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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 6  |  Issue : 1  |  Page : 6-9

A study of platelet-rich plasma in the management of chronic nonhealing ulcers


Department of Dermatology, SVS Medical College, Mahbubnagar, Telangana, India

Date of Submission11-Dec-2020
Date of Decision28-Jan-2021
Date of Acceptance06-Apr-2021
Date of Web Publication25-Feb-2022

Correspondence Address:
Angoori Gnaneshwar Rao
Department of Dermatology, SVS Medical College, Mahbubnagar, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cdr.cdr_136_20

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  Abstract 


Background: Chronic nonhealing ulcers run protracted course and require prolonged rest and complete avoidance of pressure, antibiotics, and antiseptic dressing, which at times may not yield satisfactory results. Local application of certain growth factors is known to promote healing in these cases. Objectives: To study the efficacy of autologous platelet-rich plasma in the management of chronic nonhealing ulcers. Materials and Methods: Z-statistics and Chi-square tests were used in the statistical analysis of this study. The study consisted of 30 patients of chronic nonhealing ulcers who presented to the dermatology department. Patients aged between 18 and 65 years of both sexes presenting with noninfective ulcer of duration of more than 6 weeks, treated or untreated and who have normal complete blood picture, were recruited. Diabetic patients with uncontrolled sugar levels were excluded. Ulcer examination was carried out as per clock-face method. Examination of peripheral pulses, nerves, and sensations was carried out. Routine hematological and biochemical investigations were done. Platelet-rich plasma was prepared from patient's blood, and 1.5–2 ml was injected at the healing margins using insulin syringe (26 G) after cleaning. Procedure was repeated once weekly for 6 weeks, and the ulcer healing was assessed. Results: Of the 30 cases, 21 (70%) were male and 9 (30%) were female, with a male-to-female ratio of 2.3:1. A maximum number of cases were in the fifth decade (33.3%). Trophic ulcers (TUs) due to leprosy contributed to 30 (88.23%), venous ulcers (VUs) 2 (5.88%), and diabetic ulcers 2 (5.88%). Improvement in area of TUs due to leprosy was 92.5%, in VUs 88.45%, and in diabetic ulcer 98.02% at the end of 6 weeks of platelet-rich plasma therapy. Conclusion: Platelet-rich plasma is an easily obtainable blood derivative and is a safe and potentially reasonable adjunct in the treatment of chronic nonhealing ulcers with advantage of no concern of immune reactions or cross-reactions or toxicity. It not only promotes healing but also prevents amputation necessitated by complications due to chronic ulcers.

Keywords: Diabetic ulcer, leprosy, platelet-rich plasma, trophic ulcer, venous ulcer


How to cite this article:
Rao AG, Fathima K. A study of platelet-rich plasma in the management of chronic nonhealing ulcers. Clin Dermatol Rev 2022;6:6-9

How to cite this URL:
Rao AG, Fathima K. A study of platelet-rich plasma in the management of chronic nonhealing ulcers. Clin Dermatol Rev [serial online] 2022 [cited 2022 Aug 19];6:6-9. Available from: https://www.cdriadvlkn.org/text.asp?2022/6/1/6/338588




  Introduction Top


Platelet-rich plasma (PRP) is defined as blood plasma, which has been enriched with platelets using centrifugation. The notable components of PRP include transforming growth factor-β, platelet-derived growth factors (PDGF-AB and PDGF-BB), insulin-like growth factor, vascular endothelial growth factors, epidermal growth factor, and fibroblast growth factor-2.[1] In 1986, Knighton et al. were first to demonstrate the role of platelet-derived wound-healing factors in the management of nonhealing ulcers.[2] In 1993, Yamamoto et al. described the use of PRP for hemostasis and after cardiac surgery.[3] Currently, PRP is being used in various applications, including general surgery, orthopedics, cardiovascular surgery, cosmetics, faciomaxillary surgery, and urology. Platelet-rich fibrin (PRF) was also found useful in the management of chronic nonhealing ulcers.[4] However, PRP was found to release higher growth factors than PRF.[5] The objective of this study was to assess the efficacy of autologous platelet-rich plasma in the management of chronic nonhealing ulcers.


