Platelets are small, nonnucleated cell fragments in the peripheral blood known primarily for their role in homeostasis. The normal platelet count ranges from 150,000 µL to 400,000 µL. Platelets contain numerous proteins (growth factors), cytokines, and bioactive factors that initiate and regulate tissue healing.10 The fluid portion of blood—plasma—also contains clotting factors, proteins, and ions. PRP is the result of concentrating the platelet count to at least 1 million platelets per microliter in 5 mL of plasma.^10,11

Platelets contain two unique types of granules—alpha granules and dense granules. Alpha granules in platelets function as storage units containing a variety of hemostatic proteins, inactive growth factors, cytokines, and other proteins such as adhesion proteins. Dense granules store and release bioactive factors that promote platelet aggregation, tissue modulation, and regeneration including adenosine diphosphate (ADP), adenosine triphosphate (ATP), calcium, serotonin, histamine, and dopamine.12,13

Growth factors found in these granules include platelet derived growth factor (PDGF), transforming growth factor-β₁ (TGF-β₁), vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), insulin-like growth factor (IGF-I, IGF-II), endothelial cell growth factor (ECGF), and epidermal growth factor (EGF).^{4,6,10,14–16} Platelet activation is required for discharge of granule content (B5) (Table 10-1). Upon clotting, platelets are activated, resulting in degranulation and release of their growth factors from the alpha granules. Approximately 70% of the stored growth factors are released within the first 10 minutes. The majority of growth factor release occurs within the first hour after degranulation. Continued growth factor release has been shown to occur throughout the period of platelet viability, approximately 7 days.^4,8,10

PRP is a mechanism to deliver a physiologically natural balance/ratio of growth factors, cytokines, and other bioactive proteins in supraphysiologic concentrations directly into an injured tissue to potentially optimize healing while maintaining the body’s homeostatic environment.^4,17–19 Using PRP to treat a variety of soft tissue pathologies is appealing to the clinician because of its simplicity of acquisition and administration, relatively low cost when compared with surgical treatments, and absence of significant adverse effects. Since PRP is an autologous tissue graft, the risk of tissue rejection, immune response, or disease transmission is eliminated.

The inflammatory phase, stage 1 begins with a tissue injury. Platelets are stimulated to provide hemostasis by forming a clot. Platelets in the clot then degranulate and secrete several growth factors, hemostatic factors, and cytokines from alpha granules that are necessary in the early stages of the clotting cascade. Histamine and serotonin are released from the dense granules and function to increase capillary permeability, activate macrophages, and allow inflammatory cells greater access to the injury site.10,20,21 The inflammatory phase can last up to 72 hours and is characterized by localized pain, swelling, erythema, and increased local tissue temperature. The proliferative phase (stage 2) begins when polymorphonuclear leukocytes migrate to the inflamed tissue. During the ensuing 48 hours to 6 weeks, anatomic structures begin to be restored while tissue generation occurs. Fibroblasts begin to synthesize scar tissue and capillary neoformation begins to reestablish nutrients to the injured tissue. Stage 2 ends with the beginning of wound contracture. Stage 3 is characterized by collagen remodeling. The process of tissue remodeling can last from 3 weeks to 12 months.¹⁴

PRP can only be derived from anticoagulated whole blood. Since platelets form part of the clot in coagulated blood and are activated triggering degranulation—thereby releasing their bioactive proteins, growth factors, and cytokines—clotted blood is not an appropriate source of blood to obtain PRP. PRP preparation begins by adding citrate to whole blood. Citrate binds to ionized calcium inhibiting the clotting cascade. The anticoagulated blood then undergoes a centrifugation process to first separate red and white blood cells from plasma and platelets, and then a second centrifugation cycle further separating the platelet rich from the platelet poor plasma. There are a number of commercially available devices on the market that produce PRP (Fig. 10-1). Current systems available to generate PRP differ in the amount of whole blood needed for processing, the anticoagulant used, the speed of the centrifuge, and the time necessary to spin the blood. Systems also differ in the final volume of PRP produced and the total number of platelets present in the concentrated product. As defined by the American Red Cross, PRP has 5.5 × 10¹⁰ platelets or greater per 50 mL of concentrate equaling a 2 to 7 times increase compared with whole blood. Normal platelet counts can vary between individuals. Platelet concentrations can vary greatly ranging from 2.5 to 8.0 times the concentration found in whole blood depending on the commercial system used.^4,22 Literature suggests that clinical benefits of platelet concentrations occur with the greatest predictability when a fourfold increase is achieved.^4,23 Unfortunately, evidence is lacking with regard to the appropriate and most clinically beneficial concentration of platelets.

Leukocyte concentration in PRP has become a topic of debate. Leukocyte concentrations can vary depending on the PRP system used. There is concern that the release of acid hydrolases and proinflammatory proteases from leukocytes may act as cytotoxic agents causing secondary damage to cells.^14,24

Treatment begins with the identification of the tissue (muscle, tendon, or ligament) and anatomic structures to be treated—after proper informed consent has been obtained and the procedure has been explained to the patient. Before treatment, pain medication is prescribed for the immediate postinjection period (3 to 5 days) and we instruct patients that nonsteroidal antiinflammatory medication cannot be used 2 to 3 weeks before and 6 to 8 weeks after the PRP treatment has been completed. Postinjection pain is common after PRP treatment. The duration and severity varies from patient to patient and with the specific tissue being treated. Before treatment, pre-PRP and post-PRP treatment instructions are discussed with patients and all questions are answered. The patient is advised that it is normal to experience an increase in pain at the injection site after the PRP treatment, which may last for several days (Box 10-1).

