(P-IG-2) A Curious Tale of Severe Anemia, Complex Immunohematology and RhCE Gene Sequencing Leading to an Unusual Diagnosis at the Veterans Administration

Background/Case Studies: An 82 year-old veteran with a history of triple vessel coronary artery disease, chronic kidney disease, tobacco use and iron deficiency anemia presented to the Veterans Administration with shortness of breath and fatigue. Labs were notable for hemoglobin of 4.9 g/dL and MCV of 107.2. The patient's history was negative for GI bleeding or other sources of acute blood loss. Hematology was consulted for further evaluation and management of the patient's severe anemia. The veteran reported receiving multiple red cell transfusions over the past 3 months at an outside facility in rural Tennessee.

Study

Design/Methods: A type and screen sample was sent to the blood bank to facilitate urgent red cell transfusion. Immunohematology testing was notable for an O+ forward and reverse type and positive antibody screen, prompting the completion of a full antibody identification panel.

Results/Findings: The veteran's antibody identification panel was notable for a negative autologous control and IgG alloantibodies to the anti-C, anti-K1 and anti-e (little) antigens, as well as non-specific reactivity at the anti-human globulin level, that were detected using an automated solid phase testing platform. Because erythrocyte phenotyping could not be performed prior to transfusion, a whole blood sample was sent to a reference laboratory for human erythrocyte antigen molecular genotyping, which demonstrated positivity for C, c (little), E, e (little) antigens and negativity for the K1 antigen. However, donor red cell units of the R2 haplotype (DcE) that lacked the C and e (little) antigens were consistently found to be crossmatch compatible with the veteran's serum. Due to suspicion for an RhCE allelic variant, a whole blood sample was sent for RhCE molecular genotyping, which demonstrated an RCHE genotype of RHCE*ce / RHCE*CE, leading to further work-up and the detection of an anti-Ce (rhi) antibody in this veteran's serum using DCe and dCe reagent red cells. Medium resolution testing ruled out common RHCE allelic variants.

Conclusions: Ce (rhi) is a compound antigen that is present when C and e are on the same haplotype. The Ce (rhi) compound antigen is typically produced by the DCe (R1) and Ce (r') haplotypes. Due to rarity and low clinical suspicion, antibodies to compound antigens such as Ce are infrequently detected. Elucidation of anti-Ce antibodies is typically accomplished by testing the patient's serum with reagent red cells of a variety of Rh haplotypes, showing negative reactions with DcE, dcE, Dce, dce, DCE and dCE cells, and positive reactions with DCe (R1) or dCe (r') cells. Anti-Ce (rhi) antibodies are clinically significant, and have been reported to cause hemolytic anemia and hemolytic disease of the fetus and newborn. Therefore, timely detection of these rare antibodies is essential for the safe provision of transfusions, and often requires collaboration with a reference laboratory.