Platelet rich plasma: What it is and how it fits into multidisciplinary treatment plans

Naturopathic doctors began using PRP for tendonosis and tendonitis in the late 1990s. In the early 2000s, PRP essentially became viewed as the logical next phase in regenerative injection therapy and began to be adopted by practitioners previously trained in prolotherapy. 

Platelet rich plasma is being utilized in musculoskeletal medicine with increasing frequency and effectiveness by providers in multiple specialties. PRP has been successfully used in various specialties such as maxillofacial, cosmetic, spine, orthopedic, podiatric and for general wound healing.^1,2

Soft tissue injuries treated with PRP include tendinopathy, tendonosis, acute and chronic muscle strain, muscle fibrosis, ligamentous sprains, and joint capsular laxity. PRP has also been utilized to treat intra-articular injuries. Examples include arthritis, arthrofibrosis, articular cartilage defects, meniscal injury, and chronic synovitis or joint inflammation.

The logic behind PRP is that platelets are the first to arrive at the site of tissue injury, and thus have the potential to release growth factors that play a critical role in mediating healing. PRP essentially alters cell ratios, by replacing red blood cells which do not stimulate healing and replacing them with platelets to release growth factors that facilitate healing.

Stages of healing
Wound healing is a well-orchestrated and complex series of events involving cell-cell and cell-matrix interactions, with growth factors serving as messengers to regulate the various processes involved. 

Normal platelet activation leads to four necessary stages of healing: Hemostasis, Inflammation, Proliferation, and Remodeling. If any of these stages are incomplete – or if they proceed unabated – tissue homeostasis is disrupted, and pain and loss of function may result.

With wounds, and also after surgical incisions, repair begins with platelet clot formation, activation of the coagulation cascade, and platelet degranulation with release of growth factors. The inflammatory process is initiated by migration of neutrophils and subsequently macrophages to the wound site. Activated macrophages release multiple growth factors, including transforming growth factors- and – (TGF-, TGF-), PDGF, interleukin-1 (IL-1), and fibroblast growth factor (FGF). Shortly thereafter collagen synthesis begins. This process leads to an early increase in wound breaking strength, which is the most important wound healing parameter of surgical wounds, followed by epithelization and the ultimate remodeling process.² 

Multiple studies have demonstrated a role for platelet-rich plasma (PRP) in accelerating and facilitating response to injury through enhanced cellular or molecular activity.^1,4–19 Blood plasma and platelets are responsible for hemostasis, while leukocytes and activated platelets mediate inflammation, and growth factors derived from platelet α-granules influence tissue regeneration. Specifically, the leukocyte content of PRP is thought influence the inflammatory phase, while angiogenic and mitogenic growth factor concentrations are believed to aid tissue regeneration.²⁰

The goal of any tissue regeneration therapy is to facilitate the development of a well-organized extracellular matrix capable of attaining the mechanical performance and functionality of non-injured tissue. Therefore, it is imperative to characterize the molecular constituents of these therapies when evaluating their efficacies. The cellular response to PRP is influenced by the composition of the PRP, including the relative concentrations of platelets, white blood cells (WBCs), fibrinogen and fibrin, and growth factors.

It must be mentioned that one of the major limitations in the field of PRP is that most studies include PRP formulations obtained by different methods, with different compositions and characteristics, and therefore the outcomes could be different depending on the product used, even though they are all called PRP. This makes the comparison among results of different studies often confusing and contradictory.¹²

PRP preparation demonstrate great inter-product variability based on the device and preparation methods.21 Preparations of PRP can vary in many areas, including platelet concentration, number of white blood cells, presence or absence of red blood cells, and activation status of the preparation. It is beyond the scope of this article to go into a detailed discussion, but at the very least, the physician who performed the PRP injection should be able to the the other members of the care team 1) The percent red blood cell concentration; 2) The percent increase in platelet concentration; 3) White blood cell percentage; 4) If the PRP was activated and with what; 5) Volume of injection, and 6) Whether or no ultrasound guidance was used 

Integrating PRP into Multidisciplinary Care: Post PRP Rehabilitation
In my experience, multidisciplinary post PRP care can greatly enhance the outcome and I recommend all a patients consider it. I recommend that PRP be considered after appropriate first line therapies have been exhausted prior to the utilization of these PRP matrix grafting protocols. These include relative rest, appropriate bracing and kinesiotaping, evaluation of kinetic chain mechanics, and physical therapy – with or without eccentric loading protocols.

