Platelet Rich Plasma Treatment for Chronic Achilles Tendinosis

Transcription

1 FOOT &ANKLE INTERNATIONAL DOI: /FAI Platelet Rich Plasma Treatment for Chronic Achilles Tendinosis Raymond Rocco Monto, MD Nantucket, MA ABSTRACT Background: Chronic Achilles tendinosis is a relatively common but difficult orthopedic condition to treat. In this study, autologous platelet rich plasma (PRP), a concentrated bioactive blood component rich in cytokines and growth factors, was evaluated to determine its potential long-term efficacy in treating chronic cases of Achilles tendinosis resistant to traditional nonoperative management. Methods: Thirty patients with chronic Achilles tendinosis who did not respond to a minimum of 6 months of traditional nonoperative treatment modalities were treated with a single ultrasound guided injection of PRP. AOFAS scoring was completed for all patients pretreatment and at 0, 1, 2, 3, 6, 12, and 24 months post-treatment. MRI and/or ultrasound studies were completed for all patients pre-treatment and at 6 months post-treatment. Prior to the PRP treatment all of the patients in this study were considering surgical Achilles repair for their severe symptoms. Results: The average AOFAS score increased from 34 (range, 20 to 60) to 92 (range, 87 to 100) by 3 months after PRP treatment and remained elevated at 88 (range, 76 to 100) at 24 months post-treatment. Pretreatment imaging abnormalities present in the Achilles tendon on MRI and ultrasound studies resolved in 27 of 29 patients at 6 months post-treatment. Clinical success was achieved in 28 of 30 patients. Conclusion: Platelet-rich plasma was used effectively to treat chronic recalcitrant cases of Achilles tendinosis. Level of Evidence: IV, Case Series Key Words: Platelet-Rich Plasma; Achilles Tendinosis Dr. Monto has received benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this article. Corresponding Author: Raymond Rocco Monto, MD Nantucket Cottage Hospital Orthopedic Surgery 57 Prospect Street Nantucket, MA drmonto@hotmail.com For information on pricings and availability of reprints, reprints@datatrace.com or call , x232. INTRODUCTION The treatment of chronic Achilles tendinosis has remained a complex and difficult challenge in orthopedics. The pathophysiology is not fully understood, but seems to involve microscopic degenerative injury to the tendon with local disruption of the collagen matrix and microtears rather than involving inflammatory cells. 6,37 The presence of erratic blood flow with chaotic zones of hypovascularization and hypervascularization also plays a role in the disease process. 6,8,22 Classic clinical findings of chronic Achilles tendinosis include local fusiform swelling, tenderness, and loss of ankle motion with complaints of pain with ambulation and ankle stiffness. 6,8,26,31,41,44,48 A myriad collection of nonoperative and operative approaches have been utilized without uniform or reproducible success. 1,8,35,41,43,47 Nonoperative approaches include rest, immobilization, nonsteroidal and steroidal anti-inflammatory medication, and physical therapy. 35,43 Topical glyceryl trinitrate and extracorporeal shock wave therapy have also been used with modest success. 39,42 Because traditional nonoperative management of chronic Achilles tendinosis has reported failure rates of 25%, numerous surgical treatments have been explored including operative debridement, autogenous flexor hallucis longus or flexor digitorum longus tendon transfer, and allograft augmentation, with varying clinical outcomes. 1,10,26,47,48,52 MRI and ultrasound techniques have proven useful in assessing the severity of Achilles tendon injuries and following their response to various operative and nonoperative approaches in an objective, quantifiable, comparable and reproducible manner. 23,27,38 Platelet rich plasma (PRP) is a bioactive component of whole blood with concentrations of platelets above baseline values. 17,19,33 Platelets play a critical role in the normal injury repair cycle of the body as well as modulating intercellular communication. 19,20,28 The platelets secrete a wide variety of cytokines and growth factors that act as chemo-attractants for reparative cells. 3,4,15,17,29,30 These agents include platelet-derived growth factor (PDGF), transforming growth factor-beta 1 (TGFB-1), fibroblast growth factor (FBGF), vascular endothelial growth factor (VEGF), 379

