Download PDF
J Pediatr Infect Dis 2019; 14(04): 161-167
DOI: 10.1055/s-0039-1679883
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Cytomegalovirus Has No Impact on Immune Thrombocytopenia Bleeding Scale or Prognostic Outcomes in Egyptian Pediatric Immune Thrombocytopenia

Galila Mokhtar
1   Department of Pediatrics, Hematology-Oncology Unit, Children Hospital, Ain Shams University, Cairo, Egypt
,
Iman Ragab
1   Department of Pediatrics, Hematology-Oncology Unit, Children Hospital, Ain Shams University, Cairo, Egypt
,
Salwa Bakr 
2   Department of Clinical Pathology/Hematology, College of Medicine, Fayoum University, Fayoum, Egypt
,
Ahmed Afifi
1   Department of Pediatrics, Hematology-Oncology Unit, Children Hospital, Ain Shams University, Cairo, Egypt
› Author Affiliations
Further Information

Publication History

14 September 2018

18 January 2019

Publication Date:
14 March 2019 (online)

Also available at
    Permissions and Reprints

Abstract

Background Cytomegalovirus (CMV) has been implicated as one of the etiological factors of immune thrombocytopenia (ITP) in many reports.

Objectives We aimed to estimate the frequency of CMV positivity among childhood ITP patients, and to assess its impact on severity of bleeding, chronicity of the disease, and response to therapy.

Methods A cross-sectional study was performed including 40 Egyptian pediatric patients with ITP. CMV infection was detected by serological testing and polymerase chain reaction (PCR). Clinical assessment for bleeding severity using ITP bleeding scale (IBLS) and initial response to therapy were included in the study.

Results The prevalence of CMV DNAemia among the ITP patients was 72.5%. The virus DNAemia was higher among newly diagnosed ITP cases compared with chronic ones (85 and 60% respectively, p = 0.07). There were no significant differences in age, gender, bleeding severity, or initial clinical presentation in patients who were CMV-PCR positive or negative (p > 0.05). Refractory cases were found in 17.2% of CMV-positive cases compared with 36.4% in CMV-negative ones (p = 0.29). Specificity and sensitivity of serological assay in comparison to PCR were 72.4% and 20.69%, respectively, with a negative predictive value of 25.8%, and a positive predictive value of 66.7%.

Conclusion Cytomegalovirus appears to have a high frequency among both newly diagnosed and chronic ITP patients in Egypt. CMV serological assay for IgM was not a good indicator of the presence of viral infection. CMV DNAemia seems to have no significant effect on severity of bleeding, clinical presentation, or outcomes of childhood ITP.

Keywords

thrombocytopenia - immune - cytomegalovirus - PCR

Note

The abstract of this case report was accepted as poster presentation in European Hematology Association annual congress, June 2014, Italy.


 

