Platelet Rich Plasma (PRP) Therapy: A magic bullet or pseudoscience

Platelet Rich Plasma (PRP) Therapy: A magic bullet or pseudoscience

                               DR KS Dhillon

Introduction

The use of platelet-rich plasma in humans dates back to the 1990’s when it was used in reconstructive maxillofacial surgery. Later it was used to augment tendon reconstruction in orthopaedic surgery and for the treatment of musculoskeletal injuries. In the USA, although there is no approval by the US Food and Drug Administration (FDA), PRP therapy is gaining significant popularity in the treatment of sports-related injuries (1). It is also frequently being used in the treatment of osteoarthritis.
PRP therapy has been described in various glorious terms such as ‘magic’, ‘revolutionary’, ‘breakthrough’, and a ‘paradigm shift’. The PRP market in the USA was estimated at $45 million in 2009 and about $126 million in 2016. The cost of a single treatment in the USA varies between $500 to $1200 (2). What is PRP therapy and how does it work? To understand PRP therapy the role of platelets has to be understood.

Function of platelets

The role of platelets in thrombosis and primary haemostasis is well known. We are all familiar with the use of platelets in the treatment of patients with bleeding disorders and thrombocytopenia. What is less understood is the many other good and bad roles that platelets play in the body. Platelets play an important role in host defence by providing an immune response to combat bacteria and viruses (3). They also play an important role in inflammation and blood coagulation (3). Activated platelets release many proteins which are responsible for angiogenesis, wound healing and bone formation (3). Angiogenesis is an essential component in tissue repair and tissue regeneration.
Platelets play a harmful role in autoimmune diseases such as multiple sclerosis, Rheumatoid arthritis, Crohn's disease and allergic skin disorders. Platelets can also play a harmful role in pulmonary disorders, liver disease and cancer (3).
The ability of platelets to release cytokines and growth factors (platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), vascular endothelial growth factor (VEGF), platelet-derived angiogenic factor (PDAF), and transforming growth factor beta (TGF-β)) which promote wound healing and tissue regeneration has attracted physicians to explore its use, in the form of PRP, in dental, orthopaedic, cardiac and eye surgery. PRP is also being used for skin care and repair of muscle and tendons.



What is Platelet Rich Plasma (PRP)?

Platelet Rich Plasma as the name suggests is plasma (small amounts) which contains a concentrate of autologous platelets. It is also known as plasma concentrate (PC), plasma rich in growth factors (PRGF) and autologous platelet gel (4). PRP is prepared by centrifuging the patient’s blood. Two spins are usually used, the first, a hard spin which separates the platelet poor plasma from the red fraction and the platelet rich plasma. The second spin is a soft spin which separates the red fraction from the PRP and the PRP settles at the base. Before application, the platelets are activated with bovine thrombin and 12% calcium chloride (4). A platelet concentrate thus obtained will contain about 3 to 5 times more platelets than normal plasma. The procedure takes about 12 minutes (4).

PRP for musculoskeletal conditions

Evidence for the use of PRP in the treatment of pain in musculoskeletal disorders is still lacking.
1.PRP in the treatment of musculoskeletal injury.
Reurink et al (5) did a double blind placebo controlled trial comparing the use of PRP and isotonic saline in the treatment of acute hamstring injury which is the most common muscle injury in athletes. Each athlete was given a 3 ml injection of PRP or isotonic saline (placebo) on day 5 of the injury and a second injection 5 or 7 days later. They found no difference between the two groups in term of time to return to sports and reinjury rates. The concluded that there was ‘no benefit for intramuscular PRP injections, as compared with placebo injections, in patients with acute hamstring injuries’.
Moraes et al (6) performed a literature review in 2014 for the Cochrane database to assess the usefulness of platelet-rich therapies for musculoskeletal injuries. The use of platelet-rich therapy in rotator cuff tear, shoulder impingement surgery, ACL reconstruction surgery, patella tendinopathy, Achilles tendinopathy and acute Achilles repair, was studied. The authors concluded that ‘currently there is insufficient evidence to support the use of PRT (plasma-rich therapy) for the treatment of musculoskeletal injuries’.

