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Hematologic Abnormalities Associated with Influenza A Infection: A Report of 3 Cases
Hematologic Abnormalities Associated with Influenza A Infection: A Report of 3 Cases JAMES RICE, MD,
LINDA M. S. RESAR, MD
ABSTRACT: Influenza A is associated with leukopenia, although it is not reported to cause isolated thrombocytopenia, anemia, or pancytopenia. The authors report three pediatric patients with transient cytopenias associated with influenza A infection, all of whom had evidence for influenza A infection by direct immunofluorescence from nasopharyngeal aspirates. In all patients, cytopenias were transient and improved as their viral symptoms resolved. All patients improved spontaneously. This is the first report of transient pancytopenia, anemia, or thrombocytopenia associated with influenza A infection. Given the high frequency of influenza A infections during the winter months, it is important to recognize the associated hematologic findings. KEY INDEXING TERMS: Influenza A; Pancytopenia; Thrombocytopenia. [Am J Med Sci 1998; 316(6):401-403.]
V
iral infections have been associated with various hematologic abnormalities, including leukopenia, hemolytic anemia, or pancytopenia. Pancytopenia has been described in association with several common viral infections, including human parvovirus, cytomegalovirus, Epstein-Barr virus, viral hepatitis, and, more recently, human immunodeficiency virus.1-7 Infection-associated pancytopenia can be mild and transient, or progress to fatal aplastic anemia. Influenza A has been associated with leukopenia, although it is not commonly grouped with those viruses which are known to cause isolated thrombocytopenia, anemia, or pancytopenia. 1 Here, we report three patients with tranFrom the Department of Pediatrics, Division of Hematology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Received August 22, 1997; accepted in revised form February 20, 1998. Correspondence: Linda M.S. Resar, MD, The Johns Hopkins University School of Medicine, Ross Research Building, Room 1125, 720 Rutland Avenue, Baltimore, MD 21205. THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
sient cytopenias associated with influenza A infection: one patient with pancytopenia, another with hemoglobin SC disease who developed thrombocytopenia and anemia, and a third patient with isolated thrombocytopenia. This is the first report of transient pancytopenia, anemia, or isolated thrombocytopenia in patients infected with influenza A. The literature discussing hematologic abnormalities associated with influenza A is also reviewed. Case Reports Case 1. A previously well 6·year·old white boy was admitted to an outside hospital with fever and cough. There was no history of icterus, pallor, bony pain, bruising, abnormal bleeding, or exposure to potential bone marrow toxins. Physical examination on admission was notable for a temperature of 40.2° C, a nonexudative pharyngitis, and rales heard at the bases of both lung fields. The complete blood count (CBC) showed a white blood cell count (WBC) of 6.4 X 109IL, hemoglobin of 13.1 g/dL, and hemat· ocrit of 36.7%; platelet count was not performed due to platelet clumping. The indices were normal and no morphologic abnormalities were observed on the peripheral blood smear. Radiograph of the chest revealed bilateral perihilar infiltrates. The patient was treated with intravenous ceftriaxone, and defervescence progressed gradually over 4 days. The CBC on hospital day 2 revealed WBC, 2.9 X 109IL; hemoglobin, 11.6 g/dL; and platelet count, 127 X 109/L. By hospital day 4, the counts had fallen further, with WBC, 1.4 X 109 /L; hemoglobin, 10.7 g/dL; and platelet count, 108 X 109 /L. The patient was transferred to the Johns Hopkins Hospital where laboratory findings included WBC, 1.9 X 109 /L (6% bands, 25% polymorphonuclear cells, 55% lymphocytes, 11% monocytes, 1% basophils, and 2% eosinophils); hemoglobin, 11.4; hematocrit, 34.1%; and platelet count, 130 X 109IL. The indices and red cell distribution width were normal; the reticulocyte count was 0%. Direct and indirect Coombs tests were negative. Review of the peripheral blood smear showed no morphologic abnormalities suggestive of leukemia. Electrolytes and liver function tests were also normal. The patient improved clinically and repeat CBCs demonstrated gradual improvement in all cell lines. The patient was discharged after 48 hours with WBC, 2.5 X 109IL; hemoglobin, 12.5 g/dL; hematocrit, 36.8; platelet count, 153 X 109/L; and reticulocyte count, 0.3%. In follow-up 10 days after admission, WBC was 7.0 X 109/L, hemoglobin was 12.2 g/dL, hematocrit was 35.5%, platelet count was 332 X 109IL, and reticulocyte count was 1.9%. Serologic tests for cytomegalovirus, Epstein-Barr virus, hepatitis A virus, and hepatitis B surface antigen were negative. A nasopharyngeal aspirate revealed the presence of influenza A viral antigen by indirect immunofluorescence, and influenza A virus was identified in tissue culture from this sample. Case 2. A 4-year-old black girl with hemoglobin SC disease presented to the pediatric emergency department with a I-day history of fever, cough, rhinorrhea, and headache. Medications included only prophylactic penicillin at 250 mg twice per day.
