C R A I G C O L D W E L L F R E D D A V I S L A U R I E G R O V E J E F F K N I G H T

PLATELET RICH PLASMA

DEFINITION

• Platelets are small, irregularly-shaped anuclear cell fragments (i.e. cells that do not have a nucleus containing DNA), which are derived from fragmentation of precursor megakaryocytes (bone marrow cells responsible for the production of blood platelets, which are necessary for normal blood clotting). Megakaryocytes normally account for 1 out of 10,000 bone marrow cells.

• The average lifespan of a platelet is normally just 5 to 9 days. Platelets play a fundamental role in hemostasis (a complex process which causes the bleeding process to stop) and are a natural source of growth factors (a naturally occurring substance capable of stimulating cellular growth).

• If the number of platelets is too low, excessive bleeding can occur. If the number of platelets is too high, blood clots can form, which may obstruct blood vessels and result in such events as a stroke, myocardial infarction, pulmonary embolism or the blockage of blood vessels to other parts of the body, such as the extremities of the arms or legs.

DEFINITION, CON’T

• Platelet-rich plasma (PRP), the first practical application of tissue engineering, is a concentrated source of autologous platelets (platelets which are harvested, removed from, and replaced back into the same patient). PRP contains and releases growth factors that stimulate bone and soft tissue healing.

•The separation and concentration of the platelets is an exact science. Extreme care must be taken when blood products are harvested and processed. Because of factors involving its availability and cost, platelet-rich plasma (PRP) has become an increasingly popular clinical tool as an alternative source of growth factors for several types of medical treatments, including wound healing in surgery, tendonitis, cardiac care, cartilage regeneration, cosmetic procedures, disc regeneration, and dental health

HOW PRP IS USED

• Drawing of Blood• First, a small amount of blood is drawn from the

patient's arm. The blood is then placed in a centrifuge that spins the blood for approximately 15 minutes. This step removes the unwanted components of blood that are not primarily responsible for healing including: plasma, WBC's and RBC's. What remains is an increased concentration up to 10x above baseline of platelets, which are rich in healing properties called growth factors. During this time, the patient receives either local anesthetic (injected) or conscious sedation (via IV), as determined beforehand by the physician and patient.

• PRP Injection• Using musculoskeletal ultrasound, the area of

injury is properly identified and marked. The injection is performed with ultrasound guidance to ensure that the appropriate target is reached within a millimeter.

• The patient rests afterwards for 5-10 minutes and is discharged home with post procedure instructions. Increased pain may result for approximately 7 days following the injection which is not uncommon. This represents part of the healing process

• Follow Up• Follow up is usually in 4 weeks, when another

ultrasound will be performed to reassess the area of injury. At that time it is determined if a second injection is required. For most cases between 1-3 injections is required at 4 week intervals. However for osteoarthritis injections a 3 injection series is required at 4 week intervals. Patients are encouraged to participate in physical therapy following the injection which enhances recovery.

WHY PRP IS USED

• The separation and concentration of the platelets is an exact science.[1] Extreme care must be taken when blood products are harvested and processed. Because of factors involving its availability and cost, platelet-rich plasma (PRP) has become an increasingly popular clinical tool as an alternative source of growth factors for several types of medical treatments, including wound healing in surgery, tendonitis,[2],[3][4],[5] cardiac care, cartilage regeneration, cosmetic procedures,[6] disc regeneration, and dental health

• Most recently, PRP has found popular and effective applications in sports medicine (including mending injured tendons and ligaments in joints without surgery). Essential for understanding the biologic rationale of PRP is understanding the role of platelets in wound healing as well as the clinical effect of PRP in bone regeneration[10] and soft tissue healing.

• For bone repair, platelet-rich plasma (PRP) can be added to harvested autogenous bone or to a mixture of autogenous bone and freeze-dried bone/alloplastic material to improve the consistency for handling during surgery and minimizing particulate migration as well as to add increased platelets (i.e. increased growth factors) into the area. In cases involving surgery-free repair of joints, tendons, and ligaments, blood taken from the patient is processed into PRP and then injected into the injured area to accelerate healing.

OUTCOME DATA

• Popular Blood Therapy May Not Work • The treatment has become so popular that patients with orthopedic injuries

are demanding it, willing to pay $1,000 or more out of their own pocket. Its appeal only soared higher when professional athletes like Tiger Woods and the football players Troy Polamalu and Hines Ward reported that it cured them.

