Document Detail


Thrombin generation in chronic obstructive pulmonary disease: dependence on plasma factor composition.
MedLine Citation:
PMID:  21624643     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for thromboembolic events. We investigated thrombin generation profiles in COPD patients and their dependence on plasma factor/inhibitor composition.
METHODS: Factors (f) (fII, fV, fVII, fVIII, fIX, fX), antithrombin, protein C (PC) and free tissue factor pathway inhibitor (fTFPI) from 60 COPD patients (aged 64.2 ± 10.1 years; a mean forced expiratory volume in 1 second [FEV(1)], 55.6 ± 15.8% of predicted values) were compared with those for 43 controls matched for age, sex, weight and smoking. Patients receiving anticoagulation were excluded. Using each individual's plasma coagulation protein composition, tissue factor-initiated thrombin generation was assessed computationally.
RESULTS: COPD patients had higher fII (115 ± 16 vs 102 ± 10%, p < 0.0001), fV (114 ± 19 vs 102 ± 12%, p = 0.0002), fVII (111 ± 15 vs 102 ± 17%, p = 0.002), fVIII (170 ± 34 vs 115 ± 27%, p < 0.0001), and fIX (119 ± 21 vs 107 ± 17%, p = 0.003), and lower fTFPI (17.7 ± 3.2 vs 18.9 ± 3.2 ng/ml, p = 0.047) compared with controls, while fX, antithrombin, and PC were similar in both groups. Computational thrombin generation profiles showed that compared with controls, COPD patients had higher maximum thrombin levels (+28.3%, p < 0.0001), rates of thrombin generation (+46.1%, p < 0.0001) and total thrombin formation (+14.4%, p < 0.001), together with shorter initiation phase of thrombin generation (p < 0.0001) and the time to maximum thrombin levels (p < 0.0001). Thrombin generation profiles in COPD patients can be normalized via correction of fII, fVIII , fIX and TFPI. The severity of COPD and inflammatory markers were not associated with thrombin generation profiles.
CONCLUSIONS: Prothrombotic phenotype in COPD patients is largely driven by increased prothrombin, fVIII, fIX, and lower fTFPI.
Authors:
Anetta Undas; Milosz Jankowski; Przemysław Kaczmarek; Krzysztof Sladek; Kathleen Brummel-Ziedins
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-05-31
Journal Detail:
Title:  Thrombosis research     Volume:  128     ISSN:  1879-2472     ISO Abbreviation:  Thromb. Res.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-29     Completed Date:  2012-01-19     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0326377     Medline TA:  Thromb Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e24-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. mmundas@cyf-kr.edu.pl
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MeSH Terms
Descriptor/Qualifier:
Aged
Antithrombins / blood
Blood Coagulation*
Blood Coagulation Factor Inhibitors / blood*
Blood Coagulation Factors / metabolism*
Blood Coagulation Tests
Case-Control Studies
Female
Forced Expiratory Volume
Humans
Kinetics
Lipoproteins / blood
Lung / physiopathology
Male
Middle Aged
Phenotype
Poland
Protein C / metabolism
Pulmonary Disease, Chronic Obstructive / blood*,  drug therapy,  physiopathology
Thrombin / metabolism*
Vital Capacity
Grant Support
ID/Acronym/Agency:
HL46703/HL/NHLBI NIH HHS; P01 HL046703-16A1/HL/NHLBI NIH HHS; P01 HL046703-17/HL/NHLBI NIH HHS; P01 HL046703-18/HL/NHLBI NIH HHS; P01 HL046703-19/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antithrombins; 0/Blood Coagulation Factor Inhibitors; 0/Blood Coagulation Factors; 0/Lipoproteins; 0/Protein C; 0/lipoprotein-associated coagulation inhibitor; EC 3.4.21.5/Thrombin
Comments/Corrections

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