J Hematol
Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc
Journal website http://www.thejh.org

Case Report

Volume 8, Number 1, March 2019, pages 44-45

Legionella-Induced Autoimmune Hemolytic Anemia: A Delayed and Unexpected Complication

Richard Jesse Durrancea, c, Fabiano Das Gracasa, Shetra Sivamurthyb, Bhupinder B. Singha

aDepartment of Medicine, Jamaica Hospital Medical Center, D Building: Ground Floor, 8900 Van Wyck Expressway, Richmond Hill, NY 11418, USA
bDepartment Hematology, Jamaica Hospital Medical Center, D Building: Ground Floor, 8900 Van Wyck Expressway, Richmond Hill, NY 11418, USA
cCorresponding Author: Richard Jesse Durrance, Jamaica Hospital Medical Center, 8900 Van Wyck Expressway, Jamaica, NY 11418, USA

Manuscript submitted February 21, 2019, accepted March 21, 2019
Short title: A Case of Legionella-Induced AIHA
doi: https://doi.org/10.14740/jh487


Legionella pneumophilia is a multi-systemic disease primarily affecting the pulmonary, gastrointestinal, and to a lesser extent, renal systems. We present a case of Legionella pneumonia, which after resolution of respiratory compromise, was complicated by the development of autoimmune hemolytic anemia (AIHA) as determined by a positive Coombs test, and negative workup of other causes. Steroid immunosuppression was initiated, and red cell counts subsequently improved. While AIHA has only been anecdotally described in one prior case, the separation in time of the development and resolution of respiratory symptoms with the development of anemia most likely makes this an under-appreciated entity. An in vitro mechanism has been suggested; however in vivo causation has yet to be proven. Given the prolonged deleterious clinical consequences associated with the development of AIHA and the increase in recognition of Legionella outbreaks, greater recognition of this potential complication and research into the pathophysiology is warranted for the future.

Keywords: Legionella; Autoimmune Hemolytic anemia; Hemolytic anemia


Legionella pneumophilia became well-known after the American Legion outbreak in Philadelphia in 1976 [1, 2]. While pathology is multi-systemic, pulmonary, gastrointestinal, and to a lesser extent, renal symptoms tend to dominate the clinical course [1, 3]. Hemolytic anemia has only anecdotally been associated with Legionellosis. One such case of hemolysis associated with disease was reported in an epidemiologic review of the initial Philadelphia outbreak [1]; however a Coombs test was never done. In addition, one specific case report from 1981 in which legionella was suspected to be the etiologic origin of autoimmune hemolytic anemia (AIHA) given a positive direct Coombs test [4]. While the very limited cases of association has been observed, the mechanism of the same has been proposed in vitro [5], but has yet to be elucidated in vivo [4]. We present a case of Legionella pneumonia with a clinical course marked by severe disease, which, despite overall clinical improvement, was complicated by the development of hemolytic anemia.

Case Report▴Top 

A 66-year-old female presented with 4 days of progressively worsening generalized weakness, chills, and loss of appetite, complicated by confusion and lethargy in the 24 h prior to presentation. Past medical history was remarkable for bipolar disorder, hypertension, and diabetes.

On evaluation, patient was febrile and tachycardic. Labs were remarkable for bandemia (18%), lactic acidosis, acute kidney injury, and elevated creatine phosphokinase (CPK) (> 6,000 U/L). Physical exam, imaging and initial studies were suggestive of pneumonia, and treatment for sepsis syndrome of suspected pulmonary origin was initiated. Urine antigen testing was positive for Legionella spp., and treatment with quinolone therapy was continued. Hospital course was complicated initially by respiratory failure requiring intubation and mechanical ventilation, from which the patient ultimately recovered. While the clinical course of complicated Legionella pneumonia was typical of Legionnaires’ disease [1, 3], the unexpected occurred when patient developed a persistent drop in her red blood cell (RBC) line, without clinical evidence of bleeding.

Due to religious reasons, the patient refused RBC transfusions (to which she had also never been previously exposed to), and an initial therapy trial with erythropoietin and intravenous iron was unsuccessful in reverting her persistent and worsening anemia. For this reason, workup for hemolysis was pursued, revealing a markedly elevated lactate dehydrogenase (LDH) level (1,439), elevated reticulocyte count (5.9%), unremarkable peripheral smear, and positive direct Coombs test (IgG positive, C3d negative). Family history was unremarkable. Lupus workup was negative. Given the evidence supportive of AIHA, therapy with prednisone 40 mg daily was initiated, and RBC count subsequently stabilized and improved. Without a source of bleeding, a clear explanation for the sudden onset of hemolytic anemia, or confounding medications or conditions, the patient’s AIHA was presumed to be induced by her infection to Legionella.


