Despite its wide clinical application, only a few reports have documented results for PRP in the treatment of knee degenerative lesions in the literature [24–34].
In 2008, Sanchez et al. published a retrospective observational study involving 60 patients , 30 treated with knee intra-articular injections of PRGF and 30 with injections of HA. Patients from both groups underwent 3 weekly injections and were evaluated basally and at 5 weeks of follow-up using the WOMAC score. Results were encouraging, even though the short follow-up is a weak point of the study. In 2010, Sampson et al. published a study  on 14 patients with clinical and radiographic signs of OA and previous unsuccessful conservative management (12 men and 2 women), who received 3 PRP injections 1 month apart. Evaluation was carried out up to 52 weeks using the “Brittberg-Peterson Visual Analog Pain, Activities and expectation Score”, VAS for pain, and KOOS Score: the authors found a statistically significant improvement in the scores examined, with a reduction in pain both at rest and during physical activity and, at 1 year of follow-up, 8 patients were still completely satisfied with the treatment received. In the same year, Wang-Saegusa et al.  published a prospective study on 261 patients with uni- or bilateral knee OA, symptomatic for more than 3 months. Patients received 3 injections 2 weeks apart, and clinical evaluation was conducted at 6 months using the WOMAC score, VAS, Lequesne Index and SF-36. Statistical analysis revealed significant results with an improvement in all the scores adopted. Despite the high number of patients evaluated, the absence of a control group is a limiting factor in the conclusions of this study. Napolitano et al.  treated 27 patients, either affected by simple chondropathy or initial OA, with 3 injections of 5 ml PRP performed one week apart from each other, and evaluated them up to 6 months with NRS scale for pain and WOMAC score. Significant results were obtained after treatment without occurrence of adverse events. The group led by Gobbi  published a preliminary report on a group of 50 active patients treated with 2 PRP injections one month apart, showing good results at up to 1 year of follow-up both in patients who had or had not undergone previous operative intervention for cartilage lesions. A study by Spakova et al.  compared the efficacy of PRP versus viscosupplementation on a cohort of 120 patients divided into two treatment groups and evaluated through the WOMAC score and a pain numeric rating scale. At 3 and 6 months of follow-up an increase in the clinical score was observed in both groups with statistically superior results in PRP group.
The present authors previously performed studies to evaluate this clinical application of PRP, and recorded safety and interesting findings [31–34]: the first one was a prospective study published in 2009  on 91 patients (for a total of 115 knees) treated with three injections of PRP (1 every 3 weeks). Patients underwent clinical evaluation at basal level and at 2, 6, and 12 months of follow-up. Eighty percent of the patients treated expressed satisfaction with the treatment received. The clinical outcome revealed a statistically relevant improvement in all the variables considered just 2 months after the end of treatment. These results were later confirmed at 6 months of follow-up, whereas a tendency to worsen was reported after 6 to 12 months of follow-up. Some influencing factors were detected: in particular it was observed that young male patients were the best responding group, especially in case of simple chondropathy without signs of OA. A later study  evaluating the same patients at 24 months of follow-up confirmed this trend with a further decrease in the clinical outcome, thus concluding that intra-articular therapy with PRP is time dependent with an average duration of 9 months and better and longer lasting results are achieved in younger patients with lower levels of joint degeneration. In another multi-center study , the clinical effectiveness of PRP was compared to low molecular weight HA (LWHA) and high molecular weight HA (HWHA). Three homogeneous groups of patients were respectively treated with 3 injections of PRP, LWHA, or HWHA. The results highlighted a better performance for PRP group at 6 months of follow-up. In particular, subgroup analysis (chondropathy vs early vs severe OA) revealed that in the chondropathy group PRP gave markedly better results than HA at 6 months of follow-up, whereas in the early OA group the gap in favor of PRP was reduced and in the severe OA subgroup no difference in clinical outcome was observed between treatments. Furthermore, patients under 50 years old have a greater chance to benefit from this biological approach with this GFs supplementation. Finally, the present authors recently published a comparative study between PRP with or without leukocytes used to treat 144 patients affected by knee cartilage pathology, and showed comparable positive clinical effects with both treatments, with PRP-leukocyte group suffering from more swelling and pain reaction after the injections .
