Scope of the systematic literature review
Objective
Description of the PRP concentration systems in scope for the systematic literature review
Introduction
Methods
Standard procedure and guidelines for systematic literature reviews
Information source and search strategy
Data management
Data collection and extraction
Author, year | Study type | Objective | PRP type versus control | Bacteria targeted | Results | Notes |
---|---|---|---|---|---|---|
Everts, 2006 [24] | In vitro (N = 10) | To compare properties of BC-PRP prepared using three different commercially available devices that are used to prepare platelet gel, specifically focused on the most important platelet growth factors and WBC-derived MPO | BC-PRP versus whole blood | Not studied | * Platelet and WBC yield was significantly increased by ECS and GPS * Nonsignificant increase in platelet and WBC count with AGF * Significant increase in TGF-β1 and PDGF level in PG samples after activation of the E-CS or GPS samples * No change in TGF-β1 and PDGF level in PG samples ECS-AGF samples * No significant differences between MPO concentrations in BC-PRP and whole blood * MPO concentration in the BC-PRP was significantly increased versus baseline (P < 0.001), indicating WBC activation before PG formation *No correlation of MPO release and cellular count | Healthy donors Statistics are unclear, could have randomized blood volunteers to devices |
Bielecki, 2007 [38] | In vitro (N = 20) | To analyze antibacterial effect of PRP gel in vitro | PRP gel versus thrombin | * MRSA * MSSA * Escherichia coli * K. pneumoniae * E. Faecalis * P. aeruginosa | * PRP gel inhibited growth of S. aureus and E. coli * There was no activity against K. pneumoniae, E. faecalis, and P. aeruginosa * PRP gel seemed to induce in vitro growth of Aeruginosa, suggesting that it may cause an exacerbation of infections with this organism * No correlation between antimicrobial activity and concentration of platelets and leukocytes | Review paper |
Moojen, 2008 [39] | In vitro (N = 6) | To investigate antimicrobial activity of PLG against S. aureus and the contribution of MPO present in leukocytes in this process | PLG versus PPP | S. aureus | * PLG-AT, PLG-BT, PRP inhibited the growth of S. aureus * There was release of MPO as early as 4 h in PLG-AT, PLG-BT, and PRP; MPO release was maximum at 8 h compared to PPP * No correlation between antimicrobial activity and MPO release and MPO activity | Unclear if blood from individual donors was pooled. No control for individual donor demographics or inclusion/exclusion criteria. Healthy donors may not translate to sick population |
Tohidnezhad, 2012 [40] | In vitro (N = 14) | To investigate secretion of antimicrobial peptides by thrombocytes to elucidate the mechanism of thrombocyte anti-infective capabilities | PRP versus PRP | * B. megaterium * P. mirabilis * Escherichia coli * E. coli * K. pneumonia * E. faecalis | * PRP inhibited growth of S. aureus, E. coli, B. megaterium (P < 0.036), P. aeruginosa (P < 0.008), and E. faecalis (P < 0.001) and not P. mirabalis * hBD-3 concentration is significantly increased in PRP and PPP supernatant after activation and might act as first line defense | Young healthy donors may not translate. Pooled blood from the individual healthy donors. No control for individual demographics or inclusion/exclusion criteria |
Tohidnezhad, 2011 [23] | In vitro (N = 24) | To investigate release of hBD-2 by platelets as a local antibacterial agent | PRP PRGF versus PPP | * B. megaterium * P. mirabilis * Escherichia coli * E. coli * K. pneumonia * E. faecalis | * PRP inhibited growth of E. coli, B. megaterium, P. aeruginosa, E. faecalis, and P. mirabilis * hBD-2 concentration is significantly increased in PRP compared to PPP and PRGF * Preincubation of E. coli and P. mirabilis significantly decreased antibacterial effect of PRP in these strains | Pooled blood from individual healthy donors expired platelets. No control for individual donor demographics or inclusion/exclusion criteria |
