Have you heard about platelet-rich plasma (PRP)? No, it’s not a drug, and it’s not a nutraceutical. It seems like one of the newest treatments to hit the pain medicine and rehabilitation field, but in actuality, PRP injection dates to the 1950s for treatment of dermatologic and oral maxillofacial problems in humans.1 Similar in some ways to stem cell therapy, PRP therapy utilizes components from the patient’s own system, manipulates them and then reinjects them with the goal of promoting tissue repair and resolution of injury or degradation. PRP does not require invasive harvesting of cells or a waiting period for laboratory preparation as required for autologous stem cells. While both PRP and stem cell administration might hold value in combination, the lower-cost PRP treatment is allowing many patients to reap the benefits of regenerative medicine in a safe, effective manner.2 What Is Platelet-Rich Plasma ? PRP equates to a sample of plasma with a platelet concentration that is three to five times greater than the physiologic platelet concentration found in healthy whole blood.3 PRP typically includes an anticoagulant that blocks the conversion of prothrombin to thrombin, which inhibits the initiation of the clotting cascade. In the absence of an anticoagulant, which is not mandatory for producing PRP, clotting ensues in as soon as 30 seconds. Both citrate dextrose-A and citrate phosphate dextrose have been shown to safely separate platelets while also attending to their metabolic needs prothrombin to thrombin, which inhibits the initiation of the clotting cascade. In the absence of an anticoagulant, which is not mandatory for producing PRP, clotting ensues in as soon as 30 seconds. Both citrate dextrose-A and citrate phosphate dextrose have been shown to safely separate platelets while also attending to their metabolic needs.4 What’s the Big Deal About Platelets? Tissue maintenance and repair involves a richly orchestrated system of chemical events and cellular activities. Platelets, for example, while commonly considered in the clotting cascade, play a vital role in this process, and this is what gives PRP such strong potential to reinvigorate healing for a variety of clinical conditions. Platelets perform these duties through their 1,100-plus proteins, comprising growth factors, enzymes, enzyme inhibitors, immune system messenger molecules and a host of other biologically active compounds related to tissue repair. PRP concentrates these platelet agents into an endogenous stimulatory mixture injected (usually) directed into the area of injury to kick-start recovery. At a certain dose, PRP’s proteins (e.g., growth factors) stimulate healing processes. In excess, however, these same molecules may exert an inhibitory effect on cellular function and repair.5 At present, however, PRP dosing remains inexact. Some studies have shown that PRP may lead to an overexpression of endogenous growth factors in addition to providing its own. Researchers have not determined whether this overproduction helps or hurts healing. How Is PRP Made? Clinicians create a PRP solution by placing a patient’s blood, obtained through venipuncture, into a centrifuge capable of concentrating platelets. With or without an anticoagulant, blood then undergoes one or two rounds of centrifugation using a tabletop centrifuge system. The first centrifugation, performed at 1,200 to 1,500 RPM with a low gravitational force, separates plasma and platelets from the red and white blood cells, although some white blood cells may remain in the first plasma/ platelet concentrate. The second centrifugation, run at a “hard” spin of 4,000 to 7,000 RPMs, divides the plasma into two fractions: a “platelet-rich” and a “platelet-poor” component. The resulting platelet-rich (PRP) solution is then kept under sterile conditions until ready for use the same day. It typically remains anticoagulated for at least eight hours. Each volume of whole blood yields from 10 to 16 percent PRP. No Standardization With dozens of different commercial systems available for PRP production, along with no universal classification system, PRP solutions can vary widely between clinics and even individuals, considering the wide variations in age, species, circulatory competency and comorbidities that one finds in a veterinary practice. Four Categories of PRP Although no set standards exist for deriving PRP, the solutions fall into four categories: leukocyte poor (also known as “pure” PRP), leukocyte PRP, pure platelet-rich fibrin clot and leukocyte platelet-rich fibrin clot.6 Fibrin adds value in that platelet-rich fibrin matrices encourage cellular migration and facilitate tissue repair. It may prolong the activity of growth factors within the PRP as