Subscribe to RSS
DOI: 10.1160/TH07-05-0340
Possible contribution of cytomegalovirus infection to the high risk of (recurrent) venous thrombosis after renal transplantation
Correspondence to:
Publication History
Received:
10 May 2007
Accepted after major revision:
11 November 2007
Publication Date:
24 November 2017 (online)
Summary
Renal transplant recipients are at an increased risk of venous thrombosis, which has been regarded as a postoperative complication, although it may persist afterwards. As numerous case reports have shown that active cytomegalovirus (CMV) infection can be found at time of onset of venous thrombosis, and is frequently found in renal transplant recipients, we hypothesized that one might be the result of the other. To calculate the risk of (recurrent) venous thrombosis in renal transplant recipients, and to see whether CMV infection influenced this risk, we retrospectively analysed 606 living consecutive renal transplant recipients. CMV status at time of transplantation and at time of enrolment was determined. Absolute risks of first venous thrombosis and recurrence were compared with CMV status, and were corrected for surgery related venous thrombosis, age, and anticoagulant treatment. Annual incidence of venous thrombosis was 0.88% (95% CI, 0.65–1.15) in all recipients and 0.59% (95% CI,0.41–0.83) corrected for surgery related venous thrombosis. CMV positive and seroconverted recipients tended to have an increased risk of venous thrombosis compared to CMV negative recipients; corrected relative risks were 2.0 (95% CI, 0.9–5.2) and 1.7 (95% CI, 0.6–4.7), respectively. The cumulative 10-year recurrence rate of venous thrombosis in CMV seronegative, seroconverted, and seropositive recipients was 10%,51% and 59%, respectively. We conclude that CMV infection tended to be associated with an increased risk of (recurrent) venous thrombosis. Prospective studies are warranted to establish this observation, which suggests that CMV infection influences the high risk of (recurrent) venous thrombosis in renal transplant recipients.
#
Keywords
Renal transplant recipients - cytomegalovirus - venous thrombosis - recurrent venous thrombosis
#
-
References
- 1 Humar A, Johnson EM, Gillingham KJ. et al. Venous thromboembolic complications after kidney and kidney-pancreas transplantation: a multivariate analysis. Transplantation 1998; 65: 229-234.
- 2 Poli D, Zanazzi M, Antonucci E. et al. Renal transplant recipients are at high risk for both symptomatic and asymptomatic deep vein thrombosis. J Thromb Haemost 2006; 4: 988-992.
- 3 Poli D, Zanazzi M, Antonucci E. et al. High rate of recurrence in renal transplant recipients after a first episode of venous thromboembolism. Transplantation 2005; 80: 789-793.
- 4 Patrassi GM, Sartori MT, Rigotti P. et al. Reduced fibrinolytic potential one year after kidney transplantation. Relationship to long-term steroid treatment. Transplantation 1995; 59: 1416-1420.
- 5 Ducloux D, Pellet E, Fournier V. et al. Prevalence and clinical significance of antiphospholipid antibodies in renal transplant recipients. Transplantation 1999; 67: 90-93.
- 6 Kazory A, Ducloux D, Coaquette A. et al. Cytomegalovirus- associated venous thromboembolism in renal transplant recipients: a report of 7 cases. Transplantation 2004; 77: 597-599.
- 7 Rowshani AT, Bemelman FJ, van Leeuwen EM. et al. Clinical and immunologic aspects of cytomegalovirus infection in solid organ transplant recipients. Transplantation 2005; 79: 381-386.
- 8 Span AH, van Dam-Mieras MC, Mullers W. et al. The effect of virus infection on the adherence of leukocytes or platelets to endothelial cells. Eur J Clin Invest 1991; 21: 331-338.
- 9 Grefte A, van der Giessen M, van Son W. et al. Circulating cytomegalovirus (CMV)-infected endothelial cells in patients with an active CMV infection. J Infect Dis 1993; 167: 270-277.
- 10 Uthman IW, Gharavi AE. Viral infections and antiphospholipid antibodies. Semin Arthritis Rheum 2002; 31: 256-263.
- 11 Schambeck CM, Hinney K, Gleixner J. et al. Venous thromboembolism and associated high plasma factor VIII levels: linked to cytomegalovirus infection?. Thromb Haemost 2000; 83: 510-511.
- 12 The TH, Kas-Deelen AM, de Maar EF. et al. Cellular and humoral parameters for vascular damage in blood during cytomegalovirus infections. Transplant Proc 2001; 33: 1813.
