key: cord-0703908-qgyudrrp authors: Ahmadnejad, Moharram; Mosleh, Mohammad; Ferdowsi, Shirin; Mohammadi, Saeed; Eshghi, Peyman; Oodi, Arezoo title: Cold Agglutinin Associated With COVID-19 Infection in a Thalassemia Patient with Multiple Alloantibodies: A Case of Cold Hemagglutinin Disease (CAD) with Complex Antibody Detection date: 2021-05-26 journal: Hematol Transfus Cell Ther DOI: 10.1016/j.htct.2021.04.005 sha: ed9735d09685fcefc9c75ff6d674c6a176a2e4de doc_id: 703908 cord_uid: qgyudrrp nan The new coronavirus SARS-Cov-2, which causes the pneumonia syndrome, named COVID-19, was recognized in China in December 2019 and has now spawned an emergency pandemic condition in the world. The clinical signs and symptoms vary from mild to severe, ranging from pneumonia, fever, fatigue, malaise and cough to severe complications, including cardiac injury, renal failure and life threatening coagulopathy (1, 2) . Several autoimmune disorders have also been reported in the context of the COVID-19 infection, such as the antiphospholipid syndrome, autoimmune cytopenia, Guillain-Barré syndrome and Kawasaki disease (3) . Autoimmune hemolytic anemia (AIHA) was previously described in some viral infections (4) . Recently, some reports have shown either cold or warm AIHA in COVID-19 patients (5, 6) . Herein we discuss a patient with a history of transfusion-dependent thalassemia with multiple alloantibodies, which produced cold agglutinins during the SARS-Cov-2 infection. A 49-year-old woman with thalassemia was admitted for blood transfusion due to her low Hb (4.5 g/dL). She had a history of multiple alloantibodies, including anti-c, anti Fy b , anti-JK a and anti-E. The blood specimen was sent to the immunohematology reference lab. The alloantibodies were reconfirmed with an 11-cell antibody identification panel. The direct antiglobulin test (DAT) using polyspecific anti-human globulin (AHG) was also negative. After 1 week, a phenotype-matched donor was recruited for blood donation; the cross-match test was performed and, unexpectedly, the test was incompatible with 4+, 2+ and 2+ reactions in IS, 37ºC and AHG, respectively. The antibody identification with an auto-control tube and DAT was retested and, surprisingly, the auto-control tube and DAT resulted in positive reactions. The DAT was positive with anti-C3d (4+), but negative with anti-IgG. The cold auto adsorption with rabbit erythrocyte stroma (RESt, Immucor) was performed according to the manufacturer's instructions. Preceding the adsorbing plasma, the cross-matching was examined using phenotype-matched red cells. Based on the patient red blood cell (RBC) phenotype, a phenotypematched donor was selected for the following antigens: JK a , FY b , E and c. The result revealed negative reactions in IS, 37ºC and AHG (Table 1) . Therefore, the diagnosis of COVID-19 was confirmed. The interval between admission and the onset of hemolytic anemia was 7 days, which was concurrent with the COVID-19 infection. The treatment for the COVID-19 infection began immediately, but, unfortunately, the patient passed away during hospitalization and no subsequent evaluations were possible. This report describes a patient presenting a case of thalassemia with SARS-CoV-2-associated with autoimmune hemolytic anemia having cold agglutinins. Secondary CAD has been reported in viral infections, such as the Epstein-Barr virus (EBV), influenza and mycoplasma pneumonia infection (7, 8) . The underlying mechanism might be antigen mimicry with antigens on the RBC membrane, such Maslov DV et al. described a patient with COVID-19 who presented with cold autoimmune hemolytic anemia and a high cold agglutinin titer. They also discussed the increased risk of coagulopathy in those with CAD, therefore existing the possibility of more aggressive disease (6) . Our patient did not have a history of autoantibody in her serologic tests, so cold AIHA can be attributed to her recent COVID-19 infection. Because the crossmatch was performed and positive results showed positive reactions also in the 37 o C and AHG and then, negative results in the cold auto adsorption test, we did not perform the thermic amplitude test, which constitutes one of the limitations in this study. The COVID-19 infection might complicate the management of anemia in thalassemia patients, especially those with clinically significant antibodies who need urgent compatible blood. Hence, it is imperative to investigate autoimmune hemolytic anemia in cases with COVID-19. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. 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