|Year : 2020 | Volume
| Issue : 1 | Page : 32-35
Role of platelet-rich plasma in treatment of knee osteoarthritis
Ismail A Yassin1, Faisal H Zayed1, Ahmed F Abd El-Aziz2, Mahmoud K Beltagy3
1 Department of Orthopedic Surgery, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
2 Department of Clinical and Chemical Pathology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
3 Department of Orthopedic Surgery, Damanhour Medical National Institute, Beheira, Egypt
|Date of Submission||30-Jun-2019|
|Date of Decision||14-Jul-2019|
|Date of Acceptance||21-Aug-2019|
|Date of Web Publication||26-Mar-2020|
Mahmoud K Beltagy
Department of Orthopedic Surgery, Damanhour Medical National Institute, Beheira 22511
Source of Support: None, Conflict of Interest: None
Background Osteoarthritis (OA) is a degenerative joint disease of multifactorial etiology and affects synovial joints. The risk of developing OA substantially increases with each decade after the age of 45 years. It is characterized by progressive deterioration and loss of articular cartilage with structural and functional changes in the entire joint, including the synovium, periarticular ligaments, and subchondral bone.
Objective To assess the clinical effects of intra-articular injection of platelet-rich plasma (PRP) into the knee joint with mild to moderate OA regarding pain, quality of life, and return to activity.
Patients and methods The study included 30 patients in the age range of 30–70 years complaining of knee OA grade II and III based on Kellgren and Lawrence classification and confirmed by radiographs. The patients received three intra-articular PRP injections with weekly intervals.
Results A statistically significant improvement in the joint function was observed after 6 months according to the Western Ontario and McMaster Universities Osteoarthritis Index scoring index.
Conclusion From the results of our study, intra-articular PRP injection is considered as a safe and low-cost line of knee OA treatment with few adverse effects.
Keywords: intra-articular injection, osteoarthritis, platelet-rich plasma
|How to cite this article:|
Yassin IA, Zayed FH, Abd El-Aziz AF, Beltagy MK. Role of platelet-rich plasma in treatment of knee osteoarthritis. Al-Azhar Assiut Med J 2020;18:32-5
|How to cite this URL:|
Yassin IA, Zayed FH, Abd El-Aziz AF, Beltagy MK. Role of platelet-rich plasma in treatment of knee osteoarthritis. Al-Azhar Assiut Med J [serial online] 2020 [cited 2020 Jun 2];18:32-5. Available from: http://www.azmj.eg.net/text.asp?2020/18/1/32/281358
| Introduction|| |
Osteoarthritis (OA) is the most common form of joint pathology, involving major structural changes of the joint, causing pain and functional disability . The increasing number of patients with symptomatic OA will continue to place an increasingly large economic burden on global health care systems .
It commonly affects the knee joint, causing pain, tenderness, movement limitation, and worsening of quality of life, leading to social and financial burden . Early OA treatment combines nonpharmacological methods with oral medications. In more severe or very symptomatic cases, intra-articular injection (IAI) is used: corticosteroid with local anesthetic, hyaluronic acid, or biological products such as platelet-rich plasma (PRP).
However, some studies have considered using IAI as a first-line treatment because it has proven effectiveness for relieving pain with fewer adverse effects than some oral medications . The use of IAI PRP in the management of knee OA has been extended in recent years given its high safety margin and easy preparation and administration . It is suggested that PRP is effective in patients with lower degree of cartilage degeneration than severe cases or higher OA grade . PRP includes various growth factors, whose properties differ significantly. Their anabolic abilities to induce chondrocyte differentiation are valuable properties to consider in OA. Anabolic growth factors included in PRP are transforming growth factor beta 1 (TGF-β1), platelet-derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), human growth hormone, and basic fibroblast growth factor (bFGF) .
| Patients and methods|| |
This study included 30 patients who presented to the outpatient clinic of Al-Azhar University Hospitals complaining of knee OA (Kellgren–Lawrence grade 2 or 3) diagnosed by clinical examination and radiograph imaging. Age of the studied group of patients ranged from 30 to 70 years. Each patient received three intra-articular PRP injections with weekly intervals. An informed consent was obtained from all participants in this study. Procedures followed were in accordance with the Helsinki Declaration of 1975.
Patients were assessed at baseline and after 1 and 6 months of PRP injections using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scoring index, which is a standardized questionnaire used by health professionals to evaluate the condition of patients with OA of knee, including pain, stiffness, and physical function of the joints.
Patients were excluded from the study if they had any of the following criteria: having grade 4 knee OA based on Kellgren–Lawrence classification, ipsilateral hip or ankle pathology, treated with IAI of corticosteroid in the previous 6 months, receiving anticoagulation drugs, having peripheral vascular disease, or requesting to leave the study.
