Growing interest in regenerative modalities has prompted physicians across the aesthetic and orthopedic spaces to offer platelet rich plasma (PRP) injections as a safe and minimally invasive alternative to surgery. Patients with knee osteoarthritis, for example, were shown to benefit from the deluge of growth factors released following a PRP injection. The potential for PRP therapy to heal joint pain and ligament tears depends on precise needle placement. Platelets must be perfectly placed. If platelet degranulation and growth factor release occurs outside of the afflicted tendon, ligament, or joint– healing potential is diminished, patient outcomes suffer, and adverse effects increase. Ultrasound guided imaging is often utilized to increase injection accuracy. An increase in injection accuracy will undoubtedly improve patient outcomes, but does ultrasound imaging actually improve accuracy rates? To help answer this question, researchers in Seoul, South Korea designed a study to assess the accuracy of blind compared to ultrasound-guided injections.

Clinical Study Assesses Efficacy of Ultrasound Guided Injections

ultrasound guided PRP injection

The study, published by Journal of Clinical Ultrasound in 2011, included 99 patients with radiographically confirmed knee osteoarthritis without effusion. The absence of effusion, fluid in the joint, makes finding the intra-articular space more difficult. Normally a physician would draw back synovial fluid to confirm accurate needle placement before injecting supplemental fluids. In cases of ‘dry knee’ osteoarthritis, clinicians cannot confirm needle placement with this method, which makes the use of ultrasound imaging essential.

Patients were randomly assigned to a control or test group. All patients were diagnosed 6 or more months prior to the study and experienced painful symptoms on most days in the 3 months before treatment. Both groups received a single superolateral injection with a 1.5 inch 21 gauge needle and a three-way stopcock. The ancillary valve allowed the simultaneous injection of hyaluronic acid and iopromide, an ultraviolet contrast dye solution. A single physician completed the procedure for both groups– a necessary variable to control.

The 49 patients randomized into the control group received blind injections. The physician located the injection site in the blind group by palpating the superior patella and making a mark one finger width above and one finger width lateral to the patella. After injecting 2 mls of hyaluronic acid, the stopcock valve was released and a small amount of contrast dye was injected (.5 ml). In the ultrasound test group, the contrast dye and HA were injected simultaneously and accurate needle placement, in the bursa, was detected with an Accuvix XQ 5-10MHz linear array probe.¹

Ultrasound Imaging Significantly Improves PRP Injection Outcomes

In both groups, a radiologist and a physiatrist, blinded to the injection procedure, evaluated accurate needle placement. Injections were considered a failure if contrast dye material was detected outside of the bursa. The assessors found positive results in 48 out of 50 or 96% of knees injected under ultrasound guidance compared to 41 out of 49 or 83.7% of knees in the blind injection group. The gain in accuracy achieved by the ultrasound equipment represents a statistically significant difference (p < 0.05). It’s important to note that the acting physician had over seven years of experience treating osteoarthritis with the benefit of musculoskeletal ultrasonography. The results of this study would be dramatically shifted if the experiment were performed under a physician without substantial experience.

Scientific Evidence Supports the Use of PRP injections for Knee OA

PRP for knee OA with ultrasound

The present study was not designed to assess patient outcomes, though previous studies have shown the efficacy of PRP injections to treat knee osteoarthritis– the most common articular disease. Researchers at Post Graduate Institute of Medical Education and Research in Chandigarh, India found statistically significant improvements in knee function and pain reduction when comparing intra-articular PRP injections to placebo. The study included a total of 156 knees divided into three groups; group A received one 10ml PRP injection, group B was administered two 10 ml PRP injections at a three week interval, and group C received a single saline injection. The PRP serum was prepared from 100 ml of whole blood concentrated in a single spin system with leukocyte filtration.

The researchers were careful to exclude leukocytes from the final concentration as white blood cells would unnecessarily increase adverse effects and limit the healing potential of platelet degranulation– as we will discuss later. Results, published in the American Journal of Sports Medicine in 2013, showed statistically significant improvements on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and significant pain reduction in both groups treated with PRP.²

PRP for Knee OA Compared to Hyaluronic Acid

doctor uses ultrasound to improve PRP injections

In 2014, researchers in Iran published a yearlong study comparing the effects of platelet rich plasma injections to hyaluronic acid (HA) for patients with X-ray confirmed knee osteoarthritis. The study included 160 patients divided into two groups; 87 participated in the PRP group and 73 in the HA group. Patients in the PRP group received 2 injections of PRP at a 4-week interval. The PRP was prepared in a fully enclosed dual-spin system from 35-40 ml of whole blood. The process yielded 4-6 ml of leukocyte-rich PRP with a platelet concentration 4-6 times that of whole blood.