  Materials and Methods Top


A total of 30 patients with 34 chronic nonhealing ulcers of various etiologies constituted the study population. The study was approved by the institutional ethics committee. The patients were selected randomly and obtained informed consent. Patients aged between 18 and 65 years of both sexes presenting with noninfective ulcer of duration of more than 6 week.s, treated or untreated and who have normal complete blood picture, were recruited. History of diabetes, human immunodeficiency virus (HIV) infection, serum hepatitis, and syphilis was recorded. Patients with ulcers having active infection, deep ulcers with tendon or bone exposure, pregnant or lactating women, and with bleeding tendencies and hemoglobin <11 g% and uncontrolled diabetes, on anti-coagulants, and on immunosuppressives were excluded from the study.

A detailed history including the demographic data – name, age, sex, address, occupation and history of onset of ulcer, duration, and progression – was recorded. History of diabetes, leprosy, and other systemic diseases was noted. Study patients were thoroughly examined for the length, depth, and breadth of the ulcer by “clock-face method” described by Sussman using cotton tip applicator and disposable paper ruler. In the clock-face method, 12:00 reference position is toward the head of the body, and measurements were taken from 12:00 to 6:00 and from 9:00 to 3:00.[6] A moistened cotton swab was inserted into the deepest part of the wound bed to measure the depth. Peripheral pulses, sensations, and nerve thickening were examined. Routine hematological, biochemical, and serological investigations including HIV, HBsAg, and VDRL tests were done. Wound debridement was done in needy patients. Pus for culture sensitivity was done, and appropriate antibiotics were administered.

Under aseptic precautions, 20 ml of venous blood was drawn and added to a test tube containing acid citrate dextrose in a ratio of 9:1 (blood: acid citrate dextrose) and was centrifuged at 5000 revolutions/min (rpm) for 15 min to separate the red blood cells from platelet and plasma. The lower part of the plasma was then collected and centrifuged again at 2000 rpm for 5 min. The bottom layer of about 1.5–2 ml was injected at the healing margins using insulin syringe (26 G) after cleaning with 0.9% saline and dressing done using pad and roller bandage. Maximum of 2 ml of PRP was used in one sitting, and it was used uniformly over the healing margin of the ulcer. The dressing was changed every 3rd day. The procedure was repeated once weekly for 6 weeks, and the ulcer healing was assessed.

The wound area and volume were calculated by length × width × 0.7854 and length × width × depth × 0.7854, respectively (area and volume of an ellipse, respectively, since the shape of an ulcer can be compared to that of an ellipse). Wounds were photographed at every sitting.

The treatment outcome was defined as a percentage in change of area and volume of the ulcer and was calculated as initial measurement minus assessment-day measurement divided by initial measurement. The data were statistically analyzed using Z-statistics and Chi-square tests.


  Results Top


The study included 34 chronic ulcers in 30 patients of various causes treated by autologous PRP; the age of these patients ranged from 24 to 65 years, with a mean age of 47.23 years (standard deviation [SD]: 13.17). A maximum number of cases were in the age group of 51–60 years (33.3%), with a mean of 47.23 years.

Among 30 patients, 21 (70%) were male and 9 (30%) were female, with a male-to-female ratio of 2.3:1. In the present study, 26 (86.7%) patients presented with single ulcer and 4 (13.3%) presented with 2 ulcers. Among 34 ulcers, trophic ulcers (TUs) due to leprosy contributed to 30 (88.23%) cases, venous ulcers (VUs) in 2 (5.88%) cases, and diabetic ulcers (DUs) in 2 (5.88%). The duration of ulcer ranged from 6 to 48 weeks, with a mean duration of 19 weeks. Twenty-three cases required 6 sittings of PRP [Figure 1]a, [Figure 1]b, [Figure 1]c and 3 cases required 5 sittings of PRP [Figure 2]a, [Figure 2]b and [Figure 3]a, [Figure 3]b, [Figure 3]c and the remaining 4 cases needed 4 sittings of PRP for complete healing, [Figure 4]a, [Figure 4]b, [Figure 5]a, [Figure 5]b, and [Figure 6]a, [Figure 6]b.
Figure 1: (a) Trophic ulcer on the sole of right forefoot at first visit. (b) Partially healed ulcer after 2 sittings of platelet-rich plasma. (c) Completely healed ulcer after 6 sittings of platelet-rich plasma

