As orthobiologic technology continues to advance, these authors discuss the theory behind platelet-rich plasma (PRP), offer a thorough review of the literature on PRP for Achilles tendon injuries and provide insights from their clinical experience on the role of this emerging modality.
The use of orthobiologics in the treatment of foot and ankle injuries, both in the clinical and surgical venues, is significantly increasing. The clinician and the surgeon continue to seek better ways to accelerate and mediate the healing of bone and soft tissue while incorporating less invasive techniques.
The use of autologous platelet-rich plasma (PRP) by foot and ankle specialists over the last few years has emerged in the forefront of biologic tools in this endeavor. Physicians and clinicians have utilized PRP over the last four decades. Researchers have investigated the use of PRP in the treatment of tendon injuries, chronic wounds, ligamentous injuries, cartilage injuries, muscle injuries, and bone augmentation (intraoperative fusions and fracture repair). The use of PRP is based on the theory that increased concentrations of autologous platelets yield high concentrations of growth factors and other proteins, which will subsequently lead to enhanced healing of bone and soft tissue on a cellular level.
Platelet-rich plasma is the concentration of platelets derived from the plasma portion of centrifuged or filtered autologous blood. Surgeons can then use this platelet rich solution as an adjunct to healing as with a fresh surgical fusion or to reinstate healing as with chronic tendon injuries. Platelet-rich plasma and related products have different labels throughout the literature including platelet-rich concentrate, platelet gel, preparation rich in growth factors (PRGF), platelet releasate and platelet-leukocyte-rich gel (PLRG).
When one acquires the PRP, another product may or may not activate it. Platelet rich plasma without activation is usually reserved for the treatment of tendon, muscle and other soft tissue. In regard to PRP activated into a gel or fibrin sealant, podiatrists can use this clinically and intraoperatively for tendon augmentation, wound healing and bone augmentation. There have been several studies investigating the efficacy of PRP and its applications.1
Understanding The Theoretical Benefits Of PRP
Essentially, one uses PRP to increase the concentration of platelets to an injured site. In an acute injury, platelets are normally activated during the inflammatory phase to begin healing. The addition of PRP in the acute injury increases the concentration of platelets at the local tissue above the baseline. Chronic injuries that have failed conservative therapies presumably have ceased the inflammatory phase, have a paucity of platelets and a decrease in healing potential.
The use of PRP in these situations would provide two beneficial results. First, the simple act of injecting PRP for tendon, ligament or muscle injuries will stimulate the tissue and restart the inflammatory process, thereby making the chronic injury into a “new” acute injury. Second, the addition of autologous concentrations of platelets theoretically augments the healing process. This new injury now has a known starting point and can be placed in a controlled post-injection environment (i.e. immobilization, bracing or non-weightbearing). During this time, the use of anti-inflammatory medications and therapies are restricted so as not to reverse the desired effect.
How One Acquires PRP
To acquire autologous PRP, one would collect blood from the cubital vein. The amount of blood acquired depends on the clinical application (treatment area) and desired concentration. Clinicians would then separate the platelets from the plasma via centrifugation or filtration. Many different systems are available on the market today to obtain the PRP.
When using a simple centrifugation process, the blood collected spins down between 5 and 20 minutes depending on the speed of the centrifuge and the concentration desired. There will be three relative layers of product in the tube: the plasma layer (platelets), the buffy coat layer (white blood cells) and remaining blood products (red blood cells). The platelets are at the top of the tube. There has been debate on the true concentrations obtained through simple centrifugation and the true output of platelet rich versus platelet poor product. One would then collect the platelet rich plasma using a syringe and 18-gauge needle, being careful not to collect any platelet poor or red cells.
A similar method of collection uses an automated centrifugation process, which separates the platelets from the whole blood and then automatically sends the product to a separate syringe using an infrared microprocessing sensor to differentiate between red blood cells and platelet rich plasma. This type of system seems to lead to more accuracy and allows for more reproducible concentrations. There is presumably less error with less manual manipulation of the blood product through automated separation. One such device is the Magellan Autologous Platelet Separator System (Arteriocyte Medical Systems). With either method, the tube that initially collected the blood must have an anticoagulant. The kits that come with the products usually have tubes already with anticoagulant or come with a separate anticoagulant.
