(P-TS-2) A Case of Paroxysmal Cold Hemoglobinuria associated with SARS-CoV2 Infection

Background/Case Studies: Paroxysmal cold hemoglobinuria (PCH) is a rare hemolytic anemia characterized by the presence of autoantibodies that bind to red blood cells (RBCs) in the cold, leading to complement-mediated hemolysis upon rewarming. PCH has been associated with infectious, autoimmune (AI), and lymphoproliferative disorders (LPD). There have been reports of SARS-Cov-2-associated autoimmune hemolytic anemias (AIHA); however, none were classified as PCH.

Study

Design/Methods: A 43-year-old COVID-19 immunized and boosted previously healthy male was admitted to the hospital with fatigue, dyspnea, tea colored urine, and jaundice. Two weeks prior he received Paxlovid for breakthrough respiratory COVID-19. On admission, physical examination showed pallor, scleral icterus, tachypnea, tachycardia, and normothermia, with normal blood oxygen saturation. A SARS-CoV-2 PCR test was positive.

Results/Findings: Admission laboratory testing showed hemoglobin of 5.4 g/dl and evidence of hemolytic anemia (Figure A). Serum protein electrophoresis (SPEP) revealed a 0.41 g/dL IgG small monoclonal peak, raising the possibility of an underlying LPD or acute response to infection. The RBC antibody screen was negative, however the direct antiglobulin test was positive with C3d only. The patient’s serum agglutinated ABO identical RBCs at 20 C and 4 C and cord blood cells at 4 C. Clinical assessment favored cold agglutinin syndrome (CAS); yet titer and thermal amplitude studies revealed a low-titer cold agglutinin (32 at 4 C, 2 at 21 C) which was non-reactive at 30 and 37 C. The Donath Landsteiner (DL) test was positive and based on the clinical and laboratory findings the patient was diagnosed with PCH. Tests for Mycoplasma and Syphilis were negative. He received 10 RBC units over 8 days and was discharged on hospital day 10 with a hemoglobin of 8.3 g/dL. No further transfusions were required, and no immune modulating therapy was administered during or after hospitalization.

Conclusions: Although SARS-CoV-2 related warm and cold AIHA, and SARS-CoV-2 vaccination linked PCH have been described, to our knowledge this is the first report of SARS-CoV-2 infection associated PCH. It is notable that none of the reported cases of SARS-CoV-2 related AIHA describe DL testing. Given the availability of anti-complement drug therapies for CAS it is useful to recognize those conditions that may require long term therapy versus those that are likely to be self-limited, such as PCH related to infectious processes. If SARS-CoV2-associated AIHA is suspected, DL testing may be helpful to inform the need for specific therapy as well as further work-up for underlying AI and/or LPD.

Importance of research: In the literature there are no reports of SARS-CoV2 associated PCH. A systematic review by Booth et al. compiled 50 cases of SARS-CoV2 associated autoimmune hemolytic anemias. None of the cases found in this study had Donath-Landsteiner (DL) testing performed when complement only positive DAT was found on blood bank testing. Our abstract reports the first case of SARS-CoV2 associated PCH. It highlights the potential importance of performing DL testing in SARS-CoV2 associated IHA.