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Prothrombotic state in patients with stable COPD: an observational study

Christos Kyriakopoulos, Christos Chronis, Evaggelia Papapetrou, Athina Tatsioni, Konstantina Gartzonika, Christina Tsaousi, Athena Gogali, Christos Katsanos, Aikaterini Vaggeli, Charikleia Tselepi, Georgios Daskalopoulos, Stavros Konstantopoulos, Konstantinos Kostikas, Athanasios Konstantinidis
ERJ Open Research 2021 7: 00297-2021; DOI: 10.1183/23120541.00297-2021
Christos Kyriakopoulos
1Respiratory Medicine Dept, University Hospital of Ioannina, Ioannina, Greece
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Christos Chronis
1Respiratory Medicine Dept, University Hospital of Ioannina, Ioannina, Greece
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Evaggelia Papapetrou
2University Hospital of Ioannina, Hematology Laboratory, Ioannina, Greece
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Athina Tatsioni
3Research Unit for General Medicine and Primary Health Care, University of Ioannina, Ioannina, Greece
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Konstantina Gartzonika
4Microbiology Dept, University Hospital of Ioannina, Ioannina, Greece
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Christina Tsaousi
2University Hospital of Ioannina, Hematology Laboratory, Ioannina, Greece
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Athena Gogali
1Respiratory Medicine Dept, University Hospital of Ioannina, Ioannina, Greece
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Christos Katsanos
1Respiratory Medicine Dept, University Hospital of Ioannina, Ioannina, Greece
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Aikaterini Vaggeli
1Respiratory Medicine Dept, University Hospital of Ioannina, Ioannina, Greece
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Charikleia Tselepi
1Respiratory Medicine Dept, University Hospital of Ioannina, Ioannina, Greece
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Georgios Daskalopoulos
1Respiratory Medicine Dept, University Hospital of Ioannina, Ioannina, Greece
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Stavros Konstantopoulos
1Respiratory Medicine Dept, University Hospital of Ioannina, Ioannina, Greece
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Konstantinos Kostikas
1Respiratory Medicine Dept, University Hospital of Ioannina, Ioannina, Greece
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  • ORCID record for Konstantinos Kostikas
Athanasios Konstantinidis
1Respiratory Medicine Dept, University Hospital of Ioannina, Ioannina, Greece
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  • ORCID record for Athanasios Konstantinidis
  • For correspondence: akonstan@uoi.gr
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  • FIGURE 1
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    FIGURE 1

    Selection flow chart for patients with stable COPD and non-COPD control subjects. PE: pulmonary embolism; DVT: deep vein thrombosis; ACOS: Asthma COPD overlap syndrome.

  • FIGURE 2
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    FIGURE 2

    Levels of fibrinogen FII, FV, FVIII and FX, and D-dimers in control subjects (n=42) and patients with stable COPD (n=103). Boxplots display median with interquartile range and whiskers show minimum and maximum values (*p<0.05, **p<0.001, Mann–Whitney test).

  • FIGURE 3
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    FIGURE 3

    Levels of coagulation inhibitors antithrombin (AT) and protein S in control subjects (n=42) and patients with stable COPD (n=103). Boxplots display median with interquartile range and whiskers show minimum and maximum values (*p<0.05, **p<0.001, Mann–Whitney test).

  • FIGURE 4
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    FIGURE 4

    Levels of coagulation factors II, V, VIII and X in control subjects (n=42) and Groups A–D of patients with stable COPD (n=103), classified according to GOLD COPD 2021 guidelines (*p<0.05, Kruskal–Wallis test). Group A, n=28; Group B, n=27; Group C, n=15; Group D, n=33.

Tables

  • Figures
  • Supplementary Materials
  • TABLE 1

    Baseline characteristics and comorbidities of patients with stable COPD and control subjects

    Control groupCOPDp-value#
    Subjects n42103
    Demographic factors
     Age years62.52±8.7662.91±7.270.638
     Male sex n (%)40 (96)100 (97)0.723
     Current smokers n (%)20 (47.6)43 (41.7)0.452
     Pack-years30 (20–48)60 (50–80)0.001
     BMI29.4 (26.2–32.5)26.9 (24.7–29.7)0.015
    Spirometric parameters
     FEV1 %97.74±15.9855.80±16.85<0.001
     FEV1 L3.26 (2.66–3.56)1.56 (1.22–2.02)<0.001
     FEV1/FVC %83 (78–86)61 (51–68)0.001
     RV101±14114±25<0.001
     TLC93±1087±140.007
     DLCOSB84±1056±220.001
    Comorbidities
     HEART score5 (3–7)5 (4–7)0.314
     Cardiovascular risk5 (4–5)5 (4–5)0.253
     Charlson comorbidity index3 (2–3)3 (2–3)0.129
     Arterial hypertension n (%)28 (66.7)58 (56.3)0.270
     Diabetes n (%)8 (19)19 (18.4)0.993
     Dyslipidaemia n (%)20 (47.6)37 (35.9)0.197
    Laboratory biomarkers
     Neutrophils/μL4300 (3235–5280)5040 (4130–5940)0.018
     WBC/μL6970 (6065–8760)8030 (6590–9570)0.030
     ESR mm·h−115 (11–20)19 (13–27)0.010
     CRP mg·L−14 (2–5)4 (3–8)0.128
     Ferritin ng·mL−198 (38–159)108 (59–156)0.323
     Uric acid mg·dL−16 (5.1–7.2)5.9 (5.2–6.8)0.752
     LDL mg·dL−1115.1±31.5129.9±38.40.022
     Glucose mg·dL−198 (88–108)100 (91–113)0.162
     HbA1c %5.9 (5.55–6.25)5.8 (5.5–6.3)0.995
     Insulin mIU·L−17.2 (4.7–10.7)8 (4.7–12)0.515
     HOMA-IR1.6 (1.2–3.2)1.9 (1–3)0.972

    n=145. All values are presented as mean±sd, median (interquartile range) or n (%). sd: standard deviation; BMI: body mass index; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; RV: residual volume; TLC: total lung capacity; DLCOSB: diffusing capacity of lung for carbon monoxide; WBC: white blood cells; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; LDL: low-density lipoprotein cholesterol; HbA1c %: glycated haemoglobin %; HOMA-IR: homeostatic model assessment for insulin resistance. #: Mann–Whitney U-test.

