Autoimmune hemolytic anemia (AIHA) associated with human immunodeficiency virus (HIV) infection: Two challenging cases

Abstract

Abstract Background: Patients with HIV often develop hematologic complications. While anemia is multifactorial, elevated direct antiglobulin test (DAT) rates suggest increased AIHA incidence despite rare overt hemolysis. Data on AIHA in patients with HIV remain limited. We present two cases with significant antibodies and diverse presentations where blood bank testing and transfusion were challenging. Case Report: Patient 1: A 34-year-old male with HIV and recent hospitalization for hemolytic anemia presented with altered mental status (AMS), severe anemia; hematocrit (Hct) 12.0% (41.0-53.0%), arterial hemoglobin <3.0 g/dL (12.0-18.0 g/dL), laboratory findings concerning for hemolysis with haptoglobin <20 mg/dL (51-192 mg/dL), reticulocytes 19.5% (0.50-1.50%), unconjugated bilirubin 3.6 mg/dL (0.1-1.0 mg/dL), lactate dehydrogenase (LDH) 954 U/L (116-245 U/L), and HIV-1 viral load (VL) 827 copies/mL. The patient also tested positive for metapneumovirus. Initial ABO typing was inconclusive due to a strong cold autoantibody. The DAT was positive with the antibody screen and eluate showing strong panreactivity, consistent with a warm autoantibody. He received plasma exchange and immunosuppressive therapy due to concern for AIHA. After being sent to a reference laboratory, ABO typing was resolved as O+ with anti-C, cold (cold agglutinin titer 64) and probable warm autoantibodies identified. Despite receiving 8 compatible (using pre-warmed technique), C antigen-negative packed red blood cell (pRBC) units, the patient's arterial hemoglobin remained low. Patient 2: A 29-year-old male with HIV, AIHA on prednisone, asthma, and history of anti-C, anti-E, and warm/cold autoantibodies presented with AMS with hemoglobin (Hgb) 1.2 g/dL (13.5-17.5 g/dL), Hct 3.1%, and HIV-1 VL 1,510,000 copies/mL. He tested positive for COVID-19. Antibody identification was inconclusive due to a warm autoantibody, consistent with the positive DAT. Upon presentation, he received 5 emergency-release pRBCs and immunosuppressive therapy out of concern for AIHA. The patient was found to be O+ with a probable warm autoantibody after being sent to a reference lab. Despite immunosuppressive therapy and further transfusions with 5 least-incompatible pRBCs, Hgb remained low. There was clinical concern for worsening AIHA, evidenced by elevated LDH (2,790 U/L) and undetectable haptoglobin (<20 mg/dL), along with the possibility of a delayed hemolytic transfusion reaction. Unfortunately, both patients died within a few days of admission. Conclusion: These cases highlight the complexities of AIHA management in patients with HIV, with challenges in blood bank testing and transfusion due to potent autoantibodies. Poor outcomes occurred despite aggressive treatment. Further research is needed to optimize strategies for transfusion and immunomodulation in this vulnerable population.