Skip to main content

Advertisement

SpringerLink
Log in

Thrombosis following acute cytomegalovirus infection: a community prospective study

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Infection might be associated with increased risk of venous thromboembolism (VTE) and arterial thrombosis. Specific hypotheses have been raised regarding the procoagulant response induced by acute cytomegalovirus (CMV) infection. Accordingly, we investigated the 6-month incidence of VTE and/or arterial thrombosis in patients that had been tested positive for CMV-IgM antibodies in a large health maintenance organization. Logistic regression analysis was used to identify independent risk factors for VTE and arterial thrombosis. Among 90,515 patients eligible for the VTE analysis and 90,805 patients eligible for the arterial thrombosis analysis, 6,205 (6.9 %) and 6,222 (6.9 %) patients were tested positive for CMV-IgM antibodies, respectively. During 6 months of follow-up from index date, the incidence rates per 1,000 capita of VTE among CMV-IgM seropositive and CMV-IgM seronegative patients were 3.06 (19 patients) and 1.36 (115 patients), respectively (odds ratio (OR) 2.25; 95 % confidence intervals (95 % CI) 1.38–3.66; p = 0.003). CMV-IgM seropositivity was independently associated with VTE appearance (OR 2.49; 95 % CI 1.53–4.06; p < 0.0001) following adjustment for age, sex, and other confounders. The incidence rates per 1,000 capita of arterial thrombosis among CMV-IgM seropositive and CMV-IgM seronegative patients were 1.12 (7 patients) and 1.06 (90 patients), respectively (OR 1.06; 95 % CI 0.49–2.28; p = 0.840). CMV-IgM seropositivity was not associated with arterial thrombosis. We conclude that acute CMV infection might be associated with an increased short-term VTE risk. To the best of our knowledge, this is the largest study ever to confirm this association.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Smeeth L, Cook C, Thomas S, Hall AJ, Hubbard R, Vallance P (2006) Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting. Lancet 367:1075–1079

    Article  PubMed  Google Scholar 

  2. Justo D, Finn T, Atzmony L, Guy N, Steinvil A (2011) Thrombosis associated with acute cytomegalovirus infection: a meta-analysis. Eur J Intern Med 22:195–199

    Article  PubMed  Google Scholar 

  3. Fletcher R, Fletcher S (2005) Clinical epidemiology: the essentials. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  4. Amit S, Gadoth A, Giladi M, Justo D (2012) Transient ischemic attack associated with acute cytomegalovirus infection. J Med Virol 84:487–489

    Article  PubMed  Google Scholar 

  5. Madalosso C, de Souza NF, Jr IDM, Wiesner RH, Krom RA (1998) Cytomegalovirus and its association with hepatic artery thrombosis after liver transplantation. Transplantation 66:294–297

    Article  PubMed  CAS  Google Scholar 

  6. Atzmony L, Halutz O, Avidor B, Finn T, Zimmerman O, Steinvil A, Zeltser D, Giladi M, Justo D (2010) Incidence of cytomegalovirus-associated thrombosis and its risk factors: a case–control study. Thromb Res 126:e439–443

    Article  PubMed  CAS  Google Scholar 

  7. Schimanski S, Linnemann B, Luxembourg B, Seifried E, Jilg W, Lindhoff-Last E, Schambeck CM (2012) Cytomegalovirus infection is associated with venous thromboembolism of immunocompetent adults—a case–control study. Ann Hematol 91:597–604

    Article  PubMed  CAS  Google Scholar 

  8. Tichelaar VY, Sprenger HG, Mäkelburg AB, Niesters BG, Kluin-Nelemans HC, Lijfering WM (2011) Active cytomegalovirus infection in patients with acute venous thrombosis: a case–control study. Am J Hematol 86:510–512

    Article  PubMed  Google Scholar 

  9. Berkson J (1946) Limitations of the application of fourfold table analysis to hospital data. Biometrics 2:47–53

    Article  PubMed  CAS  Google Scholar 

  10. Chodick G, Heymann AD, Shalev V, Kookia E (2003) The epidemiology of diabetes in a large Israeli HMO. Eur J Epidemiol 18:1143–1146

    Article  PubMed  Google Scholar 

  11. Shalev V, Chodick G, Goren I, Silber H, Kokia E, Heymann AD (2011) The use of an automated patient registry to manage and monitor cardiovascular conditions and related outcomes in a large health organization. Int J Cardiol 152:345–349

