Impact of acute exacerbations on platelet reactivity in chronic obstructive pulmonary disease patients

Figures & data

Table 1 Demographic and clinical characteristics

	N=37
Age (years), mean ± SD	69.8±5.7
Male, n (%)	35 (94.6)
Body mass index (kg/m^2), mean ± SD	27.7±5.1
Risk factors and medical history
Current smoking, n (%)	4 (10.8)
Pack-years, median (IQR)	45.0 (37.0–68.5)
Hypertension, n (%)	22 (59.5)
Diabetes mellitus, n (%)	4 (10.8)
Dyslipidemia, n (%)	16 (43.2)
Coronary heart disease, n (%)	5 (13.5)
Chronic heart failure, n (%)	6 (16.2)
OSAS, n (%)	7 (18.9)
Previous stroke, n (%)	2 (5.4)
Peripheral vascular disease, n (%)	2 (5.4)

Abbreviations: IQR, interquartile range; OSAS, obstructive sleep apnea syndrome.

Table 2 Baseline pulmonary function parameters, laboratory data and medical therapy

	N=37
Pulmonary function test
FEV1 post-bronchodilator % predicted, median (IQR)	38.6 (30.0–45.5)
FEV1/FVC post-bronchodilator, median (IQR)	38.5 (35.4–45.7)
Medical therapy
Aspirin, n (%)	8 (21.6)
Clopidogrel, n (%)	2 (5.4)
Statins, n (%)	14 (37.8)
PPI, n (%)	24 (64.9)
Oral antidiabetic agents/insulin, n (%)	4 (10.8)/2 (5.4)
ACEIs/ARBs, n (%)	15 (40.5)
Beta-blockers, n (%)	4 (10.8)
Calcium antagonists, n (%)	6 (16.2)
CPAP, n (%)	6 (16.2)
Oxygen at home, n (%)	15 (40.5)
Laboratory data
Hemoglobin (g/L)	137 (126–150)
Platelet count (×10^9/L)	246.0 (186.5–301.0)
Glucose (mmol/L)	5.6 (5.1–7.2)
Creatinine (μmol/L)	72.0 (62.0–91.0)

Abbreviations: ACEIs, angiotensin converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; CPAP, continuous positive airway pressure; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; IQR, interquartile range; PPIs, proton pump inhibitors.

Table 3 Characteristics of the acute exacerbations

	N=37
Severity of current exacerbation
Moderate, n (%)	29 (78.4)
Severe, n (%)	8 (21.6)
Days of worsening symptoms, median (IQR)	4.0 (3.0–7.0)
pH, median (IQR)	7.41 (7.39–7.42)
PaO2 (mmHg), median (IQR)	69.0 (64.8–74.3)
PaCO2 (mmHg), median (IQR)	44.0 (39.0–50.5)
Positive culture to bacterial infection, n (%)	26 (70.3)
Virus isolation, n (%)	1 (2.7)
Requirements of systemic corticosteroids, n (%)	36 (97.3)
Requirements of antibiotics, n (%)	34 (91.9)
Requirements of hospitalization, n (%)	8 (21.6)

Abbreviation: IQR, interquartile range.

Table 4 Platelet reactivity during the acute exacerbation and stable state

Test	Overall population, N=37			No antiplatelet therapy, N=27
	Exacerbation	Stable state	p-value	Exacerbation	Stable state	p-value
VASP
PRI (%)	75.2±1.9	68.8±2.4	0.001	76.0±1.5	71.2±2.0	0.007
LTA
MPA ADP-5 μmol/L (%)	64.2±3.4	60.6±3.6	0.076	68.7±3.5	64.1±4.2	0.069
MPA ADP-20 μmol/L (%)	69.0±2.9	67.4±2.9	0.461	72.5±2.6	69.1±2.8	0.177
MPA AA-1 μmol/L (%)	54.9±6.2	54.0±6.0	0.459	72.8±1.2	71.2±1.7	0.328
MPA Coll-2 μmol/L (%)	72.6±2.5	66.4±3.2	<0.001	78.3±1.3	73.9±1.8	0.009
MEA
ADP (AU × min)	749.6±41.3	636.4±39.3	<0.001	824.5±33.5	707.6±41.5	0.007
Coll (AU × min)	755.4±40.5	672.51±41.6	0.028	1,049.9±60.5	1,005.3±65.1	0.393
AA (AU × min)	786.0±65.4	731.28±64.9	0.124	948.3±49.0	871.6±48.4	0.067
TRAP (AU × min)	1,048.9±55.8	1,006.3±57.5	0.383	767.4±44.3	648.7±42.7	<0.001

Notes:

Platelet reactivity was measured with different platelet function assays in the overall population and in the cohort of patients not receiving antiplatelet therapy. Values are expressed as least squares mean ± SEM. The p-values were obtained using repeated-measures analysis of variance.

Abbreviations: AA, arachidonic acid; ADP, adenosine diphosphate; AU, area under the curve; Coll, collagen; LTA, light transmission aggregometry; MEA, multiple electrode aggregometry; MPA, maximal platelet aggregation; PRI, P2Y₁₂ reactivity index; SEM, standard error of the mean; TRAP, thrombin receptor activating peptide; VASP, vasodilator-stimulated phosphoprotein.

Figure 1 Platelet reactivity measured by VASP assay.

Notes: Black lines represent the least squares mean of the groups. (A) Overall population, (B) subset of patients without antiplatelet therapy, (C) subset of patients under antiplatelet therapy.
Abbreviation: VASP, vasodilator-stimulated phosphoprotein.

Figure 2 Inflammatory parameters assessed during AECOPD compared to the stable state.

Notes: Black lines represent the least squares mean of the groups. (A) Plasma leukocyte count, (B) serum IL-6 and (C) serum fibrinogen.
Abbreviations: AECOPD, acute exacerbations of chronic obstructive pulmonary disease; IL-6, interleukin-6.

Figure 3 Association between the PRI and the inflammatory parameters.

Notes: The change in PRI was evaluated as the difference: PRI during AECOPD–PRI during stable state. The difference in the inflammatory parameters during AECOPD and stable state was divided into tertiles. (A) Difference (Δ) in plasma leukocyte count, (B) difference (Δ) in serum IL-6 and (C) difference (Δ) in serum fibrinogen.
Abbreviations: AECOPD, acute exacerbations of chronic obstructive pulmonary disease; IL-6, interleukin-6; PRI, P2Y₁₂ reactivity index.