A Review Of The Anatomy And Pathomechanics With Achilles Tendon Injuries
The Achilles tendon is the distal insertion of the triceps surae, which consists of two heads of the gastrocnemius muscle and the soleus muscle. The two heads of the gastrocnemius muscle (medial and lateral) originate from the posterior aspect of the femoral condyles and coalesce as they descend down the leg until they form the Achilles tendon approximately 12 to 15 cm from its insertion on the calcaneus. The soleus muscle arises deep to the gastrocnemius muscle and originates from the posterior aspect of the proximal tibia and fibula. The soleus tendon is independent from the gastrocnemius tendon until approximately 5 to 6 cm above its insertion into the calcaneus, where it coalesces with the overlying gastrocnemius tendon. The tendon rotates as it descends to its insertion at into the posterior surface of the calcaneus.2,3
The Achilles tendon is encased by a paratenon, which is rich in vascularized tissue. The paratendon supplies a significant portion of blood to the tendon. The musculotendinous junction and the osseous insertion also supply blood to the tendon. Approximately 2 to 6 cm proximal to the insertion is a region of poor blood supply to the tendon, making it susceptible to degeneration and injury.2,3
Although the Achilles tendon is the largest and the strongest tendon in the body, it is one of the most frequently injured tendons in the body. This is due to higher participation in sport-related activities.2,3 Approximately seven in every 100,000 people will suffer from an Achilles tendon injury every year.3 The Achilles tendon can be injured either in the main body of the tendon, the osseotendinous junction or, more rarely, the myotendinous junction.4
Achilles tendon injuries may occur due to a number of intrinsic or extrinsic factors. Age, body type, gender, tendon vascularity, gastrocnemius-soleus dysfunction, overpronation, lateral heel strike, pes cavus, lateral ankle instability, poor training technique and/or improper footwear can predispose someone to an Achilles tendon injury.2-5 Repetitive microtrauma or overload can also predispose the tendon to inflammation of its sheath and intratendinous degeneration.2-5 Pain may be indicative of a partial rupture in the degenerate tendon in this area and will ultimately lead to thickening and nodularity of the tendon.5
Essential Diagnostic Keys
Paratenonitis of the Achilles tendon may present with pain and swelling to the area. This inflammatory condition develops acutely and can cause discomfort throughout the tendon. Inflammation of the paratenon may be associated with degeneration of the associated tendon. If the paratenon is chronically inflamed, it may thicken and cause adhesions to the Achilles tendon.2-6
Tendinosis or tendinopathy is the preferred term to describe the degenerative noninflammatory process of a tendon. Do not use the term tendonitis as the condition is not associated with any inflammatory cells and researchers have shown that inflammation of the tendon does not occur at any stage during the degeneration of the Achilles tendon.7 This noninflammatory process begins with mucoid or fatty material accumulating throughout the affected portion of the Achilles tendon. The fibers then thin and disorient, causing fibril ruptures. These tears can coalesce and form larger tears within the tendon. This ultimately results in thickening of the tendon that can be diffuse, nodular or fusiform.2,5,6
One can often establish a clinical diagnosis with a clinical examination. Focal or generalized swelling and pain on palpation to the Achilles tendon are indicative of a pathologic tendon. If a clinical diagnosis is not clear, one may assess the Achilles tendon with the use of plain radiography, ultrasound or magnetic resonance imaging (MRI).2,8
A lateral radiograph of the foot can somewhat show the thickness and continuity of the tendon. It can also be useful in evaluating a Haglund’s deformity, tendon calcification, calcaneal spurring or insertional tendinopathy.2,3
A MRI is very sensitive in showing changes such as intratendinous lesions and tears within the Achilles tendon. It will also show any thickening of the tendon that may be indicative of a degenerative tendon. The normal thickness of the Achilles tendon is approximately 4 to 6.7 mm. Normally on a MRI, the Achilles tendon shows homogeneously low signal intensity with a concave or flattened anterior border and a convex posterior border.2
Ultrasound examination allows for dynamic evaluation of the Achilles tendon. It allows for evaluation of normal tendon movement and glide during ankle motion. A normal Achilles tendon on ultrasound in the sagittal plane will show a homogenous and tightly packed fibrillary structure that broadens toward the calcaneal insertion. The fascicles are arranged in a regular honeycomb pattern in the axial plane. On the axial plane, the normal Achilles tendon has a concave anterior border and a convex posterior border. Ultrasound also allows for the assessment of vascularity of the tendon with the color Doppler. Pathological tendon conditions are associated with hypervascularity of the region secondary to angiogenesis.2
A Primer On Treatment Options For Achilles Paratenonitis And Tendinosis
When it comes to Achilles paratenonitis and tendinosis, one can usually treat these conditions successfully with non-operative measures such as rest, activity modifications, correction of training errors, physical therapy, and shoe modifications such as a slight heel lift to the affected extremity.