Burnouf, 2013 [30] | In vitro (N = 2) | To compare the antimicrobial activity of four distinct plasma and platelet materials from 2 donors against 4 g-positive and 4 g-negative bacteria that can colonize wounds, and to elucidate which component in PG preparation can inhibit wound bacteria | PRP supernatant PG S/D-PL versus Inactivated PRP | * P. aeruginosa * E. coli * E. cloacae * K. pneumoniae * B. cereus * B. subtilis * S. aureus * S. epidermidis | * E. coli colony was strongly inhibited with native PRP, PPP, PG, and S/D-PL at 3 h * P. aeruginosa count was strongly reduced in native PRP, PG, and S/D-PL (4.62, 4.61, and 4.80 log, respectively) but much less in PG (1.10 log) * After 3 h, there was regrowth of P. aeruginosa in all PRP preparations * K. pneumoniae was strongly inhibited in native PRP, PPP, and S/D-PL (6.71, > 7.71, and 6.71 log, respectively) and less in PG (4.63 log) * E. cloacae growth was less affected by the plasma and platelet preparations (reduction close to or < 1 log) *Growth of the 4 g-negative bacteria was not inhibited when preparations were heat-treated to inactivate complement, suggesting the role of complement in bacterial inhibition *By contrast, a close to 100-fold inhibition of S. aureus was seen with native PRP, PPP, and S/D-PL (1.50, 2.10, and 1.80 log, respectively) but not with PG (0.23 log) | Healthy volunteers, no donor information, no inclusion/exclusion criteria |
Li, 2013 [42] | Ex vivo (N = 50) | To investigate antibacterial property of L-PRP gel against MRSA in a rabbit model of osteomyelitis | L-PRP gel versus no treatment control | MRSA | *There was an increase in the concentrations of the 4 growth factors in the activated PRP versus whole blood and non-activated PRP *The highest VEGF levels in L-PRP gel supernatants were detected 1 h after activation (5.0-fold increase) *The highest PDGF-BB concentrations were observed in PRP supernatants 3 days after activation (3.4-fold increase), whereas TGF-β1 concentrations was highest at 1 day after activation *IGF-1 concentrations in supernatants from non-activated PRPs were higher than activated samples * Infection rate of control group was significantly higher than vancomycin (P = 0.035), L-PRP gel with vancomycin (P = 0.02), and L-PRP gel only (P = 0.088) * L-PRP gel could promote bone regeneration effectively only when infection was controlled | No increase in growth factors or cytokines in unactivated PRP versus whole blood except for IGF-1 |
Aktan, 2013 [25] | In vivo (N = 5) | To investigate equine platelets on bacterial growth, their ability to release products with antimicrobial properties or to influence the antimicrobial actions of neutrophils | L-PRP gel versus PRP and PPP, PBS | * E. coli * S. aureus | * PRP and PPP inhibited growth of E. coli and the effect was more prominent with activated PRP at 0.5 and 2 h * Phorbol myristate acetate stimulated platelets and caused increased superoxide production; significant platelet superoxide production was not observed in response to strong platelet stimuli such as thrombin and platelet activated factor * LPS and LTA activated platelets as measured with increased P-selectin expression * LPS and LTA had no effect on platelet superoxide production or heterotypic aggregate formation * Coincubation of activated platelets with neutrophils did not increase neutrophil superoxide production | Equine |
Li, 2013 [41] | In vitro and ex vivo (N = 5) | To evaluate the antimicrobial and wound healing properties of PRP in spine infection rabbit model | PRP versus PBS | * MSSA * MSRA * Group A streptococcus * Neisseria gonorrhoeae | * PRP treatment has no significant antimicrobial effects against E. coli and Pseudomonas * PRP could significantly (80–100 fold reduction in CFUs at 200 IU/mL thrombin) inhibit the growth of MSSA, MRSA, Group A Streptococcus, and Neisseria gonorrhoeae within the first 2 h * The concentration of thrombin played a role in the antimicrobial properties of PRP; the higher the thrombin concentration (over the range of 20 to 200 IU/mL), the better the antimicrobial properties * PRP showed the capability to improve bone healing in the presence of a severe infection | Rabbit spine |
