Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV

Laura W. Musselwhite, Virginia Sheikh, Thomas D. Norton, Adam Rupert, Brian O. Porter, Scott Robert Penzak, Jeff Skinner, Joann M. Mican, Colleen Hadigan, Irini Sereti

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: HIV infection is associated with coagulation abnormalities and significantly increased risk of venous thrombosis. It has been shown that higher plasma levels of coagulation and inflammatory biomarkers predicted mortality in HIV. We investigated the relationship between venous thrombosis and HIV-related characteristics, traditional risk factors of hypercoagulability, and pre-event levels of biomarkers. DESIGN: A retrospective case-control study of 23 HIV-infected individuals who experienced an incident venous thromboembolic event while enrolled in National Institutes of Health studies from 1995 to 2010 and 69 age-matched and sex-matched HIV-infected individuals without known venous thromboembolism (VTE). METHODS: Biomarkers of inflammation, endothelial dysfunction, coagulation, tissue fibrosis, and cytomegalovirus (CMV) reactivation were assessed by ELISA-based assays and PCR using plasma obtained prior to the event. RESULTS: VTE events were related to nadir CD4 cell count, lifetime history of multiple opportunistic infections, CMV disease, CMV viremia, immunological AIDS, active infection, and provocation (i.e., recent hospitalization, surgery, or trauma). VTE events were independently associated with increased plasma levels of P-selectin (P = 0.002), D-dimer (P = 0.01), and hyaluronic acid (P = 0.009) in a multivariate analysis. No significant differences in antiretroviral or interleukin-2 exposures, plasma HIV viremia, or other traditional risk factors were observed. CONCLUSION: Severe immunodeficiency, active infection, and provocation are associated with venous thromboembolic disease in HIV. Biomarkers of endothelial dysfunction, coagulation, and tissue fibrosis may help identify HIV-infected patients at elevated risk of VTE.

Original languageEnglish
Pages (from-to)787-795
Number of pages9
JournalAIDS
Volume25
Issue number6
DOIs
StatePublished - 27 Mar 2011

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Venous Thromboembolism
Fibrosis
HIV
Biomarkers
Cytomegalovirus
Viremia
Venous Thrombosis
P-Selectin
Thrombophilia
Opportunistic Infections
National Institutes of Health (U.S.)
Hyaluronic Acid
CD4 Lymphocyte Count
Infection
HIV Infections
Interleukin-2
Case-Control Studies
Acquired Immunodeficiency Syndrome
Hospitalization
Multivariate Analysis

Keywords

  • HIV
  • P-selectin
  • blood coagulation factors
  • fibrosis
  • hyaluronic acid
  • venous thrombosis

Cite this

Musselwhite, L. W., Sheikh, V., Norton, T. D., Rupert, A., Porter, B. O., Penzak, S. R., ... Sereti, I. (2011). Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV. AIDS, 25(6), 787-795. https://doi.org/10.1097/QAD.0b013e3283453fcb
Musselwhite, Laura W. ; Sheikh, Virginia ; Norton, Thomas D. ; Rupert, Adam ; Porter, Brian O. ; Penzak, Scott Robert ; Skinner, Jeff ; Mican, Joann M. ; Hadigan, Colleen ; Sereti, Irini. / Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV. In: AIDS. 2011 ; Vol. 25, No. 6. pp. 787-795.
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abstract = "OBJECTIVE: HIV infection is associated with coagulation abnormalities and significantly increased risk of venous thrombosis. It has been shown that higher plasma levels of coagulation and inflammatory biomarkers predicted mortality in HIV. We investigated the relationship between venous thrombosis and HIV-related characteristics, traditional risk factors of hypercoagulability, and pre-event levels of biomarkers. DESIGN: A retrospective case-control study of 23 HIV-infected individuals who experienced an incident venous thromboembolic event while enrolled in National Institutes of Health studies from 1995 to 2010 and 69 age-matched and sex-matched HIV-infected individuals without known venous thromboembolism (VTE). METHODS: Biomarkers of inflammation, endothelial dysfunction, coagulation, tissue fibrosis, and cytomegalovirus (CMV) reactivation were assessed by ELISA-based assays and PCR using plasma obtained prior to the event. RESULTS: VTE events were related to nadir CD4 cell count, lifetime history of multiple opportunistic infections, CMV disease, CMV viremia, immunological AIDS, active infection, and provocation (i.e., recent hospitalization, surgery, or trauma). VTE events were independently associated with increased plasma levels of P-selectin (P = 0.002), D-dimer (P = 0.01), and hyaluronic acid (P = 0.009) in a multivariate analysis. No significant differences in antiretroviral or interleukin-2 exposures, plasma HIV viremia, or other traditional risk factors were observed. CONCLUSION: Severe immunodeficiency, active infection, and provocation are associated with venous thromboembolic disease in HIV. Biomarkers of endothelial dysfunction, coagulation, and tissue fibrosis may help identify HIV-infected patients at elevated risk of VTE.",
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Musselwhite, LW, Sheikh, V, Norton, TD, Rupert, A, Porter, BO, Penzak, SR, Skinner, J, Mican, JM, Hadigan, C & Sereti, I 2011, 'Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV', AIDS, vol. 25, no. 6, pp. 787-795. https://doi.org/10.1097/QAD.0b013e3283453fcb

Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV. / Musselwhite, Laura W.; Sheikh, Virginia; Norton, Thomas D.; Rupert, Adam; Porter, Brian O.; Penzak, Scott Robert; Skinner, Jeff; Mican, Joann M.; Hadigan, Colleen; Sereti, Irini.

In: AIDS, Vol. 25, No. 6, 27.03.2011, p. 787-795.

Research output: Contribution to journalArticle

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T1 - Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV

AU - Musselwhite, Laura W.

AU - Sheikh, Virginia

AU - Norton, Thomas D.

AU - Rupert, Adam

AU - Porter, Brian O.

AU - Penzak, Scott Robert

AU - Skinner, Jeff

AU - Mican, Joann M.

AU - Hadigan, Colleen

AU - Sereti, Irini

PY - 2011/3/27

Y1 - 2011/3/27

N2 - OBJECTIVE: HIV infection is associated with coagulation abnormalities and significantly increased risk of venous thrombosis. It has been shown that higher plasma levels of coagulation and inflammatory biomarkers predicted mortality in HIV. We investigated the relationship between venous thrombosis and HIV-related characteristics, traditional risk factors of hypercoagulability, and pre-event levels of biomarkers. DESIGN: A retrospective case-control study of 23 HIV-infected individuals who experienced an incident venous thromboembolic event while enrolled in National Institutes of Health studies from 1995 to 2010 and 69 age-matched and sex-matched HIV-infected individuals without known venous thromboembolism (VTE). METHODS: Biomarkers of inflammation, endothelial dysfunction, coagulation, tissue fibrosis, and cytomegalovirus (CMV) reactivation were assessed by ELISA-based assays and PCR using plasma obtained prior to the event. RESULTS: VTE events were related to nadir CD4 cell count, lifetime history of multiple opportunistic infections, CMV disease, CMV viremia, immunological AIDS, active infection, and provocation (i.e., recent hospitalization, surgery, or trauma). VTE events were independently associated with increased plasma levels of P-selectin (P = 0.002), D-dimer (P = 0.01), and hyaluronic acid (P = 0.009) in a multivariate analysis. No significant differences in antiretroviral or interleukin-2 exposures, plasma HIV viremia, or other traditional risk factors were observed. CONCLUSION: Severe immunodeficiency, active infection, and provocation are associated with venous thromboembolic disease in HIV. Biomarkers of endothelial dysfunction, coagulation, and tissue fibrosis may help identify HIV-infected patients at elevated risk of VTE.

AB - OBJECTIVE: HIV infection is associated with coagulation abnormalities and significantly increased risk of venous thrombosis. It has been shown that higher plasma levels of coagulation and inflammatory biomarkers predicted mortality in HIV. We investigated the relationship between venous thrombosis and HIV-related characteristics, traditional risk factors of hypercoagulability, and pre-event levels of biomarkers. DESIGN: A retrospective case-control study of 23 HIV-infected individuals who experienced an incident venous thromboembolic event while enrolled in National Institutes of Health studies from 1995 to 2010 and 69 age-matched and sex-matched HIV-infected individuals without known venous thromboembolism (VTE). METHODS: Biomarkers of inflammation, endothelial dysfunction, coagulation, tissue fibrosis, and cytomegalovirus (CMV) reactivation were assessed by ELISA-based assays and PCR using plasma obtained prior to the event. RESULTS: VTE events were related to nadir CD4 cell count, lifetime history of multiple opportunistic infections, CMV disease, CMV viremia, immunological AIDS, active infection, and provocation (i.e., recent hospitalization, surgery, or trauma). VTE events were independently associated with increased plasma levels of P-selectin (P = 0.002), D-dimer (P = 0.01), and hyaluronic acid (P = 0.009) in a multivariate analysis. No significant differences in antiretroviral or interleukin-2 exposures, plasma HIV viremia, or other traditional risk factors were observed. CONCLUSION: Severe immunodeficiency, active infection, and provocation are associated with venous thromboembolic disease in HIV. Biomarkers of endothelial dysfunction, coagulation, and tissue fibrosis may help identify HIV-infected patients at elevated risk of VTE.

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KW - P-selectin

KW - blood coagulation factors

KW - fibrosis

KW - hyaluronic acid

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