Researchers have shown that eccentric exercises to the Achilles tendon help tendon collagen synthesis.9,10 Patients with severe pain may respond well to immobilization of the tendon with a walking boot or ankle/foot orthosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and cryotherapy can help reduce any associated inflammation. Corticosteroid injections are not recommended due to an increased risk of tendon rupture.2,3,9 Shockwave therapy of the Achilles tendon may also help stimulate soft-tissue healing and inhibit pain receptors to the area.9,10
Surgical treatment for tendinosis involves removing any fibrotic lesions or degenerate nodules, and reapproximating the edges to one another. If reapproximation is not possible, one may perform an autogenous tendon transfer or allograft reconstruction. Surgeons may reinforce the tendon with the plantaris tendon or employ an aponeurosis flap in cases of partial rupture.2,3,9 When it comes to degenerative tendons, surgeons can perform radiofrequency microtenotomy in order to induce healing and/or ablate sensory nerve fibers to reduce pain.10
Regenerative medicine has undergone study more in the field of tendinopathy and the theory is that growth factors and/or stem cells can help treat the degenerative process of tendons.11,12 Injecting PRP, platelets derived from whole blood, allows one to directly deliver growth factors to the injury site, which results in angiogenesis, chemotaxis and cell proliferation.11-13
What The Literature Reveals About PRP For Achilles Tendon Pathology
Recent studies have shown that PRP can positively affect gene expression and matrix synthesis in tendon and tendon cells.14 It is important, however, to distinguish acute tendon injury from chronic cases when discussing and studying PRP and its use for tendon pathology.
Researchers have looked specifically at the use of PRP for the treatment of Achilles pathology. Tendon injury leads to a cascade of degenerating events leading to eventual rupture. These include hypovascularity, repetitive microtrauma and the addition of fibrous tissue, which can then lead to degeneration and weakness of the tendon. Platelet-rich plasma theoretically reverses the effects of tendinopathy by stimulating revascularization and improving healing at the microscopic level.15
Alfredson and Lorentzon categorize Achilles tendon pathology into paratendinitis, paratendinitis with tendinosis and pure tendinosis.15 In paratendinitis, there are adhesions formed between the paratenon and the tendon. Paratendinitis with tendinosis involves degenerative changes within the substance of the tendon as well as inflammation in the paratenon. In cases of pure tendinosis, there is a palpable nodule that often presents. It is hypothesized that the introduction of PRP into the pathologic tendon will aid in the repair and remodeling of the tendon by tenocytes.
Lyras and colleagues studied the effect of PRP on angiogenesis during tendon healing.16 The study authors used PRP on the Achilles tendon of rats against a control group injected with saline. They found a significant increase in angiogenesis in the PRP group in comparison to the control group during the first two weeks of the healing process (i.e., the inflammatory and proliferative phases). They also noted the number of newly formed vessels in the PRP group was significantly reduced at four weeks in comparison to the controls, suggesting the healing process was shortened. They observed that the orientation of collagen fibers in the PRP group was better organized. The study authors concluded that PRP seems to enhance neovascularization, which may accelerate the healing process and promote scar tissue of better histological quality.
