title: Thrombin generation in chronic obstructive pulmonary disease: dependence on plasma factor composition.
abstract: 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.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. mmundas@cyf-kr.edu.pl
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
authors.forename: Milosz
authors.initials: M
authors.lastname: Jankowski
authors.forename: Przemysław
authors.initials: P
authors.lastname: Kaczmarek
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Sladek
authors.forename: Kathleen
authors.initials: K
authors.lastname: Brummel-Ziedins
mesh_terms: D000368:Aged; D000991:Antithrombins / Q000097:blood; D001777:Blood Coagulation; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011044:Poland; D011486:Protein C / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D013917:Thrombin / Q000378:metabolism*; D014797:Vital Capacity
chemical_list: D000991:Antithrombins; D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D008074:Lipoproteins; D011486:Protein C; C051928:lipoprotein-associated coagulation inhibitor; D013917:Thrombin