    • TABLE 2

      Coagulation factor levels in patients with stable COPD and control subjects

      Coagulation factor levelsControl groupCOPDp-value#
      Subjects n42103
      Fibrinogen mg·dL−1346±65399±82<0.001
      FII %109±19122±220.004
      FV %112±19131±250.015
      FVII %108±19115±230.113
      FVIII %122±20143±32<0.001
      FIX %111 (106–123)116 (108–126)0.126
      FX %98 (88–107)111 (94–134)0.002
      D-dimers ng·mL−1240 (180–400)360 (230–600)0.001
      INR1.01 (0.95–1.05)1.00 (0.93–1.05)0.853
      PT s14.1 (13.1–14.5)13.7 (12.8–14.4)0.184
      aPTT s29.8±3.028.2±3.40.515
      Free protein S antigen %116 (98–121)95 (85–105)<0.001
      Protein C %116.2±17.1112.6±18.10.150
      Antithrombin %102.3±13.294.4±11.50.001

      n=145. All values are presented as mean±sd or median (interquartile range). sd: standard deviation; PT: prothrombin time; aPTT: activated partial thromboplastin time. #: Mann–Whitney U-test.

      • TABLE 3

        Associations of fibrinogen, FII, FV, FVIII, FX, protein S, antithrombin (AT) and D-dimers with spirometric stages, GOLD ABCD groups, CAT score and number of exacerbations in patients with stable COPD

        n (%)IIIVVIIIXProtein SATD-dimers
        FEV1 % predicted
         ≥50%62 (60.2)403±82117±17127±24144 (110–156)102 (86–118)95 (83–107)94±11.7375 (230–560)
         <50%41 (39.2)391±81130±27138±24154 (126–182)124 (110–143)95 (85–105)95±11.3350 (200–630)
         p-value#0.5740.0030.0180.7290.0010.6560.8130.696
        GOLD groups
         A28 (27.2)407±84114±17123±22135±2994 (88–113)95 (88–112)94 (89–100)340 (252–470)
         B27 (26.2)397±82116±16133±27140±33122 (95–137)91 (76–104)94 (89–97)450 (240–750)
         C15 (14.6)420±75129±22133±22145±28128 (108–140)98 (95–109)96 (94–101)330 (220–780)
         D33 (32)383±83130±27135±26150±33114 (102–139)95 (80–105)94 (85–103)360 (225–630)
         p-value¶0.4820.0170.1470.1800.0020.1770.7700.529
        CAT score
         <1043 (41.7)389±82120±20127±22140(117–159)101 (90–128)96 (92–109)94 (89–101)330 (250–530)
         ≥1060 (58.3)411±80124±24134±26153(117–170)118 (100–138)94.5 (77–104)94 (87–100)420 (230–655)
         p-value#0.1990.4180.0660.1670.0340.0330.6080.304
        Exacerbations
         <278 (75.7)399±81114±16124±23144 (117–167)99 (89–123)95±1994±12380 (248–618)
         ≥225 (24.3)397±85127±24136±25158 (120–170)121 (101–139)94±1796±11340 (225–535)
         p-value#0.8660.0050.0180.3680.0030.7140.5120.593

        n=103. GOLD: Global Initiative for Chronic Obstructive Lung Disease; CAT: COPD assessment test; FEV1: forced expiratory volume in 1 s; #: Mann–Whitney U-test; ¶: Kruskal–Wallis test.

        Supplementary Materials

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          Supplementary material 00297-2021.figureS1

          Supplementary material 00297-2021.figureS2

          Supplementary material 00297-2021.figureS3

          Supplementary material 00297-2021.supplement

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        Prothrombotic state in patients with stable COPD: an observational study
        Christos Kyriakopoulos, Christos Chronis, Evaggelia Papapetrou, Athina Tatsioni, Konstantina Gartzonika, Christina Tsaousi, Athena Gogali, Christos Katsanos, Aikaterini Vaggeli, Charikleia Tselepi, Georgios Daskalopoulos, Stavros Konstantopoulos, Konstantinos Kostikas, Athanasios Konstantinidis
        ERJ Open Research Oct 2021, 7 (4) 00297-2021; DOI: 10.1183/23120541.00297-2021

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        Prothrombotic state in patients with stable COPD: an observational study
        Christos Kyriakopoulos, Christos Chronis, Evaggelia Papapetrou, Athina Tatsioni, Konstantina Gartzonika, Christina Tsaousi, Athena Gogali, Christos Katsanos, Aikaterini Vaggeli, Charikleia Tselepi, Georgios Daskalopoulos, Stavros Konstantopoulos, Konstantinos Kostikas, Athanasios Konstantinidis
        ERJ Open Research Oct 2021, 7 (4) 00297-2021; DOI: 10.1183/23120541.00297-2021
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