F J Sherida H Woei-A-Jin1, Willize E van der Starre2, Margot E T Tesselaar3, Patricia Garcia Rodriguez1, Cees van Nieuwkoop2, Rogier M Bertina4, Jaap T van Dissel2, Susanne Osanto5. 1. Department of Clinical Oncology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. 2. Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. 3. Department of Medical Oncology, The Netherlands Cancer Institute, 1006 BE Amsterdam, The Netherlands. 4. Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. 5. Department of Clinical Oncology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. Electronic address: s.osanto@lumc.nl.
Abstract
INTRODUCTION: Inhibition of tissue factor, the primary initiator of coagulation in sepsis, attenuates morbidity in primates infused with Escherichia coli. In a human endotoxemia model, microparticles expressing procoagulant TF (MP-TF) are released in blood concurrently with markers of inflammation and coagulation. We investigated whether the release of MP-TF into blood is accompanied by procoagulant and inflammatory changes in patients with E. coli urinary tract infection. MATERIALS AND METHODS: In a multicenter cohort study, we determined clinical disease severity using APACHE II scores and measured plasma MP-TF activity, TAT, sE-selectin, sVCAM-1, procalcitonin and monocyte count in blood of 215 patients with community-acquired febrile E. coli urinary tract infections. RESULTS: Plasma MP-TF activity on admission corresponded with clinical disease severity (APACHE II score; P=0.006) and correlated significantly but weakly with plasma markers of disease severity (sE-selectin, sVCAM-1, procalcitonin). Additionally, median plasma MP-TF activity was higher in patients than in healthy controls (197 vs. 79 fM Xa/min; P<0.0001), and highest in bacteremic patients (325 fM Xa/min). MP-TF activity showed a weak inverse correlation with monocyte count (rs -0.22; P=0.016) and a weak correlation with TAT (rs 0.23, P=0.017). After 3 days of antibiotic treatment, upon resolution of the infection, plasma MP-TF activity and TAT concentrations declined. CONCLUSIONS: Microparticle-associated procoagulant tissue factor activity is related to disease severity and bacteremia in febrile E. coli UTI patients and may contribute to the prothrombotic state in gram-negative sepsis.
INTRODUCTION: Inhibition of tissue factor, the primary initiator of coagulation in sepsis, attenuates morbidity in primates infused with Escherichia coli. In a humanendotoxemia model, microparticles expressing procoagulant TF (MP-TF) are released in blood concurrently with markers of inflammation and coagulation. We investigated whether the release of MP-TF into blood is accompanied by procoagulant and inflammatory changes in patients with E. coli urinary tract infection. MATERIALS AND METHODS: In a multicenter cohort study, we determined clinical disease severity using APACHE II scores and measured plasma MP-TF activity, TAT, sE-selectin, sVCAM-1, procalcitonin and monocyte count in blood of 215 patients with community-acquired febrile E. coli urinary tract infections. RESULTS: Plasma MP-TF activity on admission corresponded with clinical disease severity (APACHE II score; P=0.006) and correlated significantly but weakly with plasma markers of disease severity (sE-selectin, sVCAM-1, procalcitonin). Additionally, median plasma MP-TF activity was higher in patients than in healthy controls (197 vs. 79 fM Xa/min; P<0.0001), and highest in bacteremic patients (325 fM Xa/min). MP-TF activity showed a weak inverse correlation with monocyte count (rs -0.22; P=0.016) and a weak correlation with TAT (rs 0.23, P=0.017). After 3 days of antibiotic treatment, upon resolution of the infection, plasma MP-TF activity and TAT concentrations declined. CONCLUSIONS: Microparticle-associated procoagulant tissue factor activity is related to disease severity and bacteremia in febrile E. coli UTI patients and may contribute to the prothrombotic state in gram-negative sepsis.
Authors: F J Sherida H Woei-A-Jin; Margot E T Tesselaar; Patrica Garcia Rodriguez; Fred P H T M Romijn; Rogier M Bertina; Susanne Osanto Journal: Br J Cancer Date: 2016-07-12 Impact factor: 7.640