• It is a new procedure, based on an idea that once seemed revolutionary: Inject people with their own blood, concentrated so it is mostly platelets, the tiny colorless bodies that release substances that help repair tissues.

• Soon the treatment, platelet-rich plasma, or P.R.P., was extended to so many uses — treating muscle sprains and tendon pulls and tears, arthritis, bone fractures and surgical wounds — that Dr. Bruce Reider, editor of The American Journal of Sports Medicine, said in a recent editorial that perhaps it should be called “platelet-rich panacea.”

• Thousands of doctors and about 500 hospitals are offering the treatment, said Frank Stephenson, vice president for marketing and sales of Harvest Technologies, among several companies selling equipment for concentrating blood platelets.

• And another study, to be published next month in The American Journal of Sports Medicine, concludes that platelet injections may help tennis elbow, a degeneration of the tendons attaching the forearm muscles on the outside of the arm to the elbow. But some say that study had a design flaw that leads them to question its conclusions.

• “The underlying rationale for P.R.P. makes sense,” said Dr. Scott A. Rodeo, an orthopedist at the Hospital for Special Surgery in New York and author of a review of the treatment. But, Dr. Rodeo added, “We don’t know the most fundamental things about the causes of tendinopathy,” the degenerative changes in tendons underlying many injuries.

• Insurers generally decline to pay for the injections. But patients, eager for relief, have paid $1,000 or more for an injection; some even get a second or third.

• Tendon disorders, the focus of the two new studies, account for as many as half of sports injuries. Distance runners, Dr. Tol reports, have a 52 percent chance of tendon injury. Tendons heal slowly, if at all, and may keep people away from their sport for long periods.

• In their study, Dr. Tol, Dr. Robert J. de Vos of the Hague Medical Center and colleagues recruited 54 people with Achilles’ tendons that had been hurting at least two months. On average, they had symptoms for more than six months and had stopped doing their sport for three months.

• The participants were randomly assigned to have an injection of platelets or saline. They also were instructed to use the only treatment shown to be at all effective: eccentric contraction exercises — in this case, standing on a step and lowering the heel, which they were to do 180 times a day.

• Six months later, patients in both groups had improved. Their pain was an average of 20 points less on a 100 point scale. Two-thirds to three-quarters had returned to their sport. But there was no difference between saline and the platelet injections.

• The other study, of tennis elbow, compared platelet injections with injections of a steroid. After three months, patients who had a steroid injection reported less pain and disability than those who had platelets. Then patients who had received steroids started doing worse. Six months after the study began, those who had gotten platelet injections were better off.

• “We not only proved that P.R.P. gives better results, but we proved that steroids did not change pain and disability,” said Dr. Taco Gosens, an orthopedic surgeon at St. Elisabeth Hospital in Tilberg, the Netherlands, who conducted the study.

• But Dr. Freddie H. Fu, an orthopedist at the University of Pittsburgh Medical Center, said the study stacked the deck in favor of platelet injections. Steroid injections temporarily soothe pain but slow healing, Dr. Fu said. In the end, patients getting steroids were worse than if they had received no treatment.

• Although 73 percent of patients given platelet injections improved after a year, compared with 54 percent for steroid injections, Dr. Fu said that was not much success. “Any time you touch a patient, you get 70 percent success,” he said, adding that even placebos give that rate over time.

• Dr. Gosens said it would have been ethically difficult to ask patients to be randomly assigned to a treatment that might include a saline injection because steroid injections are a standard of care. He also said the difference in the two studies might be traced to the difference in the tendons. The Achilles’ tendon gets almost no blood, making healing more difficult, as compared with the smaller elbow tendon.

• Meanwhile, researchers are asking fundamental questions: Should injections be done immediately or after time has passed? Do the injected platelets quickly diffuse? If so, can they be held in place? How long should they stay in the injured area? Do people need more than one injection?

• Research now under way includes a study by Dr. Gosens of plantar fasciitis, heel pain caused by damage to tissue connecting the heel to the toes. Another center in the Netherlands is studying knee tendon injuries. Dr. Rodeo is studying platelet injections during surgery to repair rotator cuff tendons in the shoulder. And researchers like Dr. Rodeo and Dr. Tol are doing more basic research on the biology of platelet injections.

• In the meantime, Dr. Tol said, doctors in the Netherlands, who learned about the two studies at a recent conference, are starting to turn away from the platelet injections.

• As for Dr. Fu, he said he was keeping an open mind but still did not offer platelet injections. “I just do not have the heart to ask patients to pay for an unproven therapy,” he said.

