PLASMA RICH IN THROmbocyte(PRP)
Platelet rich plasma (PRP) was developed in the early 1970s as a by-product of multicomponent blood products. Although it has been known to be used especially in orthopedic, 1 periodontic, 2 maxillofacial, 3 plastic, 4 thoracic, 5 vascular surgery6-7 and ophthalmology8 since those years, its use in new indications in dermatology practice has recently attracted attention.
Autologous platelet-rich plasma; It refers to the plasma with a high concentration of platelets rich in growth factors, obtained from the person’s own blood using a centrifuge. Platelet density and activity in PRP is 4 times higher than in whole blood9. Platelets; In addition to its role in hemostasis, it also has an important role in tissue repair by secreting growth factors from α-granules in tissue damage10. alpha granules; platelet-derived growth factor ( platelet-derived growth factor: PDGF), transforming growth factors α and β ( transforming growth factor: TGF- α and TGF- β), epidermal growth factor ( epidermal growth factor: EGF) and vascular endothelial growth factor ( vascular endothelial growth factor : VEGF) also contain cytokines and chemokines. PDGF; It increases the number of fibroblasts in the damaged area by stimulating the growth of endothelial cells, and ensures the differentiation of neutrophils and monocytes. Thus, capillary vessel formation, increasing collagen production and granulation formation are supported. TGF-β is vital in the restructuring of the skin: for example, it not only stimulates collagen synthesis during the wound healing process, but also participates in the inflammatory response with PDGF and stimulates extracellular matrix synthesis12. EGF takes part in chemotaxis and stimulates the proliferation of keratinocytes and fibroblasts. Proliferating fibroblasts increase collagen production. VEGF stimulates the proliferation of endothelial cells, thereby increasing new vessel formation, increasing existing capillary permeability and contributing to the microenvironment necessary for cell growth and angiogenesis. Insulin-like growth factor ( Insulin like growth factor : IGF) has a chemotactic role for vascular endothelial cells, including IGF-1 and IGF-2. Thus, it stimulates the migration of vascular endothelial cells to the damaged area, supports angiogenesis, and increases the rate of endothelial and epidermis regeneration with PDGF 12-16.
Dermatological uses of PRP
The idea of using platelet-rich plasma in therapy stemmed from the fact that it contains a large amount of growth factor. Growth factors are clinically used in the treatment of chronic wounds, soft tissue damage, bone disorders, wrinkle removal and acute traumas. They are used in dermatological applications in various indications13-20. The results in these areas of use presented in Table 1. are based on clinical observations, and controlled studies are needed.
In a study by Eppley et al.13, it was suggested that autologous platelet factors can be used to accelerate epithelialization of granulation tissue in the treatment of chronic, non-healing cutaneous ulcers. This study is reported to be the first clinical application using autologous blood-derived activating factors that accelerate the healing of chronic skin ulcers. In another study, PRP was used in ulcers on the skin, and it was shown to be effective in accelerating the formation of granulation tissue and epithelialization in the tissue12.
Platelet-rich plasma is very effective in facial and neck wrinkles, skin sagging and pigmentation problems that occur with the decrease of the supporting tissues of the skin over time. skin aging; It is a natural result of the interaction of environmental factors such as smoking, sun exposure (photoaging) and exposure to various chemicals, as well as the decrease in the protective functions of the skin as a result of chronological aging. It has been shown that UVB, which is the most important cause of photoaging, increases collagenase production from dermal fibroblasts and stimulates collagenase gene expression21,22. In skin exposed to continuous UVB, collagen degeneration, disruption of dermal extracellular matrix integrity and changes in elastic tissue cause a decrease in skin resistance, leading to wrinkles. Application of topical growth factors; By increasing the synthesis of new collagen, it provides rejuvenation of the photo-aged facial skin and improves the clinical appearance17. Na JI et al.14 reported that after the application of PRP to patients after the fractional carbon dioxide laser applications used in wrinkle reduction and scar treatment, there was an acceleration in wound healing, a decrease in temporary undesirable effects such as erythema, and an increase in skin firmness. PRP provides adequate vascularization without causing excessive vessel formation. Thus, the period of erythema that can develop after fractional resurfacing CO2 laser is shortened14.
PRP application is successfully applied in the upper face area, forehead, eye wrinkles, zygomatic region sagging. Effective results are obtained as a result of PRP application in the wrinkles of the nose edge, sagging of the chin corners, sagging under the chin, wrinkles and sagging on the neck and décolleté in the middle and lower face area23.
Lee et al.15 observed that the addition of PRP injection to ablative carbon dioxide fractional laser application in the treatment of acne scars resulted in a faster recovery, although it was not statistically significant. In this study, after applying fractional laser, 0.3 ml of PRP was applied intradermally to 20 points, 1.5-2 cm apart, on one side of the face, and the results after 4 months were compared with the other half of the face that was applied saline. The procedure was repeated after 1 month15.
On the other hand, Jeong et al.24 reported that they obtained satisfactory results with intralesional PRP application in a case with treatment-resistant lipodermatosclerosis.
TGF-β in PRP; It stimulates basement membrane protein secretion such as laminin, collagen IV and tenascin. It has been reported that pigmentation does not develop after fractional CO2 laser applied for lesions such as incontinence pigment, thanks to the rapid repair of the basement membrane. On the other hand, TGF-β is known to reduce melanogenesis25. Thus, it can be applied to pigmentation disorders caused by pregnancy, old age, sun damage, scars and striae on the skin.
