title: Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA.
authors.forename: Laura W
authors.initials: LW
authors.lastname: Musselwhite
authors.forename: Virginia
authors.initials: V
authors.lastname: Sheikh
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Norton
authors.forename: Adam
authors.initials: A
authors.lastname: Rupert
authors.forename: Brian O
authors.initials: BO
authors.lastname: Porter
authors.forename: Scott R
authors.initials: SR
authors.lastname: Penzak
authors.forename: Jeff
authors.initials: J
authors.lastname: Skinner
authors.forename: JoAnn M
authors.initials: JM
authors.lastname: Mican
authors.forename: Colleen
authors.initials: C
authors.lastname: Hadigan
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D018791:CD4 Lymphocyte Count; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D005260:Female; D005355:Fibrosis; D015658:HIV Infections / Q000097:blood* / Q000503:physiopathology / Q000821:virology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000097:blood* / Q000503:physiopathology / Q000821:virology
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators