Immune thrombocytopenia newly diagnosed during pregnancy: Outcome for mothers and neonates and comparison with chronic immune thrombocytopenia during pregnancy
Authors: Stéphanie Guillet, Valentine Loustau, Emmanuelle Boutin, Odile Souchaud‐Debouverie, Nathalie Costedoat Chalumeau, Laurent Pascal, Laurent Gilardin, Louis Terriou, Julie Graveleau, Thibault Comont, Helene Henique, Quitterie Reynaud, Matthieu Mahévas, Marc Michel, Florence Canoui‐Poitrine, Bertrand Godeau
Journal: American Journal of Hematology (2024)

The incidence of many autoimmune diseases is increased in women of childbearing age. Recent studies gave reassuring data for women with preexisting immune thrombocytopenia (ITP) who want to become pregnant.1, 2 In particular, we recently confirmed that pregnancy does not increase the risk of severe bleeding.2 Little is known about the outcome of ITP diagnosed during pregnancy, and conflicting results have been reported. Some retrospective studies suggested that ITP newly diagnosed during pregnancy could have a more severe outcome, but a recent retrospective study reported that it was not associated with increased risk of severe neonatal ITP (NITP) or hemorrhagic complications in the neonate.1, 3 So far, no study has focused on ITP newly diagnosed during pregnancy. The main purpose of this prospective study was to better describe the characteristics and outcome of ITP newly diagnosed during pregnancy and compare its severity with preexisting chronic ITP during pregnancy. Secondary endpoints were pregnancy and birth outcomes as well as NITP incidence in these women. We also evaluated the risk of transition to chronic ITP by assessing the proportion of women with still-active ITP at 1 year after delivery and with extended follow-up. We conducted an ancillary study based on a larger nationwide prospective, multicenter, observational cohort of pregnant and nonpregnant ITP women with results already published on preexisting chronic ITP diagnosed before pregnancy (ClinicalTrials.gov: NCT02892630).2 We compared newly diagnosed to chronic ITP pregnant women from our larger cohort of 158 pregnant women with preexisting ITP at the time of pregnancy followed by the same centers during the same period and already reported.2 Newly diagnosed pregnant women were enrolled over a 4-year period, from 2014 to 2017, and followed from ITP diagnosis to the end of pregnancy and at least 12 months after delivery. Inclusion criteria were for the newly diagnosed ITP: pregnancy, age ≥18 years, platelet count nadir <50 × 109/L during pregnancy, and not known to be thrombocytopenic before pregnancy. We chose a nadir platelet count threshold <50 × 109/L to avoid misdiagnosis with gestational thrombocytopenia. We excluded women with other causes of thrombocytopenia in pregnancy such as preeclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, or acute fatty liver of pregnancy as well as secondary ITP.4 For the chronic ITP control group, we selected 61 women with chronic ITP (at least 1 year of duration according to the international consensus4) at the time of pregnancy that was active (platelet count <100 × 109/L). All newly diagnosed ITP women whose ITP was in remission at 1 year after delivery were recontacted in September 2023 to ensure that the ITP remained in remission and that the patients had not experienced a late relapse. ITP worsening during pregnancy and 6 months postpartum period was assessed by a composite end point, defined by at least one of the following: (1) occurrence of a new bleeding event and/or (2) occurrence of severe thrombocytopenia (i.e., platelet count <30 × 109/L) and/or (3) ITP treatment initiation or modification except for ITP treatment to prepare for delivery. Treatment administered in preparation for delivery was defined by treatment with corticosteroids and/or intravenous immunoglobulin (IVIg) exclusively used in preparation for delivery within 4 weeks before the expected due date. Moreover, we evaluate the risk of chronic ITP defined as ITP still active (platelet count <100 × 109/L) at 1 year after delivery. To uniformly assess the severity of bleeding events, each center used a bleeding score that is widely used for adult ITP in France and previously described by our group.5 The study was approved by the institutional review board and ethics committee of Bicêtre Hospital (PP13-013, May 15, 2013) and was performed in accordance with the Declaration of Helsinki. Comparisons between chronic and newly diagnosed ITP pregnant women for the main and secondary end points were performed using appropriate statistical tests (log-rank, Wilcoxon–Mann–Whitney, chi-squared, or Fisher exact) with statistical significance set at p < .05. Analyses were conducted using STATA v17.0 (StataCorp, College Station, TX, USA). We included 47 pregnant women with newly diagnosed ITP. Finally, 34 pregnant women were confirmed as having newly diagnosed primary ITP, 9 were excluded for platelet count before pregnancy <150 × 109/L or lost to follow-up, and 4 were ruled out because of a diagnosis of secondary ITP with an influenza-like syndrome. During pregnancy, 17/34 (50%) of newly diagnosed ITP pregnant women experienced severe thrombocytopenia, with bleeding events for 41.2%, including 11.8% of severe bleeding events defined by a French bleeding score >8 (Table 1). Moreover, 76.5% required ITP treatment during pregnancy without taking into account treatment to prepare for delivery. ITP outcome was not different between these 34 pregnant women and the control group of 61 pregnant women with preexisting chronic ITP, with no significant difference in incidence of severe thrombocytopenia and bleeding events, including severe bleeding (score >8) (Table 