401
Hematologic Abnormalities with Influenza A Infection
There was no known exposure to potential bone marrow toxins. She had a fever to 38.7° C. There was clear nasal discharge and mild posterior pharyngeal erythema; lung fields were clear to auscultation bilaterally. Remaining examination was unremarkable. The CBC showed WBC, 16.2 X 1091L (15% band forms, 64% polymorphonuclear cells, 14% lymphocytes, 2% atypical lymphocytes, 4% mononuclear cells, and 1% basophils); hemoglobin, 12.0 g/dL; hematocrit, 36.4%; and platelet count, 379 X 1091L. These values were unchanged from her baseline studies. The reticulocyte count was elevated at 18.0% (her usual reticulocyte count ranged from 2.5% to 3.5%). Blood, urine, and throat cultures were obtained, and intravenous ceftriaxone was administered. The patient was reevaluated 24 hours later, at which time a second dose of ceftriaxone was given. After 48 hours, however, she remained febrile, and was noted to be listless. Physical examination showed no meningism or focus for infection, and the patient was admitted to the hospital for further evaluation. Chest radiograph was clear and a repeat CBC showed WBC, 26.4 X 10 91L (31 % band forms, 55% polymorphonuclear cells, 6% lymphocytes, and 8% mononuclear cells); hemoglobin, 9.8 gldL; hematocrit, 29.6%; and platelet count, 73 X 109 1L. The reticulocyte count had fallen to 2.6%. A CBC obtained 2 hours later showed similar white blood cell and platelet counts, but worsening anemia with a hemoglobin of 7.8 gldL, and hematocrit of 23.5%. Electrolytes were normal, and a chemistry panel was remarkable for AST, 376 lUlL; ALT, 150 lUlL; direct bilirubin, 0.9 mg/dl; and indirect bilirubin, 0.2 mg/dl. Lumbar puncture showed 2 WBC/mm3 (100% mononuclear cells), 1 RBC/mm3 , glucose of82 mg/dL, and protein of 45 mgldL. The blood, urine, and cerebrospinal fluid cultures remained sterile. A nasopharyngeal aspirate showed influenza A by direct immunofluorescence. Her mental status, cough, and fever gradually improved over the following 4 days. A CBC obtained prior to discharge revealed WEC, 12.9 X 1091L; hemoglobin, 8.3 g/dL; hematocrit, 25.6%; and platelet count, 169 X 10 91L. Routine laboratory monitoring at a well-child visit several months later revealed WBC, 23.9 X 10 91L; hemoglobin, 11.6 g/dL; hematocrit of 34.4%; and platelet count, 324 X 10 91L. Case 3. A 5-year-old previously healthy black boy was admitted to the hospital with a 4-day history of fever to 40° C, nonbloody nonbilious emesis, cough, rhinorrhea, and diffuse body aches. The patient took no medications and there was no known exposure to potential bone marrow toxins. On physical examination, he had a temperature of 40.5° C and was coughing frequently. His mucous membranes were dry. Lung examination showed decreased breath sounds and inspiratory rales at the left base posteriorly. Remaining examination was normal. Chest radiograph confirmed a left lower lobe pneumonia. Initial laboratory studies were remarkable for moderate thrombocytopenia, with a platelet count of 92 X 1091L; other values were WEC, 11.8 X 109 1L (12% bands, 71% polymorphonuclear cells, 11% lymphocytes, 2% atypical lymphocytes, and 4% mononuclear cells); hemoglobin, 13.0 g/dL; and hematocrit, 38.8%. The patient was treated with intravenous cefuroxime and defervescence occurred within 48 hours. A blood culture drawn before antibiotics were given remained steriJe. A nasopharyngeal aspirate showed the presence of influenza A virus identified by direct immunofluorescence. The patient improved clinically, and was discharged after 36 hours on oral amoxicillin-clavulanate. A CBC obtained prior to discharge revealed WBC, 12.8 X 1Q91L; hemoglobin, 12.6 g/dL; hematocrit, 36.9%; and platelet count, 149 X 10 91L. The patient was seen in follow-up 2 weeks after discharge and was noted to have complete resolution of symptoms and a normal physical exam; follow-up CBC was not obtained.
