Abstract
Immunohematology and Genetic Testing (red cells, leukocytes and platelets)
.jpg "Jensyn Cone Sullivan, MD photo")
Jensyn Cone Sullivan, MD
Director, Blood Bank
Department of Pathology, Michigan Medicine at the University of Michigan
Ann Arbor, Michigan, United States
Disclosure(s): Hansa Biopharma: Consultant/Advisory Board (Terminated, December 24, 2023), Grant/Research Support (Terminated, December 24, 2023)
High-incidence CD36 is the newest blood group system (ISBT 045). CD36 null allele homozygosity produces platelet and monocyte CD36-deficiency (Null Type 1), capable of alloanti-CD36 (anti-CD36) formation. Conversely, anti-CD36 is not formed in platelet-only deficiency (Null Type 2). One null allele was present at high minor allele frequency among individuals of African descent in a large genome aggregation database (c.975T >G , 9% of 74968 alleles). Anti-CD36’s clinical significance is unclear, with two published case reports of fetal anemia but no clinical reports of transfusion reactions or shortened red blood cell (RBC) survival in a large French cohort.1 In vitro assays assessing anti-CD36’s clinical significance have not been reported. We present a patient with HbSS, anti-CD36 and hyperhemolysis following CD36+, otherwise-compatible RBC transfusion and in vitro evidence [Monocyte Monolayer Assay (MMA)] of anti-CD36-mediated hemolysis.
Case: A 25-year-old O+ male with HbSS, without recent transfusion, with historical antibodies [anti-c, -E, -Fy(a), -Jk(b), -s], was admitted for acute chest syndrome. RBC antibody testing revealed panreactivity against Group O panel cells, unexplained by historical antibodies. Autocontrol and cold autoantibody screen were negative. Platelet adsorbed serum (platelets are CD36-enriched) was non-reactive with all Group O panel cells tested, consistent with anti-CD36. On hospital day 5 (D5, Table 1A), the patient received three packed RBC [pRBC, each antigen negative (AN) and full-crossmatch-compatible with platelet adsorbed serum], for a Hct of 15.2%. Between D12-14, Hct precipitously declined, consistent with hyperhemolysis. No new alloantibodies were identified. On D15, one pRBC, AN and compatible as above, was transfused. Hct decreased 14.5% to 13.6%. Further transfusion was held. Erythropoietin and immunosuppressants were begun. Hct increased.
Study
Design/Methods: RBC gel antibody testing with serum and Human Platelet Concentrate (Immucor)-adsorbed serum were performed. Multichannel flow cytometry for CD36, CD36 medical exome sequencing (TruSight One Expanded, Illumina), Platelet Antibody Bead Array (PABA, Versiti), and MMA [with Group O, AN RBCs (American Red Cross)] were performed. In the MMA, a fresh complement source was added to the test system as some antibodies react better in the presence of complement. MMA monocyte reactivity of ≤5% correlated with no/minimal antibody significance.
Results/Findings: Flow cytometry was consistent with CD36 Null Type 1. WES demonstrated CD36 homozygote null allele c.975T >G with predicted CD36 Null Type 1 phenotype. PABA identified anti-CD36. MMA demonstrated increased monocyte reactivity to Group O, AN, CD36+ (presumed) RBC v. autologous CD36- RBC. (Table 1B).
Conclusions:
Clinical data and laboratory testing support anti-CD36’s clinical significance for erythrocyte transfusion.
Reference: 1. Transfusion. 2023;63(S5).