2 380 MONTO Foot & Ankle International/Vol. 33, No. 5/May 2012 epidermal growth factor (EGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), and connective tissue growth factor (CGF). These growth factors modulate neovascularization and angiogenesis, promote mitogenesis, boost local collagen production, and appear to provide antiinflammatory effects by blocking cylco-oxygenase-2 (COX- 2) enzyme production. 2,19,34,51 The different cellular sizes and densities among platelets, red blood cells, and white blood cells allow their isolation through centrifugation. 19 By mechanically concentrating the level of platelets to levels seven to 10 times baseline by simple centrifugation of whole blood, correspondingly high levels of these growth factors can be obtained. 15,20,28,29 Levels of PDGF in PRP have been measured as high as 25x baseline value, while EGF, TGFbeta, and VEGF levels can rise to 10x baseline depending on the system used. 15,20 This has led to the use of PRP as a vector to deliver growth factors to local muscle and tendon injury and repair zones to induce and accelerate healing. 5,9,12,14,17,21,32,33,40,51,53 PRP was first used in dental, maxillofacial, and plastic surgery in the early 1990 s and more recently to promote anastomotic healing in coronary bypass surgery. 20 Recently, PRP has shown promise in the treatment of various musculoskeletal conditions including chronic lateral epicondylitis, muscle strain, ligament sprain, cartilage damage, and tendon injury, and has been approved by the Internal Olympic Committee in the treatment of soft tissue injuries and tendon disorders. 3,7,14,16,17,22,24,25,30,36,44,45,46,49,50,52,55 We report our results in a group of patients with chronic Achilles tendinosis. MATERIALS AND METHODS Thirty patients with chronic unilateral Achilles tendinosis who had failed extensive traditional nonoperative management were treated with PRP. There were 17 males and 13 females. The average age was 47 (range, 36 to 66) years. The average duration of symptoms prior to PRP treatment was 8 (range, 6 to 22) months. All patients had failed a minimum 6- month trial of standard nonoperative treatment including rest, physical therapy, silicone heel lifts, CAM walker bracing, cast immobilization, night splinting, and non-steroidal medication. All patients in the study were required to have spent a minimum of 8 (range, 8 to 13) weeks in a cam walker boot and each patient was screened with either MRI scan (18 of 30) or multi-planar ultrasound examination (12 of 30). All patients gave informed consent and the study was approved by an institutional review process. The PRP preparation system used in this study was the Accelerate platelet concentration system (Exactech, Inc., Gainesville, FL). For the purposes of this study a 27 cc venous blood sample was obtained from the patient and mixed with 3 cc of anticoagulant citrate dextrose solution formula A (ACD-A) to prevent clotting of the sample. This sample was then centrifuged at 2400 rpm for 12 minutes is a soft spin (gradual start and zero braking for a gentle stop) technique to minimize mechanical damage to the platelets. A 4-cc PRP unbuffered and unactivated isolate was then obtained from the buffy coat of the centrifuged blood sample. With the patient lying in a prone position, the injury zone was prepped and then a local anesthetic field block of the skin and peritenon was placed using a 25 gauge needle and 6 cc of 1 % ropivicaine. Next, using an 18 gauge needle 2 to limit platelet damage, 2 cc of PRP was then directly injected into the injury zone from each side of the Achilles tendon (total, 4 cc PRP). In order to accurately inject the PRP isolate into the injured zone of the Achilles tendon, a dorsally positioned ultrasound probe was utilized (General Electric LOGIC Book XP) to identify the tendon injury zone and the tendon was then injected from each side using a standardized single skin entry diamond-patterned injection array technique (Figure 1). Patients were placed into a cam walker brace for 48 hours and then allowed to return to activities as tolerated along with a standard home eccentric exercise program. Nonsteroidal anti-inflammatory use was not permitted during the first 2 weeks after treatment and was discouraged throughout the entire study period. No other treatment modalities were used during the study. Interval AOFAS hindfoot scoring data and physical examinations were completed for all patients immediately prior to PRP treatment, then at 1, 2, 3, 6, 12, and 24 months following treatment. Repeat MRI or ultrasound imaging studies were completed on all patients and compared to the pretreatment findings. RESULTS Preoperative AOFAS scores averaged 34 (range, 20 to 60) with 22 of 26 patients who played sports unable to participate due to their condition. Ten of the 22 employed patients were also unable to work because of the severity of their symptoms. Pretreatment MRI findings of chronic tendinitis were seen in 18 of 18 patients. All MRI patients demonstrated significant Achilles swelling, four had tendon calcifications, Lateral Achilles (single skin puncture) Diamond PRP Injection Pattern Medial Achilles (single skin puncture) Fig. 1: Schematic of diamond injection pattern using a single skin entry point from each side of the tendon to center it in the maximal damage zone within the needling array using an ultrasound probe oriented parallel to the Achilles.