Różalski, 2013 [31] | In vitro (N = 5) | To evaluate microbicidal activity of platelets and their products against S. aureus in suspension (planktonic) and sessile (biofilm) cultures | PRP (Expired: 1–3 post shelf life) versus Müller–Hinton agar | * S. aureus | * Microbicidal activity of “expired” platelets and their lysates has been shown as a significant reduction in the population of staphylococci in their planktonic cultures by 56–87% and a decrease in metabolic activity of biofilm formation by 7–38% * Antibacterial effect was enhanced after activation with ADP * Platelet lysates showed a synergistic effect with β-lactam antibiotic (oxacillin) and glycopeptide (vancomycin) but not with oxazolidinone (linezolid) | No control for donors, pooled many donors, expired platelets |
Edelblute, 2014 [43] | In vitro and ex vivo (N = 3–7) | To quantify efficacy of human platelet gel against opportunistic bacterial wound pathogens A. baumannii, P. aeruginosa, and S. aureus on skin | PRP versus quiescent platelet pellet (minimally manipulated) | * A. baumannii * P. aeruginosa * S. aureus | * A. baumannii was significantly (P < 0.001) inactivated by both control and activated PG supernatants * S. aureus was significantly (P < 0.05) inactivated only by the thrombin- and PEF-activated supernatants * No significant inactivation was observed in the quiescent or CaCl2 enriched groups * P. aeruginosa was not inactivated in vitro; a low but significant inactivation level was observed ex vivo * PRP supernatants were quite effective at inactivating a model organism on skin in vivo | Well designed, expired platelets, multiple donors |
Intravia, 2014 [28] | In vitro (N = 2) | To investigate antibacterial properties of 2 PRP: platelet concentration preparations (PRP-LP and PRP-HP) | * PRP-LP: lower WBCs and platelet concentration * PRP-HP: high platelet and WBC concentration vs * Blood + PBS (negative control) * Cefazolin (positive control) | * S. aureus * S. epidermidis * MRSA * P. acnes | * Both PRP-LP and PRP-HP showed a significant decrease (P < 0.05) in bacterial growth at 8 h compared to whole blood * There was no statistically significant difference between PRP-LP or PRP-HP and cefazolin at 24 h * The effect of PRP-LP and PRP-HP on P. acnes and MRSA was minimal and may not be clinically significant * Despite differences in platelet and WBC concentrations, no difference in antibacterial activity was seen between PRP-LP and PRP-HP preparations | Two healthy donors; low sample size, and healthy PRP may not translate |
Frelinger, 2016 [9] | In vitro (N = 5) | To compare the ability of PEF, bovine thrombin, and TRAP to activate human PRP, release growth factors, and induce cell proliferation in vitro | PRP versus PRP treated with 0.9% sodium chloride, PPP | Not studied | * Both PEF and bovine thrombin reduced the average size of platelet-related (CD41-positive) particles, but the number of detectable CD41-positive particles after PEF activation was significantly higher than after bovine thrombin activation * Surface P-selectin was increased on particles following PEF activation but was increased to a greater extent by bovine thrombin and TRAP * PEF activation produced a higher number of procoagulant annexin V-positive particles. The total annexin V binding (a measure of phosphatidylserine expression) was similar after PEF and bovine thrombin activation * PEF activation of fresh PRP resulted in greater release of EGF than activation with bovine thrombin, whereas only TRAP activation resulted in significant release of angiostatin * Plasma containing the releasate from PEF-activated PRP induced significantly greater proliferation of an epithelial cell line than plasma recovered from vehicle-treated PRP | Healthy donors may not translate |
Mariani, 2015 [14] | In vitro (N = 10) | To compare in vitro microbicidal activity of platelets and L-PRP to P-PRP and the contribution of leukocytes to microbicidal properties | PRP versus L-PRP cryo and P-PRP | * E. coli * S. Aureus * K. pneumoniae * P. aeruginosa * E. faecalis | * L-PRP, L-PRP cryo and P-PRP generally induced comparable bacterial growth inhibition for up to 4 h incubation * The concentrations of soluble factors considered (MIP-1α/CCL3, RANTES/CCL5, GRO-α/CXCL1, NAP-2/CXCL7, IL-8/CXCL8, SDF-1α/CXCL12 and IL-6) were strongly correlated to bacterial growth inhibition, mainly from the second hour of incubation * E. coli inhibition showed correlations with RANTES, GRO-α, and SDF-1α concentrations (P ≤ 0.05) * S. aureus inhibition correlated with the concentrations of all the molecules excluded IL-6 (P ≤ 0.05) * K. pneumoniae, P. aeruginosa, and E. faecalis inhibition correlated with the concentrations of all microbicidal molecules considered (P ≤ 0.05) * L-PRP and L-PRP cryo exhibited similar microbicidal activity | Healthy donors may not translate, correlation of bacterial growth to soluble factors |
