In the previous post, I had shared a couple of comments from physicians (Drs. Sairam Atluri and Dr. Edward Marcheschi) that had been made on the trio of posts on the Arthrex Angel in which I concluded that the Arthrex Angel system was a lemon as a PRP/BMC processing technology. In exploring aspects of the physicians’ comments, I shared a number of details on the concentrations and/or numbers of the key components found in PRP, which sometimes can be cumbersome to deal with. Subsequently, I pointed out that Dr. Karli and I had created an approach to deal with the numbers or concentrations of the critical components found in whole blood and bone marrow, which we termed the “Method of Ratios” (MOR). The idea is to use the concentration or number of PLTs, RBCs, WBCs, NEUs and MONOs to create ratios. Since PLTs are considered to be responsible for the primary therapeutic benefit of PRP (delivery of growth factors), the proposed ratios use the PLT level as an indexing component, such that the ratios tell you how many PLTs are present compared to RBCs/WBCs/NEUs. For example, a PLT ratio with RBCs (PRR) of 10 indicates that there are 10 PLTs present per RBC in the preparation. Obviously, ratios are greater than, equal to or less than one, making it straightforward for a physician to quickly grasp what a patient’s therapeutic profile is for the injectate that will be implanted shortly, and over time will allow the physician to correlate the MOR profiles with patient-reported outcomes to look for trends.
Dr. Karli applied the MOR approach to the data presented in Degen, et al., since the authors provided averaged results for PLT, RBC, WBC and NEU for whole blood from seven unrelated donors that was processed in six commercial PRP-producing systems according to the manufacturers’ instructions for use. Calculating and plotting the PRR values from the Degen, et al. data set gives the following:
Since the analysis is for PRP, Dr. Karli thought that plotting the various ratios against the total platelets reported by Degen, et al. for each commercial system would be an appropriate y-axis parameter. On the other hand, it might be that for BMC you would want to use total Monocytes on the y-axis, since Monocytes are the closest surrogate indicator in a hemoanalytic data set to progenitor/stem cells.
The data point identified as “7” represents an average of 25 PRP samples that were processed to generate a reduced RBC/WBC-type PRP in a manual method performed by Greyledge Technologies for Dr. Karli, who is the founder of Greyledge. Dr. Karli started Greyledge more than eight years ago to provide customizable PRP and BMC preparations and hemoanalytic data on the injectates he was implanting in his patients at The Steadman Clinic. Thus, a critical feature of the Greyledge service is to provide physicians with a real-time hemoanalysis of the patient’s preparation prior to it being used for treatment.
A quick glance at the PRR values in the graph shows that the Arthrex Angel system at 2% Hct yields the lowest total number of PLTs on an absolute basis compared to the rest of the commercial technologies, but the PLT yield goes up when a 7% Hct setting is used. Unfortunately, the PRR value for Arthrex Angel at the 7% Hct level drops a lot, which is to be expected since there are more RBCs at 7% Hct, but without a proportional increase in PLTs. Apparently, if you are using the Angel system your choice is either to accept a lower yield of PLTs with a higher PLT-to-RBC ratio, or accept a lower ratio, by selecting a higher Hct level, but getting more PLTs. An important factor that I haven’t focused on is time-to-process, which in the Arthrex Angel system I believe depends in part on the volume of whole blood used to produce the PRP at a particular Hct level. That is, as the input volume of whole blood (or bone marrow for that matter) increases, the time to process the larger volumes increases. Perhaps Dr. Marcheschi could share his observations on the time-to-process relative to input volume of whole blood.
While Dr. Marcheschi didn’t focus on platelet yield or on RBC content in his comments to my post, he did bring up the fact that the Angel system was able to “virtually eliminate” NEUs. Although his phrase is vague, the MOR approach provides a quantitative context for his remark as shown in the Platelet-to-NEU ratio (PRN) graph for the same set of data reported in Degen, et al.:
And this is the graph for the PLT-to-WBC ratios:
From the two plots of PRN and PRW, it is evident that the technologies show device-dependent variations in the ratios of PLTs to NEUs and WBCs that might be informative for physicians trying to select a device-based system to use. I will note that the Greyledge manual method produces PRP that has a good recovery of PLTs and quite respectable ratios of RBCs, NEUs and WBCs.
As shown in the graphs in this post, it is clear the MOR approach can reveal potentially critical differences in the compositions of PRP made with commercial technologies. These differences can be reviewed by physicians in order to guide them in making better informed decisions about the kind of PRP (BMC) they might want to provide their patients. In addition, physicians can correlate the MOR profiles generated on their patients’ preparations along with the patients’ clinical outcomes. Thus, the approach of considering ratios of components could streamline the process and effort required by physicians to recognize beneficial compositions that could point to a higher probability of the patient receiving a therapeutic benefit. The Method of Ratios is a “snapshot” approach for tracking the components in PRP and BMC, which should give physicians a more readily accessible view of the hemoanalytic data versus trying to juggle the actual concentrations or total numbers of these components in real time as they walk down the hall to treat a patient.