- 13 Lebranchu Y, al Najjar A, Kapahi P. et al. The association of increased soluble VCAM-1 levels with CMV disease in human kidney allograft recipients. Transplant Proc 1995; 27: 960.
- 14 Gonzalez-Ordonez AJ, Fernandez-Carreira JM, Fernandez-Alvarez CR. et al. The concentrations of soluble vascular cell adhesion molecule-1 and lipids are independently associated with venous thromboembolism. Haematologica 2003; 88: 1035-1043.
- 15 Bank I, Libourel EJ, Middeldorp S. et al. Elevated levels of FVIII:C within families are associated with an increased risk for venous and arterial thrombosis. J Thromb Haemost 2005; 3: 79-84.
- 16 Galli M, Luciani D, Bertolini G. et al. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 2003; 101: 1827-1832.
- 17 Abgueguen P, Delbos V, Chennebault JM. et al. Vascular thrombosis and acute cytomegalovirus infection in immunocompetent patients: report of 2 cases and literature review. Clin Infect Dis 2003; 36: E134-139.
- 18 Squizzato A, Gerdes VE, Buller HR. Effects of human cytomegalovirus infection on the coagulation system. Thromb Haemost 2005; 93: 403-410.
- 19 Grattan MT, Moreno-Cabral CE, Starnes VA. et al. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. J Am Med Assoc 1989; 261: 3561-3566.
- 20 Van der Giessen M, van den Berg AP, van der Bij W. et al. Quantitative measurement of cytomegalovirusspecific IgG and IgM antibodies in relation to cytomegalovirus antigenaemia and disease activity in kidney recipients with an active cytomegalovirus infection. Clin Exp Immunol 1990; 80: 56-61.
- 21 Silverstein MD, Heit JA, Mohr DN. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158: 585-593.
- 22 White RH, Romano PS, Zhou H. et al. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998; 158: 1525-1531.
- 23 Abbott KC, Cruess DF, Agodoa LY. et al. Early renal insufficiency and late venous thromboembolism after renal transplantation in the United States. Am J Kidney Dis 2004; 43: 120-130.
- 24 Kreis HA, Ponticelli C. Causes of late renal allograft loss: chronic allograft dysfunction, death, and other factors. Transplantation 2001; 71: SS5-9.
- 25 Kas-Deelen AM, Harmsen MC, de Maar EF. et al. Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood. Kidney Int 2000; 58: 2533-2542.
- 26 Gouarin S, Vabret A, Gault E. et al. Quantitative analysis of HCMV DNA load in whole blood of renal transplant patients using real-time PCR assay. J Clin Virol 2004; 29: 194-201.
- 27 Heit JA, Mohr DN, Silverstein MD. et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 2000; 160: 761-768.
- 28 van den Belt AG, Sanson BJ, Simioni P. et al. Recurrence of venous thromboembolism in patients with familial thrombophilia. Arch Intern Med 1997; 157: 2227-2232.
- 29 Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353: 1167-1173.
- 30 Christiansen SC, Cannegieter SC, Koster T. et al. Thrombophilia, clinical factors, and recurrent venous thrombotic events. J Am Med Assoc 2005; 293: 2352-61.
Correspondence to:
-
References
- 1 Humar A, Johnson EM, Gillingham KJ. et al. Venous thromboembolic complications after kidney and kidney-pancreas transplantation: a multivariate analysis. Transplantation 1998; 65: 229-234.
- 2 Poli D, Zanazzi M, Antonucci E. et al. Renal transplant recipients are at high risk for both symptomatic and asymptomatic deep vein thrombosis. J Thromb Haemost 2006; 4: 988-992.
- 3 Poli D, Zanazzi M, Antonucci E. et al. High rate of recurrence in renal transplant recipients after a first episode of venous thromboembolism. Transplantation 2005; 80: 789-793.
- 4 Patrassi GM, Sartori MT, Rigotti P. et al. Reduced fibrinolytic potential one year after kidney transplantation. Relationship to long-term steroid treatment. Transplantation 1995; 59: 1416-1420.
- 5 Ducloux D, Pellet E, Fournier V. et al. Prevalence and clinical significance of antiphospholipid antibodies in renal transplant recipients. Transplantation 1999; 67: 90-93.
- 6 Kazory A, Ducloux D, Coaquette A. et al. Cytomegalovirus- associated venous thromboembolism in renal transplant recipients: a report of 7 cases. Transplantation 2004; 77: 597-599.