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Figure 2: (a) Trophic ulcer on right medial malleolus at first visit. (b) Improvement in healing of ulcer at the end of 5 sittings of platelet-rich plasma

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Figure 3: (a) Two trophic ulcers: One on the left medial malleolus and one at the medial aspect of left foot at first visit. (b) Ulcer on medial aspect of left foot healed and improvement in the ulcer on medial malleolus after 3 sittings of platelet-rich plasma. (c) Healed ulcer on left medial malleolus after 5 sittings of platelet-rich plasma

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Figure 4: (a) Trophic ulcer on lateral aspect of left heel at initial visit. (b) Almost completely healed ulcer after 4 sittings of platelet-rich plasma

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Figure 5: (a) Trophic ulcer on the base of left great toe. (b) Improvement of the ulcer after 4 sittings of platelet-rich plasma

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Figure 6: (a) Trophic ulcer on left lateral malleolus with deep fissure below at first visit. (b) Healed fissure and improvement of the ulcer after 4 sittings of platelet-rich plasma

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  Discussion Top


Chronic wounds occur with cost and morbidity for patients and society. These wounds are found in all types of health-care settings and are a challenge for health-care providers. Chronic nonhealing ulcers are often difficult to treat. Conventional therapies such as dressings, surgical debridement, and even skin grafting may not provide satisfactory healing since these treatments are not able to provide the necessary growth factors (GFs) to modulate the healing process.[7] Male preponderance in our study is comparable with the study by Suthar et al.,[8] Sarvajnamurthy et al.,[9] and Raslan et al.[10] This is consistent with the fact that the incidence of chronic ulcers is more common among males.

The mean age of 47.23 years (SD: 13.17) in our study is comparable with the study by Sokolov et al.[11] (46.5 years). Notably, there is a higher age group (51–60 years) involvement in our study compared to studies by Suryanarayan et al.[12] (42.5 years) and Raslan et al.[10] (41 years); TUs due to leprosy contributed to the highest number in our study, possibly due to neuropathy with consequent loss of sensation predisposing to repeated trauma, ultimately leading to formation of TU. However, Agale reported VU (60%–70%) as the most common cause of chronic leg ulcer followed by diabetes and neuropathic ulcers in his study.[12]

Out of 30 TUs, 100% improvement in area was seen in 6 (20%) ulcers, with a mean percentage of improvement in area being 92.52% at the end of 6 sittings [Chart 1]. Out of 2 VUs, 100% improvement was seen in 1 ulcer (50%), with a mean percentage of improvement in area being 88.45% at the end of 6 sittings. Out of 2 DUs, 100% improvement was seen in 1 ulcer (50%), with a mean percentage of improvement in area being 98%. The overall percentage of improvement in the size of the ulcer was 92.61% (SD: 8.18) at the end of 6 weeks.



Out of 30 TUs, 100% improvement in volume of ulcer was seen in 11 cases (36.66%), the mean percentage improvement in volume being 97.55% (SD: 3.82) at the end of 6 sittings [Chart 2]. Out of 2 VUs, 100% improvement in volume was seen in 1 ulcer (50%), the mean percentage improvement in the volume being 92.3% (SD: 10.88) at the end of 6 sittings. Out of 2 DUs, 100% improvement in the volume was seen in 1 ulcer (50%), the mean percentage improvement in the volume of the ulcers being 99.5% (SD: 0.70) at the end of 6 sittings. Thus, it can be deduced that there was a better improvement in the volume than in the area of the ulcers suggesting that PRP helps in the healing of the ulcers by the formation of granulation tissue from the depth of the ulcers. This finding of improvement in mean area and volume of ulcer in our study is comparable to the study by Sarvajanamurthy et al. who reported a mean percentage of improvement in area and volume of ulcer as 94.7% and 95.6% at the end of 6 sittings, respectively.[9] Similarly, Suryanarayana et al. also reported the efficacy of autologous PRP in the treatment of chronic nonhealing leg ulcers in a study of 33 chronic ulcers of various etiologies, with a mean duration of healing of 5.6 weeks.[13] However, Frykberg et al. reported a reduction in area and volume of the ulcers in a mean duration of 2.8 weeks with 3.2 treatments in a study on 49 patients with 65 nonhealing ulcers.[14] Conversely, Sokolov et al. reported requirement of more number of applications (10–16) of PRP and longer duration (4 months) for healing chronic nonhealing ulcers in their study.[11]



