clinical topic updates

Hemoglobin A Clearance in Sickle Cell Disease

by Stella T. Chou, MD

Overview

In patients with sickle cell disease (SCD) on chronic transfusion therapy, the hemoglobin variant quantification not only reveals whether the patients are being maintained at goal but also may be a clue that a new antibody has formed and that further evaluation by the blood bank may be warranted.

Expert Commentary

Stella T. Chou, MD

Associate Professor of Pediatrics
Chief, Division of Transfusion Medicine
Children’s Hospital of Philadelphia
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA

“Most patients with SCD receiving chronic transfusion therapy who have new antibodies will be identified because they are screened for them routinely right before their next transfusion, which typically occurs every 3 to 5 weeks."

Stella T. Chou, MD

The ability of chronic transfusion therapy to prevent SCD-related complications is dependent on maintaining a low percentage of circulating hemoglobin S–containing erythrocytes, which, in turn, is dependent on the rates of clearance of erythrocytes containing hemoglobin S and those containing normal adult hemoglobin (ie, hemoglobin A).

Among patients with SCD receiving chronic transfusion therapy, the hemoglobin quantification (quant) reveals how much hemoglobin A, F, and S they have, and the composition of these percentages may be clinically significant in a number of ways. For patients who are on chronic transfusion therapy, the goal is to decrease their percent hemoglobin S below a threshold amount, which, for most patients, is less than 30%. Some patients have a higher threshold (eg, <40% or <50%) for particular indications. In general, most evidence-based indications for chronic transfusion therapy do aim for a pretransfusion hemoglobin S of 30% or lower. The hemoglobin quant shows whether the patient is at or below the threshold for their specific indication.

Another consideration is that the hemoglobin quant may be a clue or part of the clinical presentation for a delayed hemolytic transfusion reaction. Although some patients may have delayed hemolytic transfusion reactions and present with signs and symptoms of hemolysis and pain, others are relatively asymptomatic or mildly symptomatic and do not seek medical attention. An example would be a patient who gets monthly transfusions. This individual’s hemoglobin S would typically be less than 30% because that is their goal. Because this patient is on a regular schedule for chronic transfusion therapy, the index of suspicion that a new antibody has formed would be raised if, say, their hemoglobin S rises to 45%, since this could be due to the immune-mediated clearance of the hemoglobin A–containing transfused cells.

Most patients with SCD receiving chronic transfusion therapy who have new antibodies will be identified because they are screened for them routinely right before their next transfusion, which typically occurs every 3 to 5 weeks. However, occasionally an antibody forms that is below the level of detection, and certain antibodies are known to be evanescent, meaning that they are no longer detectable soon after they have been formed. If a patient has been exposed to the offending antigen more than once, they can quickly mount another antibody response and have a delayed hemolytic transfusion reaction. Thus, when the percent hemoglobin S is elevated from baseline in a patient who is chronically transfused, it is necessary to ensure that the blood bank is aware of the situation and that a full workup for a potential new antibody is performed before that individual gets further transfusion. Delayed hemolytic transfusion reactions can be subtle. For instance, if a patient develops a new antibody against an antigen that was present in only a subset of the transfused units, they might not present with sudden, very marked anemia. Only a portion of the transfused red blood cells (with the offending antigen) may have undergone hemolysis, and, combined with partial compensation from the patient (ie, making their own red blood cells), it may be difficult to appreciate clinically. The only indication may be an elevated percent hemoglobin S at their next visit.

References

Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic & Laboratory Test Reference. 14th ed. Elsevier; 2019.

Sagiv E, Fasano RM, Luban NLC, et al. Glucose-6-phosphate-dehydrogenase deficient red blood cell units are associated with decreased posttransfusion red blood cell survival in children with sickle cell disease. Am J Hematol. 2018;93(5):630-634. doi:10.1002/ajh.25051

Yee MEM, Josephson CD, Winkler AM, et al. Hemoglobin A clearance in children with sickle cell anemia on chronic transfusion therapy. Transfusion. 2018;58(6):1363-1371. doi:10.1111/trf.14610

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