Platelet rich plasma effectiveness in bowel anastomoses: A systematic review

Table 1 Basic characteristics of the included studies

Ref.	Country	Animal model (race)	Sample size (n)	Number of groups (n)	Animal per group (n)	Day at animal sacrification	Underlying animal condition that PRP was tested	PRP amount in anastomosis (and factors mixed with PRP)	Control	Primary comparison
Daglioglu et al[9], 2018	Turkey	Rat (Winstar-Albino)	36	3	12	Day 7	Normal	0.5 mL PRP	Simple end-end colon anastomosis	PRP vs fibrin glue
Ocak et al[34], 2019	Turkey	Rat (Winstar-Albino)	35	3	10	Day 7	Hyperthermic intraperitoneal chemotherapy (HIPEC)	200 μL PRP (200 μL thrombin and 100 μL calcium solution)	Hyperthermic saline after anastomosis	PRP vs non PRP application in rats having HIPEC with cisplatin
Yol et al[10], 2008	Turkey	Rat (Sprague Danwley)	30	3	10	Day 7	Normal	1 mL PRP (0.1 mL thrombin and 1 mL calcium solution)	Simple end-end colon anastomosis	PRP vs bioglue
Buk et al[35], 2020	Turkey	Rat (Winstar-Albino)	35	3	10	Day 7	HIPEC	1 mL PRP (1 mL thrombin and 0.5 mL calcium solution)	Hyperthermic saline after anastomosis	PRP vs non PRP application in rats having HIPEC with oxaliplatin
Dzhumabekov et al[25], 2019	Kazakhstan	Rabbit (Chinchillas)	81	3	27	Day 7	Normal	0.2 mL/m2 PRP	Normal saline injected in the muscular layer of end-end small bowel anastomosis	PRP injection in bowel muscular layers vs soaking of bowel edges in PRP before anastomosis
Aydin et al[17], 2020	Turkey	Rat (Sprague Dawley)	24	3	8	Day 7	Normal	0.7 μL PRP absorbed by sutures	Simple end-end colon anastomosis	Higher vs lower platelet concentration PRP-impregnated vicryl sutures
Dauser et al[26], 2020	Austria	Pig	16	4	4	Day 0, 4, 10 and 30	Normal	PRF spray	Each group had one animal as a control: A simple anastomosis was performed with a circular stapler	PRF vs no PRF application tested in several postoperative days
Giusto et al[28], 2017	Italy	Pig (Landace X Large White)	8	2	4	Day 8	Normal	1 mL PRP (50 μL calcium solution)	2 out of 6 anastomoses performed in each animal used as a control anastomosis [no PRP or platelet rich in growth factors (PRGF) applied]	PRP vs PRGF
Zhou et al[29], 2014	China	Rat (Sprague Dawley)	30	3	10	Day 7	Open abdomen. A polypropylene mesh used for abdomen closing in the open abdomen group	1 mL PRP	Simple end-end colon anastomosis	PRP vs non PRP application in a background of open abdomen
Göksu et al[30], 2020	Turkey	Rat (Wistar Albino)	24	3	8	Day 7	HIPEC	PRP alone (dose not mentioned)	Hyperthermic saline after anastomosis	PRP vs non PRP application in rats having HIPEC with 5-fluorouracil (5-FU)
Özçay et al[16], 2018	Turkey	Rat (Sprague Dawley)	40	4	10	Day 7	Mesenteric ischemia/reperfusion injury (IR injury)	PRF membrane applied around the anastomosis	Simple end-end colon anastomosis	PRF vs non PRF application following IR injury
Fresno et al[19], 2010	Spain	Pig (White)	35	7	3 or 10	Day 1, 2, 3, 4 and 7	Normal	1 mL PRP (50 μL calcium solution)	1 out of 2 anastomoses performed in each animal used as a control anastomosis (no PRP or PRGF applied)	PRP effect on several postoperative days
Daradka et al[27], 2019	Jordan	Rabbit (mixed-breed)	30	3	10	Day 3 and 10	Normal	Sutures submerged in 1 ml PRP solution	Simple end-end ileal anastomosis	PRP vs sodium citrate coated sutures
Yalı et al[36], 2020	Turkey	Rat (Wistar-Albino)	56	4	12	Day 5	Peritonitis	1 mL PRP (1 mL calcium solution)	Simple end-end colon anastomosis	PRP in normal abdomen vs peritonitis
Pehlivanli et al[33], 2019	Turkey	Rat (Wistar Albino)	55	5	10	Day 10	Mesenteric ischemia	1 mL PRP	Simple end-end colon anastomosis	PRP vs Zeolite vs thymoquinone
Sozutek et al[31], 2016	Turkey	Rat (Wistar Albino)	50	4	10	Day 7	Peritonitis	1 mL PRP (1 mL thrombin and 50 μL calcium solution)	Simple end-end colon anastomosis	PRP in normal abdomen vs peritonitis
Yamaguchi et al[18], 2012	Japan	Rat (Sprague-Dawley)	77	4	12	Day 5	Normal	180 μL PRP (180 units of bovine thrombin and 30 μL of calcium solution).	Simple end-end colon anastomosis	Platelet poor plasma vs low vs high platelet rich plasma
Gorur et al[32], 2020	Turkey	Rat (Wistar Albino)	50	4	10	Day 7	Intraperitoneal administration of 5-FU	1 mL PRP (1 mL thrombin and 50 μL of calcium solution)	Simple end-end colon anastomosis	PRP vs non PRP application in rats having intraperitoneal administration of 5-FU

