title: Hemostatic Changes Associated With Increased Mortality Rates in Hospitalized Patients With HIV-Associated Tuberculosis: A Prospective Cohort Study.
abstract: BACKGROUND
  Mortality rates remain high for human immunodeficiency virus (HIV)-associated tuberculosis, and our knowledge of contributing mechanisms is limited. We aimed to determine whether hemostatic changes in HIV-tuberculosis were associated with mortality or decreased survival time and the contribution of mycobacteremia to these effects.
  
  
  METHODS
  We conducted a prospective study in Khayelitsha, South Africa, in hospitalized HIV-infected patients with CD4 cell counts <350/µL and microbiologically proved tuberculosis. HIV-infected outpatients without tuberculosis served as controls. Plasma biomarkers reflecting activation of procoagulation and anticoagulation, fibrinolysis, endothelial cell activation, matricellular protein release, and tissue damage were measured at admission. Cox proportional hazard models were used to assess variables associated with 12-week mortality rates.
  
  
  RESULTS
  Of 59 patients with HIV-tuberculosis, 16 (27%) died after a median of 12 days (interquartile range, 0-24 days); 29 (64%) of the 45 not receiving anticoagulants fulfilled criteria for disseminated intravascular coagulation. Decreased survival time was associated with higher concentrations of markers of fibrinolysis, endothelial activation, matricellular protein release, and tissue damage and with decreased concentrations for markers of anticoagulation. In patients who died, coagulation factors involved in the common pathway were depleted (factor II, V, X), which corresponded to increased plasma clotting times. Mycobacteremia modestly influenced hemostatic changes without affecting mortality.
  
  
  CONCLUSIONS
  Patients with severe HIV-tuberculosis display a hypercoagulable state and activation of the endothelium, which is associated with mortality.
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of cape Town.|Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine.|Center for Experimental and Molecular Medicine, Department of Infectious Diseases, Division of Internal Medicine.
authors.forename: Saskia
authors.initials: S
authors.lastname: Janssen
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of cape Town.|Department of Medicine, Groote Schuur Hospital and University of Cape Town, and.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Schutz
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of cape Town.|Department of Medicine, Groote Schuur Hospital and University of Cape Town, and.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Ward
authors.affiliation: Center for Experimental and Molecular Medicine, Department of Infectious Diseases, Division of Internal Medicine.
authors.forename: Mischa A M
authors.initials: MA
authors.lastname: Huson
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of cape Town.|Department of Medicine, Groote Schuur Hospital and University of Cape Town, and.|The Francis Crick Institute Mill Hill Laboratory, London, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.affiliation: Department of Medicine, Groote Schuur Hospital and University of Cape Town, and.|Khayelitsha Hospital, Cape Town, South Africa.
authors.forename: Rosie
authors.initials: R
authors.lastname: Burton
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town.
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of cape Town.|Department of Medicine, Groote Schuur Hospital and University of Cape Town, and.|The Francis Crick Institute Mill Hill Laboratory, London, United Kingdom.
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.affiliation: Department of Experimental Vascular Medicine.|Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands.
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.affiliation: Departments of Respiratory Medicine and Experimental Immunology, Academic Medical Center, University of Amsterdam.
authors.forename: René
authors.initials: R
authors.lastname: Lutter
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of cape Town.|Department of Medicine, Groote Schuur Hospital and University of Cape Town, and.|Khayelitsha Hospital, Cape Town, South Africa.
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.affiliation: Center for Experimental and Molecular Medicine, Department of Infectious Diseases, Division of Internal Medicine.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000328:Adult; D000349:Africa; D060085:Coinfection / Q000401:mortality* / Q000473:pathology*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006490:Hemostatics; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013019:South Africa; D016019:Survival Analysis; D014376:Tuberculosis / Q000401:mortality* / Q000473:pathology*
chemical_list: D006490:Hemostatics
keywords: HIV; coagulation; endothelium; mortality; tuberculosis