Patients randomized into the HA group received 3 injections of Hyalgan brand HA at a one week interval. Hyalgan is a high-molecular weight HA extracted from rooster combs. Researchers assessed outcomes according to WOMAC scores and general health according to PCS-36 surveys (patient-reported assessment of physical and mental wellbeing). The study found meaningful improvements in physical function, stiffness and average WOMAC scores in the PRP group. Average PCS-36 scores improved significantly in the PRP group from 178.14 at baseline to 255.96 at the one-year follow up (mean change, P<0.001). Average PSC-36 scores increased only 9 points in the HA group from 180.4 to 189.39 at week 52 (mean change, P = 0.37)

Researchers found PRP to be significantly more effective than HA injections. Patients receiving PRP injections had better outcomes with increased functionality and quality of life scores.³

How Does PRP Improve Outcomes for Knee Osteoarthritis Patients?

Platelets contain over 30 growth factors that coordinate local cells to increase healing in damaged tissues throughout the body. Growth factors such as connective tissue growth factor (CTGF) and fibroblast growth factor (FGF) are of particular interest for osteoarthritic applications. These growth factors have been shown to increase chemotaxis, differentiation of mesenchymal stem cells, chondrocyte proliferation, and synthetic activities of osseous and cartilaginous cells. PRP therapy has the potential to concentrate regenerative growth factors then deliver them directly to damaged tissues, which disrupts the progress of osteoarthritis by nourishing the local hyaluronan secreting (pseudo)fibroblast cells.

Ultrasound Guided Imaging Improves Patient Outcomes in Knee OA

Knee osteoarthritis is one of the most common degenerative diseases, effecting 20% of individuals over 45. If left unchecked, knee OA will erode ambulatory abilities while increasing pain and discomfort. Knee OA is detrimental to quality of life. Thankfully, regenerative modalities, which amplify the body’s ability to heal with no adverse side effects, are growing in popularity. If accurately administered, PRP has the potential to increase chonrogenesis and the lubricating effects of cells in the synovial membrane, thus directly increasing quality of life for patients with knee OA. The Seoul study found a 12% accuracy increase in procedures completed under ultrasound guidance compared to palpation alone. Delivering accurate PRP injections is essential to the long term success of patients, physicians, and clinics.¹

Special Note: Leukocyte Rich or Pure PRP for Intra-articular Injections?

A careful reader will notice how some researchers use leukocyte rich PRP preparations and others create pure PRP for intra articular injections. While some authors fail to specify the presence or absence of leukocytes in the final solution (even though clearly defined preparation procedures are necessary for replicable results). Researchers at Stanford looked at the differences between leukocyte rich (LR) and leukocyte poor (LP) PRP for intra-articular joint injections and found more favorable outcomes with LP-PRP. Leukocyte poor-PRP activates more anti-inflammatory and fewer proinflammatory cytokines while still delivering an adequate concentration of platelets. Alternatively, LR-PRP showed less favorable outcomes for synoviocytes.

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References

  1. Yong Bum Park MD; Won Ah Choi MD; Yong‐Kyun Kim MD, PhD; Sang Chul Lee MD, PhD; Ji Hae Lee MD. Accuracy of blind versus ultrasound‐guided suprapatellar bursal injection. Journal of Clinical Ultrasound. 2012;40(1):20-25.[wiley]
  2. Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41(2):356-64.[ncbi]
  3. Raeissadat SA, Rayegani SM, Hassanabadi H, et al. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord. 2015;8:1-8.[ncbi]
  4. Dhurat R, Sukesh M. Principles and Methods of Preparation of Platelet-Rich Plasma: A Review and Author’s Perspective. Journal of Cutaneous and Aesthetic Surgery. 2014;7(4):189-197. doi:10.4103/0974-2077.150734.[ncbi]
  5. Braun HJ, Kim HJ, Chu CR, Dragoo JL. The effect of platelet-rich plasma formulations and blood products on human synoviocytes: implications for intra-articular injury and therapy. Am J Sports Med. 2014;42(5):1204-10.[ncbi]