PRP: Platelet rich plasma.

Table 2 Anastomotic burst pressure, tissue hydroxyproline, collage deposition and inflammatory cell infiltration

Ref.	Anastomotic burst pressure (mm/hg)				Tissue hydroxyproline (μg/mg)				Collagen deposition	Inflammatory cells deposition
	PRP	Control	Other agent	P value	PRP	Control	Other agent	P value
Daglioglu et al[9], 2018	146 ± 44.55 mm/hg	119 ± 35.65 mm/hg	149.1 ± 72.29 mm/hg (Fibrin glue)	vs Control (0.026); vs Fibrin glue (0.896)	120.1 ± 51.5 μg/mg	96.2 ± 29.22 μg/mg	118.71 ± 42.18 μg/mg	vs Control (0.023); vs Fibrin glue (0,745)	No significant difference between groups	No significant difference between groups
Ocak et al[34], 2019	146 ± 21.85 mm/hg	180 ± 9.14 mm/hg	115.8 ± 18.19 mm/hg (HIPEC with cisplatin group)	vs Control (< 0.001); vs HIPEC with cisplatin (0.01)	256.59 ± 84.03 ng/mg	314.69 ± 47.56 ng/mg	148.02 ± 26.57 ng/mg (HIPEC with cisplatin)	vs Control (0.335); vs Hyperthermic saline group (< 0.001)	-	Inflammatory cell infiltration is significant decreased with PRP application in HIPEC and cisplatin model
Yol et al[10], 2008	270 ± 29.8 mm/hg	195 ± 15.3 mm/hg	214 ± 16.46 mm/hg (bioglue)	vs Control (< 0.001); vs Bioglue (< 0.001)	18.2 ± 4.95 μg/mg	10.96 ± 5.94 μg/mg	11.08 ± 5.08 μg/mg	vs Control (0.016); vs Bioglue (0.026)	Rich collagen production was observed in the PRP group. No comparison between groups	Less inflammatory cell infiltration in the PRP group
Buk et al[35], 2020	125.7 ± 15.64 mm/hg	180 ± 9.14 mm/hg	94.90 ± 9.9 mm/hg (HIPEC with oxiliplatin)	vs Control (< 0.001); vs HIPEC with oxiliplatin group (< 0.0011)	280.92 ± 45.85 ng/mg	314.69 ± 75.57 ng/mg	92 ± 26.97 ng/mg (HIPEC with oxiliplatin)	vs Control (< 0.001); vs HIPEC with oxiliplatin) (< 0.0011)	-	Inflammatory cell infiltration is significant decreased with PRP application in oxiplatin model
Dzhumabekov et al[25], 2019	1.76 ± 0.28 (PRP soakinggroup)1	1.54 ± 0.231	1.81 ± 0.171 (PRP injecting group)	vs Control (0.05); vs PRP injecting group (0.69)	-	-	-	-	No significant differences between groups	Inflammatory cell infiltration significantly lower in the PRP soaking or injection group
Aydin et al[17], 2020	121 ± 57 mm/hg	124 ± 61 mm/hg	180 ± 49 mm/hg (low concentration PRP)	vs Control (> 0.05); vs low concentration PRP (< 0.0011)	0.39 ± 0.10 μg/mg	0.25 ± 0.17 μg/mg	0.56 ± 0.37 μg/mg (low concentration PRP)	vs Control (< 0.001); vs low concentration PRP (< 0.051)	-	No significant difference between groups
Dauser et al[26], 2020	Median = 210 mm/hg (day 10)	Median = 60 mm/hg (day 10)	-	The study reports no statistically significant changes between groups due to small sample size	-	-	-	-	Matrix treated animals showed less immature collagen deposition (type III) compared to the control group (day 10). However no significant differences were observed	No significant changes in the M2 or non-M2 macrophage density in the mucosal, mural and serosal layers. No significant changes in inflammatory cell infiltration