Complete blood count (determined by automated cell counter Sysmex KX-21N; Sysmex Corporation, Kobe, Japan) was performed before the procedure to ensure that there is an adequate platelet count, and bleeding time was performed for all the study participants before the procedure to assess integrity of platelet function.
Approximately 20 ml of autologous venous blood was withdrawn with complete aseptic technique from the antecubital vein into vacuum tubes containing 10% sodium citrate. An 18 g needle was utilized to avoid trauma to the platelets which are in a resting state.
The PRP was prepared following a double-centrifugation technique. In the first centrifugation, whole blood was centrifuged at 100g for 10 min at room temperature, giving three layers: an upper layer containing platelets and white blood cells (WBC), an intermediate layer which is the buffy coat rich in WBCs, and a bottom layer containing mostly red blood cells (RBCs). In the second centrifugation, the upper layer and the buffy coat from the first tube were then transferred to an empty tube. The second spin step (hard spin) was then performed on it at 400g for 10 min. The upper portion of the volume composed mostly of platelet-poor plasma was separate to create the PRP ,.
Regarding injection technique, 2–4 ml of PRP was injected using a 22 G needle at the suprapatellar space of the knee using aseptic precautions. Immediately after injection, the patient was rested in a supine position without moving the leg for 15 min, and then the patients were asked to actively flex and extend their knees so that the PRP could spread evenly across the joint space (Fig. 1).
The PRP was activated in-vivo by platelets in contact with the endogenous collagen ,,. Nonactivated PRP can be injected directly into the injured tissue, which becomes activated upon contact with the collagen. Collagen is one of the most potent activators of platelet adhesion and aggregation . In-vivo collagen activation was chosen as it was the preferred method for activating PRP in many clinical applications, because it leads to a slower and more sustained release of growth factors .
| Results|| |
At the end of the follow-up period at 6 months, the clinical outcome was scored using WOMAC index.
The WOMAC evaluates three dimensions: pain, stiffness, and physical function, with 5, 2, and 17 questions, respectively, with lower scores indicating lower levels of symptoms or physical disability.
The mean WOMAC score preinjection was higher than the means after 1 and 6 months (66.33±3.92 vs. 57.30±5.02 vs. 52.47±5.19, respectively). The improvement in WOMAC score was highly significant after 1 and 6 months after the third injection in comparison with the preinjection WOMAC (P<0.001; [Table 1]).
|Table 1 Comparison between Western Ontario and McMaster Universities Osteoarthritis Index score before injection and 1 month and 6 months after the third injection (n=30)|
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| Discussion|| |
This study has been carried out on 30 patients experiencing knee OA grade II and III based on Kellgren and Lawrence classification.
The most significant finding of this study was that we found a statistically significant improvement in WOMAC scoring index after 1 and 6 months of three intra-articular PRP injections. The results were similar to the results of studies by Gobbi et al.  and Spaková et al. , which showed positive effects in patients with knee OA and significant improvement by means of pain reduction and improved symptoms and quality of life.
A 5-year double-blind randomized controlled trial conducted by Di Martino et al.  showed that 3 weekly administration of PRP injections was as effective as Hyaluronic acid injections in patients with knee OA on continuous assessment. Furthermore, another recent randomized placebo-controlled trail by Lin et al.  resulted in better clinical outcome by WOMAC and IKDC score in PRP group than the hyaluronic group and the normal saline (placebo) group with sustained clinical improvement only in the PRP group throughout the study duration. These findings are similar to the results of our study which supports the role of PRP in treating OA.
The patients were injected three intra-articular PRP injections at weekly intervals for a total of three injections. We found a statistically significant improvement in WOMAC scoring index after successive PRP injections. This was similar to the results of the study conducted by Gormeli et al.  which showed that multiple (3) PRP injections were useful in achieving better clinical results and was not like the study of Patel et al.  which compared the outcome following single and double PRP injections at 6 weeks, 3 and 6 months. They concluded that there was no difference between single and double injections.
In this study, we did not find a statistically significant relation between the change in WOMAC score and each of age, sex, occupation, grade of OA, and BMI. This was similar to the results of the study by Patel et al. . Better results were observed with low grades of OA and low BMI, however was not statistically significant.
In this study, we did not use local anesthesia. Bausset et al.  and Carofino et al.  did not use local anesthetics as they have been shown to decrease the positive effects of PRP.
The exclusion criteria in this study are patients with secondary OA, fourth grade of knee OA, history of steroid injection, blood diseases such as thrombocytopenia (low platelet levels), and patients receiving antiplatelet drugs. These exclusion criteria were close to the criteria chosen by Kon et al.  and Sampson et al.  in their studies about knee OA.
One of the objectives of this study was to evaluate the safety of intra-articular PRP injections. No major adverse effects were observed except pain and swelling at injection site, which is similar to the adverse effects observed by Li et al. .
