Topical application of platelet-rich plasma for diabetic foot ulcers: A systematic review

Table 1 Study demographics

	Mohammadi et al[6] 2017	Ahmed et al[7] 2017	Perez-Zabala et al[8] 2016	Saad et al[9] 2011	Kakagia et al[10] 2007	Driver et al[11] 2006	Li et al[12] 2015	Saldalam-acchia et al[13] 2004	Motolese et al[14] 2015	Shan et al[15] 2013	Kontopodis et al[16] 2016	Weighted (mean ± SD)[6]	P-value (PRP vs control)
Type of Study	PU	RP	CS	RP	RP	RDBP	RP	RP	PU	PU	RU	N/A	N/A
Level of evidence	III	II	IV	II	II	II	II	II	III	III	III	N/A	N/A
No. patients
PRP	70	28	2	12	17	19	59	7	15	21	72	29.3 ± 25.4	0.104
Control	N/A	28	N/A	12	N/A	21	58	7	N/A	N/A	N/A	25.2 ± 20.0
Age (mean ± SD, yr)
PRP	53.8 ± 10.6	43.2 ± 18.2	65.5 ± 2.1	NR	57.0 ± 12.0	58.3 ± 9.7	61.4 ± 13.1	61.1 ± 9.4	52.3 ± 11.3	66.5 ± 10.8	65	58.4 ± 7.2	0.678
Control	N/A	49.8 ± 15.4	N/A	NR	N/A	55.9 ± 8.1	64.1 ± 9.4	58.1 ± 7.8	N/A	N/A	N/A	58.7 ± 5.9
Female gender, n (%)
PRP	12 (17.1)	8 (28.6)	0 (0.0)	NR	NR	3 (15.8)	22 (37.3)	4 (57.1)	11 (73.3)	13 (61.9)	14 (19.4)	29.70%	0.407
Control	N/A	10 (35.7)	N/A	NR	N/A	5 (23.8)	20 (34.5)	4 (57.1)	N/A	N/A	N/A	35.10%
Duration of diabetes (mean ± SD, yr)
PRP	16.2 ± 7.9	NR	23.5 ± 13.4	NR	NR	NR	7.50	16.3 ± 7.9	38.20	6.8 ± 6.7	NR	14.1 ± 11.6	0.048
Control	N/A	NR	N/A	NR	N/A	NR	10.00	19.7 ± 9.9	N/A	N/A	N/A	11.0 ± 6.9
Duration of ulcer (mean ± SD, wk)
PRP	19.6 ± 4.7	12.5 ± 1.0	28.3 ± 9.5	NR	19.0 ± 8.0	NR	4.28	NR	NR	10.1 ± 12.0	NR	13.0 ± 8.4	< 0.001
Control	N/A	11.5 ± 2.8	N/A	NR	N/A	NR	3.30	NR	N/A	N/A	N/A	6.0 ± 5.8
HbA1c (mean ± SD)
PRP	6.2 ± 0.7	7.0 ± 0.5	9.4 ± 3.3	NR	8.1 ± 2.8	7.8 ± 1.5	9.8 ± 3.1	9.5 ± 1.7	NR	9.1 ± 2.2	NR	7.9 ± 1.3	< 0.001
Control	N/A	6.9 ± 0.6	N/A	NR	N/A	8.1 ± 1.8	9.80	8.8 ± 1.7	N/A	N/A	N/A	8.7 ± 1.2
Ulcer area (mean ± SD, cm2)
PRP	6.11 ± 4.37	6.24 ± 0.9	10.25	NR	28.4 ± 13.6	3.4 ± 4.5	4.10	27.3 ± 15.6	13.92	14.0 ± 32.3	4.1 ± 3.9	7.7 ± 9.3	< 0.001
Control	N/A	5.72 ± 0.8	N/A	NR	N/A	3.6 ± 4.0	2.90	17.0 ± 8.9	N/A	N/A	N/A	4.6 ± 6.6

N/A: Not applicable; PU: Prospective uncontrolled; RP: Randomized prospective; CS: Case series; RDBP: Randomized double-blind prospective; RU: Retrospective uncontrolled; NR: Not recorded; PRP: Platelet-rich plasma.