The first 48 hours post PRP involves an inflammatory response that should be monitored to ensure that it is not overly vigorous. In my experience this intensity of the inflammatory response is determined by the extent of inflammation before the procedure and by the composition of the PRP graft. The following is the protocol that I recommend to my patients for post PRP care.

Summary
Platelet-rich plasma has been safely and effectively employed in many areas, including orthopedics, sports medicine, dentistry, neurosurgery, ophthalmology, urology, wound healing, cosmetics, cardiothoracic, otorhinolaryngology and maxillofacial surgery. Research has expanded our knowledge of the role of PRP in the wound healing process. Initially, it was thought that platelets were used solely to assist in clotting. However, it has become clear that platelets are also responsible for releasing many bioactive proteins and growth factors responsible for recruitment of macrophages, mesenchymal stem cells, and osteoblasts, which not only promotes necrotic tissue removal, but also improves the quality of tissue regeneration and the healing process. Based on this principle, platelets are now used in clinical practice to stimulate cells responsible for healing and increase healing potential and has demonstrated significant promise in pain medicine and in treatment of chronic injury. 

Post prp exercise and physiotherapy protocol

0-24 hours

• Avoid NSAIDs and other anti-inflammatory drugs 3 days prior to procedure
• Ice and/or cold Laser immediately following procedure
• Rest, and avoid loading of the joint and structures where PRP was administered
• Light movement 
• REST 

24-48 hours

• Avoid NSAIDs and other anti-inflammatory drugs 
• Avoid ice unless absolutely needed 
• Avoid weight-bearing or loading activities  Keep active range of motion gentle and limited (immobilization during sleep if needed)
• LIGHT soft tissue to PRP-treated area and surrounding tissue 
• Gentle passive range of motion 
• REST

Day 3 through day 7 (beginning the regenerative phase)

• Avoid NSAIDs and other anti-inflammatory drugs 
• Begin myofascial release to hypertonic muscles and any scar tissue surrounding injury (3X/wk)
• Ice and electrical muscle stimulation (3X/wk)
• Gentle passive/active range of motion (full ROM should be reached by end of 1st week) (3X/wk)
• Light mobilization to any joint restrictions (3X/wk) 
• Light Proprioception/joint stability exercises to associated joints (3X/wk)
• Light stretches to shortened muscles (3X/wk)

Week 2 through 4 (regenerative phase)

• Avoid NSAIDs and other anti-inflammatory drugs
• Continue myofascial release to hypertonic muscles and any scar tissue surrounding injury (3/wk)
• Grade 4-5 mobilization to any joint restrictions (3X/wk)
• Ice and electrical muscle stimulation (3/wk)
• Functional exercises to stabilize associated joint (2-3 X/wk)
• Continue proprioceptive exercises
• Stretch and foam roll shortened and hypertonic muscles
• Patient returns for follow-up visit with doctor who administered PRP injection at the end of 4th week

Week 5 to 8 and following weeks as needed

(functional phase)

• Begin to use natural anti-inflammatory/NSAID’s (as directed by doctor)
• Myofascial release to hypertonic muscles and scar tissue surrounding injury (2X/wk)
• Grade 4-5 mobilization to any joint restrictions (2X/wk)
• Ice and electrical muscle stimulation (as needed)
• Continue progressing through full weight-bearing functional exercises (3X/wk)
• Continue progressing through proprioceptive exercises
• Begin gait, biomechanical, sport-specific training
• Stretching and foam rolling as directed by doctor
• Follow-up visit with injection doc at the end of 8th week
• Return to activities when fully functional or as directed by doctor

References:

