Platelet Rich Plasma

Background

• PRP therapy is a regenerative treatment that involves using a patient’s own platelets to promote healing in injured tissues
• Requires centrifugation to separate and concentrate the platelets which are then suspended in a small volume of plasma and injected back into the targeted area to stimulate tissue repair
• The increased number of platelets delivers an increased number of different types of granules inside the platelet, with the main ones being alpha granules and dense granules
• Alpha and dense granules contain growth factors and other specific molecules thought to be responsible for increased healing in injured tissues, through tissue regeneration, angiogenesis, and inflammation modulation
• Although there are numerous basic science studies, animal studies, and small case reports regarding PPR-related products, there are only a few controlled, clinical studies that provide a high level of medical evidence regarding the potential benefits of PRP

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Key mediators thought to play a role in healing process (not exhaustive)

α-granules

• Platelet-derived growth factor (PDGF) – Chemoattraction, cell proliferation

• Vascular endothelial growth factor (VEGF) - Angiogenesis

• Insulin-like growth factor (IGF-1, IGF-2) – Cell proliferation, maturation, bone matrix synthesis

• Fibroblast growth factor (FGF) – Angiogenesis, fibroblast proliferation

• Transforming growth factor-beta (TGF-β) – Promotes matrix synthesis

Dense granules

• Serotonin – Vasoconstriction, increased capillary permeability, macrophage attraction

• Histamine – Increased capillary permeability, attract and activate macrophages

• Calcium –Cofactor for platelet aggregation and fibrin formation

• Adenosine – Promotes platelet aggregation

Foster et al. (2009)

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Formulation of PRP

• Preparation of PRP begins by addition of citrate to whole blood to bind the ionized calcium and inhibit the clotting cascade.
• Current standards in PRP therapy involve a 3- to 5- fold platelet concentration, requiring a double centrifugation process

Double centrifugation technique:

• 30-60 mL whole blood is taken with 18- gauge needle in an effort to reduce irritation and trauma to the platelets such that they remain in a relative “inactive” state.
• The first spin (hard spin) separates RBCs and WBCs from plasma and platelets.
• The second spin (soft spin) further concentrates the platelets, producing the PRP separate from the platelet-poor plasma. (PPP). This will ultimately yield between 3-6 mL of platelet-rich aggregate. Regardless of the rate or time of centrifugation, a single spin cannot adequately concentrate platelets because the RBCs will interfere with the fine separation of the platelets.
• The PRP must then be clotted to allow for delivery to the desired site, leading to platelet activation, and the resulting release of the growth factors and other specific molecules from the α-granules and dense granules.
• Approximately 70% of the stored growth factors are released within 10 minutes, and nearly 100% of the growth factors are released within 1 hour. The result is that the platelets release growth factors slowly over a 7-day period.

Foster et al. (2009)

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Current clinical applications in Sports Medicine

Knee Osteoarthritis

• Filardo, G., et al. found that PRP injections improved pain and function in patients with mild to moderate knee osteoarthritis, with effects lasting up to 12 months.

Lateral Epicondylitis

• Mishra, A., et al. found that PRP provided significant pain relief and functional improvement in chronic lateral epicondylitis compared to corticosteroid injections at 6-month follow-up.

Acetabular Labrum Tear

• 8 patients improved symptoms at up to 8 weeks in a small study
• Redmond et al found intraoperative PRP injection does not appear to improve the clinical results of patients undergoing hip arthroscopy for labral treatment
• Rafols et al found PRP resulted in lower postoperative pain scores at 48 hours and fewer joint effusions at 6 months

Patellar Tendinopathy

• Vetrano, M., et al. found that PRP injections led to significant improvements in symptoms compared to extracorporeal shockwave therapy in athletes with patellar tendinopathy.

Rotator Cuff Tears

• Randelli, P., et al. found that autologous PRP reduced pain in the first postoperative months. The long-term results of subgroups of grade 1 and 2 tears suggest that PRP positively affected cuff rotator healing.

Hamstring Injuries

• Hamid, M. S. A., et al. found that a single autologous PRP injection combined with a rehabilitation program was significantly more effective in treating hamstring injuries than a rehabilitation program alone.