Table 2 Platelet-rich plasma preparation

Study	Mohamm-adi et al[6] 2017	Ahmed et al[7] 2017	Perez-Zabala et al[8] 2016	Saad et al[9] 2011	Kakagia et al[10] 2007	Driver et al[11] 2006	Li et al[12] 2015	Saldalam-acchia et al[13] 2004	Motolese et al[14] 2015	Shan et al[15] 2013	Kontopodis et al[16] 2016
PRP spinning approach	Single	Double	Single	Double	NR	Single	Double	NR	Single	Single	Single
Duration of spin (min)	10	5 and 5	7	NR	NR	1.5	4 and 6	NR	17	10	NR
Company	Arya Mabna Tashkhis Co, Iran	NR	NR	NR	Biomet Biologics, Warsaw, IN, United States	Cytomedix, Rockville, MD, United States	NR	NR	Thermogenesis, Rancho Cordova, CA, United States	Haemonetics Corp, Braintree, MA, United States	RegenLab, Le Montsur-Lausanne, Switzerland
PRP activator	CaCl2	Thrombin, CaCl2	CaCl2	Thrombin, CaCl2	Thrombin	Thrombin	Thrombin, calcium gluconate	NR	Thrombin, CaCl2	Thrombin, calcium gluconate	NR
PRP amount applied	2 mL/cm2	7 mL	3 mL	NR	NR	NR	NR	NR	5 mL	NR	NR
Platelet concentration	NR	1.0 × 106/mL-1.2 × 106/mL	1.6-1.7 x baseline	NR	NR	NR	NR	NR	NR	NR	NR
WBC concentration	NR	NR	Undetectable	NR	NR	NR	NR	NR	NR	NR	NR
PRP application method	PRP gel applied on ulcers after irrigation and debridement every week covered with non-absorbing wet dressing	PRP gel applied on ulcers after irrigation with 0.9% saline twice weekly covered with non-absorbing dressing	PRP gel applied on ulcers after irrigation twice weekly covered with foam dressings	PRP gel applied on ulcers within half an hour after preparation followed by Vaseline gauze and dressing changed every 3-4 d	PRP gel applied on ulcers covered with vapor-permeable film (Tegaderm, 3M)	PRP gel applied on ulcer with contact layer dressing covered with non-absorbent foam dressing changed every 3-4 d	PRP gel applied on ulcer after irrigation and debridement covered with Suile dressing changed every 3 d. PRP gel reapplied up to 5 times in 12 wk period if wound area reduction rate < 80%	Weekly topical application of PRP gel with covered with standard dressing changed weekly	5 mL of PRP gel applied on ulcers once a week for total of 10 wk covered with non-adherent dressing and bandage	PRP gel applied on ulces twice per week covered with occlusive dressing changed every 72 h	PRP gel applied on ulcer twice weekly after irrigation and debridement covered with standard dressings

NR: Not recorded; PRP: Platelet-rich plasma.

Table 3 Platelet-rich plasma group individual study outcome measures

Study		Mohamm-adi et al[6] 2017	Ahmed et al[7] 2017	Perez-Zabala et al[8] 2016	Saad et al[9] 2011	Kakagia et al[10] 2007	Driver et al[11] 2006	Li et al[12] 2015	Saldalam-acchia et al[13] 2004	Motolese et al[14] 2015	Shan et al[15] 2013	Kontopodis et al[16] 2016
Ulcer area (mean ± SD, cm2)	Baseline	6.11 ± 4.37	6.24 ± 0.9	10.3	NR	28.4 ± 13.6	3.4 ± 4.5	4.1	27.3 ± 15.6	13.9	14.0 ± 32.3	4.1 ± 3.9
	Final	NR	1.44	NR	NR	NR	NR	NR	8.0 ± 7.5	NR	NR	NR
Ulcer healed, n (%)	8 wk	NR	23 (82.1)	NR	NR	2 (11.8)	NR	NR	NR	NR	NR	NR
	12 wk	NR	24 (85.7)	NR	NR	NR	13 (68.4)	50 (84.8)	NR	NR	15 (71.4)	NR
Resvech 2.0 measurement	Baseline	NR	NR	13.5 ± 0.7	NR	NR	NR	NR	NR	NR	NR	NR
	Final	NR	NR	6.0 ± 1.4	NR	NR	NR	NR	NR	NR	NR	NR
% wound length decrease		NR	NR	NR	NR	14.3 ± 7.1	NR	NR	NR	NR	NR	NR
% wound width decrease		NR	NR	NR	NR	17.4 ± 8.0	NR	NR	NR	NR	NR	NR
% wound depth decrease		NR	NR	NR	NR	34.9 ± 9.9	NR	NR	NR	NR	NR	NR
Time to > 90% ulcer area healing (mean ± SD, wk)		8.7 ± 3.9	NR	7.0 ± 2.8	11.5	NR	6.40	5.1	NR	12.7	7.17 ± 5.66	11.0 ± 4.0
Healing rate per week (mean, cm2)		0.7	NR	1.46	NR	NR	0.53	0.8	NR	1.1	1.95	0.37
Adverse effects		0	2 – wound infections	0	0	0	1 – contact dermatitis	5 – wound infections	0	0	0	0

NR: Not recorded.

Table 4 Average study outcome measures included in best evidence synthesis

	Time to > 90% ulcer area healing (mean ± SD, wk)	Healing rate per week (mean ± SD, cm2)	Adverse effects
PRP	7.8 ± 2.7	0.68 ± 0.56	8 (2.5)
Control	8.3 ± 3.7	0.39 ± 0.09	15 (10.5)
P-value	0.115	< 0.001	< 0.001

PRP: Platelet-rich plasma.