Platelet-Rich Plasma Therapy: The Future of Healing?

Platelet-Rich Plasma (PRP), a purported solution for ameliorating pain and promoting healing, is as controversial as it is enticing. After all, could an injection of one’s own plasma be the antidote to many common ailments? With noticeable results reported in as little as two weeks, patients are asking and physicians are prescribing. But what is PRP and how effective is it really?

PRP has been in use for more than 30 years. Even in its early days, there was great excitement for its role in promoting tissue adhesion in wound care, facilitating healing of musculoskeletal disorders and easing the pain of osteoarthritis and other conditions. PRP works, it is thought, by promoting synthesis of connective tissues and revascularization, which leads to reduced inflammation at the site of injection, cellular proliferation and, ultimately, remodeling thanks in part to PRP’s assumed role in adaptive immunity.¹

The PRP industry is booming, estimated to be worth nearly $500 million and projected to grow more than 12 percent annually through 2026.² However, results of studies examining the effectiveness of PRP have been mixed, and with good reason. With no uniform standards in preparation or dosing, huge variability in the health of patients receiving PRP and a lack of standardization in study protocols, understanding its effectiveness is still in its infancy. Even so, PRP shows great potential.

What Is PRP?

PRP is a living biomaterial, derived from a patient’s own blood and injected back into the body. Initially dormant, once platelet rich plasma is injected, activation and aggregation of platelets begins.

U.S. Food and Drug Administration (FDA) Code of Federal Regulations 21 CFR, Part 640, subchapter F, Biologics, regulates some parts of protocols used in PRP such as how blood is to be drawn from the patient: “by a single uninterrupted venipuncture with minimal damage to and manipulation of the donor’s tissue,” as well as the time frame in which platelets must be separated from red blood cells by centrifugation: “within four hours after completion of the phlebotomy or within the time frame specified in the directions for use for the blood collecting, processing and storage system.” Once prepared, PRP is to be injected into the patient without the addition of preservatives.³ Otherwise, there are no U.S. regulations on its preparation or concentration.

FDA has approved certain class 1 and class 2 medical device centrifuges for PRP preparations. As a biologic, PRP is not an FDA-approved drug. Physicians choosing to administer PRP must use discretion if they believe there will be a healing benefit for their patient.

PRP may be administered along with a local anesthetic by injection into the injured area, or it may be used as a healing agent during surgeries through a special preparation that allows the PRP to be stitched into torn tissues.⁴

From a patient perspective, PRP injections are thought to be low-risk, with no major side effects because it uses their own blood cells. Soreness at the injection site is possible, as is feeling light-headed during the blood draw (just as a patient might when donating blood). But other risks appear to be similar to those of cortisone injections.⁴

However, the risk of adverse events is certainly heightened in the event preparation of PRP is outsourced to facilities that operate in unsanitary conditions. Some FDA inspection findings for facilities, including compounding facilities preparing PRP, include poor aseptic practices, dirty equipment and a lack of properly designed equipment to allow maintenance of appropriate levels of cleanliness.

Effectiveness of PRP

Thoughts on the effectiveness of PRP vary as do results of studies investigating its potential benefits. In part, that variability depends on the overall health of patients, any drugs they may be taking such as nonsteroidal anti-inflammatory drugs, aspirins or other medications that decrease growth factor response, the timing of the PRP administration, the type of and severity of the injury and how the PRP was prepared. Downstream, because of so many variables, it is difficult to produce consistent clinically beneficial effects.¹

One big challenge for studying the effectiveness of PRP is the number of medical devices commercially available from which PRP can be prepared. Each piece of equipment has its own validations, specifications and unique instructions, and these preparation inconsistencies negatively affect the ability to conduct reproducible studies. With no best practices for collection volumes or blood preparation, the resulting platelet density and PRP composition vary. White blood cell and red blood cell counts, platelet growth factors and the risk of contamination may all be impacted. Likewise, how the patient’s body interacts with the PRP also contributes to the challenge of defining effectiveness.

For example, common PRP uses include chronic tendon injuries at the knee, elbow and Achilles tendon. However, currently no study data confirms PRP is actually more effective than traditional treatments. Likewise, PRP appears to show little to no benefit in healing after an anterior cruciate ligament or rotator cuff surgery. And, studies looking at its effectiveness in meniscus repairs are ongoing.