Pain at the injection site was observed in 5 cases which is the main adverse effect in our study. Interestingly, another plasma derivative, PRF, used in the management of TUs has the advantage of being painless. However, PRF was found to have lesser GFs than PRP. Hence, PRP is a better option than PRF in the management of chronic nonhealing ulcers.[5]

Limitations

A number of cases in the study are less, and there is a lack of control arm.


  Conclusion Top


The injectable PRP was found to be very effective and safe in the management of TUs, particularly in TUs involving large areas due to leprosy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Dhillon RS, Schwarz EM, Maloney MD. Platelet-rich plasma therapy-future or trend? Arthritis Res Ther 2012;14:219.  Back to cited text no. 1
    
2.
Knighton DR, Fiegel VD, Austin LL, Ciresi KF, Butler EL. Classification and treatment of chronic non-healing wounds: Successful treatment with autologous platelet derived wound healing factors. Ann Surg 1986;204:322-29.  Back to cited text no. 2
    
3.
Yamamoto K, Hayashi J, Miyamura H, Eguchi S. A comparative study of the effect of autologous platelet-rich plasma and fresh autologous whole blood on haemostasis after cardiac surgery. Cardiovasc Surg 1996;4:9-14.  Back to cited text no. 3
    
4.
Prachi VG, Naziya M, Siddhi RP. Efficacy of autologous platelet rich fibrin matrix in the management of non-healing ulcers. Int J Res Dermatol 2019;5:66.  Back to cited text no. 4
    
5.
Kobayashi E, Flückiger L, Fujioka-Kobayashi M, Sawada K, Sculean A, Schaller B, et al. Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig 2016;20:2353-60.  Back to cited text no. 5
    
6.
Sussman C. Wound measurements. In: Sussman C, Bates-Jensen B, editors. Wound Care: A Collaborative Practice Manual for Physical Therapists and Nurses. Gaithersburg: Aspen; 2001. p. 120-41.  Back to cited text no. 6
    
7.
Broughton G 2nd, Janis JE, Attinger CE. A brief history of wound care. Plast Reconstr Surg 2006;117:6S-11S.  Back to cited text no. 7
    
8.
Suthar M, Gupta S, Bukhari S, Ponemone V. Treatment of chronic non-healing ulcers using autologous platelet rich plasma: A case series. J Biomed Sci 2017;24:16.  Back to cited text no. 8
    
9.
Sarvajnamurthy S, Suryanarayan S, Budamakuntala L, Suresh DH. Autologous platelet rich plasma in chronic venous ulcers: Study of 17 cases. J Cutan Aesthet Surg 2013;6:97-9.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Raslan MM, Milad NM, AlAziz AA. Effect of autologous platelet-rich plasma in the promotion of healing of chronic ulcers. Int J Surg 2018;5:15-19.  Back to cited text no. 10
    
11.
Sokolov T, Manukova A, Karakoleva S, Valentinov B, Kosev P. Platelet-rich plasma (PRP) for the treatment of problematic skin wounds. J Int Med Assoc Bulg 2016;22:1379-82.  Back to cited text no. 11
    
12.
Agale SV. Chronic leg ulcers: Epidemiology, aetiopathogenesis, and management. Ulcers 2013;2013:9.  Back to cited text no. 12
    
13.
Suryanarayan S, Budamakuntla L, Khadri SI, Sarvajnamurthy S. Efficacy of autologous platelet-rich plasma in the treatment of chronic nonhealing leg ulcers. Plast Aesthet Res 2014;1:65-9.  Back to cited text no. 13
    
14.
Frykberg RG, Driver VR, Carman D, Lucero B, Borris-Hale C, Fylling CP, et al. Chronic wounds treated with a physiologically relevant concentration of platelet-rich plasma gel: A prospective case series. Ostomy Wound Manage 2010;56:36-44.  Back to cited text no. 14
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

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