Abstract
Background: Sickle cell anemia is an autosomal recessive disorder caused by abnormal hemoglobin S, which polymerizes when deoxygenated and distorts erythrocytes into sickle cells. This can lead to vaso-occlusive crises and multiorgan damage. Sickle cell patients often require blood transfusions for acute anemia, but 15-50% develop alloantibodies that complicate future transfusions. We present a sickle cell patient with rare complex alloimmunization. Case: A 45-year-old male with sickle cell disease presented to the emergency department with worsening pain in the ankles, back, and shoulders uncontrolled with his home pain regimen. Laboratory evaluation revealed severe normocytic anemia with hemoglobin of 5.4 g/dL. He was diagnosed with vaso-occlusive sickle cell crisis, but transfusion was deferred because compatible blood was unavailable after recent complex alloimmunization. He was managed with patient-controlled analgesia, intravenous immunoglobulin, intravenous steroids, and epoetin alfa. His hemoglobin stabilized, his pain improved, and he was discharged after eight days. Significance: This case highlights the challenges of managing severe anemia in an SCA patient with rare complex alloimmunization involving anti-Fy3, anti-Jsa, and anti-Doa, including anti-Fy3 formation with a homozygous FY*02N.01 GATA-associated Duffy-null genotype. Because this genotype abolishes erythrocyte Duffy expression while preserving non-erythroid expression, anti-Fy3 is a distinct and unusual immunohematologic event rather than the expected absence of anti-Fyb. Combined with hydroxyurea intolerance, this patient illustrates an underrecognized scenario in which standard first-line SCA therapies are simultaneously inaccessible. IVIG, corticosteroids, and epoetin alfa achieved hemoglobin stabilization without transfusion when compatible blood was unavailable.