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4/19/20

PrP: Everything You Need to Know about Platelet-Rich Plasma

It was almost 4 pm at the end of a beautiful day on the slopes in Park City. My ski instructor, an older Slovenian guy, shows me the way down: a double black diamond, narrow, icy corridor with moguls and dense trees.

Next thing I know, I am sliding down on my butt, skis in the air. My skis get caught between two trees, left knee twists, and I feel my knee warming up - not good.

Two days and one MRI later I found out I had what they call “the terrible triad”: anterior cruciate ligament (ACL), medial collateral ligament (MCL) and medial meniscus tears. Stuff we used to learn in residency that made us cringe - now I had it!

Fast forward 10 weeks and 4 platelet-rich plasma (PrP) treatments for my left knee. I am standing with an orthopedic surgeon in front of a computer screen showing a second MRI of my knee. “I guess we won’t have to repair your ACL after all” he says, still incredulous, scrutinizing the images as if trying to find the missing piece of evidence to prove that he had been right before, when he told me I had to have surgery.

If I had any doubts about PrP before this, I was a convert then and there.

There is a lot of talk and a lot of noise about PrP, and, even though it has been around for at least 10-15 years, most people are still in the dark about what it is, how and why it’s used.

We’ll try to clarify the main points about PrP in what follows, at the same time trying not to turn this post into a book chapter!

First, let’s take a dive into your bloodstream and have a look around. 55% of the blood is the liquid plasma, a mixture of water, fat, protein and salts. Plasma transports blood cells along with many other chemicals throughout your body. The red blood cells or erythrocytes (40-45% of blood volume) use a protein called hemoglobin to carry oxygen and carbon dioxide. The white blood cells or leukocytes (1% of blood volume) protect the body from infection.

Unlike red and white blood cells, platelets are not actually cells but rather small fragments of cells. Platelets help the blood clotting process (or coagulation) by gathering at the site of an injury, sticking to the lining of the injured blood vessel, and forming a platform on which blood coagulation can occur. This results in the formation of a fibrin clot, which covers the wound and prevents blood from leaking out. Fibrin also forms the initial scaffolding upon which new tissue forms, thus promoting healing.

So for the longest time, all we knew about platelets is that they promote blood clotting. It’s only recently that we discovered some of their interesting other properties: they have receptors for collagen, which allows them to adhere to the collagen in the surrounding tissue, say, my ACL, MCL and medial meniscus, for example. Seconds after platelets adhere to the collagen, they become activated.

You will have to bear with me through this next paragraph, which is more technical. If it makes you feel any better, this is very complicated even for me(!). If you want, skip to the next paragraph. It will still make plenty of sense.

Platelets contain several types of granules. Once activated, these granules release their contents in the surrounding tissue to promote healing and repair. I won’t bore you with all the types of granules, but the ones pertinent to regenerative medicine are the alpha granules. They contain P-selectin, platelet factor 4, transforming growth factor-β1, platelet-derived growth factor, fibronectin, B-thromboglobulin, vWF, fibrinogen, and coagulation factors V and XIII. Platelets are rapidly deployed to sites of injury or infection, and potentially modulate inflammatory processes by interacting with leukocytes and by secreting cytokines, chemokines and other inflammatory mediators. Platelets also participate in chronic inflammatory diseases, such as synovitis or rheumatoid arthritis. Platelets are activated by collagen receptor glycoprotein IV (GPVI). Proinflammatory platelet microvesicles trigger constant cytokine secretion from neighboring fibroblast-like synoviocytes, most prominently Il-6 and Il-8. Platelets release platelet-derived growth factor (PDGF), a potent chemotactic agent; and TGF beta, which stimulates the deposition of extracellular matrix; fibroblast growth factor, insulin-like growth factor 1, platelet-derived epidermal growth factor, and vascular endothelial growth factor. Local application of these factors in increased concentrations through Platelet-rich plasma (PRP) is used as an adjunct in wound healing.

OK, you made it through the hard science! As we discovered all these wonderful anti-inflammatory and healing properties of platelets, we realized they could be useful in degenerative conditions such as osteoarthritis and also in acute injuries that cause collagen disruption, like the the terrible triad of knee injury I described above.

Naturally, this immediately spawned a cottage industry of “PrP kit makers”. These companies sell their blood separation kits and centrifuges at high prices.

Through years of research, some things became clear: the optimal platelet concentration for spine and musculoskeletal application is five to seven times the blood concentration. This of course also depends on the initial platelet numbers in whole blood, which could vary from 150,000-450,000 per cubic milliliter. Some argue for measuring the absolute platelet numbers and worry less about the concentration factor. Some proved that a platelet concentration that is too high may be detrimental to the tissue. Others noticed that the white blood cell numbers in the platelet concentrate may affect healing, as these white blood cells can be inflammatory. Therefore, controlling the white blood cell content in the PrP is probably very useful, depending on the type of injury we treat (acute versus chronic, superficial tendon versus intervertebral disc, etc).

Although we take these things for granted now, 10 years ago when we first got started with PrP, this knowledge was not (readily) available. We started, like everybody else, by using PrP kits from a company that will remain unnamed. As we started asking ourselves more and more questions, we bought a cell counter and started analyzing both the whole blood numbers and the PrP numbers in the kits. It turned out that the promised 5X concentration was 3X at best, most of the time less than that! And we were paying upwards of $500 for one kit, let alone the cost of the centrifuge, etc.

This prompted us to build our own small in-house lab and through trial and error (my staff donated many pints of blood, thank you to all of them) and, with the help of Ph.D experts smarter than us, we learned how to manually separate the platelets, and also how to control the white blood cell numbers in the PrP. This also allowed us to keep the price of our treatments down, as we eliminated the cost of the commercial kits. We then employed the same process to arrive at our own algorithms for stem cell extraction from bone marrow and fat tissue.

The next step on our PrP journey was learning to produce PrP lysate. Due to their natural “stickiness”, platelets are not the best regenerative material when injected around nerves, either in the spine or peripherally (such as the median nerve for carpal tunnel syndrome or ulnar nerve at the elbow). Because of this, we figured out a process of breaking up the platelet membranes (the sticky parts) and getting rid of them, only keeping the platelet granules we wrote about in the paragraph that you skipped (!). The result is PrP lysate (to lyse means to break up), which we now employ in the spine around the spinal nerves and also in the peripheral nerves.

So what are the take-home points of this post?

First, PrP is an alternative treatment for osteoarthritis of the joints and the spine. The decision to use PrP needs to be based on careful review of patient’s history, all of the radiological data, preferably MRIs, and the general health of the patient. As with everything else, ask questions before accepting this treatment from anyone: what are their qualifications? how long have they been doing this? are their procedures image-guided? Remember also that it is still considered an experimental treatment, which means your medical insurance company will not pay for it, and there are no guarantees of success (regardless of what that radio or social media commercial tells you).

Depending on the severity of your condition, PrP may not be the appropriate regenerative solution. Bone marrow or adipose stem cells, or even amniotic fluid or other peri-natal products may be better. Again, an experienced physician will be able to make these decisions.

Second, PrP has to be the appropriate type and composition for your problem. It has to be the right concentration, based on your initial whole blood platelet count. If you have a fresh superficial tendon injury with a lot of inflammation, maybe a higher white blood cell count is appropriate in your PrP mixture. If, on the other hand, you are treating chronic degenerative osteoarthritis, a high white blood cell count would be more inflammatory and would hurt more. Ask your physician what PrP system they use and if they are aware of the cell counts in the solution they want to deliver into your body.

Sadly, we live in an age when expertise and competence are sometimes under appreciated at the expense of the latest marketing blitz or social media campaign. Platelet-rich plasma therapy is no exception, and it is now touted as a panacea for everything, from knee pain to hair growth to sexual dysfunction. Every claim has to first pass the common sense test, and then has to be discussed and decided upon with help from a competent expert physician. We hope this primer can serve as a roadmap in your decision-making process when you ask yourself: is PrP something I should consider?

As for my knee, it has now been about 5 years since my injury. I have had absolutely no issues since my PrP treatments. Periodically, every year or so, I have another PrP injection: I don’t know if it’s needed or not, but it somehow satisfies my obsessive-compulsiveness!

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