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Case Report
Cytomegalovirus-Associated Severe Direct Antiglobulin Test Negative Hemolytic Anemia: A Case Report
Clin Pediatr Hematol Oncol 2018;25:170-4.
Published online October 31, 2018
© 2018 Korean Society of Pediatric Hematology-Oncology and Korean Society for Pediatric Neuro-Oncology

Hyun Jung Hong, M.D.1, Young Hye Cho, M.D.1, Jae-Young Lim, M.D., Ph.D.1,2, Jung Sook Yeom, M.D., Ph.D.1,2, Ji Sook Park, M.D., Ph.D.1,2, Eun Sil Park, M.D., Ph.D.1,2, Ji-Hyun Seo, M.D., Ph.D.1,2, Hyang-Ok Woo, M.D., Ph.D.1,2 and Hee-Shang Youn, M.D., Ph.D.1,2

1Department of Pediatrics, College of Medicine, Gyeongsang National University, 2Gyeongsang Institute of Health Science, Jinju, Korea
Correspondence to: Jae-Young Lim
Department of Pediatrics, College of Medicine, Gyeongsang National University, 79 Gangnam-ro, Jinju 52727, Korea
Tel: +82-55-750-8161
Fax: +82-55-752-9339
Received July 17, 2018; Revised August 10, 2018; Accepted September 18, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cytomegalovirus is a common virus that is mostly asymptomatic when infected, but rarely causes life-threatening hemolysis especially in immunocompromised children. We report a case of antiglobulin test negative severe hemolytic anemia caused by cytomegalovirus infection developed in an immune competent 9-year-old girl. The patient’s hemoglobin level was 4.8 g/dL on the day of admission. The diagnosis was achieved by exclusion of other causes of hemolytic anemia and serological evidence of recent CMV infection. The patient was successfully treated with anti-viral agents and steroids resulting in recovery from anemia. Clinicians should consider cytomegalovirus infection in the differential diagnosis of hemolytic anemia in pediatric patients.
Keywords: Hemolytic anemia, Cytomegalovirus
  1. Oneal PA, Schechter GP, Rodgers GP, Miller JL. Hemolytic anemia. In: Rodgers GP, Young NS, editors, The Bethesda handbook of clinical hematology. 3rd ed. Philadelphia:Lippincott Williams & Wilkiins, 2013;22.
  2. Markvardsen LH, Christiansen I, Harbo T, Jakobsen J. Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders. Eur J Neurol 2014;21:147-52.
    Pubmed CrossRef
  3. Murray JC, Bernini JC, Bijou HL, Rossmann SN, Mahoney DH Jr, Morad AB. Infantile cytomegalovirus-associated autoimmune hemolytic anemia. J Pediatr Hematol Oncol 2001;23:318-20.
    Pubmed CrossRef
  4. Rafailidis PI, Mourtzoukou EG, Varbobitis IC, Falagas ME. Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. Virol J 2008;5:47.
    Pubmed KoreaMed CrossRef
  5. Cheung WW, Hwang GY, Tse E, Kwong YL. Alemtuzumab induced complete remission of autoimmune hemolytic anemia refractory to corticosteroids, splenectomy and rituximab. Haematologica 2006;91:ECR13.
  6. Taglietti F, Drapeau CM, Grilli E, et al. Hemolytic anemia due to acute cytomegalovirus infection in an immunocompetent adult: a case report and review of the literature. J Med Case Rep 2010;4:334.
    Pubmed KoreaMed CrossRef
  7. Horwitz CA, Skradski K, Reece E, et al. Haemolytic anaemia in previously healthy adult patients with CMV infections: report of two cases and an evaluation of subclinical haemolysis in CMV mononucleosis. Scand J Haematol 1984;33:35-42.
    Pubmed CrossRef
  8. Khalifeh HK, Mourad YM, Chamoun CT. Infantile cytomegalovirusassociated severe warm autoimmune hemolytic anemia:a case report. Children (Basel) 2017;4:E94.
  9. Hosseeini S, Ansari Sh, Kalantar E, Sabzechian M, Alibeik A, Dorgalaleh A. A fetal hemolytic anemia in a child with cytomegalovirus infection. Iran J Ped Hematol Oncol 2014;4:78-83.
    Pubmed KoreaMed
  10. Veldhuis W, Janssen M, Kortlandt W, van Houte A, van de Ree M. Coombs-negative severe haemolytic anaemia in an immunocompetent adult following cytomegalovirus infection. Eur J Clin Microbiol Infect Dis 2004;23:844-7.
    Pubmed CrossRef
  11. Lai M, Rumi C, D'Onofrio G, Voso MT, Leone G. Clinically significant autoimmune hemolytic anemia with a negative direct antiglobulin test by routine tube test and positive by column agglutination method. Immunohematology 2002;18:109-13.
  12. van Spronsen DJ, Breed WP. Cytomegalovirus-induced thrombocytopenia and haemolysis in an immunocompetent adult. Br J Haematol 1996;92:218-20.
    Pubmed CrossRef
  13. Biagi E, Assali G, Rossi F, Jankovic M, Nicolini B, Balduzzi A. A persistent severe autoimmune hemolytic anemia despite apparent direct antiglobulin test negativization. Haematologica 1999;84:1043-5.
  14. Bardill B, Mengis C, Tschopp M, Wuillemin WA. Severe IgA-mediated auto-immune haemolytic anaemia in a 48-yr-old woman. Eur J Haematol 2003;70:60-3.
    Pubmed CrossRef
  15. Lal D, Hillyer CD. Autoimmune hemolytic anemias. In: Shaz B, Hillyer C, editors, Transfusion medicine and hemostasis. 2nd ed. Philadelphia: Elsevier Science, 2013;317-25.
  16. Shrestha C, Liu M, Mo Z. Cold agglutinin disease associated with mycoplasma infection in an individual with type 2 diabetes:An atypical case. J Diabetes Mellitus 2012;2:402-5.

October 2018, 25 (2)
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