DEPA classification: a proposal for standardising PRP use and a retrospective application of available devices

Introduction

The potential role of platelet-rich plasma (PRP) in enhancing the healing of bone, muscle, ligaments and tendons, has resulted in multiple applications within virtually all the orthopaedic subspecialties. Several uncontrolled studies have shown benefit for a variety of indications1 ,2 and more recently controlled studies have demonstrated less-favourable results.3 ,4 A common point between these studies is the lack of biological characterisation of the content of the PRP used as therapy product.

Marx,5 first described PRP as a suspension of platelets in plasma, with the platelet concentration being higher than the concentration in the original blood collected. Dohan Ehrenfest et al6 ,7 introduced the notion of leucocyte-rich PRP (LR-PRP) characterised by a leucocyte concentration higher than the whole blood baseline leucocyte level, whereas leucocyte-poor PRP (LP-PRP) or Pure PRP includes a leucocyte concentration lower than in whole blood. Accordingly, the platelet increase factor, corresponding to the platelet concentration increase in PRP compared with whole blood, is the most frequently described parameter in both scientific publications and manufacturer's promotional literature, and is thought to primarily influence the PRP efficacy. A platelet concentration in PRP below whole blood baseline level may not provide sufficient cellular response8 and platelet concentrations higher than six-fold compared with platelet whole blood baseline level may have an inhibitory effect on healing.9

Historical definitions from Marx and Dohan associated with the described influence of platelet concentrations in PRP efficacy have given rise to PRP classification10 ,11 systems, but none of these classifications have been widely adopted.

In fact, the platelet increase factor in PRP compared with whole blood is directly linked to the volume of PRP obtained; these two factors should not be interpreted alone. We previously introduced the notion of platelet doses corresponding to the quantity of platelets and growth factors (GFs) hypothetically delivered at the injection site, as we previously described a positive correlation between platelet dose and quantity of GF.12 Based on the field of haematology, which first used cells as a therapy, cell doses are the most relevant parameter to assess clinical efficacy, and cell-dose effects are now clearly established.13 Otherwise, the current classifications of PRP do not take into account the red blood cell (RBC) content in PRP, which could represent a source of released reactive oxygen species that could also be clinically detrimental. That is why the global composition of PRP in platelets, leucocytes and RBCs, should be documented to analyse the clinical impact. Finally, to compare the efficiency of the PRP preparation device, the platelet recovery rate could be provided, allowing assessment of the platelet loss due to the process, although this parameter is not directly linked to clinical efficacy.

The purpose of this article is to introduce a standardised classification based on biological parameters classically used in the Cell Therapy field. This classification has been retrospectively applied to four publications comparing and describing biological characteristics of PRP devices available in Europe.

Discussion

Several authors have demonstrated substantial differences in the content of platelet concentrates produced by various automated and manual protocols described in the literature.12 ,14–16 To face this issue, classifications recently appeared and are focused on two parameters: the increased platelet and leucocyte factor compared with whole blood. This presents some drawbacks: (1) the volume is not taken into account, directly influencing the concentration. As an example, Plateltex, described by Kaux et al, delivered an increased platelet factor of only 3.43, because a very small final volume of 0.34 mL was obtained. The corresponded dose injected was only 0.23 billion. (2) They do not assess the efficacy of the process allowing the comparison of one preparation with another and (3) they do not take into account PRP as a global product containing not only platelets and leucocytes, but also RBCs. The major challenge of PRP preparation is to remove RBCs and reverse the initial composition of blood (95% of RBCs), and this is sometimes not achieved at all—an example is the GPS II device, globally composed of 93.9% RBCs.

Through the introduction of new parameters (dose of injected platelets, recovery rate in platelets and the relative composition of PRP), the DEPA classification circumvents these issues. Thus, a PRP preparation reaching an ‘AAA’ DEPA score will mean that a very high dose of platelets was injected (>5 billion) with little contamination from RBCs, and that the preparation was optimal with minor loss of platelets from blood. A limitation to this ‘ABCD’ scoring system is that an A score will often be evaluated as better than a B, C or D score, whereas the impact of platelet dose and purity remains unknown.

It should be noted that devices corresponding to a very high dose of injected platelets will necessarily correspond to an important collected volume (minimum 30 mL). It will be also be difficult to reach a high dose of platelets for indications necessitating very small volume (ie, intratendinous requirements) and could represent a challenge for future development to manufacturers of PRP production devices.

The clinical relevance of the DEPA classification remains to be evaluated in clinical studies and review of clinical trials. This point is still limited by the absence of characterisation in the majority of clinical trials. A few randomised clinical trials17 ,18 performed a characterisation of the injected PRP, but these were restricted to the publication of platelet concentration in PRP, and did not broach the subject of the clinical impact of RBCs and leucocytes in PRP. Future clinical studies should describe the reported volumes, dose of platelets as well as the overall composition of whole blood and PRP, and the number of applications of PRP, in which the DEPA classification could be considered as a tool (1) to determine the clinical impact of the huge variability of PRP composition and (2) to assess the quality of PRP production.