Platelet Rich Plasma Injection Therapy
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Platelet Rich Plasma:
At one time medical professionals thought the only purpose of platelets was to form a clot in order to heal cuts and other injuries. This couldn’t be further from the truth. The formation of a clot is certainly important, but this is only a small part of the whole picture. Another crucially important function of platelets is the release of various growth factors responsible for almost all repair processes that occur in the body.
These growth factors, also called cytokines, are extremely important in cellular communication, having both direct and indirect effects on stem cells and other types of more mature cells. They work as a communication network between the cells, among other functions.
Platelets and accompanying stem cells are responsible for repair, whether in healing an injury or recovering from surgery. Platelets are found circulating in the blood but typically occur in relatively small numbers. Around 20 years ago the idea of concentrating platelets became widespread in cardio-thoracic surgery. Further research was carried out in the field of oral surgery in 1998 by Dr. Robert Marx at the University of Miami, who revealed what constituted a platelet-concentrated product. In the years since his research concentrated platelets have become known as Platelet Rich Plasma, or PRP, which stimulates healing.
Methods of Production
There are many different methods of preparing a PRP product, however all techniques use centrifugation. The type of centrifuge and the speed at which the centrifuge runs varies from one PRP producer to the next. The PRP product that various companies produce varies widely in the concentration and cell types that are found in a PRP product.
The problem PRP producers face is that current scientific literature has no good definition as to what constitutes a PRP. Thus, while one article may show significant positive effects from PRP the next may show that PRP is no better than a placebo. It is important to note that this problem stems largely from disparities in quality between the various companies that produce PRP products, not from lack of efficacy of PRP therapy. Later in this section we will explain the science behind what constitutes an effective PRP product.
The amount of blood needed to produce a PRP depends upon the joint or tendon requiring treatment and the type of system used . Some systems require up to 60 cc's (about 2 ounces) while others require about 10cc's. The amount of centrifugation time varies from one company to the next. Much variation exists in PRP products produced by various companies in terms of different concentration of platelets, red blood cells, white blood cells and other types of cells.
These concentrations can make a difference between success and failure of a PRP injection. While clotting agents such as thrombin have been used in the past to “activate” the platelets to release their growth factors, we do not employ any clotting agents with our PRP. It is not necessary and could actually be detrimental, since using a clotting agent releases the growth factors all at once rather than through a prolonged release.
Methods of Administration
The methods utilized to inject the PRP product depend on the area being treated. For certain joints, such as the hip, we utilize fluoroscopy, which is a "living X-ray." In other instances we utilize ultrasound guidance or simply give the injection into a joint.
The aftercare for most PRP injections is relatively simple—we allow the patient to resume activity at their own pace. We will typically restrict the use of non-steroidal anti-inflammatory drugs (NSAIDs) for a day or two. After a PRP injection we utilize a variety of techniques to help maximize stem cell output from the bone marrow, including various supplements and avoidance of smoking and alcohol intake, both of which diminish stem cell output.
We typically perform two PRP injections into an area, usually spaced four to six weeks apart. Occasionally, a third PRP injection is needed. PRP injections are replacing traditional orthopedic surgery in many instances for conditions ranging from soft tissue injuries (tendonitis, muscle tears, ligamentous injuries) to various joint afflictions, such as a torn meniscus or mild to moderate arthritis of the joint.
The pain from the process typically will last a few days, occasionally longer, and some patients have more severe or sporadic pain than others. We strongly encourage viewers to continue reading this section to learn more about the science of PRP injection. If you are considering having a PRP procedure done, you owe it to yourself to have a better understanding of the science.
Let's Talk More About The Science of PRP Injections
I have found that many patients want to know more about the science of how platelet rich plasma works. I will attempt to give an overview without making it too scientific. At one time it was thought that platelets were basically responsible for clotting the blood and that was all. Nothing could be further from the truth!! When the platelets are concentrated the growth factors are also concentrated. These growth factors are what cause things to heal. I would to give some pictures and diagrams that give the layperson a better idea of what PRP is:
In terms of diagrams the following diagrams can also give someone the concept of how the number of platelets varies from the number circulating in your blood and those found in concentrated PRP therapy.
This diagram represents the proportion of platelets, white and red blood cells in the PRP product. So we see the amount of platelets in our circulating blood represents 6% of the volume while in PRP concentration it represents 94% of the volume.
When a physician is injecting a quality PRP product the PRP concentrate will have the following components.
- Platelets which release growth factors.
- Neutrophils and Monocytes which are forms of white blood cells which are very important in helping to create the proper microenvironment for the stem cells.
- Fibroblasts produce collagen and help in the repair process.
- Endothelial cells help establish a blood supply and help in regulating inflammation.
