Abstract
Background: Hereditary spherocytosis (HS) is a congenital hemolysis that worsens during pregnancy. The extent and the timing of anemia in pregnancies affected by HS is not well understood. Due to these deficits in knowledge, there is no established clinical approach for managing anemia secondary to HS in pregnancy. This may impede hematologists and obstetricians from preventing optimal care and counseling.
Methods: All patients with pregnancies suspected to be affected by hereditary spherocytosis with a delivery within the Mass General Brigham network from January 1, 2010 to December 31, 2024 were included. Suspected HS was defined as a billing code for HS or laboratory profile consistent with HS. Laboratory criterion could be met through abnormal osmotic fragility in absence of an alternative explanation, abnormal eosin-5-maleimide (EMA), and/or genetic testing consistent with a cytoskeletal defect. Hemoglobin in earlier pregnancy (first or second trimester), third trimester, at delivery, and immediately postpartum were collected. When more than one hemoglobin measure was present within a specified time frame, the first value was used to minimize bias associated with repeated measurements. Rates of antepartum transfusion, peripartum transfusion, use of erythropoiesis stimulating agents (ESA), and intravenous iron administration were quantified. Obstetric and neonatal outcomes were measured through rates of intrauterine growth restriction (IUGR), twin gestation, preterm birth, low birth weight, cesarean section, postpartum hemorrhage, and fetal demise.
Results: From January 1, 2010 to December 31, 2024, Ob/Gyn ultrasound plus either an abnormal osmotic fragility test or an ICD 9 or ICD 10 code for hereditary spherocytosis identified 152 individuals. Restricting to those with a delivery in our network, this identified 48 pregnancies in 40 patients. Excluding those without confirmed hereditary spherocytosis ultimately identified 23 pregnancies in 16 patients for our analysis. Mean hemoglobin in early pregnancy, third trimester, at delivery, and postpartum was 12.3, 10.7, 11.5, and 10.3, respectively. Hemoglobin was less than 10 g/dL in 8.7%, 17.4%, 13.0%, and 26.1% of patients for early pregnancy, third trimester, at delivery, and postpartum, respectively. Hemoglobin was less than 9 g/dL in 4.3%, 13.0%, 13.0%, and 17.4% of patients for early pregnancy, third trimester, at delivery, and postpartum, respectively. None of the patients with a hemoglobin below 10 g/dL had a low transferrin saturation or a ferritin below 30 ng/dL. Antepartum transfusion was required in 1 pregnancy and peripartum transfusion in 2 pregnancies. ESA use occurred in 1 pregnancy. The only patient who received intravenous iron had a transferrin saturation of 23% and a ferritin of 53 ng/dL, which appears to indicate an inappropriate administration. Obstetric and neonatal outcomes were notable for IUGR in 4.3%, twin gestation in 4.3%, preterm birth in 13.0%, low birth weight in 0.0%, fetal demise in 0.0%, cesarean section in 43.4%, postpartum hemorrhage in 13.0%, a mean estimated blood loss of 541 mL.
Discussion: Gestational hemoglobin values in patients with HS reached a nadir in the third trimester, with 13.0% of patients dropping below 9 g/dL. A partial correction by the time of presentation at delivery is apparent, which is in keeping with other congenital anemia in pregnancy such as beta thalassemia minor. Transfusion antepartum and peripaturm was infrequent and neonatal outcomes did not appear to deviate from the general population, suggesting that most cases of HS in pregnancy can be managed expectantly. As only one patient received ESA, the data is insufficient to analyze efficacy of ESA for management of HS. Further investigation into the benefits of ESA use could be useful to guide the management of more severe cases of HS in pregnancy. An additional drop in hemoglobin was observed postpartum, and the rate of postpartum hemorrhage was elevated, indicating an increased risk of hemorrhage in patients with HS that clinicians should be aware of when managing deliveries. There was also an high rate of cesarean section, but given our sample size may be due to chance.
Conclusion: A substantial proportion of patients with hereditary spherocytosis having hemoglobin drop below 9 g/dL in pregnancy. While neonatal outcomes were reassuring. There is a signal for increased risk of postpartum hemorrhage raising concern about increased maternal risk.