Giusto et al[28], 2017	117.5 mm/hg (range: 80-190)	154 mm/hg (range: 50-180)	165 mm/hg (range: 100-190) (PRGF); And 175 mm/hg (range: 160-190) (intact bowel)	vs Control or PRGF (> 0.05); vs Intact bowel (0.00071)	-	-	-	-	No significant difference between groups	No significant difference between groups
Zhou et al[29], 2014	177 ± 6.95 mm/hg	184.8 ± 6.6 mm/hg	158 ± 5.08 mm/hg (open abdomen group without PRP application)	vs Control (0.398); vs non-PRP application in open abdomen (0.041)	399.7 ± 9.46 μg/mg	403.6 ± 8.55 μg/mg	353.5 ± 6.75 μg/mg (open abdomen group without PRP application)	vs Control (0.74); vs non-PRP application in open abdomen (0.001)	Significantly higher in the PRP and control group	No significant differences between groups
Göksu et al[30], 2020	143 ± 17.35 mm/hg	150 ± 20.49 mm/hg	119.38 ± 17.65 mm/hg (5-FU HIPEC without PRP application)	vs Control (0.718); vs non-PRP 5-FU HIPEC (0.047)	253.64 ± 5.35 μg/mg	259.6 ± 7.95 μg/mg	244.04 ± 7.28 μg/mg (5-FU HIPEC without PRP application)	vs Control (0.224); vs non-PRP 5-FU HIPEC (0.03)	-	Decreased lymphocytes in the PRP compared to the other groups. No statistically significant changes in neutrophil infiltration
Özçay et al[16], 2018	198.1 ± 36.5 mm/hg	205.1 ± 41.1 mm/hg	106.1 ± 33.9 mm/hg (IR injury without PRF)	vs Control (> 0.05); vs non PRF in IR injury (< 0.01)	-	-	-	-	Moderate to severe collagen deposition in all groups but no significant changes between groups	Moderate to severe cellular infiltration but no significant changes between groups
Fresno et al[19], 2010	1.34 ± 0.07 kgf 1(day 3); 1.14 ± 0.11 kgf 1(day 7)	1.21 ± 0.08 kgf 1(day 3); 1.08 ± 0.08 kgf 1(day 7)	1.8 ± 0.08 kgf 1(normal tissue)	vs Normal tissue (< 0.05); vs Control day 3 or 7 (> 0.05)	-	-	-	-	No significant difference between groups	-
Daradka et al[27], 2019	60.2 ± 5.5 mm/hg	54.5 ± 7.5 mm/hg	55.6 ± 10.2 mm/hg (sodium citrate coated sutures)	vs Control (0.211)	0.76 ± 0.1 μg/mg	0.47 ± 0.13 μg/mg	0.52 ± 0.07 μg/mg (sodium citrate- coated sutures)	vs Control (< 0.05) on day 10; vs Control (> 0.05) on day 3	Statistically significant higher collagen deposition compared to uncoated suture groups on day 10	Statistically significant less inflammatory infiltration compared to PRP uncoated suture groups
Yalı et al[36], 2020	129.66 ± 26.6 mmH20	143.25 ± 37.47 mmH20	154.9 ± 27.64 mmH20 (colon anastomosis in peritonitis) and 173.5 ± 29.49 mmH20 (colon anastomosis and PRP application in peritonitis)	vs Control (> 0.05); vs Colon anastomosis and PRP application in peritonitis (< 0.05)	-	-	-	-	Statistically significant higher collage storage values in PRP treated group compared to control and peritonitis model	Statistically significant differences between groups in terms of inflammatory reaction
