Pregnancy outcomes of mothers with immune thrombocytopenia

Background: It has been proposed that, thrombocytopenia is the most common haematological abnormality in pregnancy after anaemia. The incidence of severe immune thrombocytopenia (ITP) in pregnancy has been difficult to report because of the rarity of the disease. Objectives were to determine the prevalence, pregnancy outcomes, treatment modalities of ITP mothers over five years in a tertiary health care hospital in South India.Methods: Our study was a retrospective record study, which looked into various aspects of obstetrical outcomes and complications in ITP mothers. Records of the in-patient medical record department (MRD) folders of patients with ITP who delivered at St. Johns Medical Hospital, Bangalore were studied.Results: We identified 53 patients with ITP with a mean age of 25.6+4.6 years, age of diagnosis of ITP at 21.1+5.9 years and gestational age of 36.2+3 weeks. In our study 17 (32%) were acute and 36 (67.1%) were chronic ITP. In our study 39.6% had history of at least one prior pregnancy loss. Patients with ITP at 35-37 weeks were induced with PGE1 (35.7%) in comparison to those with PGE2 (p≤0.001). Post-partum haemorrage (PPH) was seen in 7.5% of the pregnancies and all four were mothers with chronic ITP. Severe preeclampsia in ITP mothers was seen in 2 (66.7%).Conclusions: Chronic ITP in pregnancy poses more risks to mother and foetus as seen with the higher chance of PPH etc. Mothers with ITP should be screened antenatally as the chances of anomalies are high in the foetus.

Immune Thrombocytopenic Purpura in Pregnancy- A Prospective Observational Study in a Tertiary Care Centre

Objectives: Immune thrombocytopenic purpura (ITP) in pregnancy necessitates management of two patients, the mother and the newborn. Complications like maternal bleeding, fetal and neonatal thrombocytopenia demands appropriate and timely therapy. This prospective observational study was designed to explore and summarize the current approach to the investigation, diagnosis, management and outcome of ITP in pregnancy. Materials and Methods: Women with ITP admitted in the Fetomaternal Medicine Department of Bangabandhu Sheikh Mujib Medical University (BSMMU) from 2009 -2017, were included in the study. Total number of high risk pregnancy during that period were 7704 among them 20 cases were pregnancy with Immune Thrombocytopenic Purpura (ITP). Patients were managed under joint supervision of the fetomaternal medicine specialist and the hematologist. Prednisolone was considered as a first line drug in management protocol. Platelet transfusion was considered if there were symptoms or count <20X109/L at any stage of pregnancy or <50 X109 / L in late pregnancy without symptoms. Platelet count of newborn was performed at birth and repeated on day four and count<150X109/L was considered as neonatal thrombocytopenia. Results: Frequency of ITP among high risk patients was found 2.5/1000 live birth, most were preexisting (75%). Almost all cases (95%) were treated with prednisolone. Commonest clinical presentations were gum bleeding (70 %) and purpuric rashes (60%). Though during pregnancy, severe thrombocytopenia (<50 X109/L) was found in 7 patients (35%) but none was at the time of delivery, as drugs and/or platelet transfusion was considered to make delivery process safe. Platelet transfusion needed in 77.7% cases in a range of 1-75 units. Primary PPH noted in 3 cases (17%), increased bleeding during surgery in 5 patients (33%) and one patient needed ICU support. Neonatal thrombocytopenia noted in 5 cases (28%). Though 2 of the neonates needed NICU admission but none needed platelet transfusion and all the babies were discharged healthy. Conclusion: This study documents that pregnancy with ITP need close monitoring, require agents to raise the platelet count and repeated platelet transfusion to maintain reasonable safe platelet count. There are chances of PPH, capillary oozing during surgery. However good outcome is possible for most women, fetus and neonates with appropriate and timely therapy. Bangladesh J Obstet Gynaecol, 2019; Vol. 34(1): 15-21

Rituximab – A novel therapy for severe ITP in pregnancy: A case report

Background Rituximab is a novel second-line agent for the treatment of immune thrombocytopenic purpura. Minimal data exist on the use of rituximab in pregnancy. This case illustrates the successful treatment of severe immune thrombocytopenic purpura diagnosed in pregnancy, refractory to all other medical management. Case A 32-year-old nulliparous woman was diagnosed with severe immune thrombocytopenic purpura at the time of booking for antenatal care (platelet level of 13 × 109/L). Standard treatment failed to adequately increase her platelet count. Therapy with rituximab was instituted, and her platelet count rose to normal levels, without side effects, and remained at a normal level throughout the pregnancy. There were no maternal or neonatal ill-effects of rituximab therapy. Conclusion Rituximab is potentially a safe treatment option for the management of immune thrombocytopenic purpura in pregnancy with good maternal and neonatal outcome when conventional treatments have been unsuccessful. Research is limited to case reports, and therefore limited information currently exists to guide clinicians.