Discussion
This paper describes three pediatric patients presenting with respiratory symptoms attributable to influenza A infection during a single season. All three patients also demonstrated significant hema-
402
tologic abnormalities ranging from pancytopenia to isolated thrombocytopenia. Of note, the first and second patients received doses of ceftriaxone, which may have contributed to the hematologic abnormalities that we observed. Interestingly, the cytopenias in all three patients were transient and did not appear to have clinically significant sequelae. A review of the literature on hematologic abnormalities associated with influenza A infection reveals few references addressing the subject. The usual peripheral blood response to influenza infection is a normal or decreased WBC count.1-9 In the presence of an accompanying pneumonia, a polymorphonuclear leukocytosis often occurs. In severe cases of influenza, marked leukopenia can also occur.7 There is also one report of a 53-year-old man who developed severe pancytopenia with persistently hypoplastic bone marrow after a documented influenza A infection.1° In addition, a 40-year-old woman who was immunosuppressed after a renal transplant developed transient leukopenia and thrombocytopenia with an influenza infection.ll Ours is the first report of transient cytopenias in pediatric patients with influenza A infections. Viral infections in general are implicated among the causes of pancytopenia.l,B Many cases were documented in association with infectious hepatitis. 5 In recent years, there have been published reports of pancytopenia in association with cytomegalovirus infection,3,4 Epstein-Barr virus infection,6 and human immunodeficiency virus infection. 7 Bone marrow aplasia in association with human parvovirus infection and immunodeficiency states has also been well documented. l The mechanism for hematologic abnormalities after influenza A infection is not known. Our first patient had a reticulocyte count of 0%, suggesting bone marrow suppression of erythropoiesis. The second patient with hemoglobin SC disease presented with an increased reticulocyte count that subsequently fell as she became both more anemic and thrombocytopenic. It is possible that there was peripheral red blood cell destruction initially and later inhibition in erythropoiesis. The thrombocytopenia could have been secondary to either increased destruction or decreased production. In the third patient who developed isolated thrombocytopenia, the mechanism of the thrombocytopenia could not be discerned. Of note, a recent article in the Russian literature suggests that influenza A infection can lead to bone marrow suppression. l2 In this study, bone marrow cells collected from mice inoculated intranasally with nonlethal doses of influenza A virus were given intravenously to lethally irradiated syngeneic mice. On day 3 posttransplant, the investigators observed inhibition of colony-forming units of spleen in the erythroid and granulocytic lines. Furthermore, lymph node cells of the mice inoculated with influenza were shown to inhibit the December 1998 Volume 316 Number 6
Rice and Resar
colony-forming activity of bone marrow cells from intact mice in the erythroid and granulocytic lines,12 again suggesting that Influenza A inhibits myelopoiesis and erythropoiesis. This report documents pediatric patients who developed transient hematologic abnormalities ranging from isolated thrombocytopenia to a significant decrease in all three hematopoietic cell lines in association with an influenza A infection. In all cases, the hematologic abnormalities improved spontaneously and did not lead to any significant sequelae. Given the high frequency of influenza A infections in pediatric patients during winter months, it is important to recognize the possible hematologic abnormalities that may develop.
4. 5. 6.
7.
8. 9.
