Platelet Count and Platelet Indices in Patients with Stable and Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Figures & data

Figure 1. Flow chart of study selection.

Figure 2. Forest plot of studies examining the platelet count in stable COPD patients and non-COPD subjects.

Table 1. Demographic characteristics of the studies included in the meta-analysis.

First Author Year, Country	Number		Age (years)		Gender (M/F)		NOS
	Non-COPD	COPD	Non-COPD	COPD	Non-COPD	COPD
Sin DD et al. 2003, Canada	4,559	2,070	63	67	1,860/2,699	1,139/931	8
Valipour A et al. 2008, Austria	30	30	59	60	21/9	21/9	5
Biljak VR et al. 2011, Croatia	51	109	52	71	NR	NR	4
Maclay JD et al. 2011, UK	16	18	63	65	16/0	18/0	5
Steiropoulos P et al. 2012, Greece	34	85	60	72	17/17	77/8	4
Stoll P et al. 2012, Germany	17	63	62	64	12/5	39/24	5
Ulasli SS et al. 2012, Turkey	40	47	69	71	26/14	37/10	3
Wang R et al. 2013, China	80	80	70	71	42/38	45/35	3
Wang RT et al. 2013, China	70	70	68	69	34/36	42/28	5
Günay E et al. 2014, Turkey	50	178	65	65	30/20	126/52	6
Zhang M et al. 2015, China	90	90	62	63	70/20	71/19	5
Agapakis DI et al. 2016, Greece	37	81	62	65	27/10	64/17	4
Demir M et al. 2016, Turkey	84	51	66	66	63/21	46/5	5
Karadeniz G et al. 2016, Turkey	50	60	68	68	38/12	40/20	5
Makhlouf HA et al. 2016, Egypt	40	75	59	62	30/10	60/15	4
Malerba M et al. 2016, Italy	72	403	76	74	43/29	258/145	5
Aleva FE et al. 2017, Netherlands	25	30	53	62	9/16	14/16	4
Farah R et al. 2017, Israel	15	13	NR	NR	11/4	9/4	4
Guang Y et al. 2017, China	85	45	85	76	40/45	23/22	5
El-Gazzar AG et al. 2019, Egypt	60	100	57	60	44/16	84/16	5
Hlapčić et al. 2019, Croatia	95	109	64	65	49/46	69/40	5
Şahin F et al. 2019, Turkey	50	110	62	63	45/5	90/20	4
Skoczyński et al. 2019, Poland	48	44	62	62	32/16	30/14	5
Çilingir BM et al. 2019, Turkey	159	201	42	65	81/78	121/80	3
Crisafulli et al. 2020, Italy	30	30	76	75	688/562	231/20	5
Zouaoui Boudjeltia K et al. 2020, Belgium	51	109	61	60	12/9	16/26	5
	COPD	AECOPD	COPD	AECOPD	COPD	AECOPD
De Castro J et al. 2007, Spain	15	68	60	68	NR	NR	3
Valipour A et al. 2008, Austria	30	62	60	62	21/9	23/7	5
Maclay JD et al. 2011, UK	12	68	68	68	5/7	5/7	5
Ulasli SS et al. 2012, Turkey	47	71	71	71	37/10	37/10	3
Wang RT et al. 2013, China	70	69	69	69	42/28	42/28	5
Günay E et al. 2014, Turkey	178	67	65	67	126/52	60/31	6
Zhang M et al. 2015, China	90	63	63	63	71/19	71/19	5
Agapakis DI et al. 2016, Greece	81	65	65	65	64/17	64/17	4
Karadeniz G et al. 2016, Turkey	60	67	68	67	40/20	44/6	5
Malerba M et al. 2016, Italy	403	76	74	76	258/145	43/32	5
Farah R et al. 2017, Israel	13	NR	NR	NR	9/4	52/20	4
El-Gazzar AG et al. 2019, Egypt	100	60	60	60	84/16	84/16	5
Şahin F et al. 2019, Turkey	110	65	63	65	20/90	30/110	4
Zouaoui Boudjeltia K et al. 2020, Belgium	42	65	68	65	16/26	16/15	5

Legend: COPD, chronic obstructive pulmonary disease; AECOPD, acute exacerbation of COPD; NOS, Newcastle-Ottawa quality assessment scale for case-control studies.

Table 2. Platelet indices assessed in the meta-analysis.