2.PRP in non-surgical treatment of lateral epicondylitis
Lateral epicondylitis is a self-limiting condition where pain usually resolves within 12 to 18 months without treatment. Susan et al (7) did a literature review of various modes of non-surgical treatment of lateral epicondylitis. They found that bracing, physical therapy and extracorporeal shockwave therapy did not provide definitive pain relief. They found that PRP or autologous blood injections were both more as well as less effective than corticosteroid injections in the treatment of epicondylitis.
A systematic review of the literature by de Vos et al (8) in 2014 showed that there is strong evidence that PRP injections are not effective in the treatment of chronic lateral elbow tendinopathy. There were three (75%) high-quality studies which showed no benefit and one (25%) high-quality study which showed the benefit of PRP in the treatment of lateral elbow tendinopathy.


3.PRP in treatment of patellar tendinopathy
Liddle et al (9) did a systematic review of the literature to evaluate the effectiveness of PRP in the treatment of patellar tendinopathy. The authors found that although PRP did produce improvement in pain, the results of comparative studies were not consistent and ‘superiority of PRP over control treatments could not be conclusively demonstrated’.

3.PRP in treatment of osteoarthritis
Laudy et al (10) in 2014 published a systematic review and meta-analysis of the efficacy of PRP injections in the treatment of osteoarthritis of the knee. They reviewed 10 studies which met their inclusion criteria. Six were randomised controlled trials (RCT) and 4 were non-randomised trials. Of the 6 RCTs, one compared PRP to placebo while the other 5 compared PRP to hyaluronic acid (HA). Of the 4 Non-RCT, three compared PRP to HA and one studied the use of PRP with one versus 2 spins in the preparation of PRP. The duration of the studies varied between 6 to 12 months.
One trial had a moderate risk of bias and the other 9 trials had a high risk of bias. The authors concluded that there is limited evidence, due to high risk of bias, that PRP injections are effective in relieving pain and improving function in patients with OA of the knee. They stressed the need for a large RCT of ‘good quality and low risk of bias’ to test the effectiveness of PRP injections in the treatment of knee OA.

Conclusion

Although PRP therapy has been hailed as a ‘revolutionary’ ‘breakthrough’ in the management of musculoskeletal disorders, unequivocal evidence to support its use is lacking. Despite the lack of evidence and its high cost, its use is increasing. The use of PRP therapy is not FDA approved and neither is it's use covered by medical insurance.
The use of PRP for musculoskeletal injury, epicondylitis, patellar tendinopathy and OA of the knee is not yet established and is unlikely to be established in future. Convincing studies with low risk of bias do not exist.







References

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2. Christie Aschwanden. Platelet-rich plasma treatment is popular for sports injuries, whether it works or not. The Washington Post  July 14, 2014, at https://www.washingtonpost.com/national/health-science/platelet-rich-plasma-treatment-is-popular-for-sports-injuries-whether-it-works-or-not/2014/07/14/b6293b10-0607-11e4-a0dd-f2b22a257353_story.html? Accessed on 21/4/2017.
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5. Reurink G, Goudswaard GH, Moen MH, Weir A, Verhaar JAN, Maas M et al. Platelet-Rich Plasma Injections in Acute Muscle Injury
6. N Engl J Med 2014; 370:2546-2547 June 26, 2014, DOI: 10.1056/NEJMc1402340
7. Moraes VY, Lenza M, Tamaoki MJ, Faloppa F, Belloti JC. Platelet-rich therapies for musculoskeletal soft tissue injuries. Cochrane Database Syst Rev. 2014;4: CD010071.
8. Sims S.E.G., Miller K., Elfar J.C. Hammert W. HAND (2014) 9: 419. doi:10.1007/s11552-014-9642-x.
9. de Vos RJ, Windt J, Weir A. Strong evidence against platelet-rich plasma n        injections for chronic lateral epicondylar tendinopathy: a systematic review. Br J Sports Med. 2014 Jun;48(12):952–6.
10. Liddle AD, Rodríguez-Merchán EC. Platelet-Rich Plasma in the Treatment of Patellar Tendinopathy: A Systematic Review. Am J Sports Med. 2015 Oct;43(10):2583-90. 
11. Laudy AB, Bakker EW, Rekers M, Moen MH. Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis. Br J Sports Med. 2015 May;49(10):657-72.