No abstract

Platelet-rich plasma (PRP) has emerged as a significant therapy used in medical conditions with heterogeneous results. There are some important classifications to try to standardize the PRP procedure. The aim of this report is to describe PRP contents studying celular and molecular components, and also propose a new classification for PRP. The main focus is on mononuclear cells, which comprise progenitor cells and monocytes. In addition, there are important variables related to PRP application incorporated in this study, which are the harvest method, activation, red blood cells, number of spins, image guidance, leukocytes number and light activation. The other focus is the discussion about progenitor cells presence on peripherial blood which are interesting due to neovasculogenesis and proliferation. The function of monocytes (in tissue-macrophages) are discussed here and also its plasticity, a potential property for regenerative medicine treatments.

Knee osteoarthritis is a major painful and debilitating orthopaedic disease affecting a large number of adult individuals on a