Limitations of this study are the relatively small number of patients involved and the short-term follow-up after PRP injections, so we recommend further studies with long follow-up period to evaluate the role of PRP injections regarding whether it is a temporary effect or has a modifying role in knee OA progress.
| Conclusion|| |
From the results of our study, a significant improvement in pain and function after multiple PRP injections was obtained. PRP is totally prepared from autologous whole blood and is therefore safe and of low cost. No major adverse effects were obtained.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M et al.
The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014; 73:1323–1330.
Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD. Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy 2016; 32:495–505.
Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003; 81:646–656.
Fibel KH, Hillstrom HJ, Halpern BC. State-of-the-art management of knee osteoarthritis. World J Clin Cases 2015; 3:89–101.
Smith PA. Intra-articular autologous conditioned plasma injections provide safe and efficacious treatment for knee osteoarthritis: an FDA-sanctioned, randomized, double-blind, placebo-controlled clinical trial. Am J Sports Med 2016; 44:884–891.
Gato-Calvo L, Magalhaes J, Ruiz-Romero C, Blanco FJ, Burguera EF. Platelet-rich plasma in osteoarthritis treatment: review of current evidence. Ther Adv Chronic Dis 2019; 10:118.
Doessing S, Holm L, Heinemeier KM, Feldt-Rasmussen U, Schjerling P, Qvortrup K et al.
GH and IGF1 levels are positively associated with musculotendinous collagen expression: experiments in acromegalic and GH deficiency patients. Eur J Endocrinol 2010; 163:853–862.
Dhurat R, Sukesh M. Principles and methods of preparation of platelet-rich plasma: a review and author’s perspective. J Cutan Aesthet Surg 2014; 7:189–197.
] [Full text]
Bhatia A, Ramya B, Biligi DS, BK PP. Comparison of different methods of centrifugation for preparation of platelet-rich plasma (PRP). Indian J Pathol Oncol 2016; 3:535–539.
Silva LQd, Huber SC, Montalvão SADL, Bassora FDS, de Paula EV, Annichino-Bizzacchi J. Platelet activation is not crucial for platelet-rich plasma (PRP), when used as autologous therapeutic product, and could be lyophilized without any growth factor loss. Am Soc Hematol 2016; 128:2639.
Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med 2009; 37:2259–2272.
Farndale RW, Siljander PR, Onley DJ, Sundaresan P, Knight CG, Barnes MJ. Collagen-platelet interactions: recognition and signalling. Biochemical Society Symposia. Biochemical Society symposium. London: Portland Press Limited; 2003. 81–94.
Fufa D, Shealy B, Jacobson M, Kevy S, Murray MM. Activation of platelet-rich plasma using soluble type I collagen. J Oral Maxillofac Surg 2008; 66:684–690.
Gobbi A, Karnatzikos G, Mahajan V, Malchira S. Platelet-rich plasma treatment in symptomatic patients with knee osteoarthritis: preliminary results in a group of active patients. Sports Health 2012; 4:162–172.
Spaková T, Rosocha J, Lacko M, Harvanová D, Gharaibeh A. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil 2012; 91:411–417.
Di Martino A, Di Matteo B, Papio T, Tentoni F, Selleri F, Cenacchi A et al.
Platelet-rich plasma versus hyaluronic acid injections for the treatment of knee osteoarthritis: results at 5 years of a double-blind, randomized controlled trial. The Am J Sports Med 2019; 47:347–354.
Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn JH. Intra-articular injection of platelet-rich plasma is superior to hyaluronic acid or saline solution in the treatment of mild to moderate knee osteoarthritis: a randomized, double-blind, triple-parallel, placebo-controlled clinical trial. Arthroscopy 2019; 35:106–117.
Görmeli G, Görmeli CA, Ataoglu B, Çolak C, Aslantürk O, Ertem K. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc 2017; 25:958–965.
Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med 2013; 41:356–364.
Bausset O, Magalon J, Giraudo L, Louis ML, Serratrice N, Frere C et al.
Impact of local anaesthetics and needle calibres used for painless PRP injections on platelet functionality. Muscles Ligaments Tendons J 2014; 4:18.
Carofino B, Chowaniec DM, McCarthy MB, Bradley JP, Delaronde S, Beitzel K et al.
Corticosteroids and local anesthetics decrease positive effects of platelet-rich plasma: an in vitro study on human tendon cells. Arthroscopy 2012; 28:711–719.
Kon E, Buda R, Filardo G, Di Martino A, Timoncini A, Cenacchi A et al.
Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc 2010; 18:472–479.
Sampson S, Reed M, Silvers H, Meng M, Mandelbaum B. Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis: a pilot study. Am J Phys Med Rehabil 2010; 89:961–969.
Li M, Zhang C, Ai Z, Yuan T, Feng Y, Jia W. Therapeutic effectiveness of intra-knee-articular injection of platelet-rich plasma on knee articular cartilage degeneration. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2011; 25:1192–1196.