Abstract Introduction Sickle cell disease (SCD) is marked by chronic hemolytic anemia and recurrent vaso-occlusive crises. Acute chest syndrome (ACS) is a major cause of morbidity and mortality, often managed with transfusion therapy. However, transfusions can precipitate delayed hyperhemolysis syndrome (DHHS), a rare, life-threatening immune-mediated complication occurring 5-10 days post-transfusion. DHHS involves destruction of both donor and native red blood cells (RBC), causing a paradoxical hemoglobin (Hb) drop below pre-transfusion levels. We present a young male with SCD who developed severe, refractory DHHS following exchange transfusion (ET) for ACS, successfully managed with complement inhibition after failure of conventional therapy. Description A 29-year-old male with SCD presented with acute pleuritic chest pain. CT chest revealed extensive left lower lobe consolidation, consistent with ACS. Initially on ambient air with Hb 6.7 g/dL, he developed acute hypoxemia requiring high flow nasal cannula (40 LPM delivered at 60% FiO2) with admission to the intensive care unit; he underwent RBC ET on hospital day 1, with resolution of symptoms. Post-exchange hemoglobin S (HbS) was 27.9%. Seven days later, he developed worsening diffuse pain, fever, and confusion. Hb precipitously declined from 7.0 to 4.1 g/dL despite a unit of packed RBC. Labs revealed indirect hyperbilirubinemia (total 10.8 mg/dL, direct 6.8 mg/dL) and elevated LDH (1176 U/L). Repeat HbS increased to 65.1%, confirming DHHS. He was treated with high-dose methylprednisolone, intravenous immunoglobulin (IVIG), and tocilizumab. Despite initial stabilization, Hb continuously declined to 3.5 g/dL, prompting eculizumab administration following meningococcal and pneumococcal vaccination, leading to gradual improvement. Discussion Our patient’s initial ACS, likely triggered by pneumonia, necessitated ET, complicated by refractory DHHS, evidenced by paradoxical Hb decline and rising HbS. To prevent further hemolysis, blood products were avoided. Supportive measures included minimizing phlebotomy in pediatric tubes, folate and iron supplementation, and holding hydroxyurea. Initial aggressive immunotherapy with corticosteroids, IVIG, and tocilizumab failed to halt Hb decline, highlighting the severe, refractory nature of DHHS. Hb stabilization occurred only after implementation of eculizumab, a C5 complement inhibitor. Complement blockade represents a novel and distinct therapeutic approach, targeting complement-mediated hemolysis rather than cytokine-mediated inflammation, as in this case with tocilizumab. This case highlights the complex management of DHHS, particularly when refractory to standard immunotherapy. Although data is limited, complement blockade with eculizumab represents an emerging, potentially life-saving intervention in severe DHHS. The use of eculizumab in our patient supports its promise as novel therapy to improve outcomes in life-threatening complications of SCD. This abstract is funded by: None
Shahab et al. (Fri,) studied this question.