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A Closer Look At Current And Emerging Indications For PRP
Regenerative medicine is rampant in orthopedic surgery. The beautiful thing is that platelet-rich plasma (PRP) has been used in many fields for years. Hematologists first coined the term in the 1970s in order to describe the plasma with a platelet count above that of peripheral blood, which was initially used to treat thrombocytopenia. Oral surgeons have been using platelet-rich fibrin since the 1980s for allograft adherence and the anti-inflammatory/cell proliferation characteristics.1 Other specialties, including plastic surgery, ophthalmology and cosmetic dermatology, have utilized PRP to its full potential.
Platelet-rich plasma has multiple preparations available with a variety of systems available on the market. This is confusing for the average practitioner and may discourage physicians from even contemplating the use of PRP in the office. Basically, through centrifugation of a volume of whole blood, a concentration of PRP contains growth factors, such as fibroblast growth factor (FGF), platelet derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), in quantities approximately two to five times above baseline. These growth factors and platelets increase macrophage activity, cell growth/proliferation, and angiogenesis at the cellular level.
But what does this mean for you, the busy foot and ankle surgeon?
My top three foot and ankle indications for PRP are as follows: plantar fasciitis, Achilles tendinopathy, and early-stage ankle arthritis.
Plantar fasciitis has been the most studied indication for PRP. Monto assessed PRP efficacy versus corticosteroid injections for chronic severe plantar fasciitis.2 In this prospective randomized trial involving 40 patients who previously failed conservative treatment, Monto compared single injections of 3 cc of PRP versus 40 mg of Depo-Medrol. The author found significant American Orthopaedic Foot and Ankle Society (AOFAS) score improvement for the PRP group at 24 months and noted this “may be the result of improved collagen upregulation and neovascularization.”
Another more recent randomized control trial published in the Journal of Foot and Ankle Surgery by Shetty and coworkers assessed three plantar fasciitis treatment arms: PRP, corticosteroid and a placebo.3 Researchers followed 30 patients for 18 months and quantitative measures included the visual analogue scale (VAS), Short Form 12 (SF-12) and Roles and Maudsley Scores. Each arm consisted of 2 cc PRP, 2 cc Depo-Medrol, and 2 cc normal saline. Importantly, each patient was prescribed a five-day course of non-steroidal anti-inflammatory drugs (NSAIDs) with a strict eccentric strengthening protocol. Over the course of the 18 months, the PRP group significantly improved their VAS and SF-12 scores over the other two arms, and had a lower reinjection rate. The authors also noted that three times as many patients in the corticosteroid group needed a surgical plantar fascia release than did the PRP group.
These two studies, in addition to my clinical experience, have led me to discuss using PRP very early in the treatment cascade for plantar fasciitis. I typically will inject 3 to 4 cc of leukocyte-rich PRP into the plantar fascia insertion with 5 cc lidocaine plain. I will do this three different times at two-week intervals while patients do an eccentric strengthening program and wear a controlled ankle motion (CAM) walker boot for six weeks. I have found most patients start to see a positive response around six to eight weeks but may take up to 16 weeks to return to normal activity.
The use of PRP has also been heavily studied in our literature as well as the sports medicine literature for the treatment of Achilles tendinopathy. From a cellular level, PRP has almost the same role as in plantar fascia healing: aiding in local recruitment of macrophages and fibroblasts, inducing angiogenesis and early inhibition of cyclooxygenase-2 (COX-2). The Achilles mid-substance pathology is difficult to treat and often a conservative approach is best suited to the Achilles. I have found that along with a very strict eccentric strengthening program and accountable physical therapy, PRP plays an excellent role in the transitioning of this problem from a chronic to an acute pathology.
In a randomized study out of Denmark by Krogh and colleagues, 24 patients with chronic midsubstance Achilles tendinitis received either a 6 cc injection of PRP or 6 cc of normal saline.4 The authors found no statistically significant difference and the dropout rate was high at three months due to continued pain. I would argue that more than one injection is probably necessary to see a clinical difference.