Pehlivanli et al[33], 2019	225 (range: 180-250)2	200 (range: 90-230)2	235 (range: 220-250)2 thymoquinone; 132.5 (range: 85-150)2 Zeolite	vs Control (> 0.05); vs Zeolite (< 0.05); vs Thymoquinone (> 0.05)	613.22 (range: 158.55-801.82)2	371.27 (range: 164.51-785.45)2	473.03 (range: 215.33-963.43)2 thymoquinone; 459.15 (range: 182.44-738.21)2 Zeolite	vs Control (> 0.05); vs Zeolite (> 0.05); vs Thymoquinone (> 0.05)	-	No significant difference in terms of inflammation at the anastomotic line in between groups
Sozutek et al[31], 2016	209 ± 14.4 mm/hg	179.5 ± 10.3 mm/hg	129.3 ± 14.2 mm/hg (colon anastomosis in peritonitis); 167.5 ± 7.5 mm/hg (colon anastomosis and PRP application in peritonitis)	vs Control (0.01); vs Colon anastomosis in peritonitis (0.01); vs Colon anastomosis and PRP application in peritonitis (0.01)	17.4± 1.21 μg/mg	10.8± 0.67 μg/mg	8.98 ± 1.04 μg/mg (colon anastomosis in peritonitis); 10.6 ± 0.52 μg/mg (colon anastomosis and PRP application in peritonitis)	vs Control (0.023); vs Colon anastomosis in peritonitis (0.01); vs Colon anastomosis and PRP application in peritonitis (0.012)	Application of PRP in peritonitis group did no increase collagen deposition significantly	Macrophages significantly increased in PRP vs control group and lymphocytes were significantly decreased in PRP + peritonitis compared to peritonitis group
Yamaguchi et al[18], 2012	148 ± 25 mm/hg (H-PRP)	171 ± 20 mm/hg	174 ± 23 mm/hg (PPP); 189 ± 17 mm/hg (L-PRP)	vs Control (< 0.05); vs L-PRP (< 0.05); vs PPP (< 0.05)	407 ± 143 μg/mg	515 ± 130 μg/mg	495 ± 123 μg/mg (PPP); 629 ± 120 μg/mg (L-PRP)	vs Control (< 0.05); vs L-PRP (< 0.05); vs PPP (< 0.05)	In L-PRP more collagen deposition in the serosa layer compared to other groups. H-PRP showed the lesser collagen deposition compared to other groups	-
Gorur et al[32], 2020	246.7± 25.1 mm/hg	232.6± 19.5 mm/hg	127.5± 17.7 mm/hg (colon anastomosis and 5-FU intraperitoneal); 202.9 ± 28.8 mm/hg (colon anastomosis + PRP and 5-FU intraperitoneal)	vs Control (> 0.05); vs Colon anastomosis and 5-FU intraperitoneal (< 0.05); Colon anastomosis + PRP vs non PRP and 5-FU intraperitoneal (< 0.05)	1939.5 ± 586 μg/mg	2994.6 ± 2132.4 μg/mg	591 ± 84.4 μg/mg (colon anastomosis and 5-FU intraperitoneal); 1171 ± 301.7 μg/mg (colon anastomosis + PRP and 5-FU intraperitoneal)	vs Control (0.212); vs Colon anastomosis and 5-FU intraperitoneal (< 0.05); Colon anastomosis + PRP vs non PRP and 5-FU intraperitoneal (< 0.05)	Increased but no statistically significant collagen deposition in colon anastomosis + PRP vs non PRP on a background of intraperitoneal 5-FU administration	No significant differences between groups