	Non-COPD				Stable COPD
First Author	Platelets	MPV	PDW	PLR	Platelets	MPV	PDW	PLR
Year, Country	(x10^9/L)	(fL)	(%)	Mean ± SD	(x10^9/L)	(fL)	(%)	Mean ± SD
	Mean ± SD	Mean ± SD	Mean ± SD		Mean ± SD	Mean ± SD	Mean ± SD
Sin DD et al. 2003, Canada	265 ± 121	–	–	–	270 ± 178	–	–	–
Valipour A et al. 2008, Austria	255 ± 80	–	–	–	269 ± 75	–	–	–
Biljak VR et al. 2011, Croatia	265 ± 69	8.87 ± 1.61	–	–	295 ± 95	9.57 ± 1.62	–	–
Maclay JD et al. 2011, UK	196 ± 31	–	–	–	262 ± 68	–	–	–
Steiropoulos P et al. 2012, Greece	233 ± 54	9.96 ± 1.10	12.99 ± 6.53	–	227 ± 77	10.69 ± 1.00	13.31 ± 2.27	–
Stoll P et al. 2012, Germany	331 ± 98	–	–	–	379 ± 161	–	–	–
Ulasli SS et al. 2012, Turkey	258 ± 43	9.30 ± 0.80	–	–	301 ± 30	9.30 ± 1.30	–	–
Wang R et al. 2013, China	295 ± 53	10.40 ± 1.10	–	–	283 ± 55	9.80 ± 0.90	–	–
Wang RT et al. 2013, China	273 ± 69	10.40 ± 1.10	–	–	291 ± 73	9.80 ± 0.90	–	–
Günay E et al. 2014, Turkey	215 ± 59	10.10 ± 1.31	16.69 ± 0.73	–	241 ± 73	8.80 ± 1.61	16.70 ± 0.92	–
Zhang M et al. 2015, China	189 ± 47	9.89 ± 1.19	14.00 ± 2.76	–	199 ± 61	10.30 ± 1.24	13.40 ± 2.86	–
Agapakis DI et al. 2016, Greece	219 ± 95	9.10 ± 0.90	–	–	227 ± 73	9.30 ± 1.30	–	–
Demir M et al. 2016, Turkey	–	7.50 ± 0.90	–	–	–	8.10 ± 1.50	–	–
Karadeniz G et al. 2016, Turkey	225 ± 52	10.08 ± 0.84	12.15 ± 1.94	109 ± 46	287 ± 90	9.56 ± 1.07	12.83 ± 2.55	294 ± 188
Makhlouf HA et al. 2016, Egypt	244 ± 55	8.42 ± 1.09	15.57 ± 1.89	–	266 ± 113	9.04 ± 1.42	17.79 ± 1.47	–
Malerba M et al. 2016, Italy	230 ± 62	8.44 ± 0.78	–	–	219 ± 64	8.70 ± 1.00	–	–
Aleva FE et al. 2017, Netherlands	261 ± 66	10.20 ± 0.70	12.00 ± 1.60	–	273 ± 103	10.20 ± 0.80	11.70 ± 1.80	–
Farah R et al. 2017, Israel	–	9.20 ± 1.30	–	–	–	8.60 ± 1.20	–	–
Guang Y et al. 2017, China	199 ± 57	–	–	–	168 ± 59	–	–	–
El-Gazzar AG et al. 2019, Egypt	–	–	–	103 ± 4	–	–	–	157 ± 28
