title: Impact of HIV infection on the haemostatic response during sepsis and malaria.
abstract: Patients positive for the human immunodeficiency virus (HIV) are more susceptible to sepsis and malaria, two conditions known to activate the coagulation system. As chronic HIV infection also influences haemostatic mechanisms, we determined the influence of HIV co-infection on coagulation, anticoagulation and the endothelium during sepsis or malaria. We performed a prospective observational study in 325 subjects with or without HIV infection (103 with sepsis, 127 with malaria and 95 asymptomatic controls) in an HIV endemic area in Central Africa. We measured plasma biomarkers indicative of activation of distinct haemostatic mechanisms. Sepsis and malaria had similar effects with elevated markers of coagulation, reduced anticoagulation markers and activation of endothelium. In particular, asymptomatic HIV infection reduced the plasma levels of the anticoagulant co-factor free protein S, and increased activation of the vascular endothelium, which were not normalized by combination antiretroviral therapy. HIV co-infection during sepsis and malaria caused more profound changes in free protein S and von Willebrand factor in sepsis and malaria, and ADAMTS13 in sepsis, while not influencing sepsis- or malaria-induced coagulation activation. These results show for the first time that HIV infection augments selective haemostatic changes during sepsis and malaria, which may contribute to the enhanced morbidity of these conditions in HIV patients.
authors.affiliation: Centre of Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Centre of Tropical Medicine and Travel Medicine, Division of Infectious Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Centre des Recherches Médicales de Lambaréné, Lambaréné, Gabon.
authors.forename: Michaëla A M
authors.initials: MA
authors.lastname: Huson
authors.affiliation: Centre of Tropical Medicine and Travel Medicine, Division of Infectious Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Centre des Recherches Médicales de Lambaréné, Lambaréné, Gabon.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kalkman
authors.affiliation: Centre of Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Arie J
authors.initials: AJ
authors.lastname: Hoogendijk
authors.affiliation: Centre des Recherches Médicales de Lambaréné, Lambaréné, Gabon.
authors.forename: Abraham S
authors.initials: AS
authors.lastname: Alabi
authors.affiliation: Centre of Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: van 't Veer
authors.affiliation: Centre of Tropical Medicine and Travel Medicine, Division of Infectious Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Centre des Recherches Médicales de Lambaréné, Lambaréné, Gabon.|Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands.
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.affiliation: Centre of Experimental and Molecular Medicine, Division of Infectious Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000328:Adult; D000350:Africa, Central; D000925:Anticoagulants / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D060085:Coinfection / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood*; D006487:Hemostasis; D006801:Humans; D008288:Malaria / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood*
chemical_list: D000925:Anticoagulants; D015415:Biomarkers
keywords: HIV; blood coagulation; endothelium; malaria; sepsis