Letter to the Editor

Split Viewer

Blood Res 2017; 52(1):

Published online March 27, 2017

https://doi.org/10.5045/br.2017.52.1.74

© The Korean Society of Hematology

A rare case of erythrophagocytosis by neutrophils on the peripheral blood smear

Jong Ho Lee*

Department of Laboratory Medicine, Yeungnam University College of Medicine, Daegu, Korea.

Correspondence to : Jong Ho Lee. Department of Laboratory Medicine, Yeungnam University College of Medicine, Hyunchoongro 170, Nam-gu, Daegu 42415, Korea. ae4207@naver.com

Received: April 1, 2016; Revised: April 11, 2016; Accepted: May 31, 2016

TO THE EDITOR: Erythrophagocytosis by monocytes or macrophages is occasionally seen in hematologic malignancy, autoimmune hemolytic anemia, and hemophagocytic lymphohistiocytosis [1,2]. However, erythrophagocytosis by neutrophils on the peripheral blood smear is an unusual morphological phenomenon. Erythrophagocytosis by neutrophils has been reported in patients with some hemolytic anemias, particularly paroxysmal cold hemoglobinuria (PCH), and other conditions including poisoning with potassium chlorate, sickle cell disease, and incompatible transfusion [3,4,5,6]. Cases of erythrophagocytosis by neutrophils have rarely been observed in cold agglutinin disease (CAD) [7,8,9]. We report a female patient with CAD and the presence of erythrophagocytosis by neutrophils on the peripheral blood smear.

An 80-year-old woman was referred to our hospital because of dizziness. A few days prior to referral, she had cold symptoms, with a cough and rhinorrhea. She had a history of hypertension. Physical examination revealed icteric sclera and jaundice of her torso. Her white blood cell count was 15.88×109/L (83% segmented neutrophils, 8% band forms, 1% metamyelocytes, 2% myelocytes, 3% lymphocytes, and 3% monocytes), hemoglobin concentration was 9 g/dL, and platelet count was 369×109/L. Other laboratory tests showed the following: increased lactate dehydrogenase (2,530 IU/L), total bilirubin (5.14 mg/dL), and direct bilirubin (2.05 mg/dL), and decreased haptoglobin (2 mg/dL). The peripheral blood smear showed red blood cell (RBC) agglutination with a few nucleated RBCs and erythrophagocytosis by approximately 10% of the neutrophils (Fig. 1). Cold agglutinin titer was 1:256. The direct Coombs' test returned positive results (3+) for C3d and weakly positive results for IgG. The indirect Coombs' test returned negative results. Sepsis was suspected and empirical was administered. However, the patient's condition deteriorated rapidly and she died two days after admission. Although the Donath-Landsteiner test was not examined and PCH could not completely be excluded, a diagnosis of CAD was made based on the available laboratory results.

CAD is generally classified as primary (idiopathic) or secondary. The latter is associated with underlying conditions such as malignancy, infection, or immune disorders [10]. Therefore, after diagnosis of CAD, patients should be evaluated for underlying conditions. Two sets of blood cultures returned negative results. Mycoplasma pneumoniae and Epstein-Barr virus were not detected. Evaluation for underlying malignancy or other disease was not performed because of the short clinical course. Therefore, we could not determine whether underlying disease was associated with the CAD.

The CR1 receptor of neutrophils can react with RBC-bound C3b [11]. However, the mechanism underlying erythrophagocytosis by neutrophils is unclear. To the best of our knowledge, this is the first reported case in Korea of CAD with erythrophagocytosis by neutrophils on a peripheral blood smear.

Fig. 1.

The peripheral blood smear showed red blood cell agglutination (A, B) and erythrophagocytosis by neutrophils (A, B, C; red arrows).