Gaweda and co-authors performed a prospective study on 15 patients with Achilles tendonitis.17 After following patients for 18 months, they found improvement in regard to pain scores and ultrasound imaging. The American Orthopaedic Foot and Ankle Society (AOFAS) scores improved from a median of 55 points to 96 points and the VISA-A score improved from 24 points to 96 points. They concluded that PRP is a viable treatment alternative for Achilles tendonitis.
A recent double-blind, randomized study by de Vos and colleagues looked at PRP injection in patients with chronic Achilles tendinopathy.10 The study involved 54 patients who ranged between 18 to 70 years of age and were evenly divided into the PRP group and control group. The clinical diagnosis was based on findings of a painful and thickened tendon in relation to activity and on palpation with symptoms lasting greater than two months.
Researchers used 54 mL of whole blood to derive the PRP that was mixed with sodium bicarbonate to match the pH of tendon tissue.11 Study authors injected a non-disclosed amount of PRP into five sites along the injured tendon under ultrasound guidance. Patients were only allowed to walk short distances indoors in the first 48 hours. In days three to seven, patients were allowed walks up to 30 minutes. After one week, patients started an exercise routine with one week of stretching and a 12-week daily eccentric exercise program with heel drops off a step. The study authors allowed no weightbearing sports activities for four weeks followed by a gradual return to those activities. Patients were only to use acetaminophen during the follow-up period.
The results were based on patient questionnaires that quantified pain and activity level. The results showed an improvement in 24 weeks by 21.7 points in the PRP group and 20.5 points in the placebo group. The authors concluded there was no significant difference between the groups.11 This study is limited by a number of factors. They did not identify any characteristics of the anatomy of the tendon pre- and post-injection, neither clinically nor with imaging techniques. Their sample size was small. They could not quantify the concentrations of PRP that were used in each patient.
One can use PRP in the form of a fibrin gel (when combined with thrombin) as a tendon scaffold. Surgeons can use it as a bridge and augmentation within the rupture defect, or they can wrap it around the tendon repair. In most cases, surgeons combine the fibrin gel with bone marrow aspirate for further enhancement of the PRP matrix.
Researchers have also evaluated PRP for Achilles rupture repair in the rat model.15,18,19 In one study, surgically transected tendons treated with PRP showed a 42 percent increase in their force to failure, a 61 percent increase in ultimate stress and a 90 percent increase in energy after two weeks in comparison to the control.17 In another study, those tendons treated with PRP had a 30 percent increase in strength and stiffness after one week.20
Sánchez and colleagues investigated the augmentation of Achilles tendon rupture repair with PRP in athletes (six each in the PRP group and control group).21 They used two PRP preparations on the primary repair of the Achilles in comparison with controls. Researchers mixed 4 mL of PRP with CaCl2. This mixture formed a fibrin scaffold after 30 minutes and the researchers subsequently incorporated this into the repair site between the tendon ends. They again mixed the remaining PRP with CaCl2 but immediately sprayed it onto the wound site before closure.
Sánchez and co-authors followed the patients for one year via ultrasound imaging and physical examination.21 They found that in comparison to the control, the PRP group was able to return to mild running with earlier range of motion and without wound complication.
Sarrafian and colleagues performed a study to compare a cross-linked acellular porcine dermal patch (APD) against a platelet-rich plasma fibrin matrix (PRPFM) for repair of acute Achilles tendon rupture in a sheep model.22 They reapproximated two surgically transected tendon ends in groups one and two, and left a gap between the tendon ends in group three. Sarrafian and co-workers used the acellular porcine dermal patch to reinforce the repair in group two. They employed autologous platelet-rich plasma fibrin matrix to fill the gap and reinforced this with the acellular porcine dermal patch in group three.
Tensile strength testing showed a statistically significant difference in elongation between the operated limb and the unoperated contralateral limb in groups one and three, but not in group two.22 In group one, all surgical separation sites were identifiable and healing occurred via increasing tendon thickness. In group two, healing occurred with new tendon fibers across the separation without increasing tendon thickness in two out of six animals. Group three showed complete bridging of the gap with no change in tendon thickness in two out of six animals. In groups two and three, researchers observed peripheral integration of the acellular porcine dermal patch to tendon fibers. The study authors concluded that use of the acellular porcine dermal patch, alone or with a platelet-rich plasma fibrin matrix, to augment Achilles tendon repair in a sheep model is a viable and strong repair.