References 1. Alter BP, Young NS. The bone marrow failure syndromes. In: Nathan D, Oski F, eds. Hematology of Infancy and Childhood. 4th ed. Philadelphia: WB Saunders; 1993: 216":'316. 2. Blacklock H, Mortimmer P. Aplastic crisis and other effects of the human parvovirus infection. Clin Hematol. 1984; 13:679-91. 3. Bilgrami S, Almeida GD, Quinn JJ, Tuck D, Bergstrom S, Dainiak N, et al. Pancytopenia in allogenic bone marrow
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
10. 11. 12.
transplant recipients: role of cytomegalovirus. Br J Hematol. 1994;87:357-62. Soliman SR, Burrows RF. A primary cytomegalovirus infection in pregnancy presenting with unusual hematologic manifestations: a case report. Am J Perinatol. 1993;10:348-50. Hagler L, Pastore R, Bergin J. Aplastic anemia following viral hepatitis: report oftwo fatal cases and literature review. Medicine. 1975;54:139-64. Iishi Y, Kosaka M, Mizuguchi T, Toyota K, Kawano Y, Saito S. Suppression of hematopoiesis by activated T-cells in infectious mononucleosis associated with pancytopenia. Int J Hematol. 1991;54:65-73. Sultan J, Gaur S, Sandhaus L, Frenkel LD, Ettinger LJ. Human immunodeficiency virus infection presenting as pancytopenia in an infant. Am J Pediatr Hematol Oncol. 1994; 16:334-7. Murdoch J, Smith C. Infection. Clin Hematol. 1972;1:61943. Alter B, Potter NU, Li F. Classification and aetiology of the aplastic anaemias. Clin Hematol. 1978;7:431-65. Curzon P, Muers M, Rajah S. Aplastic anemia associated with influenza A infection. Scand J Hematol. 1983;30:232-4. Karalakulasingam R, Schacht S, Lansing AM, RaffMJ. Influenza virus pneumonia after renal transplant. Postgrad Med. 1977;62:164-7. Lavrov V, Semenkov V. The infection of mice with the influenza virus suppresses bone marrow precursor differentiation in the erythroid and granulocyte directions. Voprosy Virusologii. 1991;36:284-6.
403
LINDA M. S. RESAR, MD
ABSTRACT: Influenza A is associated with leukopenia, although it is not reported to cause isolated thrombocytopenia, anemia, or pancytopenia. The authors report three pediatric patients with transient cytopenias associated with influenza A infection, all of whom had evidence for influenza A infection by direct immunofluorescence from nasopharyngeal aspirates. In all patients, cytopenias were transient and improved as their viral symptoms resolved. All patients improved spontaneously. This is the first report of transient pancytopenia, anemia, or thrombocytopenia associated with influenza A infection. Given the high frequency of influenza A infections during the winter months, it is important to recognize the associated hematologic findings. KEY INDEXING TERMS: Influenza A; Pancytopenia; Thrombocytopenia. [Am J Med Sci 1998; 316(6):401-403.]
V
iral infections have been associated with various hematologic abnormalities, including leukopenia, hemolytic anemia, or pancytopenia. Pancytopenia has been described in association with several common viral infections, including human parvovirus, cytomegalovirus, Epstein-Barr virus, viral hepatitis, and, more recently, human immunodeficiency virus.1-7 Infection-associated pancytopenia can be mild and transient, or progress to fatal aplastic anemia. Influenza A has been associated with leukopenia, although it is not commonly grouped with those viruses which are known to cause isolated thrombocytopenia, anemia, or pancytopenia. 1 Here, we report three patients with tranFrom the Department of Pediatrics, Division of Hematology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Received August 22, 1997; accepted in revised form February 20, 1998. Correspondence: Linda M.S. Resar, MD, The Johns Hopkins University School of Medicine, Ross Research Building, Room 1125, 720 Rutland Avenue, Baltimore, MD 21205. THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
sient cytopenias associated with influenza A infection: one patient with pancytopenia, another with hemoglobin SC disease who developed thrombocytopenia and anemia, and a third patient with isolated thrombocytopenia. This is the first report of transient pancytopenia, anemia, or isolated thrombocytopenia in patients infected with influenza A. The literature discussing hematologic abnormalities associated with influenza A is also reviewed. Case Reports Case 1. A previously well 6·year·old white boy was admitted to an outside hospital with fever and cough. There was no history of icterus, pallor, bony pain, bruising, abnormal bleeding, or exposure to potential bone marrow toxins. Physical examination on admission was notable for a temperature of 40.2° C, a nonexudative pharyngitis, and rales heard at the bases of both lung fields. The complete blood count (CBC) showed a white blood cell count (WBC) of 6.4 X 109IL, hemoglobin of 13.1 g/dL, and hemat· ocrit of 36.7%; platelet count was not performed due to platelet clumping. The indices were normal and no morphologic abnormalities were observed on the peripheral blood smear. Radiograph of the chest revealed bilateral perihilar infiltrates. The patient was treated with intravenous ceftriaxone, and defervescence progressed gradually over 4 days. The CBC on hospital day 2 revealed WBC, 2.9 X 109IL; hemoglobin, 11.6 g/dL; and platelet count, 127 X 109/L. By hospital day 4, the counts had fallen further, with WBC, 1.4 X 109 /L; hemoglobin, 10.7 g/dL; and platelet count, 108 X 109 /L. The patient was transferred to the Johns Hopkins Hospital where laboratory findings included WBC, 1.9 X 109 /L (6% bands, 25% polymorphonuclear cells, 55% lymphocytes, 11% monocytes, 1% basophils, and 2% eosinophils); hemoglobin, 11.4; hematocrit, 34.1%; and platelet count, 130 X 109IL. The indices and red cell distribution width were normal; the reticulocyte count was 0%. Direct and indirect Coombs tests were negative. Review of the peripheral blood smear showed no morphologic abnormalities suggestive of leukemia. Electrolytes and liver function tests were also normal. The patient improved clinically and repeat CBCs demonstrated gradual improvement in all cell lines. The patient was discharged after 48 hours with WBC, 2.5 X 109IL; hemoglobin, 12.5 g/dL; hematocrit, 36.8; platelet count, 153 X 109/L; and reticulocyte count, 0.3%. In follow-up 10 days after admission, WBC was 7.0 X 109/L, hemoglobin was 12.2 g/dL, hematocrit was 35.5%, platelet count was 332 X 109IL, and reticulocyte count was 1.9%. Serologic tests for cytomegalovirus, Epstein-Barr virus, hepatitis A virus, and hepatitis B surface antigen were negative. A nasopharyngeal aspirate revealed the presence of influenza A viral antigen by indirect immunofluorescence, and influenza A virus was identified in tissue culture from this sample. Case 2. A 4-year-old black girl with hemoglobin SC disease presented to the pediatric emergency department with a I-day history of fever, cough, rhinorrhea, and headache. Medications included only prophylactic penicillin at 250 mg twice per day.
401
Hematologic Abnormalities with Influenza A Infection