  1. Salama, R, Girgis, G, Zhou, J. Erythrophagocytosis by neutrophils associated with Clostridium perfringens-induced hemolytic anemia. Ann Hematol, 2015;94;521-522.
    Pubmed
  2. Lewandowski, K, Homenda, W, Mital, A, Complak, A, Hellmann, A. Erythrophagocytosis by neutrophils-a rare morphological phenomenon resulting in acquired haemolytic anaemia?. Int J Lab Hematol, 2011;33;447-450.
    Pubmed
  3. Santos, F, Costa, E, Pinto, RM, Barbot, J, Freitas, I. Erythrophagocytosis by neutrophils in paroxysmal cold haemoglobinuria. Eur J Haematol, 2012;89;371.
    Pubmed
  4. Mamtani, M, Sharma, M, Amin, M, Amin, A, Jawahirani, A, Kulkarni, H. Erythrophagocytosis in sickle cell anemia: statistical evidence for a biological phenomenon. Med Hypotheses, 2007;68;1065-1070.
    Pubmed
  5. Mukhopadhyay, S, Keating, L, Souid, AK. Erythrophagocytosis in paroxysmal cold hemoglobinuria. Am J Hematol, 2003;74;196-197.
    Pubmed
  6. Hernandez, JA, Steane, SM. Erythrophagocytosis by segmented neutrophils in paroxysmal cold hemoglobinuria. Am J Clin Pathol, 1984;81;787-789.
    Pubmed
  7. Walia, H, Jain, R, Bansal, RK, Gupta, GN. Cold agglutinin disease with erythrophagocytosis by neutrophils occurring during recovery phase of chickenpox. J Lab Physicians, 2013;5;146-147.
    Pubmed
  8. Beyá, MD, Pereira, A, Merino, A. Transfusion medicine illustrated. Erythrophagocytosis in cold agglutinin disease. Transfusion, 2010;50;2310.
    Pubmed
  9. Keramati, MR, Sadeghian, MH, Ayatollahi, H, Zarmehri, AM. Case of erythrophagocytosis in a patient with mantle cell lymphoma and cold agglutinin disease. Leuk Res, 2010;34;e167-e168.
    Pubmed
  10. Swiecicki, PL, Hegerova, LT, Gertz, MA. Cold agglutinin disease. Blood, 2013;122;1114-1121.
    Pubmed
  11. Garratty, G. Erythrophagocytosis on the peripheral blood smear and paroxysmal cold hemoglobinuria. Transfusion, 2001;41;1073-1074.
    Pubmed

Article

Letter to the Editor

Blood Res 2017; 52(1): 74-75

Published online March 27, 2017 https://doi.org/10.5045/br.2017.52.1.74

Copyright © The Korean Society of Hematology.

A rare case of erythrophagocytosis by neutrophils on the peripheral blood smear

Jong Ho Lee*

Department of Laboratory Medicine, Yeungnam University College of Medicine, Daegu, Korea.

Correspondence to: Jong Ho Lee. Department of Laboratory Medicine, Yeungnam University College of Medicine, Hyunchoongro 170, Nam-gu, Daegu 42415, Korea. ae4207@naver.com

Received: April 1, 2016; Revised: April 11, 2016; Accepted: May 31, 2016

Body

TO THE EDITOR: Erythrophagocytosis by monocytes or macrophages is occasionally seen in hematologic malignancy, autoimmune hemolytic anemia, and hemophagocytic lymphohistiocytosis [1,2]. However, erythrophagocytosis by neutrophils on the peripheral blood smear is an unusual morphological phenomenon. Erythrophagocytosis by neutrophils has been reported in patients with some hemolytic anemias, particularly paroxysmal cold hemoglobinuria (PCH), and other conditions including poisoning with potassium chlorate, sickle cell disease, and incompatible transfusion [3,4,5,6]. Cases of erythrophagocytosis by neutrophils have rarely been observed in cold agglutinin disease (CAD) [7,8,9]. We report a female patient with CAD and the presence of erythrophagocytosis by neutrophils on the peripheral blood smear.

An 80-year-old woman was referred to our hospital because of dizziness. A few days prior to referral, she had cold symptoms, with a cough and rhinorrhea. She had a history of hypertension. Physical examination revealed icteric sclera and jaundice of her torso. Her white blood cell count was 15.88×109/L (83% segmented neutrophils, 8% band forms, 1% metamyelocytes, 2% myelocytes, 3% lymphocytes, and 3% monocytes), hemoglobin concentration was 9 g/dL, and platelet count was 369×109/L. Other laboratory tests showed the following: increased lactate dehydrogenase (2,530 IU/L), total bilirubin (5.14 mg/dL), and direct bilirubin (2.05 mg/dL), and decreased haptoglobin (2 mg/dL). The peripheral blood smear showed red blood cell (RBC) agglutination with a few nucleated RBCs and erythrophagocytosis by approximately 10% of the neutrophils (Fig. 1). Cold agglutinin titer was 1:256. The direct Coombs' test returned positive results (3+) for C3d and weakly positive results for IgG. The indirect Coombs' test returned negative results. Sepsis was suspected and empirical was administered. However, the patient's condition deteriorated rapidly and she died two days after admission. Although the Donath-Landsteiner test was not examined and PCH could not completely be excluded, a diagnosis of CAD was made based on the available laboratory results.