3 Foot & Ankle International/Vol. 33, No. 5/May 2012 PLATELET RICH TREATMENT FOR TENDINOSIS 381 A B Fig. 2: A, MRI of Achilles tendon pretreatment with PRP. Note signal change and partial tearing at Achilles insertion (AOFAS score 34 / unable to work or participate in sports). B, MRI same patient 6 months post-treatment with PRP. Note resolution of signal changes and healing of partial tear at the calcaneal insertion of the Achilles tendon (AOFAS score 100 / working and playing ice hockey). A B Fig. 3: A, MRI of Achilles tendon pretreatment with PRP. Note signal changes and partial insertion tearing (AOFAS score 43 / working but unable to play golf). B, MRI same patient 6 months after PRP treatment. The insertional tear has healed and the swelling of the Achilles tendon has diminished. (AOFAS score 84 / working and returned playing golf. The AOFAS score rose to 90 at 24 months followup and the patient returned to all athletics). and six displayed partial Achilles tendon tears (four calcaneal insertion partial tears and two midtendon partial tears) (Figures 2A, 3A, and 5A). Pretreatment ultrasound studies were completed on the remaining 12 patients and all studies demonstrated Achilles swelling while four demonstrated intrasubstance Achilles tears (Figure 4A). There were eight patients in the study with calcaneal insertional Achilles tendinosis and 22 with noninsertional disease. One patient had a Haglunds deformity along with severe chronic Achilles tendinosis. Following PRP injection, each patient was examined and scored at 1, 2, 3, 6, 12, and 24 months. Average AOFAS scoring at 1-month post-prp treatment dramatically improved to 84 (range, 80 to 87). At 2 months post-prp treatment the average AOFAS score was 87 (range, 84 to 90). At 3 months, the average AOFAS scores had improved to 88 (range, 87 to 100). AOFAS scoring at 6 months post- PRP averaged 92 (range, 76 to 100). AOFAS scores at 12 months post-prp treatment were 90 (range, 76 to 100) and final AOFAS scores at 24 months remained elevated at 88 (range, 81 to 100) (Table 1). All patients completed the first 6 months of the study. Two patients were dropped from the study and classified as failures of treatment due to clinical dissatisfaction and intervening Achilles surgery. Post-treatment MRI and/or ultrasound studies were repeated at 6 months in 29 of 30 patients and demonstrated interval

4 382 MONTO Foot & Ankle International/Vol. 33, No. 5/May 2012 A Table 1: Efficacy of PRP for Severe Chronic Achilles Tendinosis Over a 2-Year Period MONTHS AOFAS B Fig. 4: A, Ultrasound of Achilles tendon pretreatment with PRP. Note fusiform swelling with tendon width 17 mm and intrasubstance tear (AOFAS score 37 and unable to work). B, Ultrasound of Achilles tendon 6 months post-treatment with PRP. Note decreased swelling with new tendon width 8.5 mm and improved collagen alignment (AOFAS score 86/returned to work). healing of the treated injury zone in 27 of 29 patients (Figures 2B, 3B, 4B, and 5B). Nine of the 10 patients who were disabled from work due to the severity of Achilles tendinosis returned to their former occupations and 18 of the 22 patients who could not participate in sports because of their condition returned to their previous competitive level. No complications from PRP injections were noted in any of the patients in this study. Twenty-seven of 30 were satisfied with the results of the PRP treatment at 6 months and 28 of 30 patients were satisfied at final 24-month followup. Despite significant improvement from their pretreatment state, two clinically dissatisfied patients left the study after the 6-month followup visit with persistent pain. Both patients later had surgical procedures for their residual symptoms. The first patient to leave the study had chronic calcaneal insertion Achilles pain for 6 months and could not play golf. The pre-prp treatment MRI was consistent with a high grade partial tear at the calcaneus insertion. The pre-prp treatment AOFAS score was 26 and the 6-month post-prp treatment AOFAS score had increased to 76, but the patient was still unable to play golf without pain. The patient was clinically dissatisfied with her results but declined post-prp treatment imaging and went on