In vitro study of the role of thrombin in platelet rich plasma (PRP) preparation: utility for gel formation and impact in growth factors release

Introduction: The use of PRP has been studied for different fields, with promising results in regenerative medicine. Until now, there is no study in the literature evaluating thrombin levels in serum, used as autologous thrombin preparation. Therefore, in the present study we evaluated the role played by different thrombin concentrations in PRP and the impact in the release of growth factors. Also, different activators for PRP gel formation were evaluated. Methods: Thrombin levels were measured in different autologous preparations: serum, L-PRP (PRP rich in leukocytes) and T-PRP (thrombin produced through PRP added calcium gluconate). L-PRP was prepared according to the literature, with platelets and leukocytes being quantified. The effect of autologous thrombin associated or not with calcium in PRP gel was determined by measuring the time of gel formation. The relationship between thrombin concentration and release of growth factors was determined by growth factors (PDGF-AA, VEGF and EGF) multiplex analysis. Results: A similar concentration of thrombin was observed in serum, L-PRP and T-PRP (8.13 nM, 8.63 nM and 7.56 nM, respectively) with a high variation between individuals (CV%: 35.07, 43 and 58.42, respectively). T-PRP and serum with calcium chloride showed similar results in time to promote gel formation. The increase of thrombin concentrations (2.66, 8 and 24 nM) did not promote an increase in growth factor release. Conclusions: The technique of using serum as a thrombin source proved to be the most efficient and reproducible for promoting PRP gel formation, with some advantages when compared to other activation methods, as this technique is easier and quicker with no need of consuming part of PRP. Noteworthy, PRP activation using different thrombin concentrations did not promote a higher release of growth factors, appearing not to be necessary when PRP is used as a suspension

Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee

Objective: This study aims to evaluate the clinical effects of Platelet Rich Plasma (PRP) and Hyaluronic Acid (HA) as individual treatments for mild to moderate Osteoarthritis (OA), and also examine the potential synergistic effects of PRP in combination with HA. Research continues to emerge examining the potential therapeutic efficacy of HA and PRP as autologous injectable treatments for joint arthritis. However, there is a paucity of research investigating the effects of combining HA and PRP on pain and functional status in patients with OA. Design: In this multicenter, randomized, controlled, double blind, prospective trial, 105 patients with mild to moderate knee osteoarthritis who met the study criteria were randomly allocated to one of three interventions: HA (n=36), PRP (n=36), or HA+PRP (n=33). Each patient received 3 intaarticular knee injections of their assigned substance, with 2 week intervals between each injection. Clinical outcomes were evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analogue Scale (VAS) questionnaire at baseline and after 1,3,6, and 12 months. Results: The study showed that the PRP group have significant reduction in VAS scores at 1 (p= 0.003), 3 (p= 0.0001), 6 (p= 0.0001) and 12 (p= 0.000) months when compared to HA. In addition, the PRP group illustrated greater improvement in WOMAC physical activity scale at 12 months (p= 0.008) when compared to the HA group. Combining HA and PRP resulted in a significant decreases in pain (p=0.0001) and functional limitation (p=0.0001) when compared to HA alone at 1 year post treatment; and significantly increased physical function at 1 (p=0.0004) and 3 (p=.011) months when compared to PRP alone. Conclusion: The findings of the study support the use of autologous PRP as an effective treatment of mild to moderate knee osteoarthritis. It also shows that the combination of HA and PRP resulted to better outcomes than HA alone up to 1 year and PRP alone up to 3 months. Furthermore, the results suggest that combination of PRP and HA could potentially provide better functional outcomes in the first 30 days after treatment with both PRP and HA alone

Platelet-rich plasma (PRP) therapy for knee arthritis: a feasibility study in primary care

Background: Platelet-rich plasma (PRP) is a concentrate of autologous blood growth factors which has been shown to provide some symptomatic relief in early osteoarthritis (OA) of the knee. The objective of this study was to test the feasibility and efficacy potential of platelet rich plasma (PRP) in primary care. Methods: Feasibility study to assess safety of the intervention procedures and assess primary and secondary outcome measures. Consecutive patients presenting with symptomatic knee OA were recruited in a primary care setting in Ireland. All participants received three injections of PRP 4 weeks apart. The following self-reported clinical outcomes were evaluated before and after therapy (4 months): Pain and disability (ICOAP questionnaire); health utility (EUROQol); adverse events; patient satisfaction and goal-orientated outcomes. Results: Seventeen potential patients were identified of whom 14 were eligible to participate. Twelve consented and completed the intervention and all outcome measures. There were no losses to follow-up. One patient reported pain and stiffness for 2 days after the first injection but did complete the study. No growth was detected from nine consecutive samples sent for microbiology analysis. Changes in constant, intermittent and total pain scores were reported; pain fully resolved in two patients. In addition, health utility, patient satisfaction and goal-orientated outcomes also demonstrated improvement. Conclusions: Platelet-rich plasma therapy is a simple and minimally invasive intervention which is feasible to deliver in primary care to treat osteoarthritis of the knee joint. Well-designed randomised controlled trials are needed to measure outcomes, durability of effect and cost effectiveness