Understanding Platelet Rich Plasma Injections

Introduction

Platelet rich plasma (PRP) is used commonly in orthopedic procedures and carries a wide variety of indications. PRP has been studied for use in tendinopathy, muscle strains, and osteoarthritis. The purpose of this review is to understand the different formulations and nuances in terminology associated with PRP injections.

Process

Platelet rich plasma is obtained through a venous blood draw. The whole blood is then processed through a centrifuge system to obtain a higher concentration of platelets. The rationale for obtaining the higher concentration of platelets is that the platelet rich portion contains high values of growth factor and cytokines (1). Studies have identified vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), interleukin-10, and tumor-necrosis factor B in PRP preparations (5). Each growth factor plays a different role in the anti-inflammatory cascade. VEGF plays a role in angiogenesis, FGF can stimulate fibroblast to create collagenase, and insulin-like growth factor can support collagen (6). In tendons, the cellular migration, angiogenesis, and cellular proliferation can increase tenocyte proliferation (8).

PRP growth factor

Role of PRP on tendons (9)

There is no uniform standardization for PRP. The processing of the PRP can vary widely. The final processed PRP product can have different platelet concentrations and varying levels of leukocytes. The top layer of the centrifuged product is plasma, the middle layer is the platelet and leukocyte portion, known as the buffy coat, and the bottom is the red blood cells (6). There is no consensus regarding the necessary platelet concentration for statistical benefit. There is also controversy regarding the amount of leukocytes the PRP should contain. There is also no consensus regarding adding activating agents to the PRP (6).

PRP that is leukocyte rich is defined as a WBC count greater than 100% of a whole blood sample and leukocyte poor is  defined as a WBC count less than 100% of a whole blood sample (7). Research has shown that leukocyte rich PRP can stimulate inflammatory cells and the catabolic cascade which can be used in the treatment of tendinopathy (7).

One of the most commonly used processing systems for PRP is the Arthrex Angel system. The Angel system employs a 3-sensor technology that uses three light wavelengths to separate different cell types (3). In a study done by Arthex looking at the percentage of platelet concentration using the angel machine, they found that a bone marrow aspirate provides platelet concentrations up to 8x baseline values (3). In a secondary study comparing the Arthrex PRP to Celling Biosciences ART system, they found that the PRP from whole blood had a 7.2x increase in concentration compared to a 6.2x increase in the Celling device (2).

Angel PRP

Arthrex Angel System (3)

Another popular kit is the Arthrex ACP kit. The ACP double-syringe system allows for a small 16mL blood draw which is then centrifuged down to produce the PRP (4). The ACP system was found to increase the platelet concentration by a 2x increase (4). In a study comparing Biomet PRP, Arthrex ACP, and Prodizen Prosys, the Biomet PRP system led to the highest number of platelets (10). However, in another study comparing Biomet PRP and Arthrex ACP, they found that the Biomet PRP again had higher platelet concentrations, but also included a high amount of leukocytes (11). 

Harvest technologies also has a popular PRP system that promises higher platelet concentrations compared to their competitors. The Harvest system involves a 20mL venous blood draw that produces approximately 3cc of PRP (6). 

Harvest PRP

Harvest PRP system (6)

A German company called Orthogen produces a product called autologous conditioned serum. This process involves drawing the blood in syringes with glass beads that activate monocytes. The autologous conditioned serum activates growth factor and anti-inflammatory cytokines (6).

Conclusion

PRP can be used for a wide variety of orthopedic procedures. A single blood draw that is centrifuged can produce PRP that contains platelet concentrations 3-8x whole blood. The PRP can then be injected into a variety of joints and tissue. Further research needs to be done to standard PRP protocols.

By: Gregory Rubin, DO

rubinsportsmed.com

References

1)      Bennell, Kim L., et al. “Effect of Intra-Articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial.” JAMA, vol. 326, no. 20, Nov. 2021, pp. 2021–30. PubMed, https://doi.org/10.1001/jama.2021.19415.

2)      Comparison of Arthrex Angel®  System and Cellingsm Biosciences  ART PRP and BMC Systems – Cellular Concentration.” Arthrex Research and Development, 2018.

3)      Arthrex Angel  CPRP and Aspiration System.” Arthrex Research and Development, 2018.

4)      Cavallo, Carola, et al. “Comparison of Platelet-Rich Plasma Formulations for Cartilage Healing: An in Vitro Study.” The Journal of Bone and Joint Surgery. American Volume, vol. 96, no. 5, Mar. 2014, pp. 423–29. PubMed, https://doi.org/10.2106/JBJS.M.00726.

5)      Fice, Michael P., et al. “The Role of Platelet-Rich Plasma in Cartilage Pathology: An Updated Systematic Review of the Basic Science Evidence.” Arthroscopy: The Journal of Arthroscopic & Related Surgery: Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association, vol. 35, no. 3, Mar. 2019, pp. 961-976.e3. PubMed, https://doi.org/10.1016/j.arthro.2018.10.125.

6)      Nguyen, Rosalyn T., et al. “Applications of Platelet-Rich Plasma in Musculoskeletal and Sports Medicine: An Evidence-Based Approach.” PM & R: The Journal of Injury, Function, and Rehabilitation, vol. 3, no. 3, Mar. 2011, pp. 226–50. PubMed, https://doi.org/10.1016/j.pmrj.2010.11.007.

7)      Riboh, Jonathan C., et al. “Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis.” The American Journal of Sports Medicine, vol. 44, no. 3, Mar. 2016, pp. 792–800. PubMed, https://doi.org/10.1177/0363546515580787.

8)      Hurley, Eoghan T., et al. “The Effect of Platelet-Rich Plasma Leukocyte Concentration on Arthroscopic Rotator Cuff Repair: A Network Meta-Analysis of Randomized Controlled Trials.” The American Journal of Sports Medicine, vol. 49, no. 9, July 2021, pp. 2528–35. PubMed, https://doi.org/10.1177/0363546520975435.

9)      Liu, Xueli, et al. “Effects of Leukocyte- and Platelet-Rich Plasma on Tendon Disorders Based on in Vitro and in Vivo Studies (Review).” Experimental and Therapeutic Medicine, vol. 21, no. 6, June 2021, p. 639. PubMed, https://doi.org/10.3892/etm.2021.10071.

10)   Oh, Joo Han, et al. “Comparison of the Cellular Composition and Cytokine-Release Kinetics of Various Platelet-Rich Plasma Preparations.” The American Journal of Sports Medicine, vol. 43, no. 12, Dec. 2015, pp. 3062–70. PubMed, https://doi.org/10.1177/0363546515608481.

 

11)   Dejnek, Maciej, et al. “Analysis and Comparison of Autologous Platelet-Rich Plasma Preparation Systems Used in the Treatment of Enthesopathies: A Preliminary Study.” Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University, vol. 30, no. 7, July 2021, pp. 757–64. PubMed, https://doi.org/10.17219/acem/135045.