to a second PRP treatment without further improvement. A surgical repair was later completed using a suture anchor reattachment of the distal Achilles to the calcaneus combined with flexor hallucis longus tendon transfer with good clinical results. A second patient with chronic symptoms of 6 months duration, a pre-prp treatment AOFAS score of 20 and a 6-month post-prp treatment AOFAS score of 86 was dissatisfied with their results because of persistent pain during heavy labor occupation and inability to return to sports due to persistent pain. The pre-prp treatment MRI was consistent with severe Achilles tendinosis and a partial intrasubstance tear. The 6-month post-prp MRI demonstrated interval healing in the Achilles tendon and decreased retrocalcaneal bursitis, but demonstrated a persistent Haglund deformity. Despite his increased AOFAS score, the patient still had pain with sports and work and left the study as a treatment failure. The patient went on to a repeat PRP injection without further improvement and then underwent retrocalcaneal bursectomy and resection of the Haglund deformity with excellent clinical results. At the time of surgery, the Achilles tendon was found to be in normal condition. Two patients had persistent Achilles swelling and signal change on post-treatment ultrasound exams but were satisfied and were otherwise asymptomatic. Interestingly, no statistical differences were seen between male and female subgroups or between patients above or below age 55. Although both treatment failures in this study

5 Foot & Ankle International/Vol. 33, No. 5/May 2012 PLATELET RICH TREATMENT FOR TENDINOSIS 383 were cases with calcaneal Achilles disease involvement, no statistical difference was noted between insertional and noninsertional group results overall. The presence of calcifications and partial tears seen on pretreatment studies did not appear to negatively affect long-term clinical success. DISCUSSION In this prospective longitudinal case series, the use of local PRP injection successfully treated severe chronic Achilles tendinosis in patients where prolonged traditional nonoperative management had failed. The likely mechanism of this effect is the release of growth factors and chemoattractants from the highly concentrated platelets in the Achilles tendon injury zone. 3,4,15,17,29,30 These platelet nests act as rally points for the local recruitment of macrophages and fibroblasts to gradually repair the damaged collagen of the tendon over the ensuing 4 to 8 weeks following platelet activation. This induces modulation of angiogenesis and collagen processing with migration of fibroblasts to the injury zone. 21,26 There also appears to be an early anti-inflammatory effect due to the inhibition of cyclo-oxygenase-2 (COX-2) enzymes by the cytokines in PRP. 2,50 Consistent with this theory is the finding that the majority of improvement seen in our patients occurred in the first month following the PRP injection. The long-term excellent durability of clinical success in this 2-year study may be the result of improved collagen upregulation and neovascularization. The strengths of this study are its prospective longitudinal nature, the length of followup, and its high subject retention rate. The absence of a placebo group is the primary weakness of this study. No placebo group was used for this 2-year study since all patients were considering surgical repair for their chronic end stage, highly disabling and severe Achilles disease prior to PRP treatment. Despite the treatment success seen in this study, the patients proved to be noncompliant with postoperative care. They were instructed to use the cam walker for 48 hours and refrain from NSAID use, but this was unmonitored. All patients in this study were also instructed in a home based eccentrically based exercise program but the majority of patients did their exercises sporadically. It is uncertain what role unrecorded postoperative NSAID use might have had on the clinical results. Another potential problem with this study is its reliance on the AOFAS hindfoot scoring system to differentiate clinical performance. Although another scoring system might have been preferable, this was the system chosen and