An additional study examined the utility of a 50 cc high-volume injection of bupivacaine, Depo-Medrol and normal saline versus PRP versus placebo.5 Physicians gave four injections and followed patients for a six-month period of time. Patients also performed a strict eccentric exercise program twice daily. At six months, the authors noted the highest level of clinical pain relief and improvement in Victorian Institute of Sport Assessment–Achilles (VISA-A) scores among the three treatment arms. Either a high-volume injection or PRP with an eccentric training program was the most beneficial. When it comes to treating mid-substance (non-insertional) Achilles tendinopathy with a combination of modalities, I have found PRP to be very helpful with an expected return to activity (e.g., running) in four to six months.
Lastly, in regard to using PRP for early-stage ankle arthritis, this is the least studied of the three indications I am discussing here but most of us who treat this pathology know outcomes can be variable and exhausting all conservative options would be highly advisable.
When we discuss early-stage ankle arthritis, I am referring to osteochondral defects of the talus, not global post-traumatic arthritis. Ankle arthritis obviously is from altered joint mechanics that alter the metabolism of the synovial tissue within the joint. This increases the catabolism of the synovial tissue, which leads to increased pain. The goal of a regenerative approach here is not to fix a varus ankle but to attempt to promote chondrocyte healing. Platelet-rich plasma promotes chondral remodeling, increases type II collagen and increases synoviocytes, which will release hyaluronic acid and counteract tumor necrosis (TNF) alpha and COX-2.
In 20 patients with symptomatic ankle osteoarthritis and four weekly PRP injections, Repetto and coworkers showed significant improvements in pain and patient satisfaction over an 18-month period.6 These authors advise using leukocyte-poor PRP, which is typically less painful. The most interesting studies have shown that PRP with microfracture in comparison to hyaluronic acid and saline has shown promising results at an 18-month follow-up.7,8
My experience with PRP and regenerative medicine for early-stage ankle arthritis is very promising with at least 12 months of pain relief. Office protocols are three injections, two weeks apart with a functional, multiligamentous brace.
One can institute regenerative medicine into surgical and non-surgical practice. Understanding the appropriate indications and protocols is paramount, but do your own research. Platelet-rich plasma is not a catch-all and we should not treat it as such.
Email or contact me with questions.
References
1. Alves R, Grimalt R. A review of platelet-rich plasma: history, biology, mechanism of action, and classification. Skin Appendage Disord. 2018;4(1):18-24.
2. Monto RR. Platelet-rich plasma efficacy versus corticosteroid injection treatment for chronic severe plantar fasciitis. Foot Ankle Int. 2014;35(4):313-8.
3. Shetty SH, Dhond A, Arora M, Deore S. Platelet-rich plasma has better long-term results than corticosteroids or placebo for chronic plantar fasciitis: randomized control trial. J Foot Ankle Surg. 2019;58(1):42-46.
4. Krogh TP, Ellingsen T, Christensen R, et al. Ultrasound-guided injection therapy of Achilles tendinopathy with platelet-rich plasma or saline: a randomized, blinded, placebo-controlled trial. Am J Sports Med. 2016;44(8):1990-7
5. Boesen AP, Hansen R, Boesen MI, et al. Effect of high-volume injection, platelet-rich plasma, and sham treatment in chronic midportion Achilles tendinopathy: a randomized double-blinded prospective study. Am J Sports Med. 2017;45(9):2034-2043.
6. Repetto I, Biti B, Cerruti P, et al. Conservative treatment of ankle osteoarthritis: can platelet-rich plasma effectively postpone surgery? J Foot Ankle Surg. 2017;56(2):362-365.
7. Görmeli G, Karakaplan M, Görmeli CA, et al. Clinical effects of platelet-rich plasma and hyaluronic acid as an additional therapy for talar osteochondral lesions treated with microfracture surgery: a prospective randomized clinical trial. Foot Ankle Int. 2015;36(8):891-900.
8. Guney A, Yurdakul A, Karaman I, et al. Medium-term outcomes of mosaicplasty versus arthroscopic microfracture with or without platelet-rich plasma in the treatment of osteochondral lesions of the talus. Knee Surg Sports Traumatol Arthrosc. 2016;24(4):1293-8