1). However, chronic ITP women underwent fewer ITP therapeutic interventions than newly diagnosed ITP women: 50.8% versus 76.5% (p = .039). A trend toward a more severe evolution for all aspect in obstetric outcomes including preterm delivery, frequency of epidural anesthesia, postpartum hemorrhage, and cesarean section (C-section) delivery rates was observed for newly diagnosed ITP pregnant women, although not significant, probably due to the small number of women (Table 1). According to historical French data, C-section delivery was more frequent in pregnant women with newly diagnosed ITP than the general French population (44% vs. 21%).6 Preterm delivery was also more frequent (18% vs. 6%–8% in the European population).7 As expected, epidural anesthesia with vaginal delivery was less often used in women with newly diagnosed ITP than in the general French population (47% vs. 85%),6 and risk of postpartum hemorrhage was also more frequent (11.8% vs. 5%).8 About the high frequency of C-section in the newly diagnosed ITP group, even if claimed for obstetric reasons, we cannot exclude that physicians or patient anxiety led to this unexpected high rate. Concerning the risk of NITP, platelet count was available for 31/34 neonates of women with newly diagnosed ITP. Eight (27.6%) newborns had NITP, 6 (20%) and 5 (16.7%) with platelet count <50 and <30 × 109/L, respectively. Bleeding events occurred in only one newborn, in whom platelet count was unfortunately not evaluated after delivery. At 1 month, he experienced bruising, and the platelet count revealed severe thrombocytopenia, 20 × 109/L. Minimal intracranial hemorrhage was identified on CT scan without clinical symptoms, and the outcome was favorable with IVIg treatment. Six (18.2%) and 5 (15.2%) neonates with NITP received IVIg and platelet transfusions, respectively. Overall risk of NITP was not different for newly diagnosed and chronic ITP women (Table 1). Among the 34 pregnant women with newly diagnosed ITP, at 1 year after delivery, 3 were lost to follow-up. For 12/31 women (39%), newly diagnosed ITP remained active (platelet count <100 × 109/L) and was classified as chronic. Among them, 5/12 did not require treatment, 5/12 required second-line treatments for ITP including rituximab, belimumab, thrombopoietin receptor agonists, or immunosuppressants. Two (17%) other patients developed secondary ITP with systemic lupus treated with hydroxychloroquine. For 19 (61%) women, ITP was classified as in remission (platelet count >100 × 109/L) at 1 year. After a median follow-up after delivery of 4.5 years (range, 2–8), 4 of them had a relapse of ITP during a later pregnancy, with NITP observed for 2 women and one other woman experienced a relapse of ITP 6 years later. At the end of the study, 17/31 (51.8%) women were classified as having chronic ITP. In summary, we showed that the outcome of ITP newly diagnosed during pregnancy is similar to those of chronic active ITP known before pregnancy as well as the risk of NITP. It frequently required therapeutic intervention, with a high frequency of severe thrombocytopenia, sometimes accompanied by hemorrhagic complications, but not severe in 75% of cases, with excellent maternal prognosis. Regarding ITP treatments required during pregnancy, IVIg and corticosteroids were effective to reach the target platelet count depending on the pregnancy term. In particular, none of newly diagnosed ITP women required treatments other than IVIg and corticosteroids to prepare for delivery, with only 2 women with platelet count <50 × 109/L at delivery. The risk of neonatal thrombocytopenia in women with newly diagnosed ITP was not different to that for women with chronic ITP. However, it should not be overlooked, and the observation of a late NITP diagnosis reported in our study reminds physicians of the need to systematically monitor the platelet count of the newborn in the days following delivery. A trend toward a more severe course for all aspects of obstetric outcome was observed in women with newly diagnosed ITP compared with pregnant women with preexisting ITP as well as compared with the French general population, but the obstetric prognosis remains excellent. The last important message from our study is that we observed a chronic ITP course after childbirth in more than half of the women with newly diagnosed ITP, which is not different to that observed for ITP newly diagnosed outside pregnancy. Furthermore, physicians and patients should be aware of the risk of ITP relapse and NITP in a new pregnancy even in patients whose platelet count had normalized after delivery. B.G. and V.L. designed the study and initiated this work; S.G., B.G., and F.-C.P wrote the report; and all authors made substantial contributions to acquisition of data, revised the article critically, and gave final approval of the manuscript to be submitted. We thank Laura Smales for her careful reading and editing of the manuscript, Manuel Cliquenois, Jean-Christophe Lega, Bertrand Lioger, Veronique Le Guern, and Anne Sophie Morin for patients recruitment. This work was supported by grants (PHRC; AOM12206) from the French Health Ministry. The sponsor was Assistance Publique—Hôpitaux de Paris (Délégation à la Recherche Clinique et à l'Innovation). Bertrand Godeau serves as expert for AMGEN, Novartis, Grifols, Sobi, and Borhinger. Matthieu Mahévas received funds for research from GSK and received fees from LFB. Marc Michel received consultancy fees from Amgen, Novartis, and Argenx. The remaining authors declare no competing financial interests. Written information was delivered to women by the investigators and oral consent was obtained in accordance with French law for a non-interventional study.