Immune thrombocytopenic purpura: investigation of the role of cytomegalovirus infection
Article first published online: 5 JUL 2004
British Journal of Haematology
Volume 126, Issue 4, pages 622–623, August 2004
How to Cite
Levy, A. S. and Bussel, J. (2004), Immune thrombocytopenic purpura: investigation of the role of cytomegalovirus infection. British Journal of Haematology, 126: 622–623. doi: 10.1111/j.1365-2141.2004.05068.x
- Issue published online: 9 JUL 2004
- Article first published online: 5 JUL 2004
- immune thrombocytopenic purpura;
- shell vial assay
There are several reports of thrombocytopenia temporally associated with cytomegalovirus (CMV) infection in both immunocompetent and immunosuppressed patients (Crapnell et al, 2000; Yenicesu et al, 2002). While these anecdotal and brief reports raise the question of CMV causing immune thrombocytopenic purpura (ITP), the role of CMV infection in typical acute, self-limited or persistent ITP in children and adults remains unclear.
There are several theoretical reasons why CMV infection may cause thrombocytopenia: direct cytotoxicity of CMV to haematopoietic cells; immune-mediated destruction of infected cells; or impairment of bone marrow stromal function by CMV (Crapnell et al, 2000). It is also possible that CMV infection induces non-specific autoantibodies that somehow result in antibody-mediated destruction of platelets (Toyoda et al, 1999). It has been shown that human CMV can infect megakaryocytes and their precursors in vitro, suggesting that infection of haematopoietic progenitor cells in vivo may contribute to thrombocytopenia in patients with CMV infection (Crapnell et al, 2000). In a study of CMV infection in a primate model, one of eight subjects exhibited marked thrombocytopenia that was also associated with transient leucocytosis (Lockridge et al, 1999).
To investigate the association between CMV infection and thrombocytopenia, we screened a series of 80 adult and 28 paediatric patients who presented to the Platelet Disorders Center of the New York Presbyterian Hospital–Weill Medical College of Cornell University for the management and evaluation of thrombocytopenia. All patients attending the centre with a diagnosis of ITP were screened during a 6-month period in 1999. Urine was tested for CMV by shell vial assay.
Of the 28 paediatric patients presenting with thrombocytopenia, three (11%) were positive for CMV in the urine by shell vial assay. Of these, two patients were diagnosed as having ‘routine’ ITP and one patient had Evan's syndrome. All were human immunodeficiency virus (HIV) negative.
Of the 80 adult patients, three (4%) were CMV positive in the urine. Two of these patients were HIV positive with ITP. One patient had chronic ITP and an abnormally decreased lymphoproliferative response to phytohaemagglutinin.
The mean nadir platelet count for patients who tested positive for CMV at any time was 12·4 × 109/l compared with 14·7 × 109/l for patients that were never positive for CMV (P = 0·799). There were no statistically significant differences in other blood cell indices between CMV-positive and -negative patients. There was no statistically significant difference between clinical course based on CMV status.
We screened a total of 108 patients who presented to clinic with thrombocytopenia for CMV infection by performing shell vial assays on urine samples. Shell vial assay for the detection of CMV has been shown to be more reliable than serological testing in immunocompromised subjects and neonates (Weber et al, 1992), and more sensitive in asymptomatic patients and patients receiving antiviral therapy (Manez et al, 1994).
Based on our findings, CMV infection does not appear to be involved with routine ITP. Of 108 patients, only six had CMV-positive urine results. While HIV+ patients with thrombocytopenia have improved platelet counts when HIV viral load is controlled, there were no similar findings with regard to CMV. There was no apparent correlation between CMV clearance and resolution of thrombocytopenia. The patients who did not receive anti-viral therapy still cleared the CMV.
While we did not have a control group of patients who were screened for CMV, based on the historical understanding of CMV infection and detection, it seems unlikely that CMV infection is a common cause of profound thrombocytopenia. It does not, therefore, seem merited to routinely test patients with otherwise typical ITP for CMV infection. However, screening of highly refractory patients still remains as a possible strategy, and exploration of immune function of patients infected with CMV may be appropriate.
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