While Legionella is known to incur a multi-systemic effect over the host, autoimmune hemolysis has only been reliably described once. In the previously mentioned case in which AIHA was reliably associated with Legionellosis, Jk (Kidd antigen) antibodies were identified on the patient’s erythrocytes [4]. While this mechanism is theoretically plausible, the absence of prior blood transfusions and childbirth more than 30 years ago in our patient makes it less likely. As infectious processes are known to induce the formation of IgG-mediated hemolysis, and accounts for the majority of AIHA [6], the exact mechanism or inciting antibody has not been identified. This case correlates with the slower extra-vascular IgG-mediated warm hemolysis mechanism [7, 8], and falls into this category by systematic investigation.

Given the historical under-diagnosis and increasing awareness of Legionnaire’s disease [3], along with recent outbreaks [9], this complication of Legionella is most likely under-appreciated and associated with prolonged hospitalization and increased morbidity. Therefore further study is warranted to elucidate the underlying mechanism, prevent the potential deleterious clinical course, and recognized Legionellosis associated with development of AIHA.


None to declare.

Financial Disclosure or Funding

None to declare.

Conflict of Interest

The authors declare no conflicts of interest in the preparation of this manuscript.

Informed Consent

Written informed consent was obtained from the patient for presentation and publication.

Author Contributions

All authors contributed significantly to the preparation and signed off on the final version of the manuscript.

  1. Tsai TF, Finn DR, Plikaytis BD, McCauley W, Martin SM, Fraser DW. Legionnaires' disease: clinical features of the epidemic in Philadelphia. Ann Intern Med. 1979;90(4):509-517.
    doi pubmed
  2. Fraser DW, Tsai TR, Orenstein W, Parkin WE, Beecham HJ, Sharrar RG, Harris J, et al. Legionnaires' disease: description of an epidemic of pneumonia. N Engl J Med. 1977;297(22):1189-1197.
    doi pubmed
  3. Cunha BA, Burillo A, Bouza E. Legionnaires' disease. Lancet. 2016;387(10016):376-385.
  4. Strikas R, Seifert MR, Lentino JR. Autoimmune hemolytic anemia and Legionella pneumophila pneumonia. Ann Intern Med. 1983;99(3):345.
    doi pubmed
  5. Baine WB, Rasheed JK, Maca HW, Kaufmann AF. Hemolytic activity of plasma and urine from rabbits experimentally infected with Legionella pneumophila. Rev Infect Dis. 1979;1(6):912-917.
    doi pubmed
  6. Liebman HA, Weitz IC. Autoimmune hemolytic anemia. Med Clin North Am. 2017;101(2):351-359.
    doi pubmed
  7. Barcellini W. New insights in the pathogenesis of autoimmune hemolytic anemia. Transfus Med Hemother. 2015;42(5):287-293.
    doi pubmed
  8. Guillaud C, Loustau V, Michel M. Hemolytic anemia in adults: main causes and diagnostic procedures. Expert Rev Hematol. 2012;5(2):229-241.
    doi pubmed
  9. Shah P, Barskey A, Binder A, Edens C, Lee S, Smith J, et al. Legionnaires' disease surveillance summary report, United States, 2014-2015 (CDC) [Internet]. 2018. Available: https://www.cdc.gov/legionella/health-depts/surv-reporting/2014-15-surv-report-508.pdf.

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Journal of Hematology is published by Elmer Press Inc.


Browse  Journals  


Journal of Clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics

World Journal of Oncology

Gastroenterology Research

Journal of Hematology

Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity

Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research

Journal of Neurology Research

International Journal of Clinical Pediatrics






Journal of Hematology, bimonthly, ISSN 1927-1212 (print), 1927-1220 (online), published by Elmer Press Inc.                            
The content of this site is intended for health care professionals.
This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC BY-NC 4.0)

This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.thejh.org    editorial contact: editor@thejh.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.

Disclaimer: The views and opinions expressed in the published articles are those of the authors and do not necessarily reflect the views or opinions of the editors and Elmer Press Inc. This website is provided for medical research and informational purposes only and does not constitute any medical advice or professional services. The information provided in this journal should not be used for diagnosis and treatment, those seeking medical advice should always consult with a licensed physician.