PRP is an emerging tool in the treatment of a wide variety of orthopaedic conditions especially of chronic soft tissue problems broadly termed as tendinosis. The technique involves withdrawing patients own blood, centrifuging it and injecting a part of it into the damaged area. Histological specimens from chronic cases confirm that tendinosis is not an acute inflammatory condition but rather a failure of the normal tendon repair mechanism associated with angio fibroblastic degeneration 1. This subgroup of conditions have long been treated by numerous methods including rest, non steroidal anti inflammatory drugs, bracing, rehabilitation therapy including physiotherapy, iontophersis 2, extra corporal shock wave therapy, injections including botulism toxin and corticosteroids. If all or some of the above fail then the patient has deemed to have failed conservative options and surgery is considered. Even here there is no consensus of opinion and there are a variety of techniques described including surgical release, excision of damaged tendon and re-attachment of tendons depending on the pathology treated. In this back ground it is encouraging to note that early results suggest the injection of PRP has produced a consistent improvement in patient's symptoms.
What is PRP?
Although PRP has only been in use in Orthopaedics in the recent past it has been around for about 20 years. Its use was first reported by Marx et al 3 a group of maxillo facial surgeons in 1998. They used PRP for bone graft augmentation and found significantly improved fusion rates and bone density in the mandible.
PRP is a bio active component of whole blood. The specific elements of PRP have not all been specifically defined. It is agreed in general that clinically valuable PRP contains one million platelets or more per micro litre 4. Some authors have defined PRP as only platelets whereas others note PRP may also have increased concentrations of white blood cells as well.
How does PRP work?
Thrombin and Calcium have historically been used to activate platelets. This combination results in the formation of a gel but this cannot be injected even via a wide bore needle. However platelets get activated slowly by exposure to tendon-derived collagen. When platelets are activated they release growth factors from alpha granules which include:
- Platelet-derived growth factor which stimulates cell replication, angiogenesis and acts as a mitogen for fibroblasts.
- Vascular endothelial growth factor which induces angiogenesis.
- Transforming growth factor-Beta1 which is a key regulator in balance between fibrosis and myocyte regeneration.
- Fibroblast growth factor which stimulates proliferation of myoblasts and promotes angiogenesis.
- Epidermal Growth Factor which stimulates proliferation of mesenchymal and epithelial cells and potentiation of other growth factors. 5
Platelets also contain dense granules which release adenosine, serotonin, histamine and calcium which play a role in tissue modulation and regeneration.
In addition to the above the plasma fraction contains the following
- Hepatocyte growth factor which promotes angiogenesis and acts as a mitogen for endothelial cells and as an anti fibrotic.
- Insulin-like growth factor-1 which stimulates myoblasts and fibroblasts, mediates growth and repair of skeletal muscle. 5
Also as mentioned previously PRP also has some white blood cells which may be important for long-term regeneration that is macrophage mediated. In vitro studies have also found that PRP significantly inhibits growth of Staphylococcus aureus and Escherichia coli. 5
A combination of all these factors contributes to the healing properties of PRP in the treatment of long standing tendinosis.
Usually 60mls of whole blood is collected from a peripheral vein in a syringe containing 5mls of sodium citrate. The blood is then placed in a desk top-size centrifuge with disposable cylinders for the blood. The centrifuge runs for 15 minutes at 3,200 rpms. At the end of this blood is separated into Platelet Poor Plasma (PPP), RBC and PRP. Next the PPP is extracted through a special port and discarded from the device. While the PRP is in a vacuumed space, the device is shaken for 30seconds to re-suspend the platelets. Afterwards the PRP is withdrawn and approximately 5ml PRP is obtained from 60 mls of blood. The total time from blood draw to injection time is 30 minutes.
The area of injury is marked and ideally it is recommended to use an ultrasound to accurately localize the area of pathology. Under aseptic precautions the 5mls of PRP is injected in a peppering technique to achieve a more expansive zone of delivery. The patient is usually observed supine for 15 minutes and then discharged home. The use of non steroidal anti inflammatories was usually strictly prohibited because of their actions on platelets one week prior to injection and three weeks after.
Side effects and Contra-Indications
As PRP is autologous safety concerns are very minimal. The patients should be warned of the possibility of temporary worsening of symptoms after the injection for at least a week. This is due to the stimulation of the body's natural response to the growth factors. As with any injection strict emphasis on an aseptic precaution is a must. Relative contraindications are a history of thrombo cytopenia, bleeding diathesis, use of anti-coagulant therapy, active infection at the site of injection, tumour, metastatic disease, pregnancy and lactation. So far there have been no documented cases of carcinogenesis, hyper plasia or tumour growth associated with the use of PRP.