well as support their availability and delivery to the injured site by serving as a reservoir for the growth factors. Concerning leukocyte PRP, while it may seem counterintuitive to inject white blood cells (WBC) into tissue for fear of aggravating inflammation, a few studies have indicated that WBCs may improve the healing of soft tissue injuries where infection has set in. WBCs may inhibit the growth of certain bacteria and thus reduce the risk of infection.7 However, other work has shown that by including WBCs in the PRP, one invites the generation of higher levels of inflammatory cytokines, including interleukins and tumor necrosis factor. This might deter healing and thereby lengthen recovery periods. While it might prove to be nearly impossible to remove all interleukins and tumor necrosis factor. This might deter healing and thereby lengthen recovery periods. While it might prove to be nearly impossible to remove all WBCs from the end product, knowing roughly how many remain after processing could inform clinicians about which system to purchase if the presence of WBCs confers more deleterious than clinically helpful results for conditions treated in a given practice. We must await further research to determine the relative value of each type of PRP product. Clinical Applications Evidence is accruing in the form of both clinical and experimental studies showing that PRP can reduce swelling and pain after surgery, improve and speed bone healing as well as its strength, shorten recovery time and decrease the rate of infection in wounds. PRP has been used in cardiac bypass surgery, plastic surgery, dermatology, orthopedic surgery and maxillofacial procedures for multiple indications. The most common day-today PRP applications involve tendon, muscle and ligament injuries such as cruciate and collateral ligament tears in the knee, various tendinopathies, fasciopathies, sprains, and tears of tendons and muscles.8 Researchers are investigating PRP’s ability to promote axonal regeneration and address neuropathic pain, though the mechanisms of how it might affect the latter remain unclear. Furthermore, PRP might help regenerate intervertebral disk material, and several studies have shown positive results of PRP growth factors on disks in animal models.9 An exciting aspect of PRP research pertains to the degree to which PRP aids in repairing cartilage in patients with arthritic joints. Several human trials have shown improvements in function and lessening of joint stiffness and pain.10 Perhaps PRP will prove to serve as a disease-modifying agent, and not just for symptom modification. Recommended Reading With so much more to learn about PRP, including potential risks as well as positive effects, it is wise to keep up with the literature. Knezevic et al have produced one of the best compilations on PRP thus far, which was published in the “Medical Clinics of North America” in early 2016.11 Your clients might enjoy reading it as well. Originally published in the February 2016 issue of Veterinary Practice News. Did you enjoy this article? Then subscribe today! Footnotes Knezevic NN, Candido KD, Desai R, et al. Is platelet-rich plasma a future therapy in pain management? Med Clin N Am. 2016; 100: 199-217. Angoorani H, Mazaherinezhad A, Marjomaki O, et al. Treatment of knee osteoarthritis with platelet-rich plasma in comparison with transcutaneous electrical nerve stimulation plus exercise: a randomized clinical trial. Medical Journal of the Islamic Republic of Iran. 2015;29:223. Knezevic NN, Candido KD, Desai R, et al. Is platelet-rich plasma a future therapy in pain management? Med Clin N Am. 2016; 100: 199-217. Knezevic NN, Candido KD, Desai R, et al. Is platelet-rich plasma a future therapy in pain management? Med Clin N Am. 2016; 100: 199-217. Knezevic NN, Candido KD, Desai R, et al. Is platelet-rich plasma a future therapy in pain management? Med Clin N Am. 2016; 100: 199-217. Knezevic NN, Candido KD, Desai R, et al. Is platelet-rich plasma a future therapy in pain management? Med Clin N Am. 2016; 100: 199-217. Knezevic NN, Candido KD, Desai R, et al. Is platelet-rich plasma a future therapy in pain management? Med Clin N Am. 2016; 100: 199-217. Knezevic NN, Candido KD, Desai R, et al. Is platelet-rich plasma a future therapy in pain management? Med Clin N Am. 2016; 100: 199-217. Knezevic NN, Candido KD, Desai R, et al. Is platelet-rich plasma a future therapy in pain management? Med Clin N Am. 2016; 100: 199-217. Knezevic NN, Candido KD, Desai R, et al. Is platelet-rich plasma a future therapy in pain management? Med Clin N Am. 2016; 100: 199-217. Knezevic NN, Candido KD, Desai R, et al. Is platelet-rich plasma a future therapy in pain management? Med Clin N Am. 2016; 100: 199-217.