used in this prospective study. The AOFAS system has difficulty with assessing patient satisfaction and activity levels. This is evident in our study where both treatment failures displayed fairly high AOFAS scores because of activity restrictions and one lower scoring patient (AOFAS score 76) was quite satisfied with their clinical result. The cost of use of PRP treatment compares favorably to other tertiary treatments for refractory chronic Achilles tendinosis. The current retail cost of the PRP system used in this study is $300 USD. The use of ultrasound for needle guidance was $200 USD per case. Although this study supports the use of PRP for Achilles tendinosis, a double blind, block randomized study examining the effects of platelet-rich plasma on Achilles tendinosis reached a different result. 11,13 The authors concluded that PRP was no more effective than a placebo saline Achilles injection in treating Achilles tendinosis. However, the study only examined patients with early Achilles disease and mild to moderate symptoms who had not been previously treated. A noninjected control group was not provided. In addition, although all patients in the PRP and placebo groups improved over the course of 12 months, twice as many patients in the PRP group returned to sporting activities than in the placebo group at 6 months followup. 11,13 The success of PRP treatment using our study protocol may be partially due to the aggressive injection technique targeting the injury zones from both sides, the use of ultrasound targeting for accurate injection placement, the adoption of early weightbearing and active motion, and the high levels of growth factors seen with the PRP harvesting system used. The positive mechanical effects of the injection process may be similar to the clinical improvement seen in brisement procedures, where local anesthetic injections into the body of the tendon are used to lyse adhesions and stimulate local bloodflow. 6,19 The diamond shaped injection pattern used in this study allows excellent placement of the injection within the substance of the injured Achilles tendon using ultrasound needle guidance. Marked improvement in clinical scoring was seen in the majority of the patients treated in this study. Although there were two patients classified as treatment failures in this study, both demonstrated substantial improvement from their pretreatment condition. It is important to note that no improvement was seen following repeat PRP treatment in these two patients. The accelerated healing and recovery seen with the use of PRP in Achilles tendons has been seen in another study focusing on utilizing PRP to augment Achilles reconstruction for full thickness tears. 44 The enhancing effects of PRP injection have also been demonstrated when used for chronic tennis elbow and patellar tendinitis management and following acute muscle injury. 24 Early encouraging results have also been reported in the use of PRP augmentation for rotator cuff reconstruction, flexor tendon, and anterior cruciate ligament repair. 3,11,17,22,34,52 Despite the relatively long-term success of PRP in treating these cases of chronic severe Achilles tendinosis, the fundamental treatment paradigm of rest, ice, eccentric exercise, activity modification, and selective immobilization is still successful in the majority of patients with mild to moderate disease and should not be abandoned.

6 384 MONTO Foot & Ankle International/Vol. 33, No. 5/May 2012 CONCLUSION This study was the first to demonstrate that platelet rich plasma can safely, effectively, and durably treat severe chronic Achilles tendinitis in patients who have failed to respond to traditional nonoperative management techniques. REFERENCES 1. Alfredson, CH; Cook, J: A treatment algorithm for managing Achilles tendonopathy: New treatment options. Br J Sports Med. 41: , Bendinelli, P; Matteucci, E; Dogliotti, G; et al.: Molecular basis of anti-inflammatory action of platelet-rich plasma on human chondrocytes: mechanisms of NF-(ordM) B inhibition via HGF. J Cell Physiol. 225:757 66, Anitua, E; Andia, I; Sanchez, M; et al.: Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture. 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