Review of Literature
Mishra and Pavelko were the first to prospectively evaluate the use of PRP in a pilot study which showed a 60% improvement in pain scores for patients who had chronic elbow tendinosis compared to 16% in controls. 7 Gosen and colleagues have shown in their preliminary results of an ongoing double-blinded, randomized trial evaluating PRP and cortisone injections for chronic lateral epicondylitis that those receiving PRP have demonstrated greater improvement in VAS and DASH scores. 8
Kon et al evaluated the use of PRP in treating chronic patellar tendinosis where 20 male athletes received three PRP injections at 15-day intervals. All participants had improvements in VAS Medical Outcomes Study 36-Item Short Form and Tenger activity scores at 6 month follow-up. 9
Barrett and Erredge have demonstrated that use of PRP under ultrasound guidance for plantar fasciitis where seven out of nine patients had complete resolution of pain at a year. 10
Sanchez et al compared the administration of intra articular injection of PRP for the treatment of early OA with hyaluronic acid and noted improved pain scores. 11
Sanchez et al evaluated the use of PRP to augment operative repair of Tendo Achilles injury and showed early return to sporting activity. 12
Randelli et al have shown the effect of injecting PRP into the foot print of arthroscopic rotator cuff repairs and all patients had statistically significant improvement compared to pre-operative scores. 13
Orrego et al compared the effect of PRP with autologous bone plugs in anterior cruciate ligament reconstructions. The use of PRP had an enhancing effect on the graft maturation effect. 14
In summary PRP has emerged as a promising treatment option for a lot of tendon and muscle injuries and disorders. It is autologous and prepared at the point of care and has an excellent safety profile. It seems to have the ability to transform the treatment of muscle and tendon injuries in elite athletes as well as weekend warriors. Although there have not been any long term double blinded randomized trials to prove beyond doubt the efficacy of PRP the early results are definitely encouraging.
The use of PRP may be considered as a major step in the beginning of a new medical frontier known as “orthobiologics”. Future generations of injectables will target specific cells and individual growth factors. Ultimately stem cell therapy will represent the ultimate biologic healing tool which might even make surgery irrelevant.
- Jobe F, Ciccotti M. Lateral and Medial epicondylitis of the elbow. J Am Acad Orthop Surg. 1994;2:1-8
- Nirschl R, Rodin D, Ochai D, Maartmann-Moe C. Iontophoretic administration of dexamethasone sodium phosphate for acute epicondylitis: a randomized, double-blinded, placebo -controlled study. AM J Sports Med. 2003;31:189-195
- Marx R, Carlson E, Eichstaedt R, Schimmele S, Strauss J, Georgeff K. Platelet-Rich-Plasma: growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Oral Endod.1998; 85:638-646.
- Marx R.What is PRP and what is not PRP? Implant Dent 2001; 10:225-8.
- Creaney L, Hamilton B: Growth factor delivery methods in the management of sports injuries: The state of play.Br J Sports Med 2008; 42; 314-320.
- Bielecki TM, Gazdzik TS, Arendt J et al. Antimicrobial effect of autologous platelet gel enriched with growth factors and other active substances: an invitro study JBJS Br 2007;89(3):417-20
- Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered PRP.AM J Sports Med 2006; 34:1774-1778.
- Gosen T, Sluimer J. Prospective randomized study on the effect of autologous platlets injection in lateral epicondylitis compared with corticosteroid injection. Poster presented at 13th Congress of ESS KA; May 21-24, 2008; Porto, Portugal.
- Kon E, Filardo G, Delcogliano M, et al; PRP: New clinical application: A pilot study for treatment of jumper's knee. Injury 2009;40:598- 603
- Barrett S, Erredge S; Growth factors for chronic plantar fasciitis. Podiatry Today 2004;17:37-42
- Sanchez M, Antiua E, Azofra J, Aguirre JJ, Andia I: Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: A retrospective cohort study. Clin Exp Rheumatol 2008; 26:910-913.
- Sanchez M, Anitua E, Azofra J, Andia I et al; Comparison of surgically repaired Achilles tendon tears using Platelet rich fibrin matrices. Am J Sports Med 2007; 35:245-251.
- Randelli PS, Arrigoni P, Cabitza P, Volpi P, Maffulli N: Autologous PRP for arthroscopic rotator cuff repair: A pilot study. Disabil Rehabil 2008; 30:1584-1589.
- Orrego M, Larrain C, Rosales et al: Effects of platelet concentrate and a bone plug on the healing of hamstring tendons in a bone tunnel. Arthroscopy 2008;24:1373-1380.