    Article  PubMed  Google Scholar 

  12. Chodick G, Porath A, Alapi H, Sella T, Flash S, Wood F, Shalev V (2010) The direct medical cost of cardiovascular diseases, hypertension, diabetes, cancer, pregnancy and female infertility in a large HMO in Israel. Health Policy 95:271–276

    Article  PubMed  Google Scholar 

  13. Tsai AW, Cushman M, Rosamond WD, Heckbert SR, Polak JF, Folsom AR (2002) Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology. Arch Intern Med 162:1182–1189

    Article  PubMed  Google Scholar 

  14. Hansson PO, Welin L, Tibblin G, Eriksson H (1997) Deep vein thrombosis and pulmonary embolism in the general population. ‘The Study of Men Born in 1913’. Arch Intern Med 157:1665–1670

    Article  PubMed  CAS  Google Scholar 

  15. Anderson FA Jr, Wheeler HB, Goldberg RJ, Hosmer DW, Patwardhan NA, Jovanovic B, Forcier A, Dalen JE (1991) A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 151:933–338

    Article  PubMed  Google Scholar 

  16. Ageno W, Becattini C, Brighton T, Selby R, Kamphuisen PW (2008) Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation 117:93–102

    Article  PubMed  Google Scholar 

  17. Chiu B, Viira E, Tucker W, Fong IW (1997) Chlamydia pneumoniae, cytomegalovirus, and herpes simplex virus in atherosclerosis of the carotid artery. Circulation 96:2144–2148

    Article  PubMed  CAS  Google Scholar 

  18. Sutherland MR, Raynor CM, Leenknegt H, Wright JF, Pryzdial EL (1997) Coagulation initiated on herpesviruses. Proc Natl Acad Sci U S A 94:13510–13514

    Article  PubMed  CAS  Google Scholar 

  19. Van Dam-Mieras MC, Bruggeman CA, Muller AD, Debie WH, Zwaal RF (1987) Induction of endothelial cell procoagulant activity by cytomegalovirus infection. Thromb Res 47:69–75

    Article  PubMed  Google Scholar 

  20. Schambeck CM, Hinney K, Gleixner J, Keller F (2000) Venous thromboembolism and associated high plasma factor VIII levels: linked to cytomegalovirus infection? Thromb Haemost 83:510–511

    PubMed  CAS  Google Scholar 

  21. Popović M, Smiljanić K, Dobutović B, Syrovets T, Simmet T, Isenović ER (2012) Human cytomegalovirus infection and atherothrombosis. J Thromb Thrombolysis 33:160–172

    Article  PubMed  Google Scholar 

  22. Delbos V, Abgueguen P, Chennebault JM, Fanello S, Pichard E (2007) Acute cytomegalovirus infection and venous thrombosis: role of antiphospholipid antibodies. J Infect 54:e47–50

    Article  PubMed  CAS  Google Scholar 

  23. Miendje Deyi Y, Goubau P, Bodéus M (2000) False-positive IgM antibody tests for cytomegalovirus in patients with acute Epstein–Barr virus infection. Eur J Clin Microbiol Infect Dis 19:557–560

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Departments of Internal Medicine D and E, Sourasky Medical Center, Tel Aviv, Israel

    Yael Paran, Arie Steinvil, Ofer Zimmerman, Talya Finn, Shlomo Berliner & David Zeltser

  2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Yael Paran, Varda Shalev, Arie Steinvil, Dan Justo, Ofer Zimmerman, Talya Finn, Shlomo Berliner, David Zeltser & Gabriel Chodick

  3. Medical Division, Maccabi Healthcare Services, Tel Aviv, Israel

    Varda Shalev, Dahlia Weitzman, Raanan Raz & Gabriel Chodick

  4. Department of Internal Medicine E, Sheba Medical Center, Tel Hashomer, 52621, Israel

    Dan Justo

Authors
  1. Yael Paran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Varda Shalev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arie Steinvil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dan Justo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ofer Zimmerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Talya Finn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shlomo Berliner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David Zeltser
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dahlia Weitzman
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Raanan Raz
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gabriel Chodick
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dan Justo.

Additional information

Drs. Yael Paran and Varda Shalev contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paran, Y., Shalev, V., Steinvil, A. et al. Thrombosis following acute cytomegalovirus infection: a community prospective study. Ann Hematol 92, 969–974 (2013). https://doi.org/10.1007/s00277-013-1715-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-013-1715-3

Keywords

Search

Navigation