Management of Hemorrhagic Risk in Refractory Immune Thrombocytopenia Complicating a Dichorionic Diamniotic Twin Pregnancy

Immune thrombocytopenia (ITP) in pregnancy is an autoimmune disorder characterized by antibody-mediated platelet destruction and impaired production, posing a significant risk of hemorrhage.[1] Management primarily relies on corticosteroids and intravenous immunoglobulin (IVIG), with treatment strategies largely informed by data from singleton pregnancies.[1] [2]

A distinct clinical challenge arises in cases of refractory ITP, where patients exhibit an inadequate or transient response to first-line therapy.[3] The optimal management sequence in this setting, particularly in the context of a multifetal gestation, which imposes unique physiological stresses, remains undefined and necessitates individualized, multidisciplinary care. We herein describe a representative case that underscores these challenges.

Our case is a 32-year-old woman with dichorionic diamniotic twin gestation, who presented with asymptomatic thrombocytopenia (platelet count 82 × 10⁹/L) at 14 weeks. The platelet count declined to 16 × 10⁹/L by 21^3/7 weeks, with petechiae, leading to corticosteroid therapy. Partial response was observed; however, dose reduction at 24^2/7 weeks resulted in a decline to 8 × 10⁹/L, indicating steroid refractoriness and necessitating escalation to recombinant human thrombopoietin (rhTPO). Around this time, gestational diabetes mellitus (GDM) was diagnosed via oral glucose tolerance test. Initial management with diet and exercise was insufficient, as corticosteroid therapy induced significant hyperglycemia, ultimately requiring insulin therapy for glycemic control.

At 30 weeks, the patient was hospitalized with severe thrombocytopenia (platelet count 9 × 10⁹/L) and active mucocutaneous bleeding. Management was intensified with IVIG, high-dose prednisone, and rhTPO. Concurrently, she developed significant hepatic dysfunction, with alanine aminotransferase (ALT) peaking at 579 IU/L. An extensive evaluation excluded obstetric, infectious, and metabolic etiologies. This hepatic impairment, which fully resolved postpartum, remained a critical complicating factor.

Due to this constellation of escalating maternal risks-including refractory thrombocytopenia with active bleeding, unexplained but significant hepatic impairment, and hyperglycemia complicated by high-dose immunosuppressive therapy-the multidisciplinary team determined that continuation of pregnancy posed an unacceptable risk to the mother. A planned preterm cesarean delivery was performed at 33^5/7 weeks to achieve maternal stabilization, thereby circumventing the unpredictable timing and potential duration of a twin vaginal delivery, which posed significant risks of maternal hemorrhage and exhaustion in the setting of profound thrombocytopenia.

It is noteworthy that the patient subsequently experienced a severe postpartum relapse (platelet count 3 × 10⁹/L at 17 days), which was successfully controlled with the thrombopoietin receptor agonist (TPO-RA)-eltrombopag, enabling her to achieve sustained remission (platelet count 91–269 × 10⁹/L) over a 2-year follow-up. The complete hematologic dynamics and therapeutic chronology are summarized in [Figs. 1] and [2].

Fig. 1 Hematologic dynamics during gestation and postpartum. (A) Serial platelet counts and hemoglobin levels across gestational weeks. Key interventions are annotated: prednisone initiation (▼), rhTPO administration (▪), triple therapy (*), delivery (*). (B) Platelet response to eltrombopag therapy over 24 months postpartum surveillance. HGB, hemoglobin; IVIG, intravenous immunoglobulin; PLT platelet; rhTPO, recombinant human thrombopoietin.

Fig. 2 Therapeutic chronology and critical decision points. The timeline is divided into prenatal and postnatal periods (separated by the red vertical line, indicating delivery). Red arrows in the prenatal period annotate three pivotal clinical turning points that guided management: (1) disease onset with petechiae and critical thrombocytopenia, prompting first-line therapy; (2) severe thrombocytopenia with active bleeding, necessitating hospitalization and intensive combination therapy; (3) progressive hematologic and hepatic dysfunction, leading to the decision for planned delivery. Adjacent black arrows indicate the corresponding therapeutic regimens administered at each stage. CS, cesarean section; IVIG, intravenous immunoglobulin; rhTPO, recombinant human thrombopoietin.

Collectively, this case highlights the limitations of singleton-based guidelines[1] and expands the literature by illustrating three unique challenges: the need for a sequential, multi-mechanistic treatment strategy; the complex management of concomitant GDM and hepatic injury; and the application of dynamic, pregnancy-specific risk stratification that guided delivery planning.

First, the accelerated, refractory course indicates that twin pregnancies may predispose to a more severe ITP phenotype, likely due to heightened physiological demands and platelet consumption.[2] [4] This potentially warrants more conservative intervention thresholds than in singletons to preempt hemorrhagic complications.

Second, our case illustrates a sequential therapeutic approach for refractory ITP. Glucocorticoids were used as the first-line agent,[5] which aimed at reducing antibody-mediated platelet destruction, but their transient efficacy and the coincident emergence of complex hyperglycemia and hepatotoxicity necessitated cautious management. Upon steroid failure, therapy was escalated to IVIG per international consensus.[6] During a critical bleeding episode, IVIG was combined with rhTPO to stimulate platelet production, achieving a rapid response. While the use of rhTPO was supported by Chinese data on its minimal placental transfer,[3] [7] we acknowledge these region-specific findings require broader international validation. Ultimately, sustained remission was attained postpartum with the TPO-RA eltrombopag. Although emerging evidence supports its gestational use in severe cases,[8] we reserved it for the postpartum period pending further safety data.[9] Furthermore, given limited data on its excretion in breast milk, a shared decision was made to avoid breastfeeding during treatment.[10]

The episode of marked hepatic dysfunction (ALT 579 IU/L) during intensive immunosuppressive therapy presented a considerable management challenge. Common obstetric (e.g., preeclampsia or HELLP syndrome and intrahepatic cholestasis of pregnancy), infectious, and metabolic causes were excluded based on clinical and laboratory findings. The complete and spontaneous normalization of liver indices postpartum strongly suggests the hepatic insult was intrinsically linked to the pregnant state. Given that corticosteroids treat rather than cause autoimmune hepatitis,[11] the liver injury likely stemmed from an alternative source: an idiosyncratic drug reaction, a manifestation of the underlying ITP, or an insult exacerbated by GDM and the twin gestation. This organ dysfunction became a pivotal factor in the decision for preterm delivery, underscoring that maternal health can supersede platelet count in guiding management.

Third, the decision for planned cesarean delivery at 33^5/7 weeks was driven by maternal, not fetal, indications. The mother's condition, refractory thrombocytopenia with recent bleeding and significant hepatic impairment, rendered the prospect of spontaneous or prolonged labor untenable and risky. Cesarean section (CS) allowed for a controlled procedure with the multidisciplinary team present, ensuring immediate resources to mitigate maternal hemorrhage. This approach reflects the necessary individualization of care for complex maternal morbidity, acknowledging that ITP itself is not an absolute indication for CS.

In conclusion, this case demonstrates that managing refractory ITP in twin pregnancies requires a paradigm that integrates multi-mechanistic therapy, vigilant complication management, and multidisciplinary decision-making, where delivery is guided by a holistic assessment of maternal well-being.

Data Availability Statement

The original contributions presented in the study are included in the article/supplementary material, and further inquiries can be directed to the corresponding author.

Informed Consent

Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Publication History

Received: 17 October 2025

Accepted: 15 December 2025

Article published online:
02 January 2026

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