1. Gamradt, S. C., Rodeo, S. A. & Warren, R. F. Platelet Rich Plasma in Rotator Cuff Repair. Techniques in Orthopaedics 22, 26 (2007).
2. Everts, P. A. M. et al. Platelet-rich plasma and platelet gel: a review. J Extra-corporeal Technology 38, 174–87 (2006).
3. Crane, D. & Everts, M. and P. A. M. Platelet Rich Plasma (PRP) Matrix Grafts. Practical Pain Managementhttps://www.practicalpainmanagement.com/treatments/platelet-rich-plasma-prp-matrix-grafts?page=0,3 (2011).
4. Cook, C. S. & Smith, P. A. Clinical Update: Why PRP Should Be Your First Choice for Injection Therapy in Treating Osteoarthritis of the Knee. Curr Rev Musculoskelet Medicine 11, 583–592 (2018).
5. Garbis, N. et al. Clinical Indications and Techniques for the Use of Platelet-Rich Plasma in the Shoulder. Operative Techniques in Sports Medicine19, 165–169 (2011).
6. Mishra, A. K. et al. Efficacy of Platelet-Rich Plasma for Chronic Tennis Elbow. Am J Sports Medicine 42, 463–471 (2014).
7. Virchenko, O. & Aspenberg, P. How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks?: Interplay between early regeneration and mechanical stimulation. Acta Orthopaedica 77, 806–812 (2009).
8. Sampson, S., Gerhardt, M. & Mandelbaum, B. Platelet rich plasma injection grafts for musculoskeletal injuries: a review. Curr Rev Musculoskelet Medicine 1, 165–174 (2008).
9. Kon, E. et al. Platelet-rich plasma for the treatment of knee osteoarthritis: an expert opinion and proposal for a novel classification and coding system. Expert Opin Biol Th 20, 1–14 (2020).
10. Hall, M. P., Band, P. A., Meislin, R. J., Jazrawi, L. M. & Cardone, D. A. Platelet-rich plasma: current concepts and application in sports medicine. The Journal of the American Academy of Orthopaedic Surgeons 17, 602–8 (2009).
11. Kon, E. et al. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surgery, Sports Traumatology, Arthroscopy 18, 472–479 (2010).
12. 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 26, 269–278 (2010).
13. Jia, X., Peters, P. G. & Schon, L. The Use of Platelet-Rich Plasma in the Management of Foot and Ankle Conditions. Operative Techniques in Sports Medicine 19, 177–184 (2011).
14. Mishra, A. & Pavelko, T. Treatment of Chronic Elbow Tendinosis With Buffered Platelet-Rich Plasma. American Journal of Sports Medicine 34, 1774–1778 (2006).
15. 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. The American journal of sports medicine 41, 356–64 (2013).
16. Ibrahim, V. M. et al. USE OF PLATELET RICH PLASMA FOR THE TREATMENT OF BICIPITAL TENDINOPATHY IN SPINAL CORD INJURY: A PILOT STUDY. Brit J Sport Med 47, e2 (2013).
17. Phadke, A., Singh, B. & Bakti, N. Role of platelet rich plasma in rotator cuff tendinopathy- clinical application and review of literature. J Clin Orthop Trauma 10, 244–247 (2018).
18. Platelet Rich Plasma in Musculoskeletal Practice. (2016) doi:10.1007/978-1-4471-7271-0.
19. Platelet-Rich Plasma, Regenerative Medicine: Sports Medicine, Orthopedic, and Recovery of Musculoskeletal Injuries. Lect N Bioeng (2014) doi:10.1007/978-3-642-40117-6.
20. Rozman, P. & Bolta, Z. Use of platelet growth factors in treating wounds and soft-tissue injuries. Acta Dermatovenerologica Alpina Pannonica Et Adriatica 16, 156–65 (2007).
21. Mautner, K. et al. A Call for a Standard Classification System for Future Biologic Research: The Rationale for New PRP Nomenclature. Pm&r 7, S53–S59 (2015).

Dr. Chris Spooner ND, B.Sc. is a North Okanagan naturopathic doctor with 20 years of clinical experience. In his private practice, Paradigm Integrative Medicine, Dr. Spooner works with patients looking for a balanced approach to health care that combines conventional medicine with research informed integrative approaches. Dr. Spooner has advanced certifications through the College of Naturopathic Physicians of B.C., including prescriptive authority. He has been a board member and vice chair of the College of Naturopathic Physicians of British Columbia since 2008.