  • References

  • 1 George JN, Woolf SH, Raskob GE. , et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996; 88 (01) 3-40
    CrossrefPubMedSearch in Google Scholar
  • 2 Kistangari G, McCrae KR. Immune thrombocytopenia. Hematol Oncol Clin North Am 2013; 27 (03) 495-520
    CrossrefPubMedSearch in Google Scholar
  • 3 Lilleyman JS. Management of childhood idiopathic thrombocytopenic purpura. Br J Haematol 1999; 105 (04) 871-875
    CrossrefPubMedSearch in Google Scholar
  • 4 Kühne T, Imbach P, Bolton-Maggs PH, Berchtold W, Blanchette V, Buchanan GR. ; Intercontinental Childhood ITP Study Group. Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study. Lancet 2001; 358 (9299): 2122-2125
    CrossrefPubMedSearch in Google Scholar
  • 5 Scholz M, Doerr HW, Cinatl J. Human cytomegalovirus retinitis: pathogenicity, immune evasion and persistence. Trends Microbiol 2003; 11 (04) 171-178
    CrossrefPubMedSearch in Google Scholar
  • 6 Redwan NA, Ahmed MM, Awfi MA. Prevalence study of cytomegalovirus (CMV) infection among foreign manpower in Jeddah Saudi Arabia. Afr J Microbiol Res 2011; 5 (17) 2539-2549
    PubMedSearch in Google Scholar
  • 7 Gandhi MK, Khanna R. Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis 2004; 4 (12) 725-738
    CrossrefPubMedSearch in Google Scholar
  • 8 Wei SH, Ho MC, Ni YH, Lin DT, Lee PH. Cytomegalovirus-associated immune thrombocytopenic purpura after liver transplantation. J Formos Med Assoc 2007; 106 (04) 327-329
    CrossrefPubMedSearch in Google Scholar
  • 9 Flores-Chang BS, Arias-Morales CE, Wadskier FG, Gupta S, Stoicea N. Immune thrombocytopenic purpura secondary to cytomegalovirus infection: a case report. Front Med (Lausanne) 2015; 2: 79
    PubMedSearch in Google Scholar
  • 10 Shimanovsky A, Patel D, Wasser J. Refractory immune thrombocytopenic purpura and cytomegalovirus infection: a call for a change in the current guidelines. Mediterr J Hematol Infect Dis 2016; 8 (01) e2016010
    CrossrefPubMedSearch in Google Scholar
  • 11 Levy AS, Bussel J. Immune thrombocytopenic purpura: investigation of the role of cytomegalovirus infection. Br J Haematol 2004; 126 (04) 622-623
    CrossrefPubMedSearch in Google Scholar
  • 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 (02) 487-493
    CrossrefPubMedSearch in Google Scholar
  • 13 Jin MJ, Kim Y, Choi EM. , et al. Clinical characteristics and treatment courses for cytomegalovirus-associated thrombocytopenia in immunocompetent children after neonatal period. Blood Res 2018; 53 (02) 110-116
    CrossrefPubMedSearch in Google Scholar
  • 14 Sheng Yu Z, Tang LF, Zou CC, Yan Zheng J, Zhao ZY. Cytomegalovirus-associated idiopathic thrombocytopenic purpura in Chinese children. Scand J Infect Dis 2008; 40 (11–11): 922-927
    CrossrefPubMedSearch in Google Scholar
  • 15 DiMaggio D, Anderson A, Bussel JB. Cytomegalovirus can make immune thrombocytopenic purpura refractory. Br J Haematol 2009; 146 (01) 104-112
    CrossrefPubMedSearch in Google Scholar
  • 16 Alliot C, Barrios M. Cytomegalovirus-induced thrombocytopenia in an immunocompetent adult effectively treated with intravenous immunoglobulin: a case report and review. Hematology 2005; 10 (04) 277-279
    CrossrefPubMedSearch in Google Scholar
  • 17 Smalisz-Skrzypczyk K, Romiszewski M, Matysiak M, Demkow U, Pawelec K. The influence of primary cytomegalovirus or Epstein-Barr virus infection on the course of idiopathic thrombocytopenic purpura. Adv Exp Med Biol 2015; 83-88
    PubMedSearch in Google Scholar
  • 18 Elalfy MS, Ragab I, Reda M. , et al. The impact of cytomegalovirus (CMV) reactivation on clinical course and immunomodulatory effect in children with immune-thrombocytopenia (ITP). Blood 2017; 130: 1045
    PubMedSearch in Google Scholar
  • 19 Kuwana M, Okazaki Y, Satoh T, Asahi A, Kajihara M, Ikeda Y. Initial laboratory findings useful for predicting the diagnosis of idiopathic thrombocytopenic purpura. Am J Med 2005; 118 (09) 1026-1033
    CrossrefPubMedSearch in Google Scholar
  • 20 Rodeghiero F, Stasi R, Gernsheimer T. , et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113 (11) 2386-2393
    CrossrefPubMedSearch in Google Scholar
  • 21 Edslev PW, Rosthøj S, Treutiger I, Rajantie J, Zeller B, Jonsson OG. ; NOPHO ITP Working Group. A clinical score predicting a brief and uneventful course of newly diagnosed idiopathic thrombocytopenic purpura in children. Br J Haematol 2007; 138 (04) 513-516
    CrossrefPubMedSearch in Google Scholar
  • 22 Bate SL, Dollard SC, Cannon MJ. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988-2004. Clin Infect Dis 2010; 50 (11) 1439-1447
    CrossrefPubMedSearch in Google Scholar
  • 23 Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol 2010; 20 (04) 202-213
    CrossrefPubMedSearch in Google Scholar
  • 24 Xiao Y, Lin W, Liu Q, Jin RM, Fei HB. Clinical study of human cytomegalovirus infection in colony forming unit-megakaryocyte in patients with idiopathic thrombocytopenic purpura [article in Chinese]. Zhonghua Er Ke Za Zhi 2006; 44 (05) 346-349
    PubMedSearch in Google Scholar
  • 25 Yenicesu I, Yetgin S, Ozyürek E, Aslan D. Virus-associated immune thrombocytopenic purpura in childhood. Pediatr Hematol Oncol 2002; 19 (06) 433-437
    CrossrefPubMedSearch in Google Scholar
  • 26 Lisboa LF, Åsberg A, Kumar D. , et al. The clinical utility of whole blood versus plasma cytomegalovirus viral load assays for monitoring therapeutic response. Transplantation 2011; 91 (02) 231-236
    CrossrefPubMedSearch in Google Scholar
  • 27 Watts RG. Idiopathic thrombocytopenic purpura: a 10-year natural history study at the childrens hospital of Alabama. Clin Pediatr (Phila) 2004; 43 (08) 691-702
    CrossrefPubMedSearch in Google Scholar
  • 28 Ding Y, Zhao L, Mei H, Zhang SL, Huang ZH. Role of myeloid human cytomegalovirus infection in children's idiopathic thrombocytopenic purpura. Pediatr Hematol Oncol 2007; 24 (03) 179-188
    CrossrefPubMedSearch in Google Scholar
  • 29 Cook CH. Cytomegalovirus reactivation in “immunocompetent” patients: a call for scientific prophylaxis. J Infect Dis 2007; 196 (09) 1273-1275
    CrossrefPubMedSearch in Google Scholar
  • 30 Hilal T. Fatal cytomegalovirus disease after combination therapy with corticosteroids and rituximab for granulomatosis with polyangiitis. Case Rep Rheumatol 2015; 2015: 538137
    PubMedSearch in Google Scholar
  • 31 Nishio Y, Kawano Y, Kawada JI, Ito Y, Hara S. A case of refractory cytomegalovirus-related thrombocytopenia that achieved complete remission without antiviral therapy. J Infect Chemother 2018; 24 (12) 995-997
    CrossrefPubMedSearch in Google Scholar
  • 32 Wu Z, Zhou J, Wei X. , et al. The role of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) in immune thrombocytopenia. Hematology 2013; 18 (05) 295-299
    CrossrefPubMedSearch in Google Scholar
  • 33 Shrestha R, Rondelli D, Sherpa MT. Cytomegalovirus: a possible cause of persistent refractory immune thrombocytopenic purpura. J Adv Intern Med 2014; 3: 42-45
    CrossrefPubMedSearch in Google Scholar
  • 34 Arruda VR, Oliveira GB, Annichino-Bizzacchi JM, Durante P, Costa FF, Costa SC. CMV-DNA detection in patients with thrombocytopenia. Sao Paulo Med J 2002; 120 (02) 62
    CrossrefPubMedSearch in Google Scholar