The treatment area is cleaned with an alcohol/Betadine prep solution or Hibeclens solution before injection. Blood is drawn using a large bore fenestrated needle. The amount of blood drawn is dependent on the amount of PRP required for treatment. On average, 60 mL whole blood (to obtain 5 mL PRP) is drawn from the patient. The whole blood is placed into the centrifuge and the separation process is begun requiring approximately 15 minutes. The treatment site is then anesthetized, first with an ethyl chloride spray followed by a local anesthetic injection of lidocaine.

When the separation process has been completed, the PRP concentrate is then delivered into the injured tissue through a 22-gauge needle under direct musculoskeletal ultrasound (US) guidance (Fig. 10-2). The precise placement of the PRP preparation is extremely important for overall outcome and efficacy of the procedure. The exact technique of delivery is dependent on the location of the tissue treated myotendinous, teno-osseous, or ligamentous. A “peppering” technique is used when treating tendons and ligaments. It is also important to touch bone at the osseous interface. Layering the PRP graft throughout the entire injury site in muscle, tendon, and ligamentous injuries will also help ensure complete coverage with the PRP preparation.

When treatment is completed, a sterile Band-Aid is applied. Protective splinting or bracing may be recommended after treating large weight-bearing tendons, such as the Achilles tendon, or areas where an extensive percutaneous tenotomy “peppering” has been performed. Application of heat after the procedure for 15 minutes every 2 to 3 hours is often recommended for postinjection pain management.

Strenuous activity for the first 7 days posttreatment is discouraged. Establishing normal range of motion after the procedure and performing activities of daily living (ADL) are encouraged as soon as possible posttreatment. At 4 to 6 weeks, the patient is reassessed. If pain persists at the treatment site a second PRP treatment might be considered at that time.

There are a number of conditions in which treatment with PRP is contraindicated. Absolute contraindications for the use of PRP include: platelet dysfunction syndromes, critical thrombocytopenia, hemodynamic instability, septicemia, and hypofibrinogenemia. PRP treatments are relatively contraindicated in those patients that consistently used antiinflammatory medications and systemic corticosteroid medications. It is also contraindicated in those who have received a corticosteroid injection at the treatment site within 14 days before treatment, have HGB levels less than 10 g/dL or platelet counts less than 105/µL, or have had recent fevers or illness, a rash at the donor or receptor site, bone cancer or hematopoietic cancer, or a history of, or an active infection with, Enterococcus, Pseudomonas, or Klebsiella.12,25

Despite the surge of interest in orthobiologic treatment modalities—and there recent widespread use for the treatment of a wide variety of soft tissue and boney injuries involving muscle, tendon, ligament, and articular cartilage—there remains a lack of animal and clinical studies demonstrating the efficacy of PRP. Although many studies report excellent outcomes, many of these studies unfortunately are limited case reports at best. Many of the current published studies are difficult to interpret because of the lack of standardization of PRP dosing, platelet acquisition and preparation, platelet concentration, growth factor quantity, number of treatments given, small patient sample sizes, and lack of control groups. Table 10-2 summarizes some of the recent published clinical studies regarding PRP.

The use of PRP in amateur and professional athletes remains controversial. In the United States, the use of PRP in professional sports, including the NFL, Major League Baseball, National Basketball Association, National Hockey League, Major League Soccer, National League Lacrosse, and Major League Lacrosse, is not regulated or prohibited. In addition, the National Collegiate Athletic Association currently does not regulate or prohibit the use of PRP in its participating institutions. Initially, the World Anti-Doping Agency (WADA) prohibited the use of platelet-derived preparations (PRP blood spinning) administered through an intramuscular route. Both the WADA and the U.S. Anti-doping Agency originally prohibited the injections of any growth factors affecting muscle, tendon, or ligament protein synthesis or degradation, vascularization, regenerative capacity, fiber type switching, or energy use.14 Athletes required a therapeutic use exemption if this mode of treatment is deemed necessary and recommended by a physician. Both organizations recently have changed their stance on PRP, since this is an autologous treatment of the patient’s own blood products that have not been treated with any nonautologous growth factors.

Rehabilitation progression following PRP injection is based on several individual factors: the combination of time since injection, the physiologic healing mechanism, patient’s health and age, severity of injury, tissue integrity, response to physical therapy treatment dosage, and adherence to appropriate home programs. The goal of rehabilitation following PRP injections is to progressively and therapeutically place appropriate amounts of physical stress to the injured tissue to help facilitate healing. General guidelines following physiology are listed in Box 10-2. Physical stress to the tissue (muscle tendon, ligament, and bone) may include tension, torsion, compression, and shear. The stress or loading is imparted via manual therapy techniques, dosed medical exercise therapy progressions, functional strengthening, and return to play phase exercises. There is limited evidence in the literature defining specific protocols following PRP injection and limited documentation regarding tissue healing time frames following PRP injection. There is no absolute progression or transition between phases and there can be variability between patients pending each individual case.

The goal following PRP injection is to promote adequate tissue healing such that the tissue is able to once again maximally withstand the physiologic stresses and forces placed upon it with daily functional demands or sporting activities. Collagen fibers run in parallel alignment, which affords the tissue to withstand tensile forces and unilateral stress placed upon it.²⁶ The following information is based on clinical experience with patients who have undergone PRP injections to different tissues including muscle, tendon, bone, and ligament.