De Jonge and colleagues performed a double-blinded, randomized, placebo-controlled trial with PRP treatment in chronic Achilles tendinopathy with a one-year follow-up.12 The study involved 54 patients, ranging between 18 to 70 years of age, with chronic tendinopathy 2 to 7 cm above the Achilles insertion who were randomized to receive either a blinded, ultrasound-guided injection of PRP (27 patients) or saline (27 patients) in addition to an eccentric training program.
After the injection, patients had to avoid sports activities for four weeks and start a stretching program at two weeks. At 12 weeks, they started an eccentric exercise program. Patient follow-up visits occurred at six, 12 and 24 weeks and one year with both clinical and ultrasound assessments. In using ultrasound assessments, researchers were able to measure both the structure of the tendon and neovascularization by color Doppler. Although they noted a significant improvement in the PRP treatment group, they found no clinical or sonographic benefit of a PRP injection at the six-month and one-year follow-up visits.12 They hypothesized that needle trauma may initiate a healing response and that an increase in peritendinous volume may help decrease pain by destroying vascular and neural growth.
Pertinent Insights From Our Clinical Experience With PRP
We have used PRP for the treatment of chronic Achilles tendinopathy and rupture repair in many cases. The treatment protocol is very similar to that of plantar fasciitis. We choose patients for this procedure based on the chronicity of their symptoms and the quality of the tendon. Those patients who have failed conservative therapies after three to six months are good candidates. In addition to pain, decreased activity and loss of function, most patients present with nodular thickening within the substance of the tendon. Some may even have multiple fibrotic nodules.
When it comes to patients who have an associated retrocalcaneal exostosis, we have also used PRP for these patients with varying results. One would confirm the diagnosis with ultrasound and/or MRI. Place a local anesthetic block well above the site of injection. Prepare the PRP at the desired concentration from the whole blood collection and activate it with calcium citrate. Proceed to inject between 6 and 10 cc of PRP within the substance of the tendon beginning at the site of pathology (pain and any bulbous mass).
In regard to the medial or lateral aspect of the tendon, one should approach under ultrasound guidance with the patient in a prone position. Using a 25-guage needle, inject several pulsed (peppered) doses of about 0.25 cc at a time in order to fenestrate the tendon. Then have the patient use a walking boot and crutches for up to one week. Subsequently, the patient may proceed to weightbearing in the boot for the next one to three weeks. One can then transition the patient into an athletic shoe with a slow increase in weightbearing activity over a four-week period.
We have seen a significant reduction in pain, a decrease in the size of fibrous nodules within the tendon, and an earlier return to regular and sporting activity after using PRP. Most patients have been able to return to increased exercise and activity within two months of the injection. Again, some patients have benefited from a second injection about six weeks after the first.
Regenerative medicine has been increasingly studied in the field of tendinopathy and PRP is becoming a popular application to stimulate the release of growth factors. There have been many studies in the area of PRP and they have shown mixed results in terms of the benefit of PRP. In our experience, PRP has offered promising results in the treatment of Achilles tendinosis in terms of decreased pain, faster recovery and reduced fibrous nodules within the tendon. More well designed prospective and retrospective studies are needed to measure the true effectiveness of PRP.
Dr. Soomekh is a Fellow of the American College of Foot and Ankle Surgeons, and a Diplomate of the American Board of Podiatric Surgery. He is on the faculty of the University Foot and Ankle Institute in Santa Monica, Calif.
Dr. Yau is a Fellow at the University Foot and Ankle Institute in Los Angeles.
Dr. Baravarian is an Assistant Clinical Professor at the UCLA School of Medicine. He is the Chief of Foot and Ankle Surgery at the Santa Monica UCLA Medical Center and Orthopedic Hospital. Dr. Baravarian is the Director of the University Foot and Ankle Institute in Los Angeles. He is a Fellow of the American College of Foot and Ankle Surgeons.
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