Korean J Hematol.  2010 Mar;45(1):29-35. 10.5045/kjh.2010.45.1.29.

Clinical and radiologic evaluation of cytomegalovirus-induced thrombocytopenia in infants between 1 and 6 months of age

• Kang JW
• Kim GN
• Kim SY
• Kim HJ
• Park ES
• Kim JY
• Lee YH

• KMID: 2252082
• DOI: http://doi.org/10.5045/kjh.2010.45.1.29

Abstract

BACKGROUND
Up to 90% of neonates with congenital or perinatal cytomegalovirus (CMV) infection are asymptomatic, and little is known about CMV-associated thrombocytopenia after the neonatal period. We investigated the clinical findings of a series of infants diagnosed with CMV infection and thrombocytopenia.
METHODS
From July 2005 to July 2008, infants aged younger than 6 months with thrombocytopenia were screened for CMV infection, using CMV IgM. Those who were positive for CMV IgM were then tested for CMV IgG via polymerase chain reaction (PCR) for CMV and CMV pp65 Ag and urine culture. Brain magnetic resonance imaging (MRI) and otologic and ophthalmologic evaluations were also performed.
RESULTS
Twenty-one patients aged between 1 and 6 months (11 boys and 10 girls) were admitted and tested for CMV infection. Six patients (28.6%) were positive for CMV IgM; these were also positive for CMV IgG, CMV PCR, and urine culture, and 4 were also positive for CMV pp65 Ag. The median platelet count at admission was 6,500/microliter (range, 2,000-105,000/microliter). One patient (16.7%) was diagnosed with Evans syndrome and had calcifications on brain MRI. One patient had unilateral sensorineural hearing loss.
CONCLUSION
Thrombocytopenia can be the main clinical manifestation of otherwise asymptomatic CMV infection after the neonatal period, and close follow-up of neurodevelopmental sequelae is needed.

Keyword

Thrombocytopenia; Cytomegalovirus; Infant

MeSH Terms

Aged
Brain
Cytomegalovirus
Follow-Up Studies
Hearing
Humans
Immunoglobulin G
Immunoglobulin M
Infant
Infant, Newborn
Magnetic Resonance Imaging
Platelet Count
Polymerase Chain Reaction
Thrombocytopenia
Immunoglobulin G
Immunoglobulin M

Figure

• 

  Fig. 1 Patient 1 shows normal auditory brainstem response (ABR) on the right side (up to 25 dB) and minimal response on the left side.

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  Fig. 2 Brain MRI of Patient 2 shows multiple small nodular T1-high and gradient echo-dark signal intensity lesions in the right occipital lobe (arrow). This finding is compatible with a calcified inflammatory granuloma as a sequela of previous CMV infection. Also note the subdural effusion and right frontotemporal convexity (arrowheads).

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  Fig. 3 (A) Brain images of Patient 4 during the neonatal period. Red arrows point to the small nodular T2-weighted GRE-dark signal intensity lesion in the caudo-thalamic notch on the MRI scan (left) and left germinal matrix hemorrhage on brain sonogram (right). (B) Brain MRI scan of the patient obtained at the diagnosis of thrombocytopenia showed a small nodular T2-weighted axial GRE-(left) and coronal FSE (right)-dark signal intensity lesion in the caudo-thalamic notch (red arrows).

Reference

1. Aslam M, Anderson JL, Guglietti D, Cardwell D. CMV-induced neonatal thrombocytopenia: a case report and review of the literature. Am J Perinatol. 2007; 24:429–434. PMID: 17597443.

2. Romanelli RM, Magny JF, Jacquemard F. Prognostic markers of symptomatic congenital cytomegalovirus infection. Braz J Infect Dis. 2008; 12:38–43. PMID: 18553012.

3. Benoist G, Salomon LJ, Jacquemard F, Daffos F, Ville Y. The prognostic value of ultrasound abnormalities and biological parameters in blood of fetuses infected with cytomegalovirus. BJOG. 2008; 115:823–829. PMID: 18485159.

