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Platelet / Source: Wikimedia Commons and Togopic

5 Questions Top Docs Ask About PRP

Robin Young • Tue, July 7th, 2015

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Platelet rich plasma (PRP), despite its long and rich history, is still an emerging therapy option for most orthopedists.

At the early June TOBI (The Ortho Biologics Institute) meeting in Las Vegas, a group of the top orthopedists convened to ask (and try to answer) the most important questions swirling around PRP.

Those top docs are:

  • Gerard (Gerry) Malanga, M.D.:  Director of PM&R Sports Medicine Fellowship at Atlantic Sports Health Director and Pain Management at Overlook hospital and Professor, Department of Physician Medicine and Rehabilitation UMDNJ
  • Jay Smith, M.D.:  Vice Chair, Physical Medicine and Rehabilitation, Mayo Graduate School of Medicine, Mayo Clinic College of Medicine, Department of Education Administration
  • Brian Shiple, DO, CAQSM, RMSK: Director of the Center for Sports Medicine Wellness in Philadelphia, Pennsylvania.
  • Ken Mautner, M.D.:  Assistant Professor of Orthopaedics, Assistant Professor of Physical Medicine and Rehabilitation at Emory University
  • Jay Bowen, DO: Director of New Jersey Sports Medicine and Assistant Professor of Physical Medicine and Rehabilitation, UMDNJ-Newark
  • Victor Ibrahim, M.D.:  Board certified specialist in Physical Medicine & Rehabilitation and serves as the Director of the Performance and Musculoskeletal Regeneration Center (PMR Center) in Washington, DC and team physiatrist for DC United.
  • Steve Sampson, M.D.: Chief of the Division of Foot and Ankle Surgery; Medical Director of Physical and Occupational Therapy at Stony Brook University Medical Center, and the Associate Chairman of the Department of Orthopaedics within the Stony Brook University School of Medicine.

And here are their questions and the answers…so far.

1.  Why are we still debating PRP?

PRP is increasingly accepted by physicians as a useful treatment for soft tissue injury or painful joints. Can PRP reach the status of a main-stream orthopedic treatment?  Most physicians with experience with PRP think it is possible, but not until it answers some basic questions. Like, what’s the right dosage? Or frequency, concentration levels, leukocyte count or numbers of red blood cells (RBC), white blood cells (WBC) or the right combination of all of the above? And do any of these factors change depending on the anatomy where physician wishes to deploy PRP? It would seem to be an intuitive answer that, for example, the Achilles tendon would benefit more from a formulation tailored to soft tissue injury than, say, an arthritic knee joint.

That is why PRP is still the subject of growing discussion and debate among leading orthopedists.

2.  What does the literature say about PRP?

The literature says that PRP works and the literature says that it doesn’t work. Specifically, as described in Dr. Malanga’s presentation at TOBI, there are studies on both sides of the question.

Source: Caplan,  TOBI,  2014,  Malanga,  TOBI,  2015

Source: Caplan, TOBI, 2014, Malanga, TOBI, 2015

But of course, these top researchers used different systems with different spin rates, different leukocyte concentrations, different white or red blood counts and so forth. So there is little doubt that comparing these studies to each other is like comparing apples to bananas to cranberries.

Still, as these top docs did, if you dig into the details a few insights emerge.

The following table from Dr. Malanga’s talk at TOBI illustrates one example of the types of insights which are available in the literature and which these top researchers teased out.

Source: Malanga,  TOBI,  2015

Source: Malanga, TOBI, 2015

Clearly, based on this group of studies, leukocyte-rich PRP did not perform as well in the osteoarthritis (OA) knee as leucocyte-poor PRP did. Four of the cited studies showed that PRP has the potential to deliver significantly better results over baseline, saline and HA (hyaluronic acid).

3.  Which PRP system is best?

Depends on the problem each physician wishes to address.

As Satoshi Terada, M.D. said in this paper, “Use of an Antifibrotic Agent Improves the Effect of Platelet-Rich Plasma on Muscle Healing after Injury”: “PRP cannot be all things to all tissues. The solution is to customize PRP for specific indications.”

