Platelet Rich Plasma for Osteoarthritis

                             Dr. KS Dhillon

What is Platelet Rich Plasma?

Platelet Rich Plasma (PRP) is an autologous concentration of human platelets in a small volume of plasma. Here the platelet concentration is higher, usually up to five times higher, than the normal platelet concentration in a healthy person’s blood.

Preparation of Platelet Rich Plasma

PRP is prepared by differential centrifugation. In differential centrifugation, the acceleration force is adjusted to sediment certain blood cellular constituents based on different specific gravity.

The first centrifugation is to separate red blood cells (RBC). This is followed by a second centrifugation that concentrates platelets, which are suspended in a small volume of final plasma. 

Whole blood is initially collected in tubes that contain anticoagulants. The first spin is performed at constant acceleration to separate RBCs from the remaining whole blood volume. After the first spin, the whole blood separates into three layers: an upper layer that contains mostly platelets and white blood cells (WBC), an intermediate thin layer that is known as the buffy coat that is rich in WBCs, and a bottom layer that consists mostly of RBCs. To obtain pure PRP (P-PRP), the upper layer and superficial buffy coat are transferred to an empty sterile tube. To produce leucocyte-rich PRP (L-PRP), the entire layer of buffy coat and a few RBCs are transferred. 

The second spin step is then performed. It aids in the formation of soft pellets (erythrocyte-platelet) at the bottom of the tube. The upper portion that is composed mostly of PPP (platelet-poor plasma) is removed. Pellets are homogenized in the lower 1/3rd (5 ml of plasma) to create the PRP [1].

There are many commercially marketed PRP systems that facilitate the preparation of ready to apply platelet-rich suspensions in a reproducible manner. All operate on a small volume of drawn blood (20-60 mL) [1]. 

Effect of platelet-rich plasma

There is some evidence that PRP has the potential to have a regenerative effect on certain body tissues, besides the main role that platelets play in haemostasis [2]. PRP contains alpha granules. About 70% of the growth factors in the alfa granules will be secreted in the first 10 min, and almost all the stored amount will be released in the first hour [3]. The growth factors activate the cells that are responsible for tissue healing and bone and cartilage regeneration [4].

The joint destruction in patients with osteoarthritis (OA) occurs as a result of an imbalance in the equilibrium between the breakdown and repair of the joint tissue. A combination of cellular changes and biomechanical stresses causes several secondary changes in the joint. Research has identified a number of biochemical pathways that can be targeted therapeutically through biological intervention [5] and platelet-rich plasma (PRP) is one such intervention.

Platelets contain and release numerous growth factors that promote healing, dampen inflammation, and reduce pain [6,7,8]. These blood-derived products are also used to enhance chondrogenesis [9,10], treat bone injuries [11,12], tendon injuries [13,14], and ligament injuries [15,16], and have recently emerged as a potential treatment for knee OA [17].

Studies comparing intra-articular PRP injections to other means of non-surgical intervention for knee OA report benefits for patients receiving PRP. The positive clinical response in patients with OA is mainly due to the anti-inflammatory effects of PRP rather than due to increased anabolic and reparative effects on articular cartilage [17,18]. These reports are, however, inconclusive because of the high variability in the available PRP preparations, and the lack of consensus and standardization of treatment protocols [19]. 

PRP for Osteoarthritis

Most clinical guidelines do not recommend the use of platelet-rich plasma (PRP) for knee osteoarthritis (OA). This is because there is a lack of high-quality evidence on efficacy of PRP for the treatment of knee OA. The guidelines in fact emphasize the need for rigorous studies. Despite this lack of evidence, the use of PRP in knee OA is increasing [20].

Bennell et al [20] carried out a randomized clinical trial to find out the effect of intra-articular injection of platelet-rich plasma (PRP) in patients with mild and moderate OA of the knee and compared its effect to placebo saline injection into the knee. The clinical trial included 288 adults aged 50 years or older with mild to moderate radiographic knee osteoarthritis. Half of the subjects had PRP injections and the other half had placebo injections. Of the 288 subjects, 269 (93%) completed the trial. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of −2.1 vs −1.8 points, respectively. The mean change in medial tibial cartilage volume was −1.4% vs −1.2%, respectively. Neither comparison was statistically significant.

The authors concluded that intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. Their findings do not support the use of PRP for the management of knee OA.

Dório et al [21] carried out a randomized, double-blind, placebo-controlled trial to assess the efficacy of platelet-rich plasma and plasma in the treatment of symptomatic knee osteoarthritis. Sixty-two participants were allocated to treatment groups of which 57 (92%) were female, with a mean age of 65 years and a mean BMI of 28.0 Kg/m2.

They found that PRP injected with a 2-week interval, and plasma were not superior to placebo for pain and function improvement in knee OA over 24 weeks. The main drawback of this study was the relatively small sample which may have influenced the outcome. The PRP group had a higher frequency of mild transitory increase in pain.

Khoshbin et al [22] carried out a systematic review with quantitative synthesis to assess the efficacy of Platelet-Rich Plasma in the treatment of symptomatic knee osteoarthritis. There were six Level I and II studies that satisfied their inclusion criteria (4 randomized controlled trials and 2 prospective nonrandomized studies). There were a total of 577 patients in the studies with 264 patients (45.8%) in the treatment group (PRP) and 313 patients (54.2%) in the control group (hyaluronic acid [HA] or normal saline solution [NS]). The mean age of patients receiving PRP was 56.1 years compared with 57.1 years for the group receiving HA or NS. 

The main findings of this systematic review were that multiple sequential intra-articular PRP knee injections (2 to 4 injections) improved functional outcome scores (WOMAC and IKDC) at a minimum of 24 weeks. However, no benefit of PRP over control treatment was found for other pain measures (VAS) or overall patient satisfaction scores.

The American Academy of Orthopaedic Surgeons (AAOS) evidence-based clinical practice guideline on treatment of knee OA does not recommend the use of PRP for the treatment of knee OA. The evidence rating is inconclusive which means that there is a lack of compelling evidence that has resulted in an unclear balance between benefits and potential harm [23].

The National Institute for Health and Care Excellence (NICE) guidelines on the use of PRP for knee OA states that the current evidence on platelet-rich plasma injections for knee osteoarthritis raises no major safety concerns. However, it states that the evidence on efficacy is limited in quality. Therefore, this procedure should only be used with special arrangements for clinical governance, with consent, and for audit or research [24]. 

Conclusion

Most clinical guidelines and scientific publications do not recommend the use of platelet-rich plasma (PRP) for knee osteoarthritis (OA). This is because there is a lack of high-quality evidence on efficacy of PRP for the treatment of knee OA. Despite this lack of evidence, the use of PRP in knee OA is increasing. 

The guidelines and studies in fact emphasize the need for rigorous studies. Despite this call for more rigorous studies, there is a glaring lack of such studies in the scientific literature.

References

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23. American Academy of Orthopaedic Surgeons. Treatment of Osteoarthritis of the Knee – 2nd Edition Evidence-Based Clinical Practice Guideline at   https://www.aaos.org/globalassets/quality-and-practiceresources/osteoarthritis-of-the-knee/osteoarthritis-of-the-knee-2nd-editiion-clinical-practice-guideline.pdf. 
24. Platelet-rich plasma injections for knee osteoarthritis. Interventional procedures guidance [IPG637]Published: 23 January 2019 at https://www.nice.org.uk/guidance/IPG637/chapter/1 -Recommendations.