Background/Case Studies: Alloimmunization to red blood cell (RBC) antigens, common among patients with hemoglobinopathies, often occurs secondary to transfusion or pregnancy. Women are exposed to fetal RBCs during pregnancy, particularly around the time of delivery, but only a subset develop RBC alloimmunization suggesting that antigenic exposure alone is insufficient to lead to alloimmunization. Accordingly, a recent case report (Jacobs et al, 2023) described two cases of de novo alloimmunization following antigen negative RBC transfusion, postulating the possible immunogenicity of RBC transfusion. We present a case of RBC alloimmunization (anti-E) in a previously pregnant patient with sickle cell disease following transfusion of E antigen negative RBCs.
Study
Design/Methods: Type and screen using gel technology, direct antiglobulin test (DAT) via tube testing and manual AHG crossmatch were performed at a tertiary care hospital. Antibody identification via tube testing with PEG enhancement, and antigen phenotyping via the human erythrocyte assay (HEA) were performed at a reference laboratory.
Results/Findings: The patient is a 32-year-old G7P2 woman with hemoglobin SS disease complicated by stroke in 2021 on monthly RBC exchange therapy. The patient is A positive with multiple RBC antibodies including anti-Fya, anti-Lea, Anti-S, anti-K, cold autoantibody and warm autoantibody. Obstetric history includes two normal spontaneous vaginal deliveries (most recent in May 2022), two spontaneous abortions, two elective terminations of pregnancy, and one ectopic pregnancy. The patient has received monthly RBC exchanges from April 2022 to February 2023 with phenotype-matched RBCs (E-, Fya-, K-, S-, and Lea- negative). Her antibody screens throughout this time did not reveal the presence of anti-E. The patient underwent a RBC exchange in January 2023 using six phenotype-matched RBC units. A type and screen prior to the exchange in February 2023 identified a new anti-E. The patient was not transfused in the interval between exchanges; transfusion history prior to our institution includes one transfusion in 2021 using E antigen negative RBCs. The six units transfused to the patient in January 2023 were retested using retained segments and found to lack the E antigen. The baby born in May 2022 was positive for the E antigen. Conclusions: Pregnancy and transfusion can serve as sources of RBC antigen exposure, although other factors play a role in the development of alloimmunization. While pregnancy was the likely source of antigenic exposure in this patient, the timing of alloimmunization raises the possibility of immune stimulation associated with transfusion and emphasizes the importance of antibody identification despite antigen negative RBC transfusion.
Importance of research: This case highlights the multitude of factors involved in the development of alloimmunization, and the potential immune stimulation associated with transfusion. It also reiterates the importance of accurate antibody identification.
