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927 Comparison of Alloimmunization in Pregnant People with Sickle Cell Disease Receiving Chronic Versus on-Demand Transfusions: A Multinational Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 114. Sickle Cell Disease, Sickle Cell Trait and Other Hemoglobinopathies, Excluding Thalassemias: Clinical and Epidemiological: Sickle Cell Treatment: Present and Future
Hematology Disease Topics & Pathways:
Research, Biological therapies, Sickle Cell Disease, health outcomes research, Clinical Research, Hemoglobinopathies, Diseases, Therapies, pregnant, Transfusion, Human, Study Population, Maternal Health
Monday, December 11, 2023: 5:00 PM

Clare Zarka1*, Amy Luo2*, Sacha Belinda Mapombo Choupa3, A. Kinga Malinowski, MD, FRCPC, MSc4, Kevin H.M. Kuo, MD, FRCPC, MSc5, Nadine Shehata, MD, FRCPC, MSc6, Sophie Lanzkron, MD7 and Lydia H Pecker, MD7,8

1Johns Hopkins University School of Medicine, Baltimore, MD
2Johns Hopkins Bloomberg School of Public Health, Baltimore
3Meharry Medical College, Nashville, TN
4Department of Obstetrics and Gynaecology, Division of Maternal-Fetal Medicine, Lunenfeld-Tanenbaum Research Institute, Sinai Health, University of Toronto, Toronto, ON, Canada
5Department of Hematology, University of Toronto, Toronto, ON, Canada
6Mount Sinai Hospital, Toronto, ON, Canada
7Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD
8Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD


Despite exceptional maternal morbidity and mortality risk, people with sickle cell disease (SCD) lack firm indications for chronic transfusion therapy (CTT) during pregnancy. Alloimmunization may cause hemolytic transfusion reactions and can limit the safety of future blood transfusions; thus it is a rationale for restricting CTT during pregnancy. Little data quantifies this risk. The 2020 American Society of Hematology (ASH) Guidelines for SCD Transfusion Support recommend CTT in some pregnancies, but adoption in clinical practice is unknown.

This study’s purpose is to use a large two-center SCD pregnancy cohort to describe alloimmunization rates in SCD pregnancies treated with CTT vs on-demand transfusion (ODT) and to determine the fraction of SCD pregnancies meeting the ASH Guideline to initiate CTT in pregnancy.


We reviewed SCD pregnancies delivered at Mt. Sinai Hospital, Toronto (1990-2017) and Johns Hopkins Hospital (2000-2021). We collected data on transfusions and SCD complications before and during pregnancy, delivery, and fetal outcomes.

Analyses classified subjects and pregnancies as receiving CTT or ODT. We defined CTT as pregnancies treated with scheduled, prophylactic transfusions; ODT as pregnancies transfused as-needed, including no transfusions. Sinai routinely matched transfusions for Rh and K antigens while Hopkins matched Rh only. Both centers provided extended matching if an alloantibody was detected.

The first analysis included singleton pregnancies to primigravida subjects. We compared new alloantibody development, SCD complications, and pregnancy outcomes in CTT vs. ODT groups and in genotype stratified groups. We used Chi-squared and Wilcoxon rank-sum tests for categorical and continuous variables; p < .05 was significant.

The second analysis included all cohort pregnancies and identified which met criteria for CTT per ASH Transfusion Guidelines which advise CTT for (A) severe SCD complications before or during pregnancy here defined by acute chest syndrome (ACS) or pain requiring acute care in the year before or during pregnancy, any history of venous thromboembolism (VTE), stroke, or multi-organ failure or (B) features of high-risk pregnancy, defined by multiple gestation, pre-eclampsia, gestational hypertension, cardiac comorbidities, or preterm labor history.


Among 145 singleton, primigravida pregnancies, more received ODT than CTT (119 ODT vs 26 CTT). Among ODT subjects 46/119 received at least one transfusion during pregnancy.

CTT subjects had more severe SCD than ODT subjects before pregnancy (Table 1). During pregnancy, SCD severity did not differ (Table 2).

Before pregnancy, 18 subjects were alloimmunized and did not differ by treatment group (6/26 CTT vs 12/119 ODT, p=0.07). During pregnancy, six subjects developed an alloantibody and did not differ by treatment group (1/26 CTT vs 5/119 ODT, p=0.93). Half (3/6) had a history of alloimmunization before pregnancy (1 CTT vs 2 ODT, p=0.27) and three did not (0 CTT vs 3 ODT, p=0.27). All subjects with new antibodies during pregnancy and historic alloimmunization developed anti-K antibodies (1 CTT, 2 ODT) at both sites. Those without alloimmunization history developed anti-Jk antibodies (3 ODT) at Sinai.

In the secondary analysis, we included 299 pregnancies to 203 subjects. Among them, 249 pregnancies (83%) met at least one ASH Guideline criteria for initiating CTT. This included all CTT pregnancies (61/61, 39 subjects) and 79% of ODT pregnancies (188/238, 164 subjects), 46% of which received at least one transfusion during pregnancy (86/188).


In this SCD pregnancy cohort, alloimmunization rates were low and did not differ between those treated with CTT versus ODT. As alloimmunization events were inconsistent with institutional matching practices, new antibody development may be attributable to transfusions from outside hospitals or pregnancy-associated alloimmunization. Antigen matching per ASH Transfusion Guidelines avoids C, E, K and Jk alloimmunization. Scheduled transfusions may reduce emergency transfusion which increases alloimmunization risk. Finally, all CTT and 79% of ODT pregnancies met ASH Guideline criteria for CTT in pregnancy, however the cohort predates ASH Guideline publication. Guideline adherence may lead to increased use of CTT during pregnancy. More discriminating tools are needed to inform CTT use in SCD pregnancy.

Disclosures: Kuo: Agios Pharmaceuticals: Consultancy, Research Funding; Vertex Pharmaceuticals: Consultancy; Alexion Pharmaceuticals: Consultancy; Pfizer: Consultancy; Novo/Nordisk: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Bioverativ/Sanofi/Sangamo: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Consultancy. Lanzkron: HRSA: Research Funding; Imara/Enliven Therapeutics: Research Funding; National Alliance for Sickle Cell Centers: Other: Vice president ; Global Blood Therapeutics: Research Funding; Magenta: Consultancy; Novartis: Consultancy, Research Funding; CSL-Behring: Research Funding; Takeda: Research Funding; PCORI: Research Funding; Bluebird Bio: Consultancy; Teva Pharmaceutical Industries: Current equity holder in publicly-traded company; Novo Nordisk: Consultancy; Pfizer: Consultancy. Pecker: Alexion: Research Funding; Global Blood Therapeutics: Consultancy; Novo Nordisk: Consultancy.

*signifies non-member of ASH