The posts that I write are available on the Greyledge website and are also distributed on LinkedIn. I would like to share a couple of LinkedIn comments from physicians who responded to the last three posts that have covered this question: Is the Arthrex Angel PRP/BMC processing system a lemon or has Arthrex’s marketing group made lemonade?
The analogy of lemon/lemonade is in reference to the fact that I provided a number of examples in the three posts of the odd hemoanalytic results that have been published in Oliver, et al. (2015) and Degen, et al. (2017) in which various Hematocrit (Hct) levels were used to process bone marrow aspirates (Oliver, et al.) or whole blood samples (Degen, et al.), with a hemoanalysis performed on the samples post-processing. As far as I know, despite the fairly long time the Angel system has been on the market (Angel was marketed by Cytomedix before they signed over the marketing rights to Arthrex), these are the only two papers I have seen in which results from hemoanalysis of Angel-processed PRP or BMC preparations have been published.
Since I don’t have routine contact with physicians who use the Arthrex Angel system to produce BMC to treat patients, I really appreciated the comment from Dr. Sairam Atluri, who indicated that he uses a 25% Hct setting to produce BMCs and has observed good outcomes with this type of preparation. In my response to Dr. Atluri, I indicated that sticking with a single, higher level of Hct in preparing the BMCs and tracking outcomes struck me as a good way to refine his practice of medicine; as opposed to physicians who might be encouraged to use different Hct levels in treating various types of pathologies. I haven’t seen a single paper in which using specific Hct levels of PRP and BMC preparations has been shown to be efficacious. There certainly isn’t any clinical data that points to the need to vary the Hct depending on the site of pathology; other than the trend to use reduced RBC/WBC PRP in intraarticular treatments.
Dr. Edward Marcheschi also shared his experience with the Angel (Cytomedix and Arthrex versions) for producing PRP at 2% and 7% Hct levels. He indicated that he had excellent results and was especially pleased to note that at the 2% Hct level, there were virtually no neutrophils present (“virtually eliminated”). Although Dr. Marcheschi indicated that he has had hemoanalysis performed on PRP preparations, it isn’t clear from his comment if this is done on every PRP sample or was limited to just a few samples. Also, I don’t really know what he meant by “virtually eliminated” when speaking of the reduction of neutrophils in the 2% Hct PRP preparations.
As it happens, we can (and I really encourage physicians contemplating the use of a device-based technology to get a copy of the Degen, et al. paper) review what Degen and co-workers observed when producing 2% Hct PRP preparations on seven unrelated donors with the Arthrex Angel system. They reported that at 2% Hct the PRPs had an average of 6.2 x 109 PLTs in roughly 3 mL, and that there was an average of 0.6 x 106 NEUs in the same 3 mL. While I admit that 600,000 NEUs in the PRP preparation is quite low, it isn’t zero; so I am not quite sure why Dr. Marcheschi is so pleased. From a physiological point-of-view, the PLTs present will degranulate over 24-48 hours and be reabsorbed. However, NEUs are viable cells that keep on responding to their environment—possibly for days, and could act to recruit additional NEUs to the treatment site. So, balancing the relative impacts of the two different blood components would seem to be difficult.
Since Dr. Marcheschi pointed out that he uses PRP at the 2% and 7% Hct settings, I took a look at what the Degen, et al. paper reported for PLTs and NEUs at a 7% Hct level. There was an increase in PLT concentration of 1.1x at 7% over the PLT concentration at 2%, while the NEU level increased by 3x. As I indicated in the previous three posts, the variation in fold-changes relative to the change in Hct makes these results non-linear and unpredictable in my opinion.
As illustrated by the foregoing review, dealing with the levels of various critical components in PRP and BMC preparations can become tedious. The numbers usually involve exponents, which I don’t mind, but sometimes can be off-putting to those who are more clinically-oriented. And there are several sets of numbers with exponents that a physician needs to balance when trying to assess the therapeutic benefit of a PRP preparation, including PLTs, RBCs, NEUs, WBCs, etc. It is for this reason that Dr. Karli and I created a system for trying to simplify the challenge of looking at hemoanalytic data on PRP and BMC preparations to try to get a feel for its therapeutic potential. Dr. Karli previously had summarized the approach we refer to as the Method of Ratios (MOR) in a couple of posts.
PLTs are the obvious therapeutically beneficial component in PRP, while RBCs, NEUs and WBCs (more broadly) are thought to have a more negative therapeutic impact. Recent comments in the Blog-o-sphere have suggested that some WBCs are more deleterious than others. Dr. Marcheschi points the finger at NEUs as having a more negative impact, which is an opinion shared more broadly by the regenerative medical community. So, how does the Method of Ratios address the challenge faced by physicians when reviewing a particular patient’s set of component levels?
Start with the values of selected components (either as concentrations or total number) and create a series of ratios, with PLT as the indexing component:
What results is a set of three ratios, each of which is either less than 1, equal to 1 or greater than 1. Each of these ratios is a direct indication of how many PLTs there are per RBC/WBC/NEU in the patient’s PRP. For example, if the PRR is 10 that means there are 10 PLTs per RBC in the patient’s PRP. If a physician believes it is important to have fewer RBCs and more PLTs, using hemoanalytic data to create ratios would be a good way to assess the ratio status of the preparations and make adjustments to the way PRP is produced in the clinic.
Dr. Karli presented analyses and graphs of various data sets based on the Method of Ratios approach at one of his presentations during the 2017 TOBI conference. In the next post, I will complete my review of the MOR approach by illustrating ratios for the data set presented in the Degen, et al. paper.