Lu, 2016 [36] | In vitro and ex vivo | To examine effects of a combined chitosan–gelatin sponge loaded with tannins and PRP (CSGT-PRP) on extent and rate of wound healing, antibacterial effects of the sponge, and stability of the wound dressing material | PDGF isolated from thrombocyte concentrate versus wound dressing and PRP, CSGT-PRP | * E. coli * S. aureus | * CSGT-PRP had good thermostability and mechanical properties as well as efficient water absorption and retention capacities * CSGT-PRP could effectively inhibit the growth of E. coli and S. aureus with low toxicity * CSGT-PRP healed wound quickly as observed macroscopically and by histological examinations | Healthy animals’ PRP may have different properties than those from infected animals |
Bayer, 2016 [21] | In vitro and ex vivo | To determine if Chitosan composite hydrogel system is an effective medium for antibiotic delivery in wound infection caused by S. aureus | Vivostat PRF® (thrombocyte concentrate) versus 0.9% sodium chloride | None | * PRGF increases hBD-2 expression in concentration- and time-dependent manner * PRGF mediated hBD-2 expression was mediated through EGFR and interleukin receptor (IL-6) * hBD-2 indication through PDGF required activation of transcription factor activator protein (AP-1), but not through nuclear factor kappa ĸB * Vivostat PRF mediated wound healing is mediated through hBD-2 expression | Healthy donors, no demographic information on the donors |
Nimal, 2016 [47] | In vitro | To develop a novel injectable hydrogel system for infectious wound treatment that can reduce the inflammatory phase (by inhibiting bacterial growth using tigecycline) and enhance the granulation phase (by addition of PRP) and simultaneously promote efficient wound healing | PRP from blood bank versus Tigecycline nanoparticles + chitosan hydrogel in PBS | S. aureus | * tg-ChPRP gel, and tg-ChNPs-ChPRP gel showed a significant zone of inhibition against S. aureus * ChPRP gel alone failed to demonstrate any antibacterial activity, and the incorporation of PRP in to the tg-Ch and tg-ChNPs-Ch gel did not enhance or inhibit antibacterial activity * ChPRP gel with the lowest concentration of tg-ChNPs (1 μg/mg) also showed a significant reduction in bacterial growth | No information on donor blood from blood bank; assume healthy non-infected donors |
Knafl, 2017 [33] | In vitro (N = 5) | To evaluate release kinetics of amikacin, teicoplanin, or polyhexanide from a PRF layer | PRF versus Trypsin only and PRF only (negative control) | * MSSA * MRSA * P. aeruginosa * K. pneumoniae | * Teicoplanin and amikacin released from PRF showed antimicrobial in vitro effects for almost a week * Antimicrobial effect of polyhexanide could only be verified for the first 24 h | Small sample size and limited information on donor plasma |
Bayer, 2018 [34] | In vitro | To demonstrate that PRGF induces antimicrobial peptides in primary keratinocytes and accelerates keratinocyte proliferation | Vivostat PRF® versus untreated using normal human epidermal keratinocytes cells | None | * PRGF stimulation caused a significant decrease in the Ki-67 gene expression in human primary keratinocytes, and EGFR is not essential to the PRGF-mediated reduction of Ki-67 gene expression in human primary keratinocytes * The interleukin-6 receptor (IL-6R) is not essential to the PRGF-mediated reduction of Ki-67 gene expression in human primary keratinocytes * IL-6 signaling is not involved in the PRGF-mediated reduction of the Ki-67gene expression in primary human keratinocytes | Healthy donors and no demographic information |
Cetinkaya, 2018 [44] | Ex vivo (N = 72) | To investigate antibacterial activity and wound healing effectiveness of PRP in MRSA-contaminated superficial soft tissue wounds in Wistar Rats | PRP and vancomycin versus Sham, PRP, MRSA, MRSA + PRP, MRSA + vancomycin, MRSA + vancomycin + PRP | MRSA | * MRSA counts were lowest in MRSA + vancomycin + PRP groups * Inflammation scores of MRSA + PRP, MRSA + vancomycin, and MRSA + vancomycin + PRP groups were significantly lower than the MRSA group * The inflammation score was significantly lowest in MRSA + PPRP + vancomycin suggesting synergistic effect of vancomycin | No a priori sample size calculation |