CAD is generally classified as primary (idiopathic) or secondary. The latter is associated with underlying conditions such as malignancy, infection, or immune disorders [10]. Therefore, after diagnosis of CAD, patients should be evaluated for underlying conditions. Two sets of blood cultures returned negative results. Mycoplasma pneumoniae and Epstein-Barr virus were not detected. Evaluation for underlying malignancy or other disease was not performed because of the short clinical course. Therefore, we could not determine whether underlying disease was associated with the CAD.

The CR1 receptor of neutrophils can react with RBC-bound C3b [11]. However, the mechanism underlying erythrophagocytosis by neutrophils is unclear. To the best of our knowledge, this is the first reported case in Korea of CAD with erythrophagocytosis by neutrophils on a peripheral blood smear.

Fig 1.

Figure 1.

The peripheral blood smear showed red blood cell agglutination (A, B) and erythrophagocytosis by neutrophils (A, B, C; red arrows).

Blood Research 2017; 52: 74-75https://doi.org/10.5045/br.2017.52.1.74

References

  1. Salama, R, Girgis, G, Zhou, J. Erythrophagocytosis by neutrophils associated with Clostridium perfringens-induced hemolytic anemia. Ann Hematol, 2015;94;521-522.
    Pubmed
  2. Lewandowski, K, Homenda, W, Mital, A, Complak, A, Hellmann, A. Erythrophagocytosis by neutrophils-a rare morphological phenomenon resulting in acquired haemolytic anaemia?. Int J Lab Hematol, 2011;33;447-450.
    Pubmed
  3. Santos, F, Costa, E, Pinto, RM, Barbot, J, Freitas, I. Erythrophagocytosis by neutrophils in paroxysmal cold haemoglobinuria. Eur J Haematol, 2012;89;371.
    Pubmed
  4. Mamtani, M, Sharma, M, Amin, M, Amin, A, Jawahirani, A, Kulkarni, H. Erythrophagocytosis in sickle cell anemia: statistical evidence for a biological phenomenon. Med Hypotheses, 2007;68;1065-1070.
    Pubmed
  5. Mukhopadhyay, S, Keating, L, Souid, AK. Erythrophagocytosis in paroxysmal cold hemoglobinuria. Am J Hematol, 2003;74;196-197.
    Pubmed
  6. Hernandez, JA, Steane, SM. Erythrophagocytosis by segmented neutrophils in paroxysmal cold hemoglobinuria. Am J Clin Pathol, 1984;81;787-789.
    Pubmed
  7. Walia, H, Jain, R, Bansal, RK, Gupta, GN. Cold agglutinin disease with erythrophagocytosis by neutrophils occurring during recovery phase of chickenpox. J Lab Physicians, 2013;5;146-147.
    Pubmed
  8. Beyá, MD, Pereira, A, Merino, A. Transfusion medicine illustrated. Erythrophagocytosis in cold agglutinin disease. Transfusion, 2010;50;2310.
    Pubmed
  9. Keramati, MR, Sadeghian, MH, Ayatollahi, H, Zarmehri, AM. Case of erythrophagocytosis in a patient with mantle cell lymphoma and cold agglutinin disease. Leuk Res, 2010;34;e167-e168.
    Pubmed
  10. Swiecicki, PL, Hegerova, LT, Gertz, MA. Cold agglutinin disease. Blood, 2013;122;1114-1121.
    Pubmed
  11. Garratty, G. Erythrophagocytosis on the peripheral blood smear and paroxysmal cold hemoglobinuria. Transfusion, 2001;41;1073-1074.
    Pubmed
Blood Res
Volume 59 2024

Stats or Metrics

Share this article on

  • line

Blood Research

pISSN 2287-979X
eISSN 2288-0011
qr-code Download