mandal, P. K., Dolai, T. K., Bagchi, B., Ghosh, M. K., Bose, S., & Bhattacharyya, M. (2014). B cell suppression in newborn following treatment of pregnant diffuse large B-cell lymphoma patient with rituximab containing regimen. Indian journal of pediatrics, 81(10), 1092–1094. https://doi.org/10.1007/s12098-013-1336-9
Mahey, R., Kaur, S. D., Chumber, S., Kriplani, A., & Bhatla, N. (2013). Splenectomy during pregnancy: treatment of refractory immune thrombocytopenic purpura. BMJ case reports, 2013, bcr2013201778. https://doi.org/10.1136/bcr-2013-201778
Neunert, C., Terrell, D. R., Arnold, D. M., Buchanan, G., Cines, D. B., Cooper, N., Cuker, A., Despotovic, J. M., George, J. N., Grace, R. F., Kühne, T., Kuter, D. J., Lim, W., McCrae, K. R., Pruitt, B., Shimanek, H., & Vesely, S. K. (2019). American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood advances, 3(23), 3829–3866. https://doi.org/10.1182/bloodadvances.2019000966
Patras, A., Figueroa, R., Singh, A. P., & Madan, I. (2020). Romiplostim for management of refractory immune thrombocytopenic purpura in the immediate postpartum period. BMJ case reports, 13(5), e234335. https://doi.org/10.1136/bcr-2020-234335
Perusso, S.K.G. & Santos, M.B.C. (2017). Prenatal Management of a Pregnant Woman with Corticosteroid-Refractory Immune Thrombocytopenic Purpura. PECIBES; 2, 30-40.
Pishko, A. M., & Marshall, A. L. (2022). Thrombocytopenia in pregnancy. Hematology. American Society of Hematology. Education Program, 2022(1), 303–311. https://doi.org/10.1182/hematology.2022000375
Provan, D., Arnold, D. M., Bussel, J. B., Chong, B. H., Cooper, N., Gernsheimer, T., Ghanima, W., Godeau, B., González-López, T. J., Grainger, J., Hou, M., Kruse, C., McDonald, V., Michel, M., Newland, A. C., Pavord, S., Rodeghiero, F., Scully, M., Tomiyama, Y., Wong, R. S., … Kuter, D. J. (2019). Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood advances, 3(22), 3780–3817. https://doi.org/10.1182/bloodadvances.2019000812
Putbrese, B., & Kennedy, A. (2017). Findings and differential diagnosis of fetal intracranial haemorrhage and fetal ischaemic brain injury: what is the role of fetal MRI?. The British journal of radiology, 90(1070), 20160253. https://doi.org/10.1259/bjr.20160253
Purushothaman, J., Puthumana, K. J., Kumar, A., Innah, S. J., & Gilvaz, S. (2016). A case of refractory immune thrombocytopenia in pregnancy managed with elthrombopag. Asian journal of transfusion science, 10(2), 155–158. https://doi.org/10.4103/0973-6247.177204
Ramakrishna, R., Rehman, A., Ramakrishna, S., Alexander, W., & Yeo, W. W. (2015). Use of romiplostim in patients with chronic idiopathic thrombocytopenic purpura during perioperative period. Internal medicine journal, 45(7), 718–724. https://doi.org/10.1111/imj.12794
Sun, D., Shehata, N., Ye, X. Y., Gregorovich, S., De France, B., Arnold, D. M., Shah, P. S., & Malinowski, A. K. (2016). Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy. Blood, 128(10), 1329–1335. https://doi.org/10.1182/blood-2016-04-710285
Sukenik-Halevy, R., Ellis, M. H., & Fejgin, M. D. (2008). Management of immune thrombocytopenic purpura in pregnancy. Obstetrical & gynecological survey, 63(3), 182–188. https://doi.org/10.1097/OGX.0b013e318164013c
Suzuki, N., Hiraga, J., Hariyama, Y., Takagi, Y., Ohashi, H., Kishigami, Y., Oguchi, H., & Kagami, Y. (2018). A low birth weight infant with no malformations delivered by a primary immune thrombocytopenia patient treated with eltrombopag. International journal of hematology, 108(1), 109–111. https://doi.org/10.1007/s12185-017-2383-1
Yu, J., Miao, P., & Qian, S. (2023). Application of recombinant human thrombopoietin in pregnant women with immune thrombocytopenia: a single-center experience of four patients and literature review. The Journal of international medical research, 51(8), 3000605231187950. https://doi.org/10.1177/03000605231187950
Zhang, H., Shi, L., Shang, H., & Yang, H. (2024). Immune Thrombocytopenic Purpura and Maternal and Neonatal Outcomes During Pregnancy: A Systematic Review and Meta-Analysis. American journal of reproductive immunology (New York, N.Y. : 1989), 92(5), e70008. https://doi.org/10.1111/aji.70008
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Sara Kaizer Galo Perusso; Manoel Barboza Cordeiro dos Santos; Danielle Cristine Belisario Scarpin Holsbach
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