Putting this altogether in pictorial form we see how all these components work together to produce Platelet Rich Plasma.
In the above diagram we see various abbreviations such as IGF, VEGF. These abbreviations represent various growth factors. Many of these growth factors have a direct effect on stem cells. Without these growth factors the stem cells would not function very well. The mechanism of action of the cytokines may be through endocrine (secreted by one population of cells and having distant effects), autocrine (secreted by cells which then are themselves modulated by the factor), or paracrine (secreted by cells and affecting neighboring cell populations) activity. Some Stem Cells seem to act in a similar fashion.
We can see the growth factors from the platelets are very important but the real question is how they really act on the stem cells. As the old saying goes a picture is worth a thousand words. The following diagram is a good synopsis of how platelets and stem cell interact with each other.
In the above diagram on the left we see what an activated platelet looks like. It can probably best be described as an amoeba. On the right we see the cell membrane of a mesenchymal stem cell. The cell membrane is the eyes and ears of the cell. The better the cell membrane works the more efficient the stem cell will be. Remember that the cell membrane is made up of oils thus we recommend to our patients that they utilize Omega 3 oils to replace some of the Omega 6 oils (bad oils like trans-fats) in the cell membrane.
Once the platelets have become activated they start interacting with the stem cells. Dramatic changes occur in the stem cells as can be seen in the next diagram.
The Stem cell is now activated and production of certain bio-chemicals and replication of the cells is starting to occur. In a nutshell this is a very simplified explanation of how platelets and Stem cell interact and help accomplish repair.
The Million Dollar Question is What Makes an Optimal PRP?
When we are talking about PRP injections we must actually define what a PRP is. The problem that we currently have is that there is no standard as to what constitutes a PRP. Since there is no standard or uniformity the studies concerning PRP are very inconsistent. Some studies show great promise while other studies show PRP works no better than a placebo. The reason for this is that we are not comparing apples to apples. There is a good bit of scientific literature as to what constitutes an effective PRP. The Optimal concentration of a Platelet-Rich Plasma (PRP) for angiogenesis (BLOOD VESSEL FORMATION) is 1.5–3.0 million platelets/µL (uL=micro liter). What does this mean in English? Well if we are lacking a certain number of platelets we will not get formation of blood vessels (angiogenesis) which is crucial in any repair process. Interestingly enough if the number of platelets gets too high it will actually cause inhibition of healing. No point of care PRP system can attain a level that will result in inhibition. Systems that produce platelet concentrations less than 500X103/µL support proliferation no better than platelet-poor plasma. These systems shall remain nameless. What this means is that the system is producing a product that is no better than whole blood. So a patient needs to beware that his physician is using a system that can produce the proper number of platelets. I have spoken to many doctors that have come to observe procedures at our facilities. They feel that they can perform a PRP injection for less than fifty dollars. Unfortunately, if they knew the science they would know that this is not true. They and unfortunately the patient are getting what they paid for. I have a few good diagrams that show in pictorial form what I am saying.
This diagram looks intimidating but it is not. We can see that as the number of platelets goes up the number of stem cells increase in number up to about 3000 platelet concentration than the numbers start to diminish. You want to make sure you are getting a HD PRP. Remember that too high a number of platelets will cause inhabitation of stem cells and hinder repair. This can easily be seen on the following laboratory diagram
Earlier in this section we spoke about the components of a PRP. A quality PRP does not just have high numbers of platelets but it also has other components including some stem cells and white blood cells. The white blood cells (WBCs) are important in that they secrete a certain growth factor which allows stem cells to initiate homing which means that they are attracted to areas of injury. There is some controversy concerning the use of WBCs but this controversy seems to be waning. Photo modulation of the WBCs seems to eliminate some of the inflammation caused by the WBCs. Perhaps we should leave the PRP section with the following analogy: think of an unfertile dirt field. We have grass seed (stem cells) and fertilizer (the PRP growth factors). If we plant only the seed we will get some growth but not that much. If we just add fertilizer to the field we may get some weeds to grow. If we plant the seeds and fertilizer together we will get much more of the desired growth. A joint or tendon does not work much different than this. The last two slides will hopefully sum up everything.
The above slide shows when an injury occurs. We have a whole combination of cells involved in the repair process. A high quality high density PRP contains all of the above cells in addition to others. REMEMBER THE REPAIR PROCESS IS LIKE A SYMPHONY ORCHESTRA THAT HAS MANY PARTS. THE SOUUND OF THE SYMPHONY DEPENDS UPON ITS MICRO-ENVIRONMENT AND IT CONDUCTORS. THE SAME HOLDS TRUE FOR PRP AND STEM CELLS AND THEIR INTERACTIONS.