Cetinkaya, 2019 [45] | Ex vivo (N = 10) | To demonstrate in vitro antibacterial activity of PRP against MRSA and 3 more multi-drug resistant bacteria species that are important and hard-to-treat in wound infections | PRP gel versus PBS and PPP | * MRSA * Enterococcus spp * K. pneumoniae * P. aeruginosa | * PRP and PPP significantly suppressed bacterial growth of MRSA, K. pneumoniae, and P. aeruginosa as early as 1st, 2nd, 5th, and 10th hours of incubation (P < 0.05) compared to control * The antibacterial effect of PRP was more prominent compared to PPP * PRP and PPP showed limited activity against VRE | Healthy donors may not translate to clinical use |
Cieślik-Bielecka, 2019 [46] | In vitro (N = 20) | To evaluate the antimicrobial effect of L-PRP against selected bacterial strains and assess potential correlation with leukocyte and platelet concentrations | L-PRP versus acellular plasma | * S. aureus * E. coli * Cryptococcus neoformans * Candida albicans | * L-PRP possesses an in vitro antimicrobial activity against MRSA, MSSA, E. faecalis, and P. aeruginosa * L-PRP did not exert any antimicrobial activity against E. coli (extended spectrum beta lactamase), E. coli, and K. pneumoniae * A relationship was observed among selected leukocyte subtypes (T and B lymphocytic NK cells, monocytes, and granulocytes with CD45) and L-PRP antimicrobial activity | Healthy donor plasma may not have properties of patients who have infection |
Li, 2019 [29] | In vitro (N = 21) | To examine the potential mechanism underlying roles of PRP in treating diabetic foot ulcers | PRP and extract liquid of PRG versus PPP | * S. aureus | * PRG and EPG exhibited antibacterial effect against S. aureus * PRG and EPG protect HaCaT cells from bacterial damage and promote cell proliferation * Incubation of HaCaT cells with S. aureus decreased cell proliferation * The level of programmed cell death factor 4 and activity of NF-κB were increased in HaCaTcells with concomitant increased IL-6, TNF-α and decreased IL-10, TGF-β1 in cultured supernatant * EPG increased intracellular miRNA-21 while reducing PDCD4 expression and inhibiting NF-κB activity to suppress the inflammation in HaCaT cells * Both PRG and EPG had a significant reduction in bacterial count within 12 h (P < 0.01) compared to control | Used PRP from patients with infected foot ulcers |
Ikono, 2018 [49] | In vitro | To assess use of chitosan-PRP nanoparticles to improve the viability of PRP and prolonged release of growth factors | Chitosan-PRP nanoparticles | S. mutans | * Chitosan PRP nanoparticles had strong antibacterial activity against S. mutans (90.63% inhibition), suggesting a novel mechanism to deliver PRP in wounds to promote healing | No data on donors |
Author, year | Study type | Objective | PRP type versus control | Bacteria targeted | Results |
---|---|---|---|---|---|
Nimal, 2016 [47] | Drosophila model | To develop a novel injectable hydrogel system for infectious wound treatment that can reduce the inflammatory phase (by inhibiting the bacterial growth using tigecycline) and enhance the granulation phase (by the addition of PRP) and simultaneously promote efficient wound healing | PRP from blood bank versus Tigecycline nanoparticles + chitosan hydrogel in PBS | S. aureus | * tg-ChPRP gel, and tg-ChNPs-ChPRP gel showed a significant zone of inhibition against S. aureus |
* ChPRP gel alone failed to demonstrate any antibacterial activity, and the incorporation of PRP into the tg-Ch and tg-ChNPs-Ch gel did not enhance or inhibit antibacterial activity | |||||
* ChPRP gel with the lowest concentration of tg-ChNPs (1 μg/mg) showed a significant reduction in bacterial growth | |||||
Yassin, 2019 [48] | Rat model (N = 12) | To compare the efficacy of PRP wafers and PRP powder in terms of platelet count, antibacterial and healing effects in a rat model | PRP wafer and lyophilized PRP versus PRP-free wafer | A. baumannii | * PRP had antibacterial activity against A. baumannii |
* PRP wafer showed highest percent of wound size reduction on induced wounds in rat | |||||