¹Breaking strength: Minimal force required for anastomosis rupture.

²Anastomotic bursting pressure and tissue hydroxyproline units not reported.

5-FU: 5-Fluorouracil; HIPEC: Hyperthermic intraperitoneal chemotherapy; IR injury: Ischemia/reperfusion injury; PRF: Platelet rich fibrin; PRGF: Platelet rich in growth factors; PRP: Platelet rich plasma.

Table 3 Verhofstad histopathology scale

Groups	Necrosis	Neutrophil	Lymphocyte	Macrophages	Oedema	Mucosal epithelium	Submucosal layer	Bridging	Total
Ocak et al[34]
Control	2.3 ± 0.82	2.5 ± 0.52	2.5 ± 0.52	2.5 ± 0.52	2.9 ± 0.31	2.6 ± 0.966	0.8 ± 0.63	-	-
PRP	2.6 ± 0.69	2.8 ± 0.42a	2.7 ± 0.48a	2.7 ± 0.48a	2.9 ± 0.31	2.6 ± 0.516	1.4 ± 0.69	-	-
Fibrin glue	2 ± 0.66	2.1 ± 0.31a	2.1 ± 0.31a	2.1 ± 0.31a	2 ± 0.47	2.6 ± 0.516	1.3 ± 0.67	-	-
Buk et al[35]
Control	2.3 ± 0.82	1.9 ± 0.56a	1.8 ± 0.42a	2 ± 0.47	2.1 ± 0.56a	2.6 ± 0.966	0.8 ± 0.63a	-	-
Oxaliplatin	2.5 ± 0.52	2.9 ± 0.52a	2.4 ± 0.51a	2.5 ± 0.52	2.8 ± 0.42a	2.6 ± 0.516	2 ± 0.94a	-	-
Oxaliplatin + PRP	2.7 ± 0.58	2 ± 0.47a	1.8 ± 0.42a	2.3 ± 0.67	2.1 ± 0.56a	2.5 ± 0.54	1.6 ± 0.96a	-	-
Aydin et al[17]
Control	1 ± 1	2 ± 1	-	2 ± 0	2 ± 1	3 ± 1	3 ± 0	-	-
L-PRP	0 ± 2	2 ± 1	-	2 ± 0	1 ± 0a	2.5 ± 1a	3 ± 2	-	-
H-PRP	1.5 ± 2	2 ± 2	-	2 ± 1	0 ± 0a	1 ± 2a	3 ± 0	-	-
Göksu et al[30]
Control	2.38 ± 0.51	2.38 ± 0.518	2.38 ± 0.51a	-	2.75 ± 0.46a	2.63 ± 0.51	1.75 ± 0.46	-	-
5-FU	2.63 ± 0.51	2.50 ± 0.463	2.63 ± 0.51a	-	2.75 ± 0.46a	2.50 ± 0.53	1.25 ± 0.46	-	-
5-FU + PRP	2.13 ± 0.35	2.13 ± 0.518	2 ± 1a	-	2 ± 0.53a	2.63 ± 0.51	1.25 ± 0.46	-	-
Sozutek et al[31]
Control	0.3 ± 0.48	1.3 ± 0.94	1 ± 0.47	1 ± 0a	0.4 ± 0.51	0.3 ± 0.48	-	0.6 ± 0.51	4.9 ± 1.28
Control + PRP	0.2 ± 0.42	0.7 ± 0.67	1 ± 0.47	1.6 ± 0.51a	0.3 ± 0.48	0.4 ± 0.48	-	0.2 ± 0.42	4.3 ± 1.33
Septic	1.1 ± 0.64	1.5 ± 0.53	1.6 ± 0.51a	1.1 ± 0.83	1.2 ± 0.71a	1 ± 0.53	-	1.2 ± 0.71	9.8 ± 1.12a
Septic + PRP	0.7± 0.48	1.2 ± 0.42	1.3 ± 0.48a	1.5 ± 0.52	0.4 ± 0.51a	0.5 ± 0.51	-	0.8 ± 0.42	6.1 ± 1.37a
Gorur et al[32]
Control	0.3 ± 0.67a	1.3 ± 0.9	1 ± 0.47	1 ± 0	1.1 ± 0.31a	0.3 ± 0.57a	-	1.2 ± 0.78a	-
5-FU	1 ± 1.05a	1.5 ± 0.53	1.4 ± 0.32	1.1 ± 0.83	2 ± 0.73a	1.1 ± 0.42a	-	1.5 ± 0.52a	-
Control + PRP	0a	0.7 ± 0.67	1 ± 0.67	1.8 ± 0.31	1 ± 0.47a	0.3 ± 0.57a	-	0.9 ± 0.87a	-
5-FU + PRP	0.1 ± 0.3	1.2 ± 0.42	1.5 ± 0.58	1.6 ± 0.53	1.7 ± 0.48	0.6 ± 0.57	-	1.1 ± 0.31	-

^aP < 0.05, represents a statistically significant difference between values.

5-FU: 5-Fluorouracil; PRP: Platelet rich plasma.