Sports Medicine Research: In the Lab & In the Field: How does Normal Soft Tissue React to PRP? (Sports Med Res)


Monday, June 25, 2012

How does Normal Soft Tissue React to PRP?

The Effect of Platelet-Rich Plasma on Normal Soft Tissues in the Rabbit

Harris NL, Huffer WE, von Stade E, Larson AI, Phinney S, Purnell ML.  J Bone Joint Surg  Am. 2012 May 2;94(9):786-93.

The fascination of using biologics in the field of sports medicine has been a growing area of interest over the past few years.  Unfortunately, much of the clinical data for its use has been anecdotal and well-designed clinical studies have been lacking in the past.  However, more clinically relevant trials have and are being carried out to determine the true efficacy of autologous platelet-rich plasma (PRP) for musculoskeletal injuries.  The authors in this study hoped to add a new piece to this puzzle by examining the effects of PRP injection into various normal soft tissues.  Eighteen adult New Zealand White rabbits were injected with 0.5 mL of PRP into the quadriceps muscles, Achilles tendon, medial lateral ligament (MCL), subcutaneous tissue, tibial periosteum, and ankle joint.  The PRP was prepared by drawing 50 mL of blood from each rabbit, centrifuging the sample, and activating the plasma with a combination of topical thrombin and calcium chloride to form the final gel.  A saline solution was injected into each contralateral site that served as controls.  Soft tissues were examined histologically at 2 and 6 weeks (6 rabbits each), with the 6 remaining rabbits undergoing reinjection at 6 weeks and then examined histologically at 12 weeks.  The authors observed calcification in these first 3 groups within muscular and subcutaneous tissues after injections, so added a 4th group of rabbits that used a calcium-free solution with the PRP to examine the development of soft-tissue deposition.  With gross examination, the authors found a superficial skin reaction of a raised red lesion in 17 of 18 rabbits that resolved after 6 days.   Muscle tissue showed an inflammatory cell (monocytic and lymphocytic) infiltrate with edema, necrosis, and calcium deposition in the muscle fibers at 2 weeks.  Subcutaneous sites demonstrated collagen nodules and new fibrous tissue at 2 weeks.   The tendon site and MCL showed monocytic and lymphocytic inflammatory cells with thickening of the soft tissues at 2 weeks, along with collagen deposition.  Ankle joint tissue showed villous synovial hyperplasia (increase in epithelial cells and finger like projections of the tissue that lines the joint) and chronic synovitis at 2 weeks.  These sites at 6 and 12 weeks showed persistent but diminished inflammatory infiltrates.  The periosteum did not show any evidence of new bone formation at any of the time frames. 

PRP has long been used for various clinical applications.  However, new data is needed to determine what musculoskeletal conditions would benefit most, if at all, from this therapy and at what stage of treatment should it be utilized.  The authors found that PRP injected into healthy tissue caused a similar acute inflammatory reaction as seen with an acute injury or healing response.  The potential benefits seen after 6 weeks may be viewed as beneficial to healing in tissues with chronic degenerative changes, but detrimental to normal tissue.  The third rabbit group, which was reinjected with PRP at 6 weeks, mimicked a clinical situation where sometimes a patient is reinjected at a later time point to boost the effect of the initial injection.  This study did not show a return of the acute inflammatory response or increase in vascularity or scar formation.  This is another clinically relevant point that needs to be further studied as some provider’s protocols include a series of PRP injections, but this study does not support that practice if pathologic tissue would have a similar response.  Negative effects found from this study include the local skin reaction and the reaction from the intramuscular injection of PRP that included thrombosis and necrosis (cell death).  Also, with the results from the 4th group of rabbits having less calcium deposition, further studies need to look at calcium being used as a thrombin activator.  One limitation of this study is that authors only examined normal tissue and these results might not be similar with pathologic tissue.  This study can add to the list of potential risks and benefits that need to be discussed with each patient prior to injection.  How do you view the results from this study?  Does this study make you more or less likely to recommend PRP to patients?

Written by: Kris Fayock, MD and Peter Vitanzo, MD
Revised by: Jeffrey Driban

Related Posts:

Harris NL, Huffer WE, von Stade E, Larson AI, Phinney S, & Purnell ML (2012). The effect of platelet-rich plasma on normal soft tissues in the rabbit. The Journal of Bone and Joint Surgery. American volume, 94 (9), 786-93 PMID: 22552667


William said...

Dr. Fayock, Dr. Vitanzo

I would have to agree with your closing statements; future research definitely needs to be conducted especially on injured subjects/pathologic tissue.

I have no first hand experience dealing with PRP however I have seen its reported use by a number of professional athletes (Tiger Woods, Hines Ward, Troy Polomalu etc.) in which no negative effects were noted, to my knowledge. Of course the aforementioned athletes are apart of a specialized elite group and I am far from agreeing that PRP is for everyone at all levels let alone professional athletes.

Having read the study I would have to say that depending on the injury PRP can still be considered as a possible treatment option (neglecting time/money). I do not find the results from the study to sway me to be more for PRP or against PRP compared to how I felt before reading the study. This is due to the fact that healthy tissue was treated and also on rabbits.

Based on the results, hypothetically if similar results from the study translate to humans I do not believe PRP is a treatment that should be used to treat a "healthy" person. However I do believe this study does provide some insight on ruling PRP out as a preventative measure.

I do not believe that at this time it is appropriate to rule anything completely out this early in the research stage.

What are your experiences with PRP and your thoughts on its effectiveness and appropriate "general" application timetable?

Kris Fayock said...

Thanks for your comments Williams. I think PRP remains an option after all other non-surgical options have been attempted for the general population. I have seen it work in some cases, but be ineffective in others as well. The timetable for when it will be used is dependent on the type of injury and the patients own decision on weighing the risks and benefits, which includes the cost.

For elite athletes, if there is a treatment option available that might get them back to playing faster, then they should be offered that treatment. One thing to think about is when PRP is used early on in an acute injury and the athlete recovers, was it definitely the PRP, the fenestrations of the needle, or just time? Also for how many times it does successfully get an athlete back faster, how many times does it not make a difference? These results probably aren't publicized.

One of the results that might be more clinically relevant is with the group of rabbits that received a 2nd injection and didn't have any additional benefits. Some physicians use a series of PRP injections in their protocols. This might double or triple the cost for the patient and we need to make sure there is evidence to support this additional cost. A few times I have seen patients that received multiple injections of PRP in cases that might not typically use PRP. We need to make sure patients aren't taken advantage of due to poor patient education and with the financial incentives of some providers to offer PRP.

Overall, I think there is a role for PRP and it is beneficial, and eventually we'll figure out which injuries it is appropriate for and where it falls on the timetable. In the meantime, we need to make sure patients are properly educated when it is offered.

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