* PRP wafers achieved the shortest healing time followed by lyophilized PRP powder and finally PRP-free wafer | |||||
Shibata, 2018 [37] | Rabbit model (N = 16) | To evaluate the effectiveness of the controlled release of PRP from biodegradable gelatin hydrogel used to promote healing in a rabbit ischemic sternal model | PRP versus no treatment | Sternal healing, no particular bacteria flora studied | * PRP gel group showed a significantly higher proportion of fibrosis within the fracture area (an indicator of sternal healing) than the other groups |
* PRP significantly increased the mean intensity of osteocalcin, suggesting bone regeneration | |||||
Farghali, 2018 [50] | Canine (N = 6) | To compare healing and bacterial clearance of MRSA-infected wounds and wound tissue expression of TNF-α, and VEGFA and the concentration of malondialdhyde and gluthathione reductase in wound tissue over time | PRP versus clindamycin | MRSA | The PRP experimental group demonstrated superior healing by all measures: clinical examination/measurement, clinical examination, bacterial growth evaluation, biochemical assessment of oxidative stress, quantification of the expression of growth factor and cytokine genes, histopathological analysis, and immunohistochemical evaluation. PRP had a strong effect on MRSA; notably however, this effect was only observed when PRP was activated with CaCl2 |
Li, 2013 [41] | New Zealand rabbits (N = 50) | To compare MRSA-induced osteomyelitis treatment outcomes radiologically, microbiologically, and histologically | L-PRP gel versus no treatment, debridement and parenteral treatment with vancomycin (VAN) alone, L-PRP gel + VAN, L-PRP gel injection | MRSA | L-PRP gel + VAN group exhibited best therapeutic efficacy for bone healing and infection elimination. Best in vivo efficacy was for vancomycin, although PRP also demonstrated antibiotic efficacy |
Author, year | Design, no. subjects | Indication | Objective | PRP type used | Control | Types of bacteria targeted | Results | Oxford level bias notes |
---|---|---|---|---|---|---|---|---|
Dorge, 2013 [5] | Randomized (N = 196) (underpowered and no a priori power and sample size estimate so no stopping criteria) | DSWI | To investigate whether topical application of autologous PRP reduced the incidence of DSWI in patients with high risk undergoing cardiac surgery with full sternotomy | PRP (N = 97) | Wound care (N = 99) | Not reported | * In PRP group 6 (6.2%) patients had DSWI versus 3 (3.0%) patients in control group | 2b |
Serraino, 2015 [32] | Retrospective (N = 1093) | DSWI | To evaluate whether PRP applied inside the sternotomy wound would reduce the effect of sternal wound infections, both superficial and deep | PRP | Median sternotomy but without PRP application | Not reported | * Occurrence of DSWI was significantly higher in control than PRP group (10/671, 1.5% versus 1/422, 0.2%, P = 0.043) | 2b |
* Superficial sternal wound infections (SSWIs) were significantly higher in control than PRP group (19/671, 2.8% versus 2/422, 0.5%, P = 0.006) | ||||||||
* PRP can significantly reduce occurrence of DSWI and SSWI in cardiac surgery | ||||||||
Hamman, 2014 [3] | Retrospective (N = 1866) | Severe DSWI | To evaluate impact of vancomycin, calcium-thrombin, and PRP in practice on incidence of severe DSWIs in a single surgeon’s patient population | PRP (N = 548) | Historical control (N = 1318) received routine antibiotic prophylaxis | Not reported | * Overall, 11 patients (0.59%) developed severe DSWIs (categories 5 and 6) in control group | 2c |
* No severe incidence of DSWI in the intervention group (548 patients) | ||||||||
Patel, 2016 [4] | Prospective (N = 2000) | DSWI | To analyze addition of PRP using a rapid point of care bedside system to standard wound care in all patients undergoing sternotomy for cardiac surgical procedures | Autologous PRP (N = 1000) | Standard of care sternal closure including preoperative antibiotics (N = 1000) | Not reported | * PRP reduced incidence of DSWI from 2.0 to 0.6%, SWI from 8.0 to 2.0%, and readmission rate from 4.0 to 0.8% | 2b |
* PRP reduced costs associated with development of deep and superficial wound complications from $1,256,960 to $593,791 | ||||||||