The raw material from which PRP is derived (blood, bone marrow, adipose tissue) is rich with growth factors (PDGF, VEGF, TGFbeta, IGF, HGF, FGF-2), chemokines and cytokines (IL-1beta, PGP, PF4, CCL5), proteases/antiproteases (MMPs, alpha-2-macroglobulin), adhesive proteins (fibronectin, vitamin D binding protein, plasminogen) and small molecules.

This gumbo of therapeutically valuable material and different systems with which to isolate or concentrate them, create tantalizingly attractive therapeutic options. The goal is within sight, but still a long ways off.

If the objective is to, for instance, maximize growth factor content while minimizing white blood cell content, here are how three commonly used systems stack up.

Source: Malanga,  TOBI,  2015

Source: Malanga, TOBI, 2015

Of these three systems (and this is by no means an exhaustive list—there are several other excellent systems on the market), Magellan maximized the amount of growth factors but also had a significantly higher level of white blood cells than, for example, Cascade.

Which system is best?  A better question might be, ‘what are you trying to accomplish’?

4.  What determines the success (or failure) of PRP?

Based on the literature and the best thinking from these top doctors, four elements appear to determine the level of success or failure of a PRP system.

First, since the raw material for PRP comes from the patients themselves, the first and possibly most important variable is the patient. Can the best PRP system in the world overcome poor starting material?  These top doctors all point to a simple fact: platelet counts vary based on each individual patient’s own blood morphology as well as other variables like the time of day! Normally, a patient’s platelet counts range from 150, 000/ml to 350, 000/ml.

Next, the early literature is pointing toward platelet concentrations of 2.5-3.0x baseline as being close to an ideal level. But, increasing platelet counts to higher concentration levels is NOT necessarily a positive since that may, somewhat counterintuitively, inhibit tissue healing.

As Malanga showed in his TOBI presentation, Haynesworth demonstrated that accelerated wound healing required at least 4-5x baseline platelet concentrations and that mesenchymal stem cell recruitment increased exponentially as platelet concentrations increased from 2.5x to 5-10x. Then, as Malanga pointed out, Guisti noted in his research that platelet counts greater than 2 million/ml were inhibitory to tenoctye behavior and when Kevy replicated Giusti’s work, he reported an ideal platelet concentration level of 1.5 million/ml and he did not see any inhibitory effects up to 3 million/ml—which was 10x baseline.

The third key determinant of success is your target therapy. Are you hoping for tissue healing or stem cell recruitment? Or pain relief? Or something else? Each target likely requires a different PRP development methodology.

And the final key element is: have you selected the ideal platelet concentration and system for the specific target clinical scenario? Have you selected the best PRP formula for tendinopathy? Or for anti-inflammatory applications in the OA knee?

Unfortunately, the last two determinants of success remain terrific subjects for further research and investigation—which is a nice way of saying that the answers to those last two elements of success are largely unknown.

5.  Where does PRP evolve from here?

For quite a while now, both leading researchers and a few advanced suppliers of PRP systems have been asking the tough questions and organizing their research accordingly. What we found so fundamentally encouraging about 2015 TOBI was the way that these top doctors came together and put forth a framework for describing and using these PRP systems.

Under the leadership of these top docs, here is where PRP could evolve to:

  • A PRP classification system, and several have been proposed, will be universally adopted by PRP equipment suppliers and researchers. The one these top researchers recommend is the PRLA PRP classification system.
  • All scientific publications and presentations would include information about cellular concentrations (platelets, WBCs and RBCs), volume of PRP delivered and the frequency of PRP treatment.
  • The nomenclature for “PRP” will change to become specific to the clinical orthopedic conditions being targeted and will facilitate more pointed scientific inquiry.

At the end of this year’s excellent TOBI meeting, the general feeling is that PRP, as a treatment modality, is maturing. Work needs to be done, but under the leadership of this group of physicians and, again, some of the leading companies supplying these systems, the right questions are being asked which, in turn, sets up future research in this extremely promising area.

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