4. Malm G, Engman ML. Congenital cytomegalovirus infections. Semin Fetal Neonatal Med. 2007; 12:154–159. PMID: 17337260.

5. Ornoy A, Diav-Citrin O. Fetal effects of primary and secondary cytomegalovirus infection in pregnancy. Reprod Toxicol. 2006; 21:399–409. PMID: 16580941.

6. Rivera LB, Boppana SB, Fowler KB, Britt WJ, Stagno S, Pass RF. Predictors of hearing loss in children with symptomatic congenital cytomegalovirus infection. Pediatrics. 2002; 110:762–767. PMID: 12359792.

7. Walker A, Petheram SJ, Ballard L, Murph JR, Demmler GJ, Bale JF Jr. Characterization of human cytomegalovirus strains by analysis of short tandem repeat polymorphisms. J Clin Microbiol. 2001; 39:2219–2226. PMID: 11376060.

8. Lazzarotto T, Guerra B, Lanari M, Gabrielli L, Landini MP. New advances in the diagnosis of congenital cytomegalovirus infection. J Clin Virol. 2008; 41:192–197. PMID: 18054840.

9. Ahlfors K, Ivarsson SA, Harris S. Report on a long-term study of maternal and congenital cytomegalovirus infection in Sweden. Review of prospective studies available in the literature. Scand J Infect Dis. 1999; 31:443–457. PMID: 10576123.

10. Revello MG, Zavattoni M, Baldanti F, Sarasini A, Paolucci S, Gerna G. Diagnostic and prognostic value of human cytomegalovirus load and IgM antibody in blood of congenitally infected newborns. J Clin Virol. 1999; 14:57–66. PMID: 10548131.

11. Levy AS, Bussel J. Immune thrombocytopenic purpura: investigation of the role of cytomegalovirus infection. Br J Haematol. 2004; 126:622–623. PMID: 15287958.

12. Crapnell K, Zanjani ED, Chaudhuri A, Ascensao JL, St Jeor S, Maciejewski JP. In vitro infection of megakaryocytes and their precursors by human cytomegalovirus. Blood. 2000; 95:487–493. PMID: 10627453.

13. Toyoda M, Petrosian A, Jordan SC. Immunological characterization of anti-endothelial cell antibodies induced by cytomegalovirus infection. Transplantation. 1999; 68:1311–1318. PMID: 10573069.

14. Yenicesu I, Yetgin S, Ozyürek E, Aslan D. Virus-associated immune thrombocytopenic purpura in childhood. Pediatr Hematol Oncol. 2002; 19:433–437. PMID: 12186367.

15. Kylat RI, Kelly EN, Ford-Jones EL. Clinical findings and adverse outcome in neonates with symptomatic congenital cytomegalovirus (SCCMV) infection. Eur J Pediatr. 2006; 165:773–778. PMID: 16835757.

16. Dollard SC, Grosse SD, Ross DS. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol. 2007; 17:355–363. PMID: 17542052.

17. Grosse SD, Ross DS, Dollard SC. Congenital cytomegalovirus (CMV) infection as a cause of permanent bilateral hearing loss: a quantitative assessment. J Clin Virol. 2008; 41:57–62. PMID: 17959414.

18. Fowler KB, Dahle AJ, Boppana SB, Pass RF. Newborn hearing screening: will children with hearing loss caused by congenital cytomegalovirus infection be missed. J Pediatr. 1999; 135:60–64. PMID: 10393605.

19. Fowler KB, Stagno S, Pass RF. Maternal age and congenital cytomegalovirus infection: screening of two diverse newborn populations, 1980-1990. J Infect Dis. 1993; 168:552–556. PMID: 8394857.

20. Revello MG, Gerna G. Pathogenesis and prenatal diagnosis of human cytomegalovirus infection. J Clin Virol. 2004; 29:71–83. PMID: 14747024.

21. Gindes L, Teperberg-Oikawa M, Sherman D, Pardo J, Rahav G. Congenital cytomegalovirus infection following primary maternal infection in the third trimester. BJOG. 2008; 115:830–835. PMID: 18485160.

22. Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007; 17:253–276. PMID: 17579921.