Hemostatic changes associate with mortality in hospitalized patients with HIV-associated tuberculosis: a prospective cohort study
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
BACKGROUND
Mortality of HIV-associated tuberculosis (HIV-TB) remains high and knowledge of contributing mechanisms is limited. We aimed to determine whether hemostatic changes in HIV-TB associate with mortality and the contribution of mycobacteremia herein.
METHODS
We conducted a prospective study in Khayelitsha, South Africa, in hospitalized HIV-infected patients with CD4 counts <350 cells/μL and microbiologically-proven TB. HIV-infected out patients without TB served as controls. Plasma biomarkers reflecting activation of pro-and anti-coagulation, fibrinolysis, endothelial cell activation, matricellular protein release and tissue damage
were measured on admission. Cox-proportional hazard models were used to assess variables associated with 12-week
mortality.
RESULTS
Of 59 HIV-TB patients, 16 (27%) died after a median of 12 (interquartile range 0-24) days; 29/45 (64%) of those not on anticoagulants fulfilled criteria for disseminated intravascular coagulation. Mortality was associated with higher concentrations of markers of fibrinolysis, endothelial activation, matricellular protein release and tissue damage, and with decreased markers of anticoagulation. In patients who died coagulation factors involved in the common pathway were depleted (factor II, V, X),
which corresponded with increased plasma clotting times. Mycobacteremia modestly influenced hemostatic changes without affecting mortality.
Mortality of HIV-associated tuberculosis (HIV-TB) remains high and knowledge of contributing mechanisms is limited. We aimed to determine whether hemostatic changes in HIV-TB associate with mortality and the contribution of mycobacteremia herein.
METHODS
We conducted a prospective study in Khayelitsha, South Africa, in hospitalized HIV-infected patients with CD4 counts <350 cells/μL and microbiologically-proven TB. HIV-infected out patients without TB served as controls. Plasma biomarkers reflecting activation of pro-and anti-coagulation, fibrinolysis, endothelial cell activation, matricellular protein release and tissue damage
were measured on admission. Cox-proportional hazard models were used to assess variables associated with 12-week
mortality.
RESULTS
Of 59 HIV-TB patients, 16 (27%) died after a median of 12 (interquartile range 0-24) days; 29/45 (64%) of those not on anticoagulants fulfilled criteria for disseminated intravascular coagulation. Mortality was associated with higher concentrations of markers of fibrinolysis, endothelial activation, matricellular protein release and tissue damage, and with decreased markers of anticoagulation. In patients who died coagulation factors involved in the common pathway were depleted (factor II, V, X),
which corresponded with increased plasma clotting times. Mycobacteremia modestly influenced hemostatic changes without affecting mortality.
Date Issued
2016-11-07
Date Acceptance
2016-10-28
Citation
Journal of Infectious Diseases, 2016, 215 (2), pp.247-258
ISSN
1537-6613
Publisher
Oxford University Press (OUP)
Start Page
247
End Page
258
Journal / Book Title
Journal of Infectious Diseases
Volume
215
Issue
2
Copyright Statement
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of
America. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted
reuse, distribution, and reproduction in any medium, provided the original work is properly
cited. DOI: 10.1093/infdis/jiw532
America. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted
reuse, distribution, and reproduction in any medium, provided the original work is properly
cited. DOI: 10.1093/infdis/jiw532
License URL
Sponsor
Wellcome Trust
Grant Number
104803/Z/14/ZR
Subjects
HIV
coagulation
endothelium
mortality
tuberculosis
Adult
Africa
Coinfection
Female
HIV Infections
Hemostatics
Hospitalization
Humans
Male
Middle Aged
Prospective Studies
South Africa
Survival Analysis
Tuberculosis
11 Medical And Health Sciences
06 Biological Sciences
Microbiology
Publication Status
Published