With the PRP application, successful results are obtained in people with complaints of hair loss, broken hair, lifelessness and dull appearance on the scalp. Besides stopping hair loss, it activates hair growth by stimulating hair follicles. When the growth of thin hair is activated, they gain a thicker, healthier appearance. PRP application does not ensure the regrowth of the hair that has been completely shed over time, it ensures that the existing hair is healthier, the shedding stops, and the hair becomes healthier. Takikawa M et al.26 also reported positive results in hair growth with PRP applications.
PRP preparation and application
Although there are various PRP preparation methods, few of them have been approved by the FDA (Ex: Smart PReP and platelet concentration collection system: PCCS). Platelet concentrations in plasma obtained with different systems increase 2-8 times, so the growth factors they contain are different27,28. Practitioners should prefer FDA-approved systems that can obtain more growth factors. To prepare the PRP, venous blood (anticoagulant/blood ratio: 1/10) is taken from the patient into anticoagulant tubes containing acid citrate dextrose (ACD), and shaken for 10 seconds to mix with each other. When centrifuged at low speed (3000rpm, 3 minutes), three sections are distinguished in the tube. erythrocytes in the lower part, in the middle part buffy coatThe platelet-leukocyte mixture called the platelet, and the plasma at the top. buffy coatConcentrated PRP can be used by carefully withdrawing or buffy coat and when the upper platelet-poor plasma is centrifuged again at 4000 rpm for 3 minutes, concentrated PRP is obtained15. The plasma obtained is only 10% of the blood taken. It is activated by adding platelet agonists such as thrombin, calcium gluconate or calcium chloride. Thus, platelets degranulate and growth factors are given to the environment. The release of these factors begins 10 minutes after blood clotting, and 95% is secreted within the first hour. The in vivo life of platelets is about 9-10 days, they can be stored at room temperature for 5 days under certain conditions, but the growth factor release is already very low. It is very important to use low G power during centrifugation to preserve the membrane stabilization of the platelets and to avoid platelet degranulation before the procedure15, 29,30.
Platelet-rich plasma can be administered topically or by injection. Injections are usually made intradermally or subdermally. Filling injection or injection techniques applied in mesotherapy can be used. Although there are no specific protocols about the application technique, for the scalp; point technique, nappa and point technique can be used together for skin rejuvenation, and tunnel technique can be used for filling. Before treating acne scars subcision and PRP can be given to that area. Significant clinical improvement is observed in 1-2 weeks after PRP applications. For maximum effect, 3-4 applications with 2-3 week intervals are required18,31.
Patients with thrombocytopenic, hypofibrinogenemia, liver disease, malignancy; The use of PRP should be avoided in acute and chronic infections, pregnant and lactating women, people with autoimmune diseases, and people with known sensitivity to blood and blood products32.
PRP side effects
The risk of side effects in PRP application is very low since the patient’s own platelets are used. Since the application is made by injection; Depending on the technique of injecting the injector into the skin, some local side effects may occur. Ecchymoses that may occur at the injection site are small in diameter and heal within a few days without the need for treatment. The redness that occurs during the application also disappears spontaneously in 30-40 minutes without the need for treatment. After the application, the feeling of tension on the skin disappears within 1-2 hours. Since the patient’s own blood is used in PRP application, there is no allergic reaction.
As a result, PRP is a practical method and it attracts attention as an alternative treatment method because it does not have serious side effects, does not cause widespread scar tissue, does not cause malignant transformations, is easily available and can be obtained cheaply. However, these findings need to be supported by clinical studies with a large series and experimental studies confirming its effects on fibroblasts.
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2. Hanna R, Trejo PM, Weltman RL. Treatment of intrabony defects with bovine-derived xenograft alone and in combination with platelet-rich plasma: a randomized clinical trial. J Periodontol 2004;75:1668-77.
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4. Powell DM, Chang E, Farrior EH. Recovery from deep-plane rhytidectomy following unilateral wound treatment with autologous platelet gel: a pilot study. Arch Facial Plast Surg 2001;3:245-50.
5. Englert SJ, Estep TH, Ellis-Stoll CC. Autologous platelet gel applications during cardiovascular surgery: effect on wound healing. J Extra Corpor Technol 2005;37:148-52.
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8. Korobelnik JF, Hannouche D, Belayachi N, Branger M, Guez JE, Hoang-Xuan T. Autologous platelet concentrate as an adjunct in macular hole healing: a pilot study. Ophthalmology 1996;103:590-4.
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11. Weibrich G, Hansen T, Kleis W, et al. Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration. Bone 2004;34:665-671
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14. Na JI, Choi JW, Choi HR, Jeong JB, Park KC, Youn SW, Huh,CH. Rapid healing and reduced erythema after ablative fractional carbon dioxide laser resurfacing combined with the application of autologous platelet-rich plasma. Dermatol Surg 2011;37:463–468.
15. Lee JW, Kim BJ, Kim MN, Mun S K. The Efficacy of autologous platelet rich plasma combined with ablative carbon dioxide fractional resurfacing for acne scars: A simultaneous split-face trial. Dermatol Surg 2011;37:931–938.
16. Crovetti G, Martinelli G, Issi M, Barone M, Guizzardi M, Campanati B, Carabelli A. Platelet gel for healing cutaneous chronic wounds. Tranfusion and Apheresis Sci 2004;30:145-151.
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19.Lemperle G, Holmes RE, Cohen SR et al. A classification of facial wrinkles.Plast Reconstr Surg 2001;108:1735-1750.
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Table 1. Dermatological Uses of PRP
Chronic skin ulcer
Wrinkle removal, skin rejuvenation
ablative laser, chemical peeling, rollerswound in applications
to increase and accelerate healing