Platelet-rich Plasma - Solution or Delusion?

Ryan Hodgins, M.D., FRCSC
Fellow Orthopaedic Sports Medicine & Arthroscopy
University of British Columbia

Robert McCormack, M.D., FRCSC, Dip Sport Med.
University of British Columbia
Vancouver, BC

Over the last decade, with the aid of mainstream media, the popularity of platelet-rich plasma (PRP) has increased dramatically. Media coverage surrounding the use of PRP by professional athletes such as Tiger Woods, Rafael Nadal, and Alex Rodriguez, purporting that PRP led to accelerated healing and a quicker return to sport, helped fuel this rapid rise in the use of PRP. Shortly after, the demand and use of PRP began increasing in the general population.

PRP is defined by the American Red Cross as a concentration of platelets greater than or equal to 5.5 x 1010 per 50 mL. This concentration equals a two to seven fold increase over the normal whole blood platelet concentration1. Once activated, the platelets degranulate releasing growth factors with potential to increase healing2. Proponents of PRP point to the basic science and animal studies, which demonstrate that the growth factors in PRP have beneficial effects on tendon and muscle healing3,4, and chondrocyte proliferation5. However, the clinical evidence regarding PRP use in orthopaedic injuries is not as clear.

Currently, PRP is used for many orthopaedic indications including: anterior cruciate ligament reconstruction (ACLR), lateral epicondylitis, tendinopathies (acute or chronic), acute tendon injuries, rotator cuff repair, osteoarthritis, spinal fusions, total knee arthroplasty, and non-unions. Table 1 shows a summary of the results of Level 1 and 2 studies comparing PRP to a placebo, or control, for common orthopaedic sports medicine problems. The variability in the conclusions is evident; most studies show limited or no clinical benefit.

A meta-analysis by Sheth et al. concluded, "current evidence is insufficient to discern whether autologous blood concentrates provide a clinical benefit in the treatment of orthopaedic conditions"6. Sixteen of the twenty-three randomized controlled trials (RCTs) in their review showed no improvement in functional outcomes between PRP and a control group. Moreover, in pooled analyses there was no significant difference between the PRP and control group in Visual Analog Scale scores, number of solid spinal fusions at one year, or the number of patients with low MRI signal intensity around the autograft in ACLR6.

An earlier systematic review, by De Vos et al., focused on the use of autologous blood products in patients with chronic tendinopathy. Eleven studies were included in this review and all showed no difference in pain scores when the treatment group was compared to a control group. They also demonstrated that there was limited evidence for the use of PRP in chronic tendinopathy7. Subsequently, De Vos et al. performed his own double-blind RCT comparing PRP injections to saline injections in chronic Achilles tendinopathy and found no difference between the groups with respect to Victorian Institute of Sports Assessment - Achilles Scores (validated outcome for evaluating pain and function outcomes in Achilles tendinopathy), subjective patient satisfaction or return to desired sport at 24 weeks8.

Table 1: Summary of Level I and II Randomized Controlled Trials (RCTs) for Various Sports Medicine Orthopaedic Conditions. PRP=Platelet Rich Plasma

Condition

Number of Level I and II RCTs

Number of Studies that show positive effect of PRP

Number of studies that show no difference or negative effect

Lateral Epicondylitis12-15

3

2

1

ACL16-22

6

2

4

Knee OA23-25

3

2

1

Rotator Cuff Tears26-32

7

1

6

Achilles Tendinosis8,33

2

0

2

Finally, a Cochrane review by Griffin et al. looked at PRP and bone healing and concluded that there was "insufficient evidence to support the routine use of PRP injections for augmentation of long bone healing"9.

One of the difficulties in assessing the literature is the marked variability of PRP preparations on the market. There are wide variations in the final concentration of platelets, presence of activating agent, use of anticoagulant, time and speed of centrifugation, volume injected, number of injections and inclusion of leukocytes (leukocyte-rich PRP vs. leukocyte-poor PRP)10,11. Since no clear consensus regarding any of these factors has been established, the first requirement is to determine the optimal preparation and dosing of PRP. Once the optimal regimen of PRP has been determined, rigorous properly designed RCTs are needed to test PRP for the various orthopaedic indications.

Despite the lack of convincing evidence, proponents focus on selective literature and the safety of the procedure. However, there are multiple examples in orthopaedics where early enthusiasm led to indiscriminant application of a technique, with significant complications becoming evident only later on. Electrothermal Arthroscopic Capsulorrhaphy and synthetic ligaments are good examples to remember when enthusiastically embracing new technology that lacks good clinical evidence to support its use.

Furthermore, even if the procedure is safe, the significant costs ($500 to $1000 per injection) have to be considered when we make recommendations to patients.