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ADDITIONAL OUTCOME DATA

• Investigation of platelet rich plasma in rabbit cranial defects: A pilot study. Aghaloo, Moy and Freymiller Section of Oral and Maxillofacial surgery , UCLA, School of Dentistry LA

• Purpose: The purpose was to evaluate the effect of platelet-rich plasma (PRP) on hone healing. Materials and Methods: Fifteen rabbits were included in this randomized, blinded, prospective pilot study. Four equal 8 mm diameter cranial bone defects were created and immediately grafted with autogenous bone, PRP alone, autogenous bone and PRP, and no treatment as a control. The defects were evaluated by digital subtraction radiography with step-wedge calibration, histology, and histomorphometric analysis performed at 1, 2, and 4 months. Results: The results showed a significant increase in histomorphometric bone area and radiographic bone density in both bone and bone and PRP samples as compared with the control and PRP alone. No ignificant increase in bone formation was seen with the addition of PRP to autogenous bone. No significant difference in bone formation was seen between defects treated with PRP alone and control sites. Conclusions: No significant improvement, radiographically or histomorphometrically, was seen with the addition of PRP in bone formation in noncritical sized defects in the rabbit cranial model. However. bone and bone and PRP showed a histomorphometric tendency toward increased bone formation at 1, 2, and 4 months.

ADDITIONAL OUTCOME DATA

• Positive Effect of an Autologous Platelet Concentrate in Lateral Epicondylitis in a Double-Blind Randomized Controlled Trial

• Platelet-Rich Plasma Versus Corticosteroid Injection With a 1-Year Follow-up• Joost C. Peerbooms, MD*, • Jordi Sluimer, MD†, • Daniël J. Bruijn, PhD* and • Taco Gosens, PhD†‡• + Author Affiliations• * Department of Orthopaedic Surgery, HAGA Hospital, The Hague, Netherlands • † Department of Orthopaedic Surgery, St Elisabeth Hospital, Tilburg, Netherlands • ‡Address correspondence to Taco Gosens, PhD, St Elisabeth Hospital, Hilvarenbeekseweg 60,

Tilburg, 5022 GC, Netherlands (e-mail: t.gosens@elisabeth.nl) Joost C. Peerbooms, MD*, • Jordi Sluimer, MD†, • Daniël J. Bruijn, PhD* and • Taco Gosens, PhD†‡• + Author Affiliations• * Department of Orthopaedic Surgery, HAGA Hospital, The Hague, Netherlands • † Department of Orthopaedic Surgery, St Elisabeth Hospital, Tilburg, Netherlands • ‡Address correspondence to Taco Gosens, PhD, St Elisabeth Hospital, Hilvarenbeekseweg 60,

Tilburg, 5022 GC, Netherlands (e-mail: t.gosens@elisabeth.nl)

• Background Platelet-rich plasma (PRP) has shown to be a general stimulation for repair. • Purpose To determine the effectiveness of PRP compared with corticosteroid injections in patients with

chronic lateral epicondylitis. • Study Design Randomized controlled trial; Level of evidence, 1. • Patients The trial was conducted in 2 teaching hospitals in the Netherlands. One hundred patients

with chronic lateral epicondylitis were randomly assigned in the PRP group (n = 51) or the corticosteroid group (n = 49). A central computer system carried out randomization and allocation to the trial group. Patients were randomized to receive either a corticosteroid injection or an autologous platelet concentrate injection through a peppering technique. The primary analysis included visual analog scores and DASH Outcome Measure scores (DASH: Disabilities of the Arm, Shoulder, and Hand).

• Results Successful treatment was defined as more than a 25% reduction in visual analog score or DASH score without a reintervention after 1 year. The results showed that, according to the visual analog scores, 24 of the 49 patients (49%) in the corticosteroid group and 37 of the 51 patients (73%) in the PRP group were successful, which was significantly different (P <.001). Furthermore, according to the DASH scores, 25 of the 49 patients (51%) in the corticosteroid group and 37 of the 51 patients (73%) in the PRP group were successful, which was also significantly different (P = .005). The corticosteroid group was better initially and then declined, whereas the PRP group progressively improved.

• Conclusion Treatment of patients with chronic lateral epicondylitis with PRP reduces pain and significantly increases function, exceeding the effect of corticosteroid injection. Future decisions for application of the PRP for lateral epicondylitis should be confirmed by further follow-up from this trial and should take into account possible costs and harms as well as benefits.

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