Approximately 30 to 35 percent of pregnant women with immune thrombocytopenia purpura (ITP) require therapeutic intervention during pregnancy, frequently with either corticosteroids or intravenous immune globulin (IVIg). Data supporting these treatments, though, comes predominantly from studies of non-pregnant patients with ITP.
In a retrospective study published in Blood, Dongmei Sun, MD, MSc, from the Department of Medicine at the Schulich School of Medicine and Dentistry at Western University in Ontario, Canada, and authors evaluated whether treatment with corticosteroids or IVIg led to improved responses and how these drugs affected maternal and neonatal platelet counts, in women diagnosed with ITP prior to their pregnancies.
Dr. Sun and colleagues analyzed data from 195 women who had 235 pregnancies (women who had subsequent pregnancies were included as long as they still met the eligibility criteria). Patients were recruited from two tertiary care centers in Canada – Mount Sinai Hospital in Toronto and McMaster University Medical Centre in Hamilton – between January 2000 and August 2014.
Patients were identified through hospital medical records using International Classification of Diseases 10 codes for thrombocytopenia (platelets <100×109/L).
Patients were excluded if they had:
- thrombocytopenia of an alternate etiology, including preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), or sepsis
- platelet counts that remained above 70×109/L in pregnancy and normalized in the postpartum period (this was deemed gestational thrombocytopenia)
Treatment intervention was not required in 137 pregnancies (58%). For the remaining 98 pregnancies (in 91 women), IVIg was the initial treatment in 47 pregnancies (48%), and corticosteroids were used in 51 pregnancies. Selection of the initial agent was determined by individual physicians.
The mean dose of IVIg was 1 g/kg (standard deviation = 0.22). For those who received corticosteroids, the agents included:
- prednisone (n=46; 92%; median initial dose = 50 mg/day)
- dexamethasone (n=4; 7.8%; 40 mg/day)
- both prednisone and dexamethasone (n=1; 2%)
A total of 231 neonates were alive at birth; of the 235 pregnancies, 161 had one baby (83%), 28 had two babies (14%), and six had three babies (3%). Four of the 235 pregnancies ended in intra-uterine deaths; 56 (28%) had a platelet count <150×109/L and 18 (9%) had a platelet count <50×109/L, though, the authors reported, “there was no correlation between maternal platelet count at delivery and the nadir neonatal platelet count.”
“There was no difference in maternal platelet counts at delivery between those treated with IVIg and those treated with corticosteroids as the initial agent (69×109/L and 77×109/L; p=0.71),” Dr. Sun and colleagues wrote. A rise in platelet count occurred in 18 of 47 pregnancies initially treated with IVIg (38%) and 20 of 51 pregnancies initially treated with corticosteroids (39%; p=0.85).
“The sole difference between the treatments was a higher [rate of] maternal composite outcome [consisting of higher rates of postpartum hemorrhage, pre-delivery platelet transfusion, peripartum transfusion of any blood product, or postpartum reduction in the hemoglobin concentration of 30g/L or more] noted in the IVIg group,” the authors added. Rates among IVIg- and corticosteroids-treated women were 46.8 percent versus 23.5 percent (p=0.02).
Neonatal outcomes were also similar between each treatment group: The mean nadir of neonatal platelet counts was 182×109/L for pregnancies treated with IVIg, compared with 181×109/L for pregnancies treated with corticosteroids (p=0.89). The natal/neonatal composite outcome rate (consisting of any adverse neonatal event including stillbirth, preterm birth before 34 weeks of gestation, or small for gestational size) was 19.2 percent in the IVIg group and 17.7 percent in the corticosteroids group (p=0.87).
Adverse events (AEs) were reported in 13 percent of those taking IVIg at any point during gestation (n=7/53), including hemolytic anemia (n=1; 2%), headache (n=3; 6%), and other (including swelling, flushing, and chills/rigors plus light-headedness; n=3; 6%). Similarly, AEs were reported in 13 percent of those taking corticosteroids at any point during gestation (n=9/67). These AEs included hyperglycemia requiring treatment (n=6; 9%), hyperglycemia with neonatal hypoglycemia (n=1; 2%), infection (n=1; 2%), and other (insomnia and jitteriness; n=1; 2%). No critical maternal bleeding events occurred in the study.
“The choice [between steroids and IVIg] will be based on several factors, including the need for a rapid response to, for example, maternal or fetal bleeding, the need to avoid side effects of the intervention, patient preferences, and – potentially – cost,” Dr. Sun told ASH Clinical News when asked about the study’s implications for treatment choice. “IVIg would be the first choice for maternal or fetal bleeding, as IVIg results in a rapid increment in platelet counts. IVIg may also be used for patients with comorbid illnesses that may be exacerbated by corticosteroids, such as diabetes or hypertension.”
Corticosteroids, however, “remain the first option for treatment for ITP, as the use of corticosteroids is associated with a longer response duration,” she added “Patients may prefer corticosteroids to avoid intravenous administration and where cost may be prohibitive.”
“All neonates delivered to mothers with ITP need to have platelet counts monitored frequently in the first week, whether or not the maternal platelet count is normal and whether or not the cord platelet count was normal,” Dr. Sun added. This includes splenectomized women whose platelet counts may have normalized, she noted.
The study is limited by its retrospective design and lack of formal randomization to different treatment arms. In addition, the AE data may not have been adequately captured, as it was collected from medical records and may underrepresent more minor events. The data did not allow for an analysis of hypertension, diabetes, or other pregnancy-related adverse outcomes, given the similar efficacy of IVIg and corticosteroids.
Sun D, Shehata N, Ye XY, et al. Corticosteroids compared to intravenous immune globulin for the treatment of immune thrombocytopenia in pregnancy. Blood. 2016 July 5. [Epub ahead of print]