Hlapčić et al. 2019, Croatia	226 ± 48	10.53 ± 0.92	12.93 ± 1.85	117 ± 38	245 ± 48	10.03 ± 0.85	12.37 ± 2.00	132 ± 47
Şahin F et al. 2019, Turkey	233 ± 37	8.79 ± 0.70	14.77 ± 1.95	85 ± 24	257 ± 73	9.56 ± 1.37	15.99 ± 0.85	121 ± 62
Skoczyński et al. 2019, Poland	223 ± 63	–	–	–	231 ± 82	–	–	–
Çilingir BM et al. 2019, Turkey	258 ± 70	8.40 ± 2.60	18.30 ± 5.70	–	247 ± 83	8.30 ± 1.20	16.90 ± 1.20	–
Crisafulli et al. 2020, Italy	235 ± 92	–	–	–	239 ± 98	–	–	–
Zouaoui Boudjeltia K et al. 2020, Belgium	248 ± 68	10.57 ± 1.31	–	–	264 ± 68	10.57 ± 1.00	–	–
	Stable CODP				AECOPD
First Author Year, Country	Platelets (x10^9/L) Mean ± SD	MPV (fL) Mean ± SD	PDW (%) Mean ± SD	PLR Mean ± SD	Platelets (x10^9/L) Mean ± SD	MPV (fL) Mean ± SD	PDW (%) Mean ± SD	PLR Mean ± SD
De Castro J et al. 2007, Spain	190 ± 54	–	–	–	250 ± 63	–	–	–
Valipour A et al. 2008, Austria	269 ± 75	–	–	–	276 ± 125	–	–	–
Maclay JD et al. 2011, UK	290 ± 54	–	–	–	333 ± 127	–	–	–
Ulasli SS et al. 2012, Turkey	301 ± 30	9.30 ± 1.30	–	–	269 ± 91	8.50 ± 1.03	–	–
Wang RT et al. 2013, China	291 ± 73	9.80 ± 0.80	–	–	306 ± 81	9.50 ± 0.90	–	–
Günay E et al. 2014, Turkey	241 ± 73	8.80 ± 1.60	16.70 ± 1.20	–	296 ± 76	8.00 ± 1.70	16.80 ± 1.65	–
Zhang M et al. 2015, China	199 ± 61	10.30 ± 1.24	13.40 ± 2.86	–	204 ± 72	11.40 ± 1.45	13.70 ± 3.09	–
Agapakis DI et al. 2016, Greece	227 ± 73	9.30 ± 1.30	–	–	243 ± 55	8.50 ± 0.90	–	–
Karadeniz G et al. 2016, Turkey	287 ± 90	9.56 ± 1.07	12.83 ± 2.55	294 ± 188	310 ± 110	8.36 ± 0.72	15.23 ± 2.17	350 ± 209
Malerba M et al. 2016, Italy	219 ± 64	8.70 ± 1.00	–	–	211 ± 97	8.90 ± 1.00	–	–
Farah R et al. 2017, Israel	–	8.60 ± 1.20	–	–	–	8.90 ± 1.10	–	–
El-Gazzar AG et al. 2019, Egypt	–	–	–	157 ± 28	–	–	–	180 ± 22
Şahin F et al. 2019, Turkey	257 ± 73	9.56 ± 1.37	15.99 ± 0.85	121 ± 62	241 ± 82	8.56 ± 1.07	16.59 ± 9.29	190 ± 138
Zouaoui Boudjeltia K et al. 2020, Belgium	264 ± 68	10.60 ± 1.00	–	–	271 ± 81	10.20 ± 0.60	–	–

