Current Management of Pregnant Persons with ITP: Systematic Literature Review

Introduction: Immune thrombocytopenia (ITP) often occurs during pregnancy and thrombocytopenia can worsen as the pregnancy progresses. Thrombocytopenia during pregnancy is significant because of concerns regarding risk of postpartum hemorrhage and neonatal thrombocytopenia. Ideally, patients are managed jointly by hematologists and high-risk obstetricians with a treatment goal to minimize the risk of bleeding complications.

The 2019 American Society of Hematology ITP guidelines do not address pregnancy. The 2019 International ITP Consensus Report recommends initial therapy with steroids or intravenous immunoglobulin (IVIG), and patients refractory to initial therapy may need anti-D (Rh(D) positive nonsplenectomized persons), combination therapy, thrombopoietin receptor agonists (TPO-RAs), or rituximab in severe cases. Although the 2019 American College of Obstetricians and Gynecologists (ACOG) guidelines agree with initial management, they disagree with 2nd and 3rd line recommendations stating there is not enough evidence to recommend either anti-D or rituximab during pregnancy and do not mention TPO-RAs at all. Therefore, the purpose of this study was to perform a systematic literature review to describe current management of pregnant persons with ITP.

Methods: In March 2023, we conducted a systematic search in the MEDLINE, Embase and Web of Science databases to identify articles on treatment of ITP in pregnancy from 2001-present. Keywords included terms for primary ITP and terms for pregnancy. Inclusion criteria included: 1) English language, 2) humans, and 3) at least 10 pregnant persons in the cohort. Exclusion criteria were: 1) did not contain original data, 2) conference abstracts, 3) unable to separate primary vs secondary ITP, and 4) unable to separate data for only the patients managed after 2001.

Three persons independently reviewed articles and performed data abstraction. The online Covidence systematic review management system was utilized to standardize data abstraction and determine consensus. Adverse outcomes were abstracted as reported in the original article.

Results: After removal of duplicates, a total of 1396 articles were screened for eligibility, 420 full articles were reviewed and 30 met eligibility criteria (Figure 1). Of the included articles, the majority were retrospective cohort studies (18/30), 6 prospective cohort, 2 case-control, 2 cross-sectional, and 2 clinical trials.

These 30 articles represented 3282 pregnant persons aged 16-45 years, with 3868 total pregnancies managed across 14 different countries. Fifty-seven percent of pregnancies (2207/3868) required treatment during the pregnancy and of those treated, 36% (805/2207) only required steroids. Other common treatments included: 17% (372/2207) IVIG + steroids, 14% (307/2207) IVIG only, 11% (232/2207) TPO-RAs, and 10% (225/2207) received platelet transfusions. Only 8 pregnancies were treated with rituximab and 0 with anti-D.

Nine articles described management during delivery. The majority (58%; 695/1203) reported no treatment was administered during delivery. When treatment was administered during delivery, it was a platelet transfusion (59%; 302/508) or steroids (40%; 204/508).

Only 2 maternal deaths were reported. There were 2 neonatal deaths and 68 intrauterine deaths. Also 7% of the total pregnancies were reported to have a post-partum hemorrhage complication.

Conclusion: As expected, pregnant persons with ITP were initially managed with steroids and IVIG. However, results from this study suggest hematologists are comfortable treating pregnant persons with off-label TPO-RAs. Patients were rarely treated with rituximab and 0 were treated with anti-D. Pregnancy in ITP was not without maternal risk as 7% of the pregnancies were complicated by hemorrhage. In comparison, the rate of postpartum hemorrhage in 2019 in the United States was reported to be 4.3% (Corbetta-Rastelli, Obstetrics & Gynecology 2023; 141:152-161). Although despite the hemorrhage rate, there were only 2 maternal deaths. Strengths of this study include the number of countries and pregnancies represented; however, limitations include the country-level differences in access to therapies and differences related to risk of pregnancy complications. The treatment landscape for ITP continues to expand; therefore, guidelines reflecting current management options are critical.