We are not entirely against the use of PRP for orthopaedic conditions and use it selectively in our practice. However, we believe orthopaedists should proceed with caution regarding the extensive use of PRP until many of the questions and controversies are resolved and further high quality studies are completed. Given the cost and somewhat invasive nature, it is probably ethical to advise patients it is "unproven" or "experimental".

Prudent adoption of PRP, based on quality evidence, will allow us to recommend the most appropriate preparation and dosing of PRP and determine the clinical situations that will benefit the most from this novel treatment.

References

  1. Cole B.J., Seroyer S.T., Filardo G., Bajaj S., Fortier L.A. Platelet-Rich Plasma: Where Are We Now and Where Are We Going? Sports Health: A Multidisciplinary Approach. 2010;2:203-210.
  2. Lopez-Vidriero E., Goulding K.A., Simon D.A., Sanchez M., Johnson D.H. The Use of Platelet-Rich Plasma in Arthroscopy and Sports Medicine: Optimizing the Healing Environment. Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2010;26:269-278.
  3. Aspenberg P., Virchenko O.: Platelet concentrate injection improves Achilles tendon repair in rats. Acta Orthop Scand 2004;75:93-99.
  4. Menetry J., Kasemkijwattana C., Day C.S., et al: Growth factors improve muscle healing in vivo. J Bone Joint Surg Br 2000;82:131-137.
  5. Schmidt M.B., Chen E.H., Lynch S.E.. A review of the effects of insulin-like growth factor and platelet derived growth factor on in vivo cartilage healing and repair. Osteoarthritis Cartilage. 2006;14:403-412.
  6. Sheth U., Simunovic N., Klein G., et al. Efficacy of Autologous Platelet-Rich Plasma Use for Orthopaedic Indications: A Meta-Analysis. J Bone Joint Surg Am. 2012;94:298-307.
  7. de Vos R.J., van Veldhoven P.L.J., Moen M.H., et al. Autologous growth factor injections in chronic tendinopathy: a systematic review. British Medical Bulletin. 2010;95:63-77.
  8. de Vos R.J., Weir A., van Schie H.T.M., Bierma-Zeinstra S.M.A., Verhaar J.A.N., Weinans H., et al. Platelet-rich plasma injection for chronic Achilles tendinopathy: a randomized controlled trial. JAMA. 2010;303:144-149.
  9. Griffin X.L., Wallace D., Parsons N., Costa M.L. Platelet rich therapies for long bone healing in adults. Cochrane Database Syst Rev. 2012;7:CD009496.
  10. McCarrel T.M., Minas T., Fortier L.A. Optimization of Leukocyte Concentration in Platelet-Rich Plasma for the Treatment of Tendinopathy. J Bone Joint Surg Am. 2012;94:e1431-8.
  11. Sampson S., Gerhardt M., Mandelbaum B. Platelet rich plasma injection grafts for musculoskeletal injuries: a review. Curr Rev Musculoskelet Med. 2008; 1:165-74
  12. Krogh T.P., Fredberg U., Stengaard-Pedersen K., Christensen R., Jensen P., Ellingsen T. Treatment of Lateral Epicondylitis With Platelet-Rich Plasma, Glucocorticoid, or Saline: A Randomized, Double-Blind, Placebo-Controlled Trial. American Journal of Sports Medicine. 2013;41:625-635.
  13. Thanasas C., Papadimitriou G., Charalambidis C., Paraskevopoulos I., Papanikolaou A.. Platelet-Rich Plasma Versus Autologous Whole Blood for the Treatment of Chronic Lateral Elbow Epicondylitis: A Randomized Controlled Clinical Trial. American Journal of Sports Medicine. 2011;39:2130-2134.
  14. Peerbooms J.C., Sluimer J., Bruijn D.J., Gosens T. Positive Effect of an Autologous Platelet Concentrate in Lateral Epicondylitis in a Double-Blind Randomized Controlled Trial: Platelet-Rich Plasma Versus Corticosteroid Injection With a 1-Year Follow-up. American Journal of Sports Medicine. 2010;38:255-262.
  15. Gosens T., Peerbooms J.C., van Laar W., Oudsten den B.L. Ongoing Positive Effect of Platelet-Rich Plasma Versus Corticosteroid Injection in Lateral Epicondylitis: A Double-Blind Randomized Controlled Trial With 2-year Follow-up. American Journal of Sports Medicine. 2011 Jun;39:1200-1208.
  16. Mirzatolooei F., Alamdari M.T., Khalkhali H.R. The impact of platelet-rich plasma on the prevention of tunnel widening in anterior cruciate ligament reconstruction using quadrupled autologous hamstring tendon: a randomised clinical trial. Bone Joint J. 2013;95:65-69.
