APPLICATION OF AUTOLOGOUS PLATELET RICH PLASMA (APRP) AS AN ADJUVANT THERAPY IN PLASTIC SURGERY

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1 Plastic Surgery Original Article International Journal of Clinical And Diagnostic Research ISSN Volume 4, Issue 6, Nov-Dec Glorigin Lifesciences Private Limited. APPLICATION OF AUTOLOGOUS PLATELET RICH PLASMA (APRP) AS AN ADJUVANT THERAPY IN PLASTIC SURGERY Pandey S, Chittoria RK *, Friji MT, Mohapatra DP, Dinesh KS Abstract To study the role of Autologous Platelet Rich Plasma (APRP) as an adjunct therapy for various indications in plastic surgery. This is a retrospective analysis of 31 patients (7 groups) in whom APRP was given as an adjuvant therapy for various indications. In each group, APRP helped as an adjuvant therapy for optimizing the outcome in various cases of plastic surgery. Being a rich source of various growth factors, APRP can act as an adjuvant therapy in optimizing the outcome in various cases of Plastic Surgery. Author Affiliations: Department of Plastic Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India Keywords: APRP, Plastic Surgery, Adjuvant therapy *Corresponding Author: Dr. Ravi Kumar Chittoria, Professor & Head, Department of Plastic Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India drchittoria@yahoo.com

2 Shilpa shree, et al., INTRODUCTION Wound healing is an integrated and complex procedure. It consists of a series of overlapping events [1]. Various growth factors are needed for the optimum healing and Platelet is one of the important factors responsible for wound healing [2]. Role of platelet in wound healing has been proven in several studies. Platelets help in release of several growth factors essential for wound healing. Another action of platelet is release of bioactive proteins responsible for attracting macrophages, mesenchymal stem cells, and osteoblasts. These cells are known to promote removal of necrotic tissue and enhances tissue regeneration and healing [3]. Autologous Platelet Rich Plasma (APRP) is also helpful in acceleration of wound healing [4]. Platelet-Rich Plasma (PRP) is defined as a portion of the plasma having a higher concentration of platelet. It consists of platelets with clotting and growth factors [5]. Platelet derived growth factor (PGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EDF) and fibroblast growth factor (FGF) are also present in APRP and in concentration multiple times higher than normal plasma [6]. Because of properties of enhancing tissue regeneration and healing, APRP may be used as an adjunct therapy for Assessment of thiobarbituric acid reactive substance various cases in plastic surgery. This article highlights the importance of APRP as an adjunct therapy in plastic surgery. Apart from wound healing APRP is also used in various orthopedic conditions [7,8,9]. MATERIALS AND METHODS This study was conducted in the department of Plastic Surgery, JIPMER, Pondicherry, India. This is a retrospective study done during the period, March 2013 to June Thirty one cases of plastic surgery were analyzed in whom APRP was used for different indications as an adjuvant therapy. The patients were grouped into seven groups (Table 1) based on various indications of APRP. Patient s demographic profile was recorded in the study proforma. APRP was prepared using standard and validated technique described by Li, Weiwei et al [10,11]. After taking informed consent 4.5 ml of whole blood was taken from peripheral vein with sterile precautions and 0.5 ml of 3.2% Sodium Citrate was added to make it 5 ml (blood: anticoagulant at 9:1). The centrifugation tube was placed in centrifugation apparatus. The solution was centrifuged at 3000 rpm for 10 minutes. Three portions were seen (Figure 1a) after first centrifugation. Upper portion containing plasma and platelets, middle portion

3 containing White blood cells (WBCs) with some platelets (Buffy coat) and lower portion containing Red blood cells (RBCs). Middle and lower portions are discarded. Upper portion was transferred taken in a new tube for re-centrifugation at 4000 rpm for 10 minutes. Following which two portions were seen. Upper 2/3rd portion containing platelet poor plasma and lower 1/3rd portion containing platelet rich plasma & erythrocyte with platelet Clump (Figure 1 b). Lower 1/3 rd portion was used for APRP therapy [12, 13]. Figure 1a. Centrifuged tube showing three layers after first rotation In Group 1 subcutaneous injection of APRP was given around the wound margin circumferentially using 23 G needle and repeated every week, if required (till the complete healing is achieved or wound bed got ready for cover by skin graft or flap). In Group 2 APRP was sprayed over the recipient raw area before applying the graft, and injected at graft-normal skin junction. In Group 3 APRP was injected at suture line of flap inset and into the flap. In Group 4 after the release of contracture APRP was sprayed over the raw area before applying skin graft and injected at junction of graft-normal skin. In case of primary closure APRP was injected at suture line. In cases of Flaps, APRP was injected into the flap and at the site of inset. In Group 5 After excision of hypertrophic scar, APRP was injected over raw area before applying skin graft and at skin-graft junction. In Group 6 APRP was used as an adjunct for hair transplantation. In Group 7 APRP was used as an adjunct to bone healing in Cranioplasty Figure 1 b After re centrifugation two portions are seen RESULTS

