How to Select Cases and Use Platelet Rich Plasma for Tendon and Joint Injuries

1. Introduction

Regenerative medicine is a commonly used term that broadly applies to the use of biologics to enhance tissue repair. In the context of equine medicine, regenerative therapies are more commonly used to enhance the quality of repair in musculoskeletal tissues following injury. The most commonly used biologics include platelet rich plasma (PRP), stem cells, and interleukin-1 receptor antagonist protein (IRAP). The popularity of biologics is increasing, with owners looking for more “natural” therapies and their reluctance to treat their horses with drugs such as corticosteroids. Traditionally, PRP was used for tendons and ligaments, IRAP for joint injections, and stem cells for either soft tissue or joint injections. However, there is evidence for use of PRP for tendon or joint injuries. It should be remembered that all biologics are heterogeneous in their final composition because they are based in biology, not chemistry. Biologics are not drugs and there are many subtypes of each biologic. For example, PRP preparations vary considerably in the concentration of platelets and leukocytes. There is tremendous controversy over which type of biologic (PRP, stem cell, or IRAP) is best for a specific tissue or injury and then what specific type of PRP, etc, is best for a given application. Current evidence suggests that leukocyte-low PRP preparations with platelet concentrations 2 to 4-fold over baseline are optimal for increased tissue repair. There are no head-to-head comparison studies to answer those questions, thus some extrapolation between studies is required to formulate a recommendation for clients. Recent reviews on regenerative medicine in horses are cited in the following text for further reading.^1–6 

2. Methods and Results

PRP for Joint Pain

There is evidence that PRP can increase hyaluronic acid (HA) synthesis by synoviocytes and decrease joint pain and inflammation, which should help enhance early rehabilitation.¹ Platelet rich plasma is not just for tendons and can be considered as a first line of joint therapy. Case selection is those horses with mild to moderate joint disease. Like all other joint medications, PRP is not effective in end stage arthritis cases. Many practitioners use PRP as a postoperative adjunctive therapy following arthroscopic chip removal or fracture repair. The first injection is given 3 weeks postoperatively with a second injection 2 weeks later.

Platelet rich plasma is generated using sterile principles per a manufacturer’s directions. This can be by centrifugation of blood or by gravity filtration using a bag system. Approximately 2 to 4 mL/fetlock or carpus or 5 to 8 mL/stifle is injected twice at 10 to 14 day intervals. Based on evidence in the human literature, a third injection is not necessary. In long-term outcome data regarding the use of PRP for treatment of human knee arthritis, PRP is as, or more, effective as HA in restoring function and decreasing pain, but the effect lasts longer.² The effects of HA typically last 6 months, while the effects of PRP are reported to last for a year or longer.

No activation step such as thrombin is necessary. When platelets in PRP are exposed to joint tissue, they are activated and degranulate, thereby releasing their growth factor contents. Residual PRP can be frozen and used at a later date without loss of growth factor activity (unpublished data). There is no need for rest after a PRP injection. One of the major benefits of intra-articular PRP injections is diminished pain signaling, which should allow for aggressive rehabilitation in cases of mild to moderate arthritis.³ If there is no response within a week after a second injection, it is unlikely that a third injection will help. If there is a response, then routine joint maintenance (with 2 injections, as previously described), or treatment as needed can be performed, according to your practice philosophy. There are no published “flare rates” following PRP injections, but they have been anecdotally reported.

PRP for Tendon or Ligament Injury

Platelet rich plasma injections into tendons and ligaments increases normal tendon matrix synthesis, such as collagen type I, and decreases cytokines associated with matrix degradation.⁴ If PRP is administered into a lesion within a few days of injury, it can stop the progression and growth of a lesion.^5,6 The effectiveness of PRP for tendonitis appears to be related to the chronicity and severity of the lesion. Therapeutic intervention with PRP should be considered as soon as a lesion is diagnosed, not after weeks or months of failed rehabilitation. Once scar tissue has formed and remodeled, the regenerative capacity of tissues is limited. This time frame for successful intervention depends on the site and severity of the injury, but is likely limited to those injuries less than 3 to 6 months old.

Ultrasound guidance should be performed for injections, so two sets of hands, one to run the ultrasound and one to do the injection, is ideal. A convex probe is best for ultrasound guided injections. A sterile probe cover should be used. The volume of PRP for injection is simply enough to fill the lesion, which can be visualized under ultrasonography. A small 23 gauge needle can be used to minimize damage to normal tendon during injection.

After PRP treatment, the horse resumes active rest with a minimum of 30 min in hand walking per day. A recheck examination in 2 to 3 weeks and a second injection can be considered if the lesion has not significantly improved with a 50% improvement in palpation, lameness, and ultrasound appearance of the lesion. Platelet rich plasma injections into bowed tendons appear to result in a more rapid resolution of lameness and early return to linear fiber orientation in the injured region.^5,6 It is unclear if the ultimate time to return to performance is diminished by the injection of PRP.

3. Discussion

For tendon and joint injections, PRP appears to both enhance tissue repair and to decrease pain. The diminished pain allows for a faster return to rehabilitation, which is particularly important in middle-aged horses that are prone to secondary lameness issues with extended rest. The use of PRP is an attractive method of therapy because of the growth factors that are delivered, but it must be remembered that none of the biologics are drugs and, therefore, each preparation will vary, as will the clinical outcome. It is unclear which biologic is best for any given situation, but given the devastating loss of time and performance associated with musculoskeletal injuries in horses, a dual PRP/stem cell approach is commonly employed. Regenerative therapies should be applied early after injury, within a week if possible, so that they can change the healing environment before scar tissue begins to form.

Acknowledgments

Conflict of Interest

The Author is a consultant to Arthrex, Inc.

References

1. Sundman EA, Cole BJ, Karas V, et al. Anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med 2014;42(1):35– 41.
2. Filardo G, Kon E, Roffi A, et al Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration. Knee Surg Sports Traumatol Arthrosc 2013;e-pub ahead of print.
3. Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med 2011; 39(10):2135–2140.
4. Boswell SG, Schnabel LV, Mohammed HO, et al. Increasing platelet concentrations in leukocyte-reduced platelet-rich plasma decrease collagen gene synthesis in tendons. Am J Sports Med 2014;42(1):42–49.
5. Bosch G, van Weeren PR, Barneveld A, et al. Computerised analysis of standardised ultrasonographic images to monitor the repair of surgically created core lesions in equine superficial digital flexor tendons following treatment with intra-tendinous platelet rich plasma or placebo. Vet J 2011; 187(1):92–98.
6. Bosch G, Moleman M, Barneveld A, et al. The effect of platelet-rich plasma on the neovascularization of surgically created equine superficial digital flexor tendon lesions. Scand J Med Sci Sports 2011;21(4):554 –561.