New Areas of Consensus for the Management of Sickle Cell Disease (SCD) in Pregnancy: An International Delphi Panel

Abstract

Introduction and aim Sickle cell disease (SCD) is an autosomal recessive disorder characterized by a single nucleotide substitution in the beta-globin gene, resulting in the production of hemoglobin (Hb) S, and is the most common hematologic genetic disorder worldwide. As a result of Hb polymerization, oxidative stress and chronic hemolysis, complications occur during pregnancy for women with SCD, impacting both maternal and fetal health. We aimed to identify areas of consensus for the management of pregnancy-related complications in SCD, with a focus on prophylactic transfusion therapy (PTT). Methods A Delphi panel consisting of 13 experts from 4 countries replied to 2 rounds of questions (1 panelist dropped out between the 1st and 2nd survey). The 1st survey (October-November 2021) consisted of open-ended questions, while the 2nd one (April-May 2022, used to identify the degree of consensus or changes in opinion among panelists) was comprised of multiple-choice or closed questions based on the answers from the 1st survey. The thresholds were: <9/12 panelists (<75%) for no consensus, 9-10/12 panelists (75-90%) for consensus, and ≥11/12 panelists (>90%) for strong consensus. The Delphi panel covered topics where no global standardization or little evidence exists to guide management and prevention of maternal complications during pregnancy in SCD. These included antenatal care, hydroxyurea (HU) therapy, transfusion, prevention and treatment of complications, delivery and follow-up, bottlenecks and knowledge gaps. Results The panelists achieved strong consensus in the following areas of management: antenatal care (specifically, that pregnant women with SCD should be followed at least every 4 weeks by a multi-disciplinary team of specialists who would decide on the required tests and treatments), HU (discontinuation ≥3 months before conception; experts would not recommend discontinuation of pregnancy in case of exposure to HU during pregnancy), delivery and follow-up (that a multidisciplinary team should decide on labor induction or elective cesarean section). For the following areas of management, no consensus was achieved: continuation of HU therapy (could be considered during pregnancy/lactation if the risks of stopping HU therapy outweigh the benefits and if the patient understands the risks and agrees with continuing therapy), Hb level targeted prior to delivery, or preferred transfusion modality (simple transfusions versus automated red cell exchange [aRCX]) for a pregnant woman with SCD who was not on PTT during pregnancy but needed to be transfused prior to delivery. The input collected for transfusion (including details on when to recommend PTT) is summarized in the Table. The experts felt that target Hb and hematocrit should be set by clinical experience and would be impacted by the time interval between transfusions and the clinical indication for transfusion. There was no consensus on the most suitable transfusion modality. The experts identified a strong interest to prioritize the use of routine PTT in pregnant women with SCD as an area of research. Conclusion The experts did not achieve uniform consensus to support the standardized use of PTT in pregnant women with SCD. They achieved consensus that PTT should be routinely used in pregnant women with ≥2 acute vaso-occlusive pain episodes in a 4-week period regardless of genotype, with a preference for peripheral venous over central venous access, and the use of aRCX over simple transfusion (target HbS <30%) for the prevention of transfusional iron overload. The experts also achieved a strong consensus that prophylactic red cell exchanges should be used to reduce frequency of acute pain episodes in women taking high-dose opioids daily, and recommended consideration of on-demand transfusions for acute fetal complications. Consensus was not achieved on frequency of prophylactic transfusions, timing of PTT initiation during pregnancy in relation to HU discontinuation, target hematocrit levels, methods for the prevention of alloimmunization (extended red cell phenotyping versus genotyping) and the use of PTT for secondary prevention of fetal complications and pregnancy loss. In general, the areas of non-consensus seemed to correspond to areas with the widest knowledge gaps and lack of evidence, highlighting the need for further research in the use of PTT in pregnant women with SCD. Funding: Terumo Blood and Cell Technologies Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal