Transient Aplastic Crisis in Patients With Sickle Cell Disease B19 Parvovirus Studies

During a 7-Year Period

Sreedhar P. Rao, MD; Scott T. Miller, MD; Bernard J. Cohen, PhD \s=b\ Objective.\p=m-\Todetermine (1) the proportion of cases of transient aplastic crisis (TAC) in patients with sickle cell disease due to B19 parvovirus infection in several years, (2) longitudinally, the immune response to B19 parvovirus infection, and (3) whether patients with sickle cell disease experience recurrent or chronic B19 parvovirus infection. Design.\p=m-\Prospectiveevaluation of patients with sickle cell disease and TAC to find evidence of B19 parvovirus infection and, if present, to document the pattern of serologic response with time. Setting.\p=m-\Largeurban teaching hospital. Patients.\p=m-\Patientsyounger than 18 years with sickle cell disease who were admitted to the hospital with a diagnosis of TAC or who developed TAC while in the hospital for other reasons. Follow-up serologic studies of B19 parvovirus infection were done in eight patients. Measurements/Main Results.\p=m-\Serumwas tested for B19 parvovirus DNA/viral particles and specific anti-B19 parvovirus IgM and IgG antibodies. B19 parvovirus DNA /viral particles were detected in 11 (21%) of 53 patients with

TAC.

the last decade, infection with B19 parvovirus has been shown During be associated with several ill¬ crisis humans. These include

rus

to

nesses

(TAC)

in in

transient

aplastic

patients with chronic hemolytic anemia1-2; erythema infectiosum, or fifth disease3; polyarthralgia syndrome4; chronic anemia or bone marrow failure in per¬ sons with congenital immunodeficiency or an acquired immunodeficiency state5-6; and fetal infection resulting in severe anemia and death.7 Transient aplastic crisis in pa¬ tients with sickle cell disease is characterized by profound reticulocytopenia and worsening anemia. Most patients require red blood cell transfusion. Reports from different areas of the world show that most episodes of TAC in pa¬ tients with sickle cell disease are caused by B19 parvoviAccepted for publication June 26, 1992. From the Department of Pediatrics, Division of Hematology/ Oncology, State University of New York Children's Medical Center of Brooklyn (Drs Rao and Miller), and the Central Public Health Laboratory, London, England (Dr Cohen). Reprint requests to State University of New York Children's Medical Center of Brooklyn, Box 49, 450 Clarkson Ave, Brooklyn, NY 11203 (Dr Rao).

Specific anti-B19 parvovirus IgM antibodies were detected in 34 (64%) of the 53 patients. Overall, 36 (68%) of 53 patients with TAC had evidence of acute B19 parvovirus infection as shown by the detection of B19 DNA parvovirus and/or specific anti-B19 parvovirus IgM antibodies in acute-phase serum. Follow-up serologic studies in eight patients with acute infection revealed disappearance of B19 parvovirus DNA/viral particles and anti-B19 parvovirus IgM antibodies and persistence of anti-B19 parvovirus IgG antibodies for up to 3\m=1/2\years after the diagnosis of acute B19 parvovirus infection. No patient had evidence of recurrent or chronic B19 parvovirus infection. Conclusions.\p=m-\Approximately70% of cases of TAC in patients with sickle cell disease identified in a 7-year period were caused by acute B19 parvovirus infection. Once detected, anti-B19 parvovirus IgG antibodies remain detectable for several years. There was no evidence of chronic or recurrent B19 parvovirus infection in patients with sickle cell disease. (AJDC. 1992;146:1328-1330) infection.2-8 There are no reports of sequential antibody determinations in patients with sickle cell disease and proven B19 parvovirus infection. In addition, there are no reports of recurrent B19 parvovirus infection in patients with sickle cell disease. We have reviewed serologie and clinical data collected for our patients with TAC since 1984 to (1) determine the proportion of cases of TAC in patients with sickle cell disease due to B19 parvovirus infection in a 7-year period, (2) evaluate longitudinally the immune response to B19 parvovirus infection, and (3) determine whether patients with sickle cell disease develop recurrent or chronic B19 parvovirus infection similar to that seen in patients with immunodeficiency.

PATIENTS, MATERIALS, AND METHODS Transient aplastic crisis was diagnosed if reticulocytopenia and lower-than-usual hemoglobin levels were present in a patient with sickle cell disease. Between 1984 and 1990, an attempt was made to collect serum samples from all children with TAC admitted to the pediatrie service at Kings County Hospital Center, Brooldyn, NY, and University Hospital of Brooldyn. Eight patients with proven acute B19 parvovirus infection had follow-up B19 studies from 2 months to 3Vi years after acute infection.

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patients with TAC. Eleven (21%) of these 53 patients had parvovirus DNA in serum (Table 1), and anti-B19 parvovirus IgM antibodies were detected in 34 (64%) of 53 patients; overall, 36 (68%) of the 53 patients had evidence of acute B19 parvovirus infection. When analyzed on a yearly basis, 62% to 100% of the cases of TAC were due to B19 parvovirus infection. The large variation may have been due to the small number of patients studied in certain years (1984, 1985, and 1988). Eight patients with documented acute B19 parvovirus

Virologie studies were performed at the Central Public Health Laboratory, London, England. Electron microscopy and dot hy¬ bridization (for patients admitted in 1986 or later) were used for demonstration of virus particles and viral DNA, respectively.9 Radioimmunoassay with monoclonal antibodies was used to as¬ say for anti-B19 parvovirus IgM and IgG antibodies.10

B19

RESULTS Seventy-eight patients with sickle cell disease and TAC were hospitalized between 1984 and 1990. The age of the pa¬ tients ranged from 1 to 17 years, with a mean age of 7.6 years. Hemoglobin levels ranged between 30 and 70 g/L, with a mean of 55 g/L; the reticulocyte count was between 0 and 45X10"3, with a mean of lOXlO"3. Transfusion histories were available for only 30 patients. Six patients had received a prior red blood cell transfusion, four within 8 months before TAC. Of interest, a 13-year-old girl who was receiving longterm transfusion because of a history of cerebrovascular accident was diagnosed as having TAC (hemoglobin level, 30 g/L, and reticulocyte count, lOXlO"3) due to B19 parvo¬ virus infection 19 days after a transfusion. It is not known whether the blood donor had B19 parvoviremia. While ep¬ isodes of TAC were seen throughout the year, they were more common in winter months in some years; incidence varied considerably from year to year. Acute-phase serum was collected from 53 (68%) of 78

two with detectable B19 DNA and six with de¬ tectable anti-B19 parvovirus IgM antibodies, underwent subsequent determination of the presence of DNA and anti-B19 parvovirus IgM and IgG antibodies. The number of follow-up samples tested ranged between one and four per patient. However, Table 2 shows the results of the first and the last samples collected from each patient and dem¬ onstrates disappearance of B19 parvovirus DNA/viral particles and anti-B19 parvovirus IgM antibodies and ap¬ pearance and/or persistence of anti-B19 parvovirus IgG antibodies. One patient who had B19 parvoviremia with¬ out anti-B19 parvovirus IgM and IgG antibodies at diag¬ nosis had anti-B19 parvovirus IgM and IgG antibodies 2 months later. The longest interval between the serologie studies was 43 months; in this patient, anti-B19 parvovi¬ rus IgG antibodies were still detectable.

infection,

Table 1.—Results of Serologie Tests for B19 Parvovirus in Patients With Sickle Cell Disease and TAC* No. of

No. of Patients With B19 DNA/Viral

Patients Tested

Particles

1984

5

3

0

3

1985

NA

2

0

2

1986

14

11

1

6

1987

16

9

3

8

1988

5

2

2

1

1989

18

13

2

6

1990

20

13

3

Year

Detectable Levels of Anti-B19 IgM Antibodies

2.—Follow-up Serologie Data for Patients With Sickle Cell Initial Data B19

Patient No.

DNA/Viral Particles

Level of Anti-B19

IgM Antibodies,

ND

>100

ND

>100

Positive ND

Positive

>100 1.5

34 (68) serum

indicated acute infection.

Disease and Proven Parvovirus B19 Infection*

Follow-up Data Level of Anti-B19

IgG Antibodies, RIA U

B19 DNA/ Viral Particles

Level of Anti-B19

Level of Anti-B19

IgM Antibodies,

IgG Antibodies,

Interval Between

RIA U

Specimens, mo

RIA U

ND

100

26

ND

100

22

ND

100

33

ND

Transient aplastic crisis in patients with sickle cell disease. B19 parvovirus studies during a 7-year period.

To determine (1) the proportion of cases of transient aplastic crisis (TAC) in patients with sickle cell disease due to B19 parvovirus infection in se...
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