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Skin Integrity and Pressure Injuries

Sustained-Release Platelet-Rich Plasma Therapy in Grade IV Pressure Injuries

Platelet-rich plasma is an enriched source of growth factors and cytokines that are critical to tissue regeneration and resolution of inflammation. PRP therapy has been used successfully in orthopedic medicine for the repair of cartilaginous and ligamentous damage (Alsousou et al. 2009). People with SCI often have multiple co-morbidities that contribute to chronic inflammation and non-healing ulcers. PRP therapy has also been used for the treatment of chronic skin ulcers (Anitua et al. 2008).

Author Year
Country
Research Design
Sample Size

Methods

Outcome

Singh et al. 2015
India
Prospective Controlled
Trial
N=25
Population: Mean age=36.84 yr; Gender: males=19, females=6; Level of injury: cervical=6, D1-D11=6, D12-L1=11,
lumbar=2; ASIA classification: A=13, B=4, C=7, D=1; Pressure injury stage: Treatment ulcers: IV=25; Control ulcers: II=11, III=4, IV=10.
Intervention: Secondary analysis of Singh et al., 2014 to evaluate antimicrobial properties of platelet-rich plasma (PRP) in pressure injuries. Participants received treatment (PRP dressing) for one ulcer with the other ulcer serving as a control (saline dressing).
Outcome Measures: Bacterial colonization.
1. Colonization rate decreased from 92% at enrollment to 24% at 5 wk for treatment ulcers and from 84% at enrollment to 76% at 5 wk for control ulcers.
2. At 5 wk, treatment ulcers had significantly fewer positive bacteria cultures than control ulcers (p=0.007).
Singh et al. 2014
India
Prospective Controlled
Trial
N=25
Population: Mean age=36.84 yr; Gender: males=19, females=6; Level of injury: cervical=6, D1-D11=6, D12-L1=11, lumbar=2; ASIA classification: A=13, B=4, C=7, D=1; Pressure injury stage: Treatment ulcers: IV=25; Control ulcers: II=11, III=4, IV=10.
Intervention: Each participant had one pressure injury receive treatment and one pressure injury serve as a control (twice weekly dressings with a minimum of 10 dressings). Treatment group: Wound dressed with about 6 mL of platelet-rich plasma (PRP) and calcium chloride in addition to usual care (normal saline cleaning and debridement). Control group: Wound dressed with normal saline and usual care.
Outcome Measures: Wound-site measurement; Pressure injury Scale for Healing (PUSH); Clinical examination.
1. At 5 wk post-intervention, both treatment and control ulcers showed
statistically significant decreases in PUSH (p<0.001) but no significant differences between groups.
2. From baseline to final follow-up at 6 wk, wound surface area decreased significantly more in the treatment than the control ulcers (p=0.002). Mean percentage of surface area healed was 57.94% in treatment ulcers and 2.36% in control ulcers. 3. 96% of treatment ulcers improved compared to 68% of control ulcers.
Biglari et al. 2015
Germany
Post-test
N=15
Population: Mean age=38.2 yr; Gender: males=7, females=8; Level of injury: paraplegia=13, tetraplegia=2; ASIA classification: A=15; Pressure injury stage: III=12, IV=3.
Intervention: Participants with nonhealing fistulas following multiple surgical interventions for pressure injuries received 7-9 mL of platelet-rich plasma (PRP) and thrombin from autologous blood after debridement of the fistula.
Outcome Measures: Secretion; Closure of fistulas; Recurrence of pressure injuries
1. At 3 d post-intervention, there was minimal secretion from suture lines in all participants and at 1 wk, there was no secretion around the bandages.
2. At 3 wk post-intervention, fistulas from all participants were closed with no allergic reactions or incompatibilities.
3. At 12 mo follow-up, no participants returned for treatment of their pressure injuries.
Sell et al. 2011
USA
Case Series
N=3
Population: Mean age: 50 yr; Gender: male=3, female=0; Level of injury: paraplegic=1, tetraplegic=2; Wound status: grade IV ulcer=3.
Intervention: Treated with a sustained release platelet-rich plasma (PRP) therapy to stimulate wound healing.
Outcome Measures: Formation of tissue, vascularity, ulcer area, and volume.
1. Treatment resulted in the formation of granulation tissue.
2. Improved vascularity for each patient treated.
3. Overall ulcer area and volume decreased.