4 31 Patients with different etiology treated with APRP were analyzed over two year duration in our department. Mean age was 39.3 years, male to female ratio was 3.5 : 1, most common etiology was trauma and most common site was lower limb. All patients were given APRP. Mean duration of APRP therapy 2.5 weeks. Mean Bates Jansen Wound Assessment Score was 45.5 and maximum size of wound was 30 x 20 cm. The most common organism grown in tissue culture was pseudomonas (3 wounds, 9.6%)). Methicillin Resistant Staphylococcus Aureus (MRSA) was positive in 2 cases (6.45 %). The most common co-morbidity was anemia, in 18 cases (58.06 %), followed by diabetes mellitus, 3 cases (0.67 %). Osteomyelitis was present in 2 patients (6.45 %). The mean duration of wound bed preparation (WBP) was 2.11 weeks. The average duration of systemic antibiotic was 10 days to 3 weeks. Mean duration of Negative Pressure Wound Therapy (NPWT) was 2.11 weeks. Average duration of wound healing was 4 weeks. Number of patients managed with APRP alone were 12 (38.70%) (Figure 1a, 1 b). Figure 1 a Diabetic foot - before APRP Figure 1 b Wound healed after 3 weeks Number of patients managed with primary suturing along with APRP were 3 (9.67%) (Figure 2a, 2 b). Figure 2a Hemi facial avulsion with compromised viability of skin

5 bone dust which was used at bone- bone graft junction as osteogenic agent (Figure 8a, 8b). Figure 2b showing no skin loss primary suturing with APRP, 5 patients (16.12%) patients were managed with APRP assisted skin grafting (Figure 3a, 3b) APRP was injected around the wound circumferentially before applying the skin graft and. 5 patients (16.12%) patients were managed with APRP assisted flaps (Figure 4a, 4b). Three patients (9.67%) of post burn contracture (figure 5a, b) release were managed with APRP before graft/flap. Number of cases of hypertrophic scar in which APRP was used were 2 (6.45%) (Figure 6a, 6b), where scar excision and skin grafting was done and APRP was sprayed over the raw area and graft- skin junction. In one patient (3.22%) APRP was used in hair restoration surgery, where APRP was injected before transplanting the hair (Figure 7a, 7b). In one patient (3.22%) autologous Cranioplasty was done with the help of APRP where APRP was used to mix with the Figure 3a Post amputation raw area Figure 3 b Graft take 100%

6 Shilpa shree, et al., Assessment of thiobarbituric acid reactive substance Figure 4a Post traumatic raw area Figure 4b abdomen flap with APRP Figure 5a Post burn contracture B/L groin Figure 5b Contracture release with APRP and SSG Figure 6a Hypertrophic scar over chin and neck Figure 6b After APRP chin scar contracted Excision with primary closure done

7 Figure 7a Scalp Alopecia figure 7b APRP assisted hair transplantation Figure 8a pre operative Figure8b APRP mixed with Figure 8c application of bone Bone dust dust In all patients wound healed satisfactorily. All grafts were taken fully, all flaps were settled well without necrosis, and no complications were noted in 6 months follow up period (Case summary Table 1).

8 Table 1. Case Summary S. No Groups Indication of Number APRP of cases Diabetic foot ulcers 1 Post infection raw 1 area 1 Group 1: Wound healing Pressure sore 2 Post Trauma Raw 1 Area Venous ulcer 1 Ischemic ulcer 1 Donor Site of Split 1 Thickness Skin Graft At the site of 2 primary closure for Hand injuries At the site of 1 primary closure for Facial injuries Post burn raw area 4 Palate Surgery 1 2 Group 2: Skin graft surgery Split Thickness 3 Skin Graft Full Thickness skin 1 Graft 3 Group 3: Flap surgery Local flaps 2