There was no known exposure to potential bone marrow toxins. She had a fever to 38.7° C. There was clear nasal discharge and mild posterior pharyngeal erythema; lung fields were clear to auscultation bilaterally. Remaining examination was unremarkable. The CBC showed WBC, 16.2 X 1091L (15% band forms, 64% polymorphonuclear cells, 14% lymphocytes, 2% atypical lymphocytes, 4% mononuclear cells, and 1% basophils); hemoglobin, 12.0 g/dL; hematocrit, 36.4%; and platelet count, 379 X 1091L. These values were unchanged from her baseline studies. The reticulocyte count was elevated at 18.0% (her usual reticulocyte count ranged from 2.5% to 3.5%). Blood, urine, and throat cultures were obtained, and intravenous ceftriaxone was administered. The patient was reevaluated 24 hours later, at which time a second dose of ceftriaxone was given. After 48 hours, however, she remained febrile, and was noted to be listless. Physical examination showed no meningism or focus for infection, and the patient was admitted to the hospital for further evaluation. Chest radiograph was clear and a repeat CBC showed WBC, 26.4 X 10 91L (31 % band forms, 55% polymorphonuclear cells, 6% lymphocytes, and 8% mononuclear cells); hemoglobin, 9.8 gldL; hematocrit, 29.6%; and platelet count, 73 X 109 1L. The reticulocyte count had fallen to 2.6%. A CBC obtained 2 hours later showed similar white blood cell and platelet counts, but worsening anemia with a hemoglobin of 7.8 gldL, and hematocrit of 23.5%. Electrolytes were normal, and a chemistry panel was remarkable for AST, 376 lUlL; ALT, 150 lUlL; direct bilirubin, 0.9 mg/dl; and indirect bilirubin, 0.2 mg/dl. Lumbar puncture showed 2 WBC/mm3 (100% mononuclear cells), 1 RBC/mm3 , glucose of82 mg/dL, and protein of 45 mgldL. The blood, urine, and cerebrospinal fluid cultures remained sterile. A nasopharyngeal aspirate showed influenza A by direct immunofluorescence. Her mental status, cough, and fever gradually improved over the following 4 days. A CBC obtained prior to discharge revealed WEC, 12.9 X 1091L; hemoglobin, 8.3 g/dL; hematocrit, 25.6%; and platelet count, 169 X 10 91L. Routine laboratory monitoring at a well-child visit several months later revealed WBC, 23.9 X 10 91L; hemoglobin, 11.6 g/dL; hematocrit of 34.4%; and platelet count, 324 X 10 91L. Case 3. A 5-year-old previously healthy black boy was admitted to the hospital with a 4-day history of fever to 40° C, nonbloody nonbilious emesis, cough, rhinorrhea, and diffuse body aches. The patient took no medications and there was no known exposure to potential bone marrow toxins. On physical examination, he had a temperature of 40.5° C and was coughing frequently. His mucous membranes were dry. Lung examination showed decreased breath sounds and inspiratory rales at the left base posteriorly. Remaining examination was normal. Chest radiograph confirmed a left lower lobe pneumonia. Initial laboratory studies were remarkable for moderate thrombocytopenia, with a platelet count of 92 X 1091L; other values were WEC, 11.8 X 109 1L (12% bands, 71% polymorphonuclear cells, 11% lymphocytes, 2% atypical lymphocytes, and 4% mononuclear cells); hemoglobin, 13.0 g/dL; and hematocrit, 38.8%. The patient was treated with intravenous cefuroxime and defervescence occurred within 48 hours. A blood culture drawn before antibiotics were given remained steriJe. A nasopharyngeal aspirate showed the presence of influenza A virus identified by direct immunofluorescence. The patient improved clinically, and was discharged after 36 hours on oral amoxicillin-clavulanate. A CBC obtained prior to discharge revealed WBC, 12.8 X 1Q91L; hemoglobin, 12.6 g/dL; hematocrit, 36.9%; and platelet count, 149 X 10 91L. The patient was seen in follow-up 2 weeks after discharge and was noted to have complete resolution of symptoms and a normal physical exam; follow-up CBC was not obtained.
Discussion
This paper describes three pediatric patients presenting with respiratory symptoms attributable to influenza A infection during a single season. All three patients also demonstrated significant hema-
402
tologic abnormalities ranging from pancytopenia to isolated thrombocytopenia. Of note, the first and second patients received doses of ceftriaxone, which may have contributed to the hematologic abnormalities that we observed. Interestingly, the cytopenias in all three patients were transient and did not appear to have clinically significant sequelae. A review of the literature on hematologic abnormalities associated with influenza A infection reveals few references addressing the subject. The usual peripheral blood response to influenza infection is a normal or decreased WBC count.1-9 In the presence of an accompanying pneumonia, a polymorphonuclear leukocytosis often occurs. In severe cases of influenza, marked leukopenia can also occur.7 There is also one report of a 53-year-old man who developed severe pancytopenia with persistently hypoplastic bone marrow after a documented influenza A infection.1° In addition, a 40-year-old woman who was immunosuppressed after a renal transplant developed transient leukopenia and thrombocytopenia with an influenza infection.ll Ours is the first report of transient cytopenias in pediatric patients with influenza A infections. Viral infections in general are implicated among the causes of pancytopenia.l,B Many cases were documented in association with infectious hepatitis. 