A Multicenter Open-Labeled Pilot Study on Recombinant Human Thrombopoietin in the Management of Immune Thrombocytopenia in Pregnancy

Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by transient or persistent decrease of platelet count. ITP is the most common cause of thrombocytopenia in early pregnancy. Patients with severe thrombocytopenia (platelet count < 20 ×109/L) are at risk of spontaneous bleeding, postpartum hemorrhage and placental abruption. The aim of this study is to determine the efficacy and the safety of recombinant human thrombopoietin (rhTPO) in the management of ITP in pregnancy. This study is registered at www.clinicaltrials.gov as NCT02391272. Patients at eight centers in China were enrolled. Enrollment criteria were pregnant women aged between 18 and 50, who failed to respond to first-line treatments of ITP and/or were refractory to platelet transfusion. Patients' platelet counts were below 30×109/L with bleeding manifestations. Gestational age of the patients was over 12 weeks. Informed consent was obtained from each patient in accordance with the Declaration of Helsinki. Thirty-one patients were enrolled into the study. The median age of the pregnant ITP patients was 26 years (range 19 - 39 years) and 90.6% (29/31) were primigravidae. The median gestational age was 24 weeks (12 - 38 weeks). The median baseline platelet count was 10×109/L (range 1 - 29×109/L). 74.2% (23/31) of these patients were diagnosed as ITP before pregnancy and 25.8 % (8/31) during pregnancy. All eligible participants received rhTPO at an initial dose of 300U/kg once daily subcutaneously for 14 days, 74.2% (23/31) of these patients responded to the initial 14-day rhTPO therapy, including 10 CR and 13 R. Eight patients were NR though their platelet counts rose mildly. The median platelet count of responder was 100×109/L (range from 30 to 250×109/L) at day 14. Then the responders received sequential maintenance therapy through the end of week 12 after delivery. To reduce the risk of thrombocytosis during maintenance, dose was tapered to 300U/kg every other day when platelet counts exceeded 50 ×109/L and treatment stopped when platelet counts above 100×109/L. Only one responder had a transient loss of response due to influenza. After dose adjustment of rhTPO from 300U/kg every other day to 300U/kg every day, the platelet count exceeded 50×109/L in the next visit. The platelet counts gradually dropped after withdrawal of rhTPO. The relapse free survival (platelet count at least 30×109/L) at week 4 and week 12 after withdrawal of rhTPO was 69.6%(16/23) and 21.7%(5/23), respectively (Figure 1). Safety and adverse events were evaluated in all 31 participants. rhTPO was well tolerated. Only mild previously reported adverse events were observed, including one case of dizziness, one of fatigue and one of pain at injection site. There were no new reported adverse events during the observation period and no adverse event-related study withdrawals. In all the 31 newborns, the median age of gestation was 39 weeks (range 36-40, 3 cases had age of gestation< 37 weeks); median birth weight was 3.1 kg (range 2.3-4.2kg, 2 had birth weight<2.5 kg) and the median platelet count at birth was 132×109/L (range 53-263 ×109/L, 9 with platelet<100×109/L) (Table 1). The incidence of premature labor, birth weight and platelet count were similar to previous study on pregnancy outcome in patients with ITP. None of the neonates had bleeding at birth. All 31 infants were evaluated for safety. No adverse effect on the development of newborns was observed during 6 months follow-up. One case of abdominal distension had been reported, which was supposed not associated with rhTPO. This study demonstrates that rhTPO is a potentially effective, safe and fast-onset treatment for ITP in pregnancy refractory to fist-line therapy and platelet transfusion. Our study paved the way for the clinical application of rhTPO and other thrombopoietic agents in the management of ITP in pregnancy. Disclosures No relevant conflicts of interest to declare.