Wozniak, 2016 [51] | Prospective (N = 34) | Leg ulcers | To perform qualitative analysis of microbial flora in venous leg ulcers treated with PRP | PRP | Pretreatment microbial flora | * P. aeruginosa | * PRP given as intradermal injection and after PRP therapy, a significant healing improvement was shown in 21 subjects (61.8%), as assessed by decrease in wound size | 4; underpowered |
* S. aureus | * There was no improvement in 13 subjects (38.2%) | |||||||
* E. faecalis | * S. aureus and P. aeruginosa were most commonly identified bacteria | |||||||
* B. fragilis | * 83 different microbial flora were identified from wound | |||||||
* 83 microbial flora identified from wound | * After PRP therapy, 110 bacterial isolates were obtained from samples collected after a single, local application of PRP | |||||||
* The mean number of bacterial species isolated per subject was 2.44 ± 0.22 before and 3.24 ± 0.29 after PRP | ||||||||
Englert, 2005 [53] | Prospective, randomized (N = 34) | Cardiovascular surgery | To examine effects of autologous platelet gel on postoperative sternal wound healing by subjective reports of chest and leg pain, amount of measurable bruising, and platelet indices pre- and postoperatively | PRP gel | Standard of care | * There was a significant decrease in chest and leg pain with PRP treatment | 4 | |
* PRP decreased bruising but was not statistically significant compared to control | ||||||||
Tran, 2014 [54] | Prospective, single arm (N = 6) | Diabetic foot ulcer | To examine effects of autologous platelet gel on postoperative sternal wound healing by subjective reports of chest and leg pain, amount of measurable bruising, and platelet indices pre- and postoperatively | PRP gel | Not reported | * PRP and PPP application caused increased wound healing (100%) by week 7 | 4 | |
Vang, 2017 [55] | Prospective, randomized (N = 38) | Surgical wound healing | To examine whether autologous platelet gel to sternum and saphenous vein harvest site was beneficial to patients undergoing coronary artery revascularization in terms of pain, blood loss, discoloration, and surgical site infection | PRP gel | Standard wound care without PRP | * 8 patients discontinued the study due to complication with coronary artery bypass graft surgery | 4 | |
* There was no incidence of deep or superficial sternal infections | ||||||||
* One patient from treatment and control group experienced a leg infection at the saphenous vein harvesting site after hospital discharge | ||||||||
* Patients reported less postoperative pain in PRP group versus control group |
Data synthesis
Study selection, risk of bias, and quality assessment
Level | Therapy/prevention/etiology/harm |
---|---|
1a | Systematic review (SR) (with homogeneity*) of RCTs |
1b | Individual randomized controlled trial (RCT) (with narrow confidence interval”) |
1c | All or none§ |
2a | SR (with homogeneity*) of cohort studies |
2b | Individual cohort study (including low quality RCT; eg, < 80% follow-up) |
2c | “Outcomes” Research; Ecological studies |
3a | SR (with homogeneity*) of case–control studies |
3b | Individual Case–Control Study |
4 | Case-series (and poor-quality cohort and case–control studies§§) |
5 | Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles” |
A | Consistent level 1 studies |
---|---|
B | Consistent level 2 or 3 studies or extrapolations from level 1 studies |
C | Level 4 studies or extrapolations from level 2 or 3 studies |
D | Level 5 evidence or troublingly inconsistent or inconclusive studies of any level |
* | By homogeneity we mean a systematic review that is free of worrisome variations (heterogeneity) in the directions and degrees of results between individual studies. Not all systematic reviews with statistically significant heterogeneity need be worrisome, and not all worrisome heterogeneity need be statistically significant. As noted above, studies displaying worrisome heterogeneity should be tagged with a “-” at the end of their designated level |
“ | Clinical Decision Rule. (These are algorithms or scoring systems that lead to a prognostic estimation or a diagnostic category) |
“¡ | See note above for advice on how to understand, rate and use trials or other studies with wide confidence intervals |