9 Pedicle flaps 1 Free flaps 1 4 Group 4: Contracture surgery Release and 1 Primary closure Release and SSG 1 Release and Flap 1 cover 5 Group 5: Hypertrophic scar Excision and 2 SSG 6 Group 6: Hair restoration Surgery Before implanting hair 1 7 Group 7: Cranioplasty Autologous bone 1 grafting Total 31 DISCUSSION Wound healing is a complex series of overlapping events which includes three phases- Phase of Inflammation, Phase of proliferation, Phase of remodeling [14]. Platelets play important role and it is crucial for wound healing especially in initial phases [15]. Among other factors platelets is an important factor to mediate wound healing and their deficiency may cause impaired wound healing [16]. Optimum wound healing cannot be achieved in absence of growth factors. The concentration of these proteins decreases after 3-5 days [17]. Construction of new connective tissue, hemostasis, and revascularization is done by Platelets. Platelet Rich Plasma (PRP) is defined as a portion of the plasma fraction of autologous blood having a platelet concentration. PRP functions as a tissue sealant and drug delivery system, platelet helps in wound repair by releasing locally acting growth factors via α- granules degranulation. Being an Autologous component PRP is safe as it is free of antigenic components. It is easy to prepare, less time taking and cost effective [14, 15]. We prepared APRP in our department for various kinds of wounds reconstructive procedures. Depending on the nature of wound and its response APRP was repeated weekly. We used this modality in almost all kinds of

10 wounds and procedures, ranging from chronic wounds to Microvascular flaps and cosmetic surgery. We found this modality as an effective technique for enhancing wound healing and improving outcomes in various fields of surgeries in plastic surgery. Due to small sample size and absence of control group statistical analysis could not be done. A prospective, controlled, large sample size study with statistical analysis is needed for further evaluation. CONCLUSION It is helpful in wound healing in variety of cases whether acute or chronic and irrespective of etiology. It is also helpful in burns and cosmetic surgery field. Based on our case series we can conclude that APRP enhances wound healing in all kinds of wounds. CONFLICTS OF INTEREST- None REFERENCES 1. Anderson JM. The cellular cascades of wound healing. In Davies JE, editor. Bone Engineering. Toronto: EM Squared 2000: p Harding KG, Morris HL, Patel GK. Science,medicine and the future: Healing chronic wounds. Br Med J 2002; 324: Marx RE. Platelet-rich plasma: Evidence to support its use. J Oral Maxillofac Surg 2004; 62: Knighton DR, Fiegal VD, Doucette M et al. The use of topically applied platelet growth factors in chronic non-healing wounds: A review. Wounds 1989; 1: Mehta S, Watson JT. Platelet rich concentrate: basic science and current clinical applications. J Orthop Trauma 2008; 22: Eppley B, Woodell J, Higgins J. Platelet Quantification and growth factor analysis from platelet-rich plasma: Implications for wound healing. Plast Reconstr Surg. 2004;114(6): Dhillon RS, Schwarz EM, Maloney MD. Platelet-rich plasma therapy - future or trend? Arthritis Research & Therapy. 2012; 14(4):219. doi: /ar Mehta S, Tracy J; Platelet Rich Concentrate: Basic Science and Current Clinical Applications;J orthop Trauma;2008; Travis A. Motley. Incorporating Platelet Rich Plasma and Platelet Poor Plasma into Open Reduction Internal Fixation of Closed Calcaneus Fractures to Reduce Wound Complication: A Case Study; The Foot and Ankle Online Journal 2 (11): 1

11 10. Franco D, Franco T. Protocol for obtaining PRP for autologous use. Aesthetic Plast Surg 2012; 36: Li W, Enomoto M, Ukegawa M et al. Subcutaneous Injections of Platelet-Rich Plasma. Plast Reconstr Surg 2012; 129: Nandagopal V. et al. Role of Autologous Platelet Rich Plasma APRP in Wound Healing; JSWCR 2014: 7(1): dentistry. J Clin Pediatr Dent 2006; 30: Nandagopal V et al. Role of Jet Force Technology in Wound Management. Plast Aesthet Res 2015; 2: Ursula Mirastschijski, Andreas Jokuszies, and Peter M. Vogt Skin wound healing: Repair biology, wound, and scar treatment. Peter C Neligan (3), vol 1, 2013 ; Anitua E, Andia, I, Ardanza B et al. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost 2004; 91: Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 2004; 114: Shashikiran ND, Reddy VV, Yavagal CM, Zakirulla M. Applications of plateletrich plasma in contemporary pediatric