PLASMA RICH PLASMA AND THE TISSUE REPAIR PROCESS IN CHRONIC WOUNDS PLASMA RICO EM PLAQUETAS E O PROCESSO DE REPARAÇÃO TECIDUAL EM FERIDAS CRÔNICAS

Objective: To verify the topical use of platelet-rich plasma in the tissue repair process of chronic wounds. Method: narrative review in the Scielo, Lilacs and Medline databases through controlled health descriptors. The search resulted in the selection of a sample made up of 10 studies, according to inclusion and exclusion criteria. Data analysis was performed based on an analysis of thematic categorical content. Results: It was evident that scarcity of research that addresses the theme and discrepancy between studies found, since some claim that platelet-rich plasma is effective and others report that there is no clinical efficacy. As a result, it can be concluded that these false negatives may occur because they do not have a specific protocol for obtaining platelet-rich plasma, which may alter the concentration of platelets. Conclusion: There is a need for more studies with a sample and longer observation time, as well as to see the need to establish a procurement protocol that must be followed in all surveys. Studies need to be carried out with a sample and longer observation time, as it is necessary to establish a procurement protocol that must be followed in all surveys in order to arrive at a more solid result.


INTRODUCTION
A wound is represented by the lost of skin continuity, and it could reach deeper skin structures such as muscles, tendons and bones, being caused by any kind of trauma, being it physical, chemical, mechanical or triggered by a clinical condition that activate the organic defense for counter-attack. (1) They can be classified according to evolution, which could be acute or chronic; according to the presence of infection, which could be not contaminated clean, clean contaminated, contaminated or unclean and infected; according to how deep it is and/or the cause, being classified as intentional or not intentional; and surgical or traumatic. (2) Chronic wounds are those which do not heal spontaneously and require a bigger time period than 12 weeks to heal and, frequently, show relapses and infectious process or even when associated with systemic pathologies could harm the healing process (3)(4)(5)(6) . Among the surgical wounds, diabetic ulcers, vein ulcers and pressure lesions are highlighted, which generally are harder to treat and affect the patient's quality of life and the financial costs of health in Brazil (4,7) . Due to that, wounds are considered an issue of public health, tackling, specially, about 4% of the elderly population worldwide (8)(9) .
In the face of the complexity, the healing process of wounds is a dynamic process that involve cellular and molecular phenomena that interact so that the tissue repair can happen (10) . It is regulated by events of coagulation, inflammation, formation of granulated tissue, epithelialization and tissue remodeling, which are mediated and modulated by cytokines and growing factors (11) .
Some studies show that in chronic wounds there is reduction of the growing factors (FC) by decrease of production and decrease in liberation, or even by its fast metabolism, due to protainases present in the wound, originated by bacteria or cells. In diabetic ulcers and vein insuffiency, however, the decrease of FC is due to the kidnapping mechanism by the fibrin that surrounds the capillaries, and with that, the plasma rich in platelets (PRP) can be used to put back these growing factors (12) .
The PRP is a product originated by the laboratorial processing of autogenous blood, rich in growing factors that come from alphaplatelets granules. It is a organic, not toxic and not immunerreactive, that has been used to accelerate the wound repair, from the various growing factors it holds. The FCs don't get inside the cell or its core, eliminating the possibility of any mutagenic effects. On the other hand, it stimulates the normal healing of the tissue, promoting a higher speed for the healing process. The use of PRP is safe, not showing any tendency to tumor activation (13) .

METHOD
This study is a narrative review, which is defined as the one that condensates previous researches and takes global conclusions from a specific body of literature, allowing the construction of wide analysis, contributing for discussions about methods and research results and resulting in a new learning (14) .
Six steps were taken for the elaboration of this study: elaboration of northing question, search in literature, data collection, critical analysis of the studies included, discussion of the results and presentation of the review (15) .

RESULTS
The production about PRP is very wide, but it has more emphasis in the area of oral, musculoskeletal and joint surgeries and esthetic medicine. Apart from that, this theme has been more spoken about when it comes to the repair of chronic skin lesions.
However, most studies are clinical trials with animals, which made it harder to the search for the review analysis. As it can be observed, after utilization of filter and rigorous analysis, contemplating the criteria of inclusion delineated, it came to ten articles, which are described in Chart 1, with the variable: title, author, year and periodic. It was observed the decrease of healing time in comparison to conventional treatment, but it is still not possible to recommend this treatment due to the lack of rigorous studies.

Chart 1 -Characterization of publication with titles, authors, year of publication and periodic
2 Report the use of PRP therapy singly and in combination with a skin substitute genetically modified as skin graft rich in platelets in wound.

Case Report
The combination brought dramatic results, eliminating tunneling and reducing the wound's dimension, but indicates that more studies are needed. 3 Show results of the utilization of PRP and PRP activated by CaCl 2 for liberation supported by FC and cytokines to stimulate the healing process in pressure ulcers.

Case Report
The treament with PRP consistently resulted in the formation of granulated tissue and improved the vascularization for each of the three patients treated, while reducing the area and general volume of the ulcer. 4 Evaluate the local application of PRP in relation to the healing process of pressure ulcers in one (case) versus saline curative in another PrU (control) in the same patient.

Prospective Study
The area of the surface of the wound of the pressure lesion (case) decreased significantly.

5
Analyze bibliographic information about the use of alternative and conventional ways for the management of vein ulcers.

Integrative Review
The publications approach various themes, such as its use in the treatment of chronic wounds in diabetic patients, in the evaluation of the speed of epithelialization of areas that could be donated for skin grafts and closing of chronic ulcers due to vascular insuffiency, among others. 9 To evaluate the results of PRP application in surgeries of skin graft in chronic wounds.

Random Prospective Study
There was a better integration of the grafts in the side that received PRP than in the other side of the same wound, but without PRP. 1 0 To establish a cheap and efficient method for the preparation of plasma rich in platelets and growing factors for utilization in plastic surgery.

Laboratory Research
The use of a strength and time of centrifugation in two steps had a platelet concentration different from the sample.

DISCUSSION
For discussion, three categories were identified: process of acquisition of plasma rich in platelets, PRP components and PRP in the Healing Process Chronic Wounds.

Category 1: Process of acquisition of plasma rich in platelets (PRP)
The plasma rich in platelets is obtained through the blood of the patient through steps to reach cellular separation: blood sampling, centrifugation, separation of the plasma rich in platelets, activation of coagulation by adding calcium chloride and topical application of PRP after gelation (7,16) . In another way, 50 to five minutes later, the gel is formed (7,17,18) .  (19,20) .
Considering the ways shown for PRP acquisition, it can be observed that there isn't a specific protocol, which can cause variations and differences in the platelet concentration and, consequently, in growing factors.
From a relation between the blood sample and the strength and time it was observed that in the first centrifugation higher platelet concentration were obtained when using a strength of 300g for 10min, in which it was obtained an average 4,54 times higher than the blood sample. In the second centrifugation were reached when using the strength of 640g for 10min, obtaining an average 4,96 times higher than the blood sample (17) .

Components
The healing properties of PRP are based by the platelets, that have growing factors with an important part in tissue repair.
These factors could contribute to the formation of tissue and epithelialization, with the platelets having at least five of these: growing factor derived from platelets (PDGF), platelet factor 4, transformative growing factor β, angiogenesis factor derived from platelets and epidermal growing factor derived from platelets, that when are liberate stimulate and modulate multiple biological processes that are important for the wound's healing (16,17,20,21,22) .
In another studies, it was observed that after the activation with calcium, the platelets and interferonalpha (INFα).

Category 3: PRP in the Healing Process of Chronic Wounds
The PRP is used as treatment in many types of lesions, such as corneal ulcers, vasculitic, neuropathic, diabetic foot and skin grafts, among others (16,22) . It has growing factors that help accelerate the healing process wounds (7,17,19,22,23) .

It can be observed results in Pressure
Lesions (LP), vein and diabetic ulcers, with the formation of granulated tissue, vascularization and epitheliazation. It is believed that therapy with PRP is a promising technique that could reduce the economic impact for the patient and for the health system, because its cost of acquisition is reasonably low (7,16,19) .
The decrease of costs could be associated with the decrease of the time of the healing process when compared to conventional treatment, and besides that, contribute to the improvement of the patient's quality of life (7,16,19,24) .  (22) .
It has been observed that some authors can't find pre-clinical evidences of the use of PRP in LP, but there were few studies that showed that it led to reactivation and accelerated the healing process of the LPs (19) .
In diabetic ulcers it was also observed the acceleration of the healing process, with an average of 12 weeks of treatment and variations of 8 to 40 weeks (20) .
Since the researchers couldn't reach an agreement on the adequate values for acquisition of the plasma, this could be one of the difficulties found for the evaluation and comparison of results of scientific works.
Because of this, it is highlighted the concern in obtaining a standardization for the acquisition of these components (22) . This discrepancy makes some professionals fear making use of these new treatment because of the lack of scientific basis that makes it easier for an integral approach (24) .
However, it must be pointed out that, due to the fact that it is autologous, there is no counter indications for its utilization and it has no risks for transmission of infectious diseases, but the handling should be done with caution, and utilizing aseptic techniques so that there isn't contamination. Besides, it is a minimally invasive technique and very well accepted by the patients that could be used weekly (18,23) .
Another important fact that should be highlighted is that in autologous PRP treatment, no complication was observed, however 2% to 5% of patients could show adverse effect such as pain or local edema, or a decline in the hemoglobin levels (19,20) .
However, PRP turned out to be an alternative treatment or as adjuvant in another therapeutic, which could be implanted in public hospitals, because it is low cost, although it needs trained personnel for the plasma acquisition (18,24) .

CONCLUSION
The research has determined that in spite of PRP being a technique used in esthetic procedures, buccomaxillary facial and musculoskeletal surgeries, it still is considered "news" in the process of tissue repair, but it presents itself as a promising therapy in many types of skin lesions. However, it becomes clear that there is a need of more studies with a sample and higher time of observation, and also to see the need to establish an acquisition protocol that should be followed in every study to improve the viability of its practical application.