- 7 Rowshani AT, Bemelman FJ, van Leeuwen EM. et al. Clinical and immunologic aspects of cytomegalovirus infection in solid organ transplant recipients. Transplantation 2005; 79: 381-386.
- 8 Span AH, van Dam-Mieras MC, Mullers W. et al. The effect of virus infection on the adherence of leukocytes or platelets to endothelial cells. Eur J Clin Invest 1991; 21: 331-338.
- 9 Grefte A, van der Giessen M, van Son W. et al. Circulating cytomegalovirus (CMV)-infected endothelial cells in patients with an active CMV infection. J Infect Dis 1993; 167: 270-277.
- 10 Uthman IW, Gharavi AE. Viral infections and antiphospholipid antibodies. Semin Arthritis Rheum 2002; 31: 256-263.
- 11 Schambeck CM, Hinney K, Gleixner J. et al. Venous thromboembolism and associated high plasma factor VIII levels: linked to cytomegalovirus infection?. Thromb Haemost 2000; 83: 510-511.
- 12 The TH, Kas-Deelen AM, de Maar EF. et al. Cellular and humoral parameters for vascular damage in blood during cytomegalovirus infections. Transplant Proc 2001; 33: 1813.
- 13 Lebranchu Y, al Najjar A, Kapahi P. et al. The association of increased soluble VCAM-1 levels with CMV disease in human kidney allograft recipients. Transplant Proc 1995; 27: 960.
- 14 Gonzalez-Ordonez AJ, Fernandez-Carreira JM, Fernandez-Alvarez CR. et al. The concentrations of soluble vascular cell adhesion molecule-1 and lipids are independently associated with venous thromboembolism. Haematologica 2003; 88: 1035-1043.
- 15 Bank I, Libourel EJ, Middeldorp S. et al. Elevated levels of FVIII:C within families are associated with an increased risk for venous and arterial thrombosis. J Thromb Haemost 2005; 3: 79-84.
- 16 Galli M, Luciani D, Bertolini G. et al. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 2003; 101: 1827-1832.
- 17 Abgueguen P, Delbos V, Chennebault JM. et al. Vascular thrombosis and acute cytomegalovirus infection in immunocompetent patients: report of 2 cases and literature review. Clin Infect Dis 2003; 36: E134-139.
- 18 Squizzato A, Gerdes VE, Buller HR. Effects of human cytomegalovirus infection on the coagulation system. Thromb Haemost 2005; 93: 403-410.
- 19 Grattan MT, Moreno-Cabral CE, Starnes VA. et al. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. J Am Med Assoc 1989; 261: 3561-3566.
- 20 Van der Giessen M, van den Berg AP, van der Bij W. et al. Quantitative measurement of cytomegalovirusspecific IgG and IgM antibodies in relation to cytomegalovirus antigenaemia and disease activity in kidney recipients with an active cytomegalovirus infection. Clin Exp Immunol 1990; 80: 56-61.
- 21 Silverstein MD, Heit JA, Mohr DN. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158: 585-593.
- 22 White RH, Romano PS, Zhou H. et al. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998; 158: 1525-1531.
- 23 Abbott KC, Cruess DF, Agodoa LY. et al. Early renal insufficiency and late venous thromboembolism after renal transplantation in the United States. Am J Kidney Dis 2004; 43: 120-130.
- 24 Kreis HA, Ponticelli C. Causes of late renal allograft loss: chronic allograft dysfunction, death, and other factors. Transplantation 2001; 71: SS5-9.
- 25 Kas-Deelen AM, Harmsen MC, de Maar EF. et al. Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood. Kidney Int 2000; 58: 2533-2542.
- 26 Gouarin S, Vabret A, Gault E. et al. Quantitative analysis of HCMV DNA load in whole blood of renal transplant patients using real-time PCR assay. J Clin Virol 2004; 29: 194-201.
- 27 Heit JA, Mohr DN, Silverstein MD. et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 2000; 160: 761-768.
- 28 van den Belt AG, Sanson BJ, Simioni P. et al. Recurrence of venous thromboembolism in patients with familial thrombophilia. Arch Intern Med 1997; 157: 2227-2232.
- 29 Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353: 1167-1173.
- 30 Christiansen SC, Cannegieter SC, Koster T. et al. Thrombophilia, clinical factors, and recurrent venous thrombotic events. J Am Med Assoc 2005; 293: 2352-61.