One common use of PRP is in treating knee osteoarthritis, and some report the benefits can last as long as two years. Even so, clinical guidelines generally do not recommend PRP for osteoarthritis due to a lack of definitive clinical efficacy,⁵ which could be demonstrated in double blind, peer-reviewed study data where no bias enters into the results.²

Finally, long-term studies on the effectiveness of PRP are not only limited but challenging since they must take into account consistent rehabilitation programs and patient compliance with them, particularly with home-based programs. However, Phase I and II studies on post-injection PRP for Achilles tendinopathy have found supervised rehabilitation programs increased exercise compliance and improved outcomes.¹

PRP Preparation

PRP originates from a peripheral blood draw that is then placed into a centrifuge that separates whole blood components into plasma and red blood cells, leukocytes and other proteins, the concentrations of which are dependent on preparation, both device- and protocol-specific. There are various schools of thought on the platelet concentration needed for beneficial effect. In some literature reviews, it is suggested that PRP should have anywhere from a five to 10 times greater concentration of platelet growth factors than whole blood, with leukocytes and monocytes (part of the innate immune system), T and B lymphocytes (adaptive immune system) and other components present in varying amounts, depending on the preparation method used. Others suggest lower concentrations such as 1.6 to five times that of whole blood⁴ with 80 percent platelet recovery.⁵ While preparation methods and formulations are unique, many think that leukocyte-rich PRP may have a greater therapeutic impact thanks to its potential for tissue healing and remodeling.¹

There are two main types of PRP preparation devices. In medical office settings, a gravitational centrifuge is often used to isolate the buffy coat layer from the blood. This process can take about five minutes, and fresh PRP preparations are given to the patient at each visit. Another preparation uses a continuous flow disk separation technique. Not only are the yields between the two techniques different, but so are the concentration, purity and viability. Platelet surface receptors, called integrins, and adhesion molecules will also affect PRP.¹

Unfortunately, PRP clinical studies are often inconsistent in referencing how formulations are prepared, making their outcomes difficult to extrapolate in a larger discussion of PRP effectiveness.

Platelet Dosing

Theoretically, one would assume that higher platelet counts would equate to better healing outcomes, but this has not necessarily been demonstrated. Neither a definitive optimal PRP concentration nor PRP dosing as of yet has been determined. Differences between base platelet counts, a patient’s age, PRP preparation methods, delivery modes, etc., can all impact healing.

In fact, at least one study showed that very high concentrations of platelet growth factors may be counterproductive, with detrimental effects possibly due to too few available receptors.¹ That being said, high concentrations of PRP are commonly delivered to the target site, particularly for regenerative therapies.

The age of a patient plays into the quantity of PRP needed to be effective since aging has a negative effect on the quality of stem cells, growth factor receptors, etc. However, some preliminary studies demonstrate it may be possible that PRP could have a positive impact on cellular senescence, particularly in aging cartilage. Decreases in inflammation in osteoarthritic patients have also been demonstrated when PRP is injected into the subchondral bone, particularly when combining high concentrations of PRP with bone marrow aspirate concentrates.¹

PRP Applications

PRP is frequently used to help ease chronic pain, and clinical evidence of PRP in these modalities appears to be favorable treatment for inflammatory responses associated with osteoarthritis of the knee. However, a recent double blind study of PRP found no significant difference in patient outcomes over a saline placebo, echoing an earlier double blind study of PRP in ankle arthritis. In fact, in the osteoarthritis trial, patients receiving PRP had a statistically greater significant incidence of cartilage thinning. However, participants who received PRP also generally reported better functional movement in a year follow-up, although the investigators did not believe that PRP had slowed disease progression.²

Costs and Insurance

PRP can cost a patient hundreds of dollars per treatment and is generally not covered by insurance. A review of the Centers for Medicare and Medicaid Services (CMS) website shows CMS covers PRP only for certain chronic, non-healing wounds when all the following conditions are met: 1) The patient is enrolled in a clinical research study that addresses a particular set of questions regarding chronic non-healing diabetic, pressure and/or venous wounds using validated and reliable methods of evaluation; and 2) Clinical study applications for coverage pursuant to this National Coverage Determination must be approved by Aug. 2, 2014.⁶

Final Thoughts

Despite the questions and inconsistencies surrounding PRP, demand continues to grow, and physicians are challenged with meeting that demand while counseling patients on a lack of definitive information that confirms its effectiveness. While some believe PRP can speed healing and reduce painful inflammation, until confirmation of these results are demonstrated in repeatable double blind clinical studies, the question concerning its effectiveness remains inconclusive.