Document Detail


Activated factor XI and tissue factor in chronic obstructive pulmonary disease: links with inflammation and thrombin generation.
MedLine Citation:
PMID:  21236471     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Increased cardiovascular mortality and risk of venous thromboembolism are serious extra-pulmonary complications of chronic obstructive pulmonary disease (COPD). Previously, circulating active tissue factor (TF) and factor XIa (FXIa) have been reported to be associated with acute coronary syndromes.
OBJECTIVE: To measure plasma FXIa and active TF, prothrombin fragment 1.2 (F1.2), and markers of systemic inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], tumor necrosis factor α [TNFα] and matrix metalloproteinase 9 [MMP-9]) in 60 patients with documented stable COPD free of previous thromboembolic events.
METHODS: In-house clotting assays using inhibitory monoclonal antibodies against FXIa and TF.
RESULTS: FXIa was detected in 9 (15%) and TF activity in 7 (11.7%) COPD patients. Subjects positive for FXIa and/or TF (n=10; 16.7%) had higher F1.2 (median [interquartile range], 398 [216] vs 192 [42] pM, p<0.000001), fibrinogen (5.58 [2.01] vs 3.97 [2.47] g/L, p=0.0007), CRP (14.75 [1.20] vs 1.88 [2.95] mg/L, p<0.000001), IL-6 (8.14 [4.74] vs 2.45 [2.24] pg/mL, p=0.00002), and right ventricular systolic pressure (47 [15] vs 38 [12] mmHg, p=0.023), and lower vital capacity (66 [15] vs 80 [17] % predicted, p=0.04) than COPD patients without detectable FXIa and TF. COPD severity was not associated with the presence of circulating FXIa and active TF.
CONCLUSIONS: This is the first study to show that active FXIa and TF are present in stable COPD patients, who exhibit enhanced systemic inflammation and thrombin generation. Our findings suggest a new prothrombotic mechanism which might contribute to elevated risk of thromboembolic complications in COPD.
Authors:
Milosz Jankowski; Anetta Undas; Przemyslaw Kaczmarek; Saulius Butenas
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-01-13
Journal Detail:
Title:  Thrombosis research     Volume:  127     ISSN:  1879-2472     ISO Abbreviation:  Thromb. Res.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-21     Completed Date:  2011-06-01     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  0326377     Medline TA:  Thromb Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  242-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Medicine, Jagiellonian University School of Medicine, Krakow, Poland.
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MeSH Terms
Descriptor/Qualifier:
Aged
Factor XIa / metabolism*
Female
Humans
Inflammation / complications*
Male
Middle Aged
Pulmonary Disease, Chronic Obstructive / complications*,  metabolism
Thrombin / metabolism*
Thromboplastin / metabolism*
Grant Support
ID/Acronym/Agency:
P01 HL046703-09/HL/NHLBI NIH HHS; P01 HL46703/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
9035-58-9/Thromboplastin; EC 3.4.21.27/Factor XIa; EC 3.4.21.5/Thrombin
Comments/Corrections

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