5 In recent years, there have been published reports of pancytopenia in association with cytomegalovirus infection,3,4 Epstein-Barr virus infection,6 and human immunodeficiency virus infection. 7 Bone marrow aplasia in association with human parvovirus infection and immunodeficiency states has also been well documented. l The mechanism for hematologic abnormalities after influenza A infection is not known. Our first patient had a reticulocyte count of 0%, suggesting bone marrow suppression of erythropoiesis. The second patient with hemoglobin SC disease presented with an increased reticulocyte count that subsequently fell as she became both more anemic and thrombocytopenic. It is possible that there was peripheral red blood cell destruction initially and later inhibition in erythropoiesis. The thrombocytopenia could have been secondary to either increased destruction or decreased production. In the third patient who developed isolated thrombocytopenia, the mechanism of the thrombocytopenia could not be discerned. Of note, a recent article in the Russian literature suggests that influenza A infection can lead to bone marrow suppression. l2 In this study, bone marrow cells collected from mice inoculated intranasally with nonlethal doses of influenza A virus were given intravenously to lethally irradiated syngeneic mice. On day 3 posttransplant, the investigators observed inhibition of colony-forming units of spleen in the erythroid and granulocytic lines. Furthermore, lymph node cells of the mice inoculated with influenza were shown to inhibit the December 1998 Volume 316 Number 6
Rice and Resar
colony-forming activity of bone marrow cells from intact mice in the erythroid and granulocytic lines,12 again suggesting that Influenza A inhibits myelopoiesis and erythropoiesis. This report documents pediatric patients who developed transient hematologic abnormalities ranging from isolated thrombocytopenia to a significant decrease in all three hematopoietic cell lines in association with an influenza A infection. In all cases, the hematologic abnormalities improved spontaneously and did not lead to any significant sequelae. Given the high frequency of influenza A infections in pediatric patients during winter months, it is important to recognize the possible hematologic abnormalities that may develop.
4. 5. 6.
7.
8. 9.
References 1. Alter BP, Young NS. The bone marrow failure syndromes. In: Nathan D, Oski F, eds. Hematology of Infancy and Childhood. 4th ed. Philadelphia: WB Saunders; 1993: 216":'316. 2. Blacklock H, Mortimmer P. Aplastic crisis and other effects of the human parvovirus infection. Clin Hematol. 1984; 13:679-91. 3. Bilgrami S, Almeida GD, Quinn JJ, Tuck D, Bergstrom S, Dainiak N, et al. Pancytopenia in allogenic bone marrow
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
10. 11. 12.
transplant recipients: role of cytomegalovirus. Br J Hematol. 1994;87:357-62. Soliman SR, Burrows RF. A primary cytomegalovirus infection in pregnancy presenting with unusual hematologic manifestations: a case report. Am J Perinatol. 1993;10:348-50. Hagler L, Pastore R, Bergin J. Aplastic anemia following viral hepatitis: report oftwo fatal cases and literature review. Medicine. 1975;54:139-64. Iishi Y, Kosaka M, Mizuguchi T, Toyota K, Kawano Y, Saito S. Suppression of hematopoiesis by activated T-cells in infectious mononucleosis associated with pancytopenia. Int J Hematol. 1991;54:65-73. Sultan J, Gaur S, Sandhaus L, Frenkel LD, Ettinger LJ. Human immunodeficiency virus infection presenting as pancytopenia in an infant. Am J Pediatr Hematol Oncol. 1994; 16:334-7. Murdoch J, Smith C. Infection. Clin Hematol. 1972;1:61943. Alter B, Potter NU, Li F. Classification and aetiology of the aplastic anaemias. Clin Hematol. 1978;7:431-65. Curzon P, Muers M, Rajah S. Aplastic anemia associated with influenza A infection. Scand J Hematol. 1983;30:232-4. Karalakulasingam R, Schacht S, Lansing AM, RaffMJ. Influenza virus pneumonia after renal transplant. Postgrad Med. 1977;62:164-7. Lavrov V, Semenkov V. The infection of mice with the influenza virus suppresses bone marrow precursor differentiation in the erythroid and granulocyte directions. Voprosy Virusologii. 1991;36:284-6.
403