§ | Met when all patients died before the Rx became available, but some now survive on it; or when some patients died before the Rx became available, but none now die on it |
§§ | By poor quality cohort study we mean one that failed to clearly define comparison groups and/or failed to measure exposures and outcomes in the same (preferably blinded), objective way in both exposed and non-exposed individuals and/or failed to identify or appropriately control known confounders and/or failed to carry out a sufficiently long and complete follow-up of patients. By poor quality case–control study we mean one that failed to clearly define comparison groups and/or failed to measure exposures and outcomes in the same (preferably blinded), objective way in both cases and controls and/or failed to identify or appropriately control known confounders |
§§§ | Split-sample validation is achieved by collecting all the information in a single tranche, then artificially dividing this into “derivation” and “validation” samples |
” “ | An “Absolute SpPin” is a diagnostic finding whose Specificity is so high that a Positive result rules-in the diagnosis. An “Absolute SnNout” is a diagnostic finding whose Sensitivity is so high that a Negative result rules-out the diagnosis |
“¡”¡ | Good, better, bad and worse refer to the comparisons between treatments in terms of their clinical risks and benefits |
”” “ | Good reference standards are independent of the test and applied blindly or objectively to applied to all patients. Poor reference standards are haphazardly applied, but still independent of the test. Use of a non-independent reference standard (where the ‘test’ is included in the ‘reference’, or where the ‘testing’ affects the ‘reference’) implies a level 4 study |
””” “ | Better-value treatments are clearly as good but cheaper, or better at the same or reduced cost. Worse-value treatments are as good and more expensive, or worse and the equally or more expensive |
** | Validating studies test the quality of a specific diagnostic test, based on prior evidence. An exploratory study collects information and trawls the data (eg, using a regression analysis) to find which factors are ‘significant’ |
*** | By poor quality prognostic cohort study we mean one in which sampling was biased in favor of patients who already had the target outcome, or the measurement of outcomes was accomplished in < 80% of study patients, or outcomes were determined in an unblinded, non-objective way, or there was no correction for confounding factors |
**** | Good follow-up in a differential diagnosis study is > 80%, with adequate time for alternative diagnoses to emerge (for example 1–6 months acute, 1–5 years chronic) |
Author year | Selection bias | Performance bias | Detection bias | Attrition bias: complete outcome data? | Reporting bias: non-selective outcome reporting? | No other sources of bias? | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
Randomization? | Random sequence generation? | Baseline characteristics equal? | Allocation concealment? | Random housing? | Blinding? | Random selection outcome assessment? | Blinding? | ||||
Yassin, 2019 [48] | No | No | No | No | No | No | No | No | Yes | Yes | Yes |
Farghali, 2018 [50] | No | No | Yes | No | No | No | No | No | Yes | Yes | Yes |
Shibata, 2018 [37] | Yes | No | Yes | No | No | No | No | No | Yes | Yes | Yes |
Nimal, 2016 [47] | No | No | No | No | No | No | No | No | Yes | Yes | Yes |
Cetinkaya, 2018 [45] | Yes | No | Yes | No | No | No | No | No | Yes | Yes | Yes |
Literature search results
Study selection
Variable methods of PRP separation
Bench experiments
Preclinical literature
Clinical studies
Discussion
Does PRP exert an antibacterial effect?
Required sample size a priori | Achieved power post hoc | ||
---|---|---|---|
Input | |||
Proportion p2 | 0.01 | 0.016 | 0.026 |
Proportion p1 | 0.03 | 0.006 | 0.1 |
α err prob | 0.05 | 0.05 | 0.05 |
Power (1 − β err prob) | 0.8 | 0.8 | – |
Allocation ratio N2/N1 | 1 | 1 | – |
Sample size group 1 | – | – | 1000 |
Sample size group 2 | – | – | 1000 |
Output | |||
Critical z | 1.9599640 | 1.9599640 | − 1.9599640 |
Power (1 − β err prob) | – | – | 0.9999995 |
Sample size group 1 | 769 | 1707 | – |
Sample size group 2 | 769 | 1707 | – |
Total sample size | 1538 | 3414 | – |
Actual power | 0.8005067 | 0.8000975 | – |