Despite the increasing number of reports, there is a lack of high level studies: only one randomized clinical trial has been recently published . This is a multicenter study led by Sanchez who compared at short-term follow-up PRGF (a single spinning procedure giving a leukocyte free PRP with a low platelet concentration) with HA administered on a weekly basis for the treatment of symptomatic knee OA. With these treatments, adverse events were mild and evenly distributed between the PRP and HA groups. The rate of response to PRGF was higher in all outcome measures, although no significant differences were found; however, compared with the rate of response to HA, the rate of response to PRGF (primary outcome measure) was 14.1 percentage points significantly higher.
In the present authors’ studies a different platelet concentrate was used, obtained through a double-spinning procedure which provides many platelets but also leukocytes. Cellularity is one of the most debated aspects when evaluating PRP properties and the results obtained with its application. In fact, not only platelets but also leukocytes, monocytes, macrophages, and mast cells are contained in many platelet concentrates. Some authors define PRP as only platelets and attribute better results to leucocyte depletion, because of the deleterious effects of proteases and reactive oxygen released from white cells; others consider them as a source of important cytokines and enzymes, that may be important also for the prevention of infections, and report that PRP significantly inhibits the growth of Staphylococcus Aureus and Escherichia Coli .
This is the first double-blind randomized clinical trial available in the literature on this kind of double-spinning high concentrate leukocyte PRP, and more in general it is also the first randomized trial with such a high number of patients evaluated at 12 months of follow-up. For these reasons, despite being preliminary with respect to the objective of the entire study, the present results on the evaluated cohorts of patients are already significant representing up to now one of the highest available evidence on PRP use for knee degenerative pathology, and already give us some indications on the potential of this biological approach.
The analysis of the results obtained with this randomized trial has already underlined important aspects. The safety and the significant clinical improvement of this procedure were confirmed. A higher pain reaction after PRP injection was found, probably due to the leukocyte content of our platelet concentrate, but without jeopardizing clinical results up to 1 year follow-up. Conversely to what was shown by the current literature of comparative studies [25, 30, 33, 35], PRP did not offer better results compared to HA in this series. However, it has to be emphasized that the average age of the enrolled patients was higher than those of other studies and the present authors previously observed a worse outcome for older patients treated with PRP [31, 32], and a sub-analysis of different patient categories showed some interesting findings. In fact, a tendency towards better results at both 6 and 12 months of follow-up in favor of PRP treatment was seen for the less degenerated cases. It is important to consider that this is a subanalysis, and therefore the sample size is smaller and less supportive of the preliminary results found. The completion of the entire planned 192 patient evaluation will confirm whether this trend will reach a statistical and clinical significance, thus demonstrating a clear indication for this biological treatment approach, as well as the potential of the double spinning high concentrate leukocyte PRP with respect to the single spinning low concentrate leukocyte free PRP that recently showed better results with respect to HA .
For now, the results of this trial suggest a possible effect of this platelet concentrate on the treatment of knee degenerative pathology, with a clinical subjective improvement but not significantly better results with respect to HA; a tendency towards better improvement only in patients affected by earlier degrees of knee degeneration was observed, thus suggesting that the clinical application of PRP should be mainly restricted to this patient subgroup, whereas the indication of this treatment for high grade degeneration is lower. Due to the not significantly better results with respect to HA, PRP cannot be considered as the first line of treatment for knee OA and should be therefore restricted to patients who do not benefit from other conservative or injective treatments such as HA or, if used as first line treatment, it should be mainly targeted to patients affected only by early degrees of knee cartilage degeneration.