Unintended First-Trimester Exposure to Two Distinct Thrombopoietin Receptor Agonists in Consecutive Pregnancies Without Maternal or Fetal Harm

To the Editor, Managing immune thrombocytopenia (ITP) during pregnancy remains challenging, particularly in women refractory to corticosteroids and intravenous immunoglobulin (IVIG).Thrombopoietin receptor agonists (TPO-RAs) may be considered as rescue therapy, but their use in pregnancy is off-label and current guidelines advise caution, especially during the first trimester (1).Available evidence is limited; observational studies report high maternal platelet response rates and generally acceptable neonatal outcomes, while exposure during organogenesis remains rare (2,3,4).In a registry of 186 romiplostim-exposed pregnancies, no specific teratogenic pattern was identified (4).Pharmacokinetic data indicate that romiplostim can be detected in breast milk and in infant serum at low levels, whereas direct human data on placental transfer remain limited (5).Case reports describe eltrombopag use in refractory or late pregnancy, including isolated first-trimester exposure without adverse outcomes (6, 7, 8).Additional experience with recombinant human thrombopoietin and hetrombopag has also reported reassuring maternal and neonatal results, although mostly outside early gestation (9, 10).Overall, first-trimester exposure to TPO-RAs remains uncommon, and data during organogenesis are particularly limited.We describe a young woman with chronic, steroid-refractory ITP who experienced two consecutive pregnancies with unintended first-trimester exposure to two different TPO-RAs.The first pregnancy was diagnosed at 8 weeks' gestation while the patient was receiving romiplostim (3 g/kg weekly; last dose 5 days before confirmation).Given documented steroid refractoriness, corticosteroids were not pursued.After counseling, the patient elected to continue the pregnancy.Romiplostim was discontinued immediately, and intravenous immunoglobulin (IVIG) was initiated at 2-3 week intervals.Platelet counts showed a dynamic course throughout pregnancy; management aimed to avoid platelet counts <50 10/L during the first and second trimesters and <80 10/L during the third trimester.Key platelet values at pregnancy recognition, predelivery, postpartum week 6, and neonatal platelet counts are summarized in Table 1.The pregnancy progressed without maternal hemorrhagic complications, and a healthy term infant without structural anomalies was delivered.The neonate had transient thrombocytopenia at birth (51 10/L) without bleeding, which resolved spontaneously.Fetal surveillance included routine obstetric follow-up and a detailed fetal anatomy ultrasound, which revealed no abnormalities.IVIG was continued during breastfeeding without adverse events.Following cessation of breastfeeding, eltrombopag was initiated for ongoing ITP.Despite contraception counseling, a second unplanned pregnancy was diagnosed at 7 weeks' gestation while the patient was taking eltrombopag 75 mg daily.The drug was discontinued immediately, and IVIG was restarted at 2-3 week intervals.Platelet targets similar to those in the first pregnancy were maintained, with a delivery goal of 100 10/L.The second pregnancy and delivery were uncomplicated, and the neonate had normal platelet counts.TPO-RAs were deliberately avoided during lactation because of limited human safety data and pharmacokinetic evidence of romiplostim transfer into breast milk and infant serum.This case documents sequential unintended first-trimester exposure to romiplostim and eltrombopag during organogenesis with favorable maternal and fetal outcomes.In contrast, most published experience with TPO-RAs is