Recently, I staffed Greyledge’s booth at the AOSSM meeting held in San Diego, CA in early July. And I have to say it was an interesting experience due to the number of enquires I fielded from physicians who wanted to know if the Greyledge manual processing method in a biological safety cabinet with hemoanalysis of the injectate could be as “precise” as the Arthrex Angel system for preparing PRP and BMC. I wasn’t aware that the Angel system provided anything that was precise. But I was assured that the hematocrits (Hct) of samples were fairly accurate.
If you aren’t aware of the Angel system, let me give you a brief overview. Arthrex obtained the marketing rights to the Angel system from a company called Cytomedix a few years back. The Angel system produces PRP and BMC by spinning the patient’s sample (whole blood or bone marrow) in a flow-based centrifuge, such that the centrifuged fluid moves through tubing to a location in the pathway where one or more LEDs are present to scan the contents of the fluid flowing past the LEDs. Some sort of algorithm is used such that the signals from the LEDs are interpreted to divert the fluid that has platelets in it for PRP and whatever the algorithm diverts for BMC.
To their credit, realizing that the only thing going for the Angel system over the other device technologies on the market is its ability to specify a Hct level, Arthrex apparently went into marketing overdrive and suddenly physicians thought they needed to have a certain level of Hct in treating various orthopedic pathologies. Hence the questions we were getting at the Greyledge booth at AOSSM. In response, I would ask the surgeons who were so keenly focused on Hct in their use of PRP and BMC, if they knew, given a particular Hct, how many platelets were present in their PRP? Or how many monocytes were present in their BMC preparations? The answer, of course, was no, since the Angel system doesn’t provide any data on the levels of RBCs, Platelets, WBCs, etc. in the preparations. Even the Hct level is selected, not measured. Furthermore, I have been following the clinical literature for treating patients with PRP and BMC for years and never once has a paper appeared extolling the virtues of a patient’s Hct as an indicator of therapeutic benefit. I think it is fair to say that Hct is a parameter that is obscure at best in assessing therapeutic potential of a particular patient’s PRP or BMC.
In addition, there are some operational quirks with the Angel system. For one, the composition of the output preparation would seem to be highly dependent on the patient’s hematocrit. For example, if you specify the Hct level of the output, you don’t have a clue as to the volume you will be receiving. On the other hand, if you need a definite volume, you won’t know what the Hct is for the sample, or so I have been told. A number of surgeons who came to the booth admitted that in fact the output volume did vary in unpredictable ways.
I am not aware of any compositional data published for samples prepared by the Angel system in the context of clinical trials assessing utility of a certain Hct level in treating any musculosketal pathologies. However, there is a paper that was published in 2015 that has a very interesting Table 7, which sheds light on the practical implications of using Hct as the only criterion for producing PRP and BMC, as well as the operational quirkiness of the Angel system.
The paper to which I am referring is by Oliver, et al., in which six patients had their BMC prepared with a 15% Hct level, and an additional five patients had their BMC prepared with a 2% Hct level. An aliquot of each patient’s BMC preparation was sent off for hemoanalysis on a Sysmex hemoanalyzer (XN-5000). The results of the averaged values of Platelets (Plt), White Blood Cells (WBC), Neutrophils (NE), Lymphocytes (LY), Monocytes (MO), Red Blood Cells (RBC), Total Nucleated Cells (TNC), and Hematopoietic Progenitor Cells (HPC; a Sysmex measurement of CD34+ cells—aka hematopoietic stem cells) for each Hct cohort were reported in Table 7. The following is a list of the fold-differences in the measured component for the 15% Hct (higher absolute value) versus the 2% Hct level (lower absolute value):
In other words, the fold-change in Hct is a reduction of 7.5x in going from 15% to 2% Hct. As seen in the list, the fold change in Platelets—7.1x—is the only component that comes close to the fold change in Hct. All of the other components show much higher reductions in going from 15% Hct to 2% Hct, which means that a lower Hct setting will result in substantially lower recoveries of the various cellular components in a patient’s BMC.
I will review the implications of these widely varying fold-decreases in terms of operational aspects of the Angel system in the next post.