  17. Vadalà A., Iorio R., Carli A., Ferretti M., Paravani D., Caperna L., et al. Platelet-rich plasma: does it help reduce tunnel widening after ACL reconstruction? Knee Surg Sports Traumatol Arthrosc. 2012;21:824-829.
  18. de Almeida A.M., Demange M.K., Sobrado M.F., Rodrigues M.B., Pedrinelli A., Hernandez A.J. Patellar Tendon Healing With Platelet-Rich Plasma: A Prospective Randomized Controlled Trial. American Journal of Sports Medicine. 2012;40:1282-1288.
  19. Cervellin M., de Girolamo L., Bait C., Denti M., Volpi P. Autologous platelet-rich plasma gel to reduce donor-site morbidity after patellar tendon graft harvesting for anterior cruciate ligament reconstruction: a randomized, controlled clinical study. Knee Surg Sports Traumatol Arthrosc. 2011;20:114-120.
  20. Nin J.R., Gasque G.M., Azca ́rate A.V., Beola J.D., Gonzalez M.H. Has platelet-rich plasma any role in anterior cruciate ligament allograft healing? Arthroscopy. 2009; 25:1206-1213.
  21. Vogrin M., Rupreht M., Dinevski D., Hašpl M., Kuhta M., Jevsek M., et al. Effects of a Platelet Gel on Early Graft Revascularization after Anterior Cruciate Ligament Reconstruction: A Prospective, Randomized, Double-Blind, Clinical Trial. Eur Surg Res. 2010;45:77-85.
  22. Vogrin M., Rupreht M., Crnjac A., Dinevski D., Krajnc Z., Rečnik G. The effect of platelet-derived growth factors on knee stability after anterior cruciate ligament reconstruction: a prospective randomized clinical study. Wien Klin Wochenschr. 2010 May;122:91-95.
  23. Patel S., Dhillon M.S., 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. American Journal of Sports Medicine. 2013;41:356-364.
  24. Filardo G., Kon E., Di Martino A., Di Matteo B., Merli M.L., Cenacchi A., et al. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskeletal Disorders. 2012;13:229.
  25. Cerza F., Carni S., Carcangiu A., Di Vavo I., Schiavilla V., Pecora A., et al. Comparison Between Hyaluronic Acid and Platelet-Rich Plasma, Intra-articular Infiltration in the Treatment of Gonarthrosis. American Journal of Sports Medicine. 2012;40:2822-2827.
  26. Kesikburun S., Tan A.K., Yilmaz B., Yasar E., Yazicioglu K. Platelet-Rich Plasma Injections in the Treatment of Chronic Rotator Cuff Tendinopathy: A Randomized Controlled Trial With 1-Year Follow-up. Am J Sports Med. 2013 Jul 26. DOI: 10.1177/0363546513496542.
  27. Ruiz-Moneo P., Molano-Muñoz J., Prieto E., Algorta J. Plasma Rich in Growth Factors in Arthroscopic Rotator Cuff Repair: A Randomized, Double-Blind, Controlled Clinical Trial. Arthroscopy: The Journal of Arthroscopic and Related Surgery; 2013;29:2-9.
  28. Weber S.C., Kauffman J.I., Parise C., Weber S.J., Katz S.D. Platelet-Rich Fibrin Matrix in the Management of Arthroscopic Repair of the Rotator Cuff: A Prospective, Randomized, Double-Blinded Study. American Journal of Sports Medicine. 2013;41:263-70.
  29. Gumina S., Campagna V., Ferrazza G., Giannicola G., Fratalocchi F., Milani A., et al. Use of platelet-leukocyte membrane in arthroscopic repair of large rotator cuff tears: a prospective randomized study. J Bone Joint Surg Am. 2012;94:1345-1352.
  30. Rodeo S.A., Delos D., Williams R.J., Adler R.S., Pearle A., Warren R.F. The Effect of Platelet-Rich Fibrin Matrix on Rotator Cuff Tendon Healing: A Prospective, Randomized Clinical Study. American Journal of Sports Medicine. 2012;40:1234-1241.
  31. Randelli P., Arrigoni P., Ragone V., Aliprandi A., Cabitza P. Platelet rich plasma in arthroscopic rotator cuff repair: a prospective RCT study, 2-year follow-up. J Shoulder Elbow Surg. 2011;20:518-528.
  32. Castricini R., Longo U.G., De Benedetto M., Panfoli N., Pirani P., Zini R., Maffulli N., Denaro V. Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a randomized controlled trial. Am J Sports Med. 2011;39:258-265.
  33. de Jonge S., de Vos R.J., Weir A., van Schie H.T.M., Bierma-Zeinstra S.M.A., Verhaar J.A.N., et al. One-year follow-up of platelet-rich plasma treatment in chronic Achilles tendinopathy: a double-blind randomized placebo-controlled trial. Am J Sports Med. 2011;39:1623-1629.

Submit Community Content

If you have orthopedic information that you would like to share with the Orthogate Community, please register/login and submit your news, event, job, article, case or workshop from the Submit Content menu under the My Account area. Learn more!