Legend: COPD, chronic obstructive pulmonary disease; AECOPD, acute exacerbation of COPD; MPV, mean platelet volume, PDW, platelet distribution width; PLR, platelet to lymphocyte ratio.

Table 3. Parameters used in meta-regression analysis.

First Author Year, Country	BMI		FEV1/FVC		FEV1 (%)		WBC (x10^3µL)		CRP (mg/L)
	Non-COPD	COPD	Non-COPD	COPD	Non-COPD	COPD	Non-COPD	COPD	Non-COPD	COPD
Sin DD et al. 2003, Canada	27.9	26.2	–	–	–	–	7.0	7.6	7.1	7.7
Valipour A et al. 2008, Austria	26	25	82	39	84	34	–	–	2.2	4.0
Biljak VR et al. 2011, Croatia	–	–	86	63	105	40	6.8	10.1	6.8	22
Maclay JD et al. 2011, UK	28	26	79	42	102	48	5.3	7.0	1.6	3.2
Steiropoulos P et al. 2012, Greece	–	–	85	54	99	42	7.1	10.6	–	–
Stoll P et al. 2012, Germany	33.7	27.1	84	47	88	44	8.9	10.0	–	–
Ulasli SS et al. 2012, Turkey	27.8	26	79	53	55	123	7.5	7.5	2.5	6.7
Wang R et al. 2013, China	25.2	24.9	–	–	–	–	–	–	1.6	10
Wang RT et al. 2013, China	25	26	84	47	88	46	6.5	7.3	1.2	8.9
Günay E et al. 2014, Turkey	–	–	–	–	–	–	6.3	8.5	12	20
Zhang M et al. 2015, China	24.5	24	96	50	95	53	6.3	6.7	0.4	2.3
Agapakis DI et al. 2016, Greece	–	–	–	–	–	–	7.4	8.5	5.0	21
Demir M et al. 2016, Turkey	29.7	25.3	98	58	–	–	–	–	4.0	5.0
Karadeniz G et al. 2016, Turkey	–	–	–	–	–	–	7.3	7.8	–	–
Makhlouf HA et al. 2016, Egypt	–	–	–	–	–	–	7.6	9.6	3.6	11.7
Malerba M et al. 2016, Italy	27.8	28.5	93	51	98	49	7.6	9.6	46	46
Aleva FE et al. 2017, Netherlands	–	–	84	43	98	79	6.5	7.0	–	–
Farah R et al. 2017, Israel	–	–	–	–	–	–	–	–	4.2	16.2
Guang Y et al. 2017, China	–	–	–	–	–	–	7.4	10.0	–	–
El-Gazzar AG et al. 2019, Egypt	26.1	28.6	–	–	90	41	–	–	–	–
Hlapčić et al. 2019, Croatia	–	–	85	50	94	44	6.2	7.6	1.7	2.7
Şahin F et al. 2019, Turkey	–	–	–	–	–	–	7.1	9.2	2.4	15
Skoczyński et al. 2019, Poland	–	–	–	–	–	–	–	–	–	–
Çilingir BM et al. 2019, Turkey	–	–	–	–	–	–	11.8	10	–	–
Crisafulli et al. 2020, Italy	–	–	–	–	–	–	12.8	13.4	–	–
Zouaoui Boudjeltia K et al. 2020, Belgium	25	26.1	–	–	–	–	6.6	8.6	1.3	3.3
	COPD	AECOPD	COPD	AECOPD	COPD	AECOPD	COPD	AECOPD	COPD	AECOPD
De Castro J et al. 2007, Spain	25.4	25	85	57	88	45	–	–	–	–
Valipour A et al. 2008, Austria	25	25	42	39	34	34	–	–	4.0	12.6
Maclay JD et al. 2011, UK	26	24	42	42	48	39	7.9	14.8	3.0	41
Ulasli SS et al. 2012, Turkey	26	26	–	–	–	–	7.5	9.6	6.7	46.3
Wang RT et al. 2013, China	26	26	47	41	46	35	7.3	12.2	9.1	22.7
Günay E et al. 2014, Turkey	–	–	62	59	55	49	8.5	9.0	2.0	4.0
Zhang M et al. 2015, China	24	24	–	–	–	–	6.7	9.7	1.9	11.2
Agapakis DI et al. 2016, Greece	–	–	–	–	55	48	8.5	10.5	2.1	3.9
Karadeniz G et al. 2016, Turkey	–	–	–	–	56	39	7.6	13.6	–	–
Malerba M et al. 2016, Italy	28.5	26.9	51	56	49	26	9.6	10.6	46	42
Farah R et al. 2017, Israel	–	–	–	–	–	–	–	–	16.2	39.7
El-Gazzar AG et al. 2019, Egypt	26.1	26.1	–	–	–	–	–	–	–	–
Şahin F et al. 2019, Turkey	–	–	–	–	–	–	9.2	13.6	15	85
Zouaoui Boudjeltia K et al. 2020, Belgium	26	25	45	52	29	35	8.6	10.1	3.0	21.5

Legend: COPD, chronic obstructive pulmonary disease; AECOPD, acute exacerbation of COPD; BMI, body mass index; CRP, C-reactive protein; FEV₁, forced expiratory volume in the 1^st second; FVC, forced vital capacity; WBC, white blood cell count.

Figure 3. Forest plot of studies examining the MPV in stable COPD patients and non-COPD subjects.

Figure 4. Forest plot of studies examining the PDW in stable COPD patients and non-COPD subjects.

Figure 5. Forest plot of studies examining the PLR in stable COPD patients and non-COPD subjects.

Figure 6. Forest plot of studies examining the platelet count in AECOPD and stable COPD patients.

Figure 7. Forest plot of studies examining the MPV in AECOPD and stable COPD patients.

Figure 8. Forest plot of studies examining the PDW in AECOPD and stable COPD patients.

Figure 9. Forest plot of studies examining the PLR in AECOPD and stable COPD patients.

Data availability

The data that support the findings of this systematic review and meta-analysis are available from the corresponding author, AZ, upon reasonable request.