New research indicates that 75% of patients with sickle cell disease (SCD) who will make antibodies to red blood cells (RBCs) do so by the 17th RBC unit (RBCu) transfused or by the 20th unit transfused if warm autoantibodies are excluded. Aline Floch, MD, PhD, an associate professor at the French National Institute for Health and Medical Research in Paris, and colleagues concluded that 20 units is the point before which it is most important for clinicians to monitor patients receiving transfusions. They published their findings in Blood Advances.
The large retrospective study reviewed records of 6,496 patients who were transfused at least once for a total of 239,944 units. Researchers focused on the evolution of transfusion needs in patients with SCD and the consequent alloimmunization. They extracted the dataset from Paris’ regional database of all patients and all transfusions and found that 1,742 patients (27%) made antibodies and that a patient’s first antibodies were predictive of subsequent antibodies.
“Patients who are able to form antibodies (also termed “responders” or “high responders”) will do so when they are first exposed to the cognate antigen(s),” Dr. Floch said. “We were not sure whether the first antibodies to appear could be predictive of future antibody formation, and when we tested the hypothesis, we were pleasantly surprised that this was indeed the case.”
When the researchers compared data from 2008 with data from 2018 by age at transfusion, they found an increase in total RBCu count in all age groups and an increase in mean units per patient for adults aged 26-55 years.
“The study shows the significant increase in RBC consumption per patient since 2015, driven by an extended life expectancy and more intensive treatment of adult patients to prevent chronic organ damage,” Dr. Floch said. “The increasing demand does not appear to be slowing down… The extent to which RBC consumption has increased in recent years far exceeded what we had anticipated.”
Dr. Floch noted that while the study was limited by its retrospective design, controlled prospective studies are an infeasible way to address the question of immunization in patients with SCD.
“Transfusion is a major therapy for patients with SCD,” Dr. Floch said. “However, patients are at risk of forming antibodies to RBC antigens, especially because of the differences of blood groups between patients of African descent and donors of Caucasian background. It is the case in France and in many high-income countries.” She explained that this alloimmunization can result in additional antibody formation, such that it becomes difficult to find RBCus that are compatible with the patient. Incompatibility may cause alloimmunization, which increases the risk for hemolytic transfusion reactions (HTR) and possible hyperhemolysis, a severe and potentially fatal complication.
For many years, the incidence of HTR has been underestimated, Dr. Floch said, because it manifests as vaso-occlusive symptoms days or weeks after RBC transfusion. While guidelines from the American Society of Hematology have promoted increased awareness of HTR and its consequences, treatment options remain limited, and the mechanisms behind HTR remain poorly understood. What is known is that the risk factors for HTR include a small number of previous transfusions, transfusion for an acute event as opposed to transfusion programs, and a history of HTR and alloimmunization.
By identifying the threshold of 20 units, the current findings help to stratify patients by risk and guide clinical decisions. “We were surprised by the robustness of the threshold before which patients are most likely to have made their first antibody,” Dr. Floch said. She acknowledged that future studies will likely refine this number as new data homes in on specifics of the donor population.
Any conflicts of interest declared by the authors can be found in the original article.
Floch A, Viret S, Malard L, et al. Eleven years of alloimmunization in 6496 transfused patients with sickle cell disease in France [published online ahead of print, 2023 Sep 12]. Blood Adv. doi: 10.1182/bloodadvances.2022009328.