Discussion

A prospective controlled trial by Singh et al. (2014) evaluated the local application of platelet-rich plasma (PRP) in relation to pressure injury (PI) healing on one PI case versus saline dressing on another PI (control) in the same patient. Twenty-five SCI patients with ³2 PIs were included. A statistically significant decrease in mean PUSH scores and wound surface area of PIs (case) (P=0.000 respectively) was observed after five weeks. Mean PUSH scores decreased significantly in controls (P=0.000), however, the decrease in wound surface area of PI (control) was not significant (P=0.924). Advanced wound therapy using local applications of PRP seems to be a promising alternative to standard saline dressings in PI healing. With the advantages of simple preparation, biocompatible safety, low cost, and significant clinical effectiveness, it may be beneficial to study the effects of PRP in large-scale trials to validate it as an ideal therapy for enhanced wound healing in PIs.

Singh et al. (2015) conducted a follow-up to their previous prospective controlled trial to study the source of microbial colonization and antimicrobial properties of autologous platelet-rich plasma (PRP) in controlling it in PIs. Colonization rate of PIs (case) decreased from 92%-24% from enrollment to the 5th week but did not significantly decrease in PIs (control). Association between PI (case) and perineal cultures was observed for Staphylococcus aureus at enrollment 41% (P< 0.01) and at the 2nd week 47% (P< 0.05). 47% association between PI (control) and perineal cultures at enrollment (P< 0.05) and 29% association at the 2nd week (P< 0.01) were observed for Staphylococcus aureus. Thus, the study authors concluded that there is a significant association between PIs colonization and bacteria present in local environment (urine and feces). Local application of autologous PRP changes the “biological milieu” of the PIs through its antimicrobial properties leading to reduction in bacterial colonization.

A post-test by Biglari et al. (2015) aimed to determine the effectiveness of platelet-rich plasma (PRP) in the treatment of nonhealing fistulas in 15 SCI patients. After one week of treatment with PRP, the authors observed low levels of secretion from the fistulas. After two weeks, they noted no further secretion from the fistulas. After three weeks, MRI showed the complete disappearance of the fistulas. No negative effects and no allergic reactions were noted in the use of PRP. These results suggest that the application of PRP combined with debridement is an effective therapy option and good alternative to recurrent surgical interventions for treating nonhealing fistulas resulting from the surgical closure of PIs.

Sell et al. (2011) sought to use immediate and sustained-release CaCl2-activated PRP therapy for the purpose of improving stage IV (sacral or greater trochanter) pressure injury healing in three veterans with SCI. Each patient underwent a different course of treatment (e.g., one patient underwent vacuum therapy and skin allograft) before healing rates stalled or plateaued. PRP therapy accelerated pressure injury healing in all three patients but more so in the patient whose pressure injury was not undermined. The two patients with severely undermined pressure injuries did improve with respect to increased granulation and vascularity of tissue in-growth. These latter two patients’ pressure injuries were also in more pressure-sensitive locations which may have additionally contributed to slower improvement. This small case study of reactivated pressure injury healing in three patients is a promising indicator for a larger scale study to investigate the invigoration of healing in severe, non-healing pressure injuries.

Although SCIRE criteria do not allow for single case studies, the single case study by De Angelis et al. (2012) increases the total sample size of patients by 33% and therefore is added here until future studies involving a larger sample size is available. In total, all four severe, non-healing ulcers reflected in these two studies showed improvement in healing as a result of PRP therapy.

Conclusion

There is level 2 evidence (from one prospective controlled trial: Singh et al. 2014) that advanced wound therapy using local applications of PRP seems to be a promising alternative to standard saline dressings in PI healing.

There is leve 2 evidence (from one prospective controlled trial: Singh et al. 2015) that local application of PRP may reduce bacterial presence and colonization in PIs.

There is level 4 evidence (from one case series and one post-test: Sell et al. 2011; Biglari et al. 2015) that supports the possibility of platelet-rich plasma therapy facilitation of reactivated healing in severe, non-healing pressure injuries, post-SCI.

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