Meniscus Injuries

• Weng, L.Z., et al. found that although meniscus repairs augmented with PRP led to significantly lower failure rates and better postoperative pain control compared with those of the non-PRP group, there is currently insufficient RCT evidence to support PRP augmentation of meniscus repair improving functional outcomes.

Plantar Fasciitis

• Sharma, R., et al. found that PRP injection showed better performance than the steroid injection for the treatment of plantar fasciitis in six months.

Hip Osteoarthritis

• Anthony Lim, BA., et al. found that PRP reduces pain and improves function at the end-point follow-up of studies compared with the baseline.

Ulnar Collateral Ligament (UCL) Injuries

• Podesta, L., et al. found that PRP injections facilitated return to play in baseball pitchers with partial UCL tears, avoiding surgery in most cases.

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Types of PRP products

• Pure PRP (P-PRP): Platelet-rich but leukocyte-poor. Designed for intra-articular injections and soft tissue injuries where excessive inflammation could be counterproductive.
• Leukocyte-rich PRP (L-PRP): can enhance the inflammatory response, making it a good option for chronic tendon injuries such as lateral epicondylitis or patellar tendinopathy, where some degree of inflammation is beneficial for tissue remodeling.
• Pure Platelet-Rich Fibrin (P-PRF): preparations without leukocytes and with a high-density fibrin network, forming a scaffold, and creating a slow-release matrix that delivers growth factors over time.

Dohan et al. (2009)

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PRP Injection Technique & Clinical Protocols

Site Identification & Preparation:

• Injury location is determined via physical exam, imaging (MRI, ultrasound), and palpation of maximal tenderness.
• Ultrasound-guided injection enhances precision, ensuring accurate PRP delivery and needle depth control.

Injection Technique:

• Use of local anesthetic is controversial—it may alter pH and potentially reduce PRP efficacy. Some protocols favor buffered lidocaine or superficial anesthesia to mitigate pain without affecting bioactivity. PRP is commonly injected with an 18-gauge needle, though 22-25G needles are preferred for tendinous applications to reduce tissue trauma.
• Multiplanar injection technique (fenestration/peppering) can enhance PRP dispersion and stimulate local healing responses.

Post-Injection Monitoring:

• Patients observed for 15-20 minutes post-injection to monitor pain response and ensure safe ambulation
• Activity modification protocols vary by injury type but typically include relative rest for 48-72 hours post-injection.

Multi-Injection Protocols:

• Many regimens involve 2-3 injections, spaced 2-4 weeks apart, to sustain growth factor release and optimize tissue repair.
• Chronic tendinopathy protocols often use serial injections over several weeks to enhance tendon healing.
• Protocols are injury-specific, with ongoing research refining optimal dosing, spacing, and patient selection criteria.

Foster et al. (2009)

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Current Limitations of PRP

While PRP therapy has shown promise in various applications, several limitations contribute to mixed results across studies:

• Lack of Standardization: Variability in PRP preparation—differences in platelet concentration, the presence of leukocytes, and activation methods. This makes it difficult to compare outcomes across studies. This inconsistency can lead to conflicting results regarding its efficacy.

• Heterogeneous Study Designs: Many studies have small sample sizes, varying protocols, and differences in outcome measures. This heterogeneity often results in mixed conclusions about PRP’s effectiveness for conditions like tendinopathies and osteoarthritis.

• Inconsistent Clinical Outcomes: Some clinical trials report significant improvements in pain and function, while others show little to no difference compared to placebo or standard treatments. These discrepancies highlight the need for more rigorous, well-controlled research.

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Future Directions

Future directions in PRP therapy are focused on optimizing its formulation, application, and integration with other regenerative strategies. Key areas of development include:

• Standardization of PRP Formulations: Ongoing research aims to establish uniform protocols for PRP preparation—determining the optimal platelet concentration, leukocyte content, and activation methods—to reduce variability and improve clinical outcomes.

• Combination Therapies: There is growing interest in exploring the synergistic effects of combining PRP with stem cells, hyaluronic acid, or biomaterial scaffolds. These combination therapies may enhance tissue regeneration and repair, particularly in complex musculoskeletal injuries.

• Personalized and Precision Medicine Approaches: Future studies are focusing on tailoring PRP treatments to individual patient profiles and specific injury pathologies. Innovations such as imaging-guided injections and controlled-release systems are being investigated to achieve more precise and effective delivery of bioactive factors.

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