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What have Leukocytes Got to do With It?

PRP is a treatment that utilizes growth factors produced by platelets to promote tissue repair.  PRP is harvested from the blood. Platelets are collected and concentrated by separating them from the liquid plasma and red blood cells. In this process, the leukocytes often come along for the ride. This can create “leukocyte-rich” PRP. Alternatively, in the case where leukocytes are removed from the PRP in some processing step, one may create “leukocyte-poor” PRP.

Unfortunately, the vast majority of studies do not have a strict definition on what is considered “rich” (LR) vs. “poor” (LP) leukocyte content, or the methods of leukocyte depletion from the sample. Without this information, it is nearly impossible to properly asses the clinical effectiveness of LR vs. LP PRP. Is the presence of leukocytes beneficial, or do they somehow impede the function of PRP to do its job? The short answer, (and there really isn’t one) is that “it depends”. Factors that affect this include the site of injection, the tissue in need of repair, the system used to remove leukocytes, the concentration of leukocytes in the sample.

What do Leukocytes do?

The role of leukocytes, in general, is to coordinate the inflammatory response to deal with wound healing and infections. Therefore, in theory, these cell-types can have both positive and negative effects on the healing process supported by PRP.

The inflammation these cell types trigger has been demonstrated to trigger catabolic cascades, cell death, and pro-inflammatory factors which may cause symptoms such as increased pain and swelling, putting added stress on already stressed-out tissues. However, in response to tissue injury, leukocytes are attracted to the area and clear cellular debris and bacteria. This aspect of the inflammation process is essential for healing to begin.

LP-PRP

Despite this lack of consensus, some studies have investigated specifically the impact of leukocyte concentration on PRP efficacy. One network meta-analysis (NMA) specifically examined this question in the context of knee osteoarthritis(OA). It directly compared LR vs. LP PRP to control and/or placebo treatment in several studies, six of which were randomized control trials, and three were prospective comparative studies. These studies included a total of 1055 knee OA patients.   LR-PRP was defined as PRP having a WBC concentration greater than 100% that of whole blood. Conversely, LP-PRP was defined as PRP having a WBC concentration less than 100% of whole blood.

Three results variables assessed treatment efficacy (1) WOMAC score, (2) IKDC subjective score, and (3) the number of adverse reactions. This NMA concluded that the leukocyte POOR PRP produced improved results in the context of knee OA as compared to leukocyte RICH PRP. However, both PRP treatments demonstrated improvements compared to the control treatments. These findings suggest that the inflammation associated with the presence of leukocytes may be impacting the efficacy of PRP in the case of knee OA. (1)

LR-PRP

However, it is important to know that other conditions may benefit from the presence of leukocytes. For example, a clinical study investigating the presence of LR-PRP on wound closure in oral and maxillofacial surgery suggested that in this context, the patients that received LR-PRP healed faster when compared to placebo. The initial inflammation was less pronounced in the LR-PRP group and subsided after 14 days in both groups. These results suggest that the presence of leukocytes in some contexts is beneficial to healing. (2)

What kind of PRP does the HARVEST system produce?

Unlike other systems, HARVEST PRP is a two-dimensional system, equipped with the ability to customize the PRP sample based on clinical indications. The HARVEST system initially produces PRP samples that are considered Leukocyte-rich (100% above baseline). Other one-dimensional systems that do not retain the leukocyte-rich fraction do not have the possibility of treating the indications that benefit from a high leukocyte content. In other words, once they’re gone, there’s no way of returning them to the sample when needed. For cases that require an LR-PRP, the HARVEST system produces a high-quality product.

However, one of the assets of the HARVEST PRP system is the level of customization possible with our PRP Clear product. Clear PRP enables efficient removal of 99% of the red cell content from PRP preparations while maintaining a high concentration of platelets in one additional processing step that takes less than 5 minutes. This allows for the second dimension of PRP treatment for situations that benefit from a PRP free-from leukocytes.

The presence or absence of leukocytes is not a one-size-fits-all solution. Rather, they may be used strategically to improve treatment where the clinical use demands. For example, it is possible that leukocyte presence is beneficial in soft-tissue contexts, whereas intra-articular contexts benefit from leukocyte-poor PRP. It is therefore imperative to do more research in order to understand exactly when and where the inclusion/exclusion of leukocytes from PRP is most beneficial. To achieve this, more research specifically comparing the leukocyte concentration in a variety of contexts is essential. Until then, we can rely on the knowledge, training and experience of the medical professionals who utilize PRP in their practice and the HARVEST system to produce both LR and LP-PRP when needed.

 

References:

(1) Riboh, J. C., Saltzman, B. M., Yanke, A. B., Fortier, L. & Cole, B. J. Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis. The American Journal of Sports Medicine 44, 792–800 (2016).

(2) Cieślik-Bielecka, A., Glik, J., Skowroński, R. & Bielecki, T. Benefit of Leukocyte- and Platelet-Rich Plasma in Operative Wound Closure in Oral and Maxillofacial Surgery. BioMed Research International 2016, 1–5 (2016).