Parvovirus as a Cause of ITP?
Parvovirus as a Cause of ITP?
ABSTRACT & COMMENTARY
Synopsis: Parvovirus B-19 DNA was demonstrated in the bone marrow of six of 47 (13%) children with recently diagnosed acute idiopathic thrombocytopenic purpura (ITP) using a polymerase chain reaction technique (PCR).
Source: Heegaard ED, et al. Role of parvovirus B-19 infection in childhood idiopathic thrombocytopenic purpura. Acta Paediatr 1999;88:614-617.
Acute parvovirus b-19 infections may be accompanied by varying degrees of thrombocytopenia and reports in adults have associated idiopathic thrombocytopenic purpura (ITP) with laboratory findings suggestive of parvovirus infections. Heegaard and associates from Copenhagen studied children 6 months to 14 years of age with acute ITP admitted to hospitals in Denmark between April 1991 and October 1992. Bone marrow aspiration specimens obtained at the time of admission had been saved and were available for examination of the presence of intact DNA and subsequently for specific parvovirus DNA by PCR techniques. No serum samples were available from these patients. Specific parvovirus DNA was demonstrated in six of 47 bone marrow specimens. The six cases with demonstrable parvovirus DNA were severely thrombocytopenic. Three cases had a history of a preceding nonspecific illness, but none had erythema, a facial rash, or arthralgia findings characteristic of fifth disease. There was no difference in the seasonal onset of the parvovirus positive or negative cases. All six children were treated with either IV immunoglobulin or pulsed methylprednisolone therapy. Three responded within one to eight weeks but the other three children remained thrombocytopenic after six months. Three children were treated with immunoglobulin and had a short course of thrombocytopenia, while those treated with methylprednisolone had more protracted courses.
Comment by Howard A. Pearson, MD, FAAP
One of the characteristic features of childhood ITP is a frequent history of an antecedent infection. Almost all of these antecedent infections are nonspecific respiratory illnesses, although occasionally an association with a specific viral infection or immunizations is seen. There is almost always a one- to two-week delay between the infection and the onset of thrombocytopenia, and it is assumed that during this period, antiplatelet antibodies, triggered by the viral infection, are produced that coat platelets and lead to their rapid destruction. Unfortunately, assays for antiplatelet antibodies are of little value in the diagnosis of acute ITP of children.
Parvovirus B-19 is known to have a high affinity for bone marrow erythroid progenitor cells and most of the parvovirus-related hematological syndromes are associated with aregenerative anemias; however, there have been a few reports that seem to implicate parvovirus in cases of ITP. The most striking of these reports by Murray and associates found evidence of parvovirus DNA in nearly 60% of cases of acute ITP studied in Houston during a local epidemic of clinical parvovirus B-19 infections.1 In both the Heegaard and Murray studies, bone marrows were assayed for the presence of parvovirus DNA using PCR techniques. This method is notoriously hypersensitive. Presumably as little as one DNA molecule could be recognized because of the enormous DNA amplification of PCR. Notable in both studies was the lack of non-ITP controls, although it is recognized that it would be virtually impossible to obtain a large number of control bone marrow specimens from normal children. Until the PCR data are confirmed by other means, including appropriate acute and convalescent serology, I believe the possible etiological role of parvovirus B-19 in a significant number of cases of acute ITP remains unproven. Despite the small numbers of patients studied, the fact that immunologlobulin therapy, which is effective therapy in other parvovirus-related hematologic diseases, was associated with better outcome of acute ITP is provocative. (Dr. Pearson is Professor of Pediatrics, Yale University School of Medicine.)
Reference
1. Murray JC, et al. Childhood idiopathic thrombocytopenic purpura: Association with human parvovirus B19 infection. Am J Pediatr Hematol Oncol 1994; 16:314-319.
Parvovirus B-19 infections:
a. have been consistently proven to be the etiologic factor in most cases of acute ITP in children.
b. have caused a recognized exanthem in cases who subsequently had marrow parvovirus DNA demonstrated by PCR.
c. may be overdiagnosed in ITP bone marrow because of the sensitivity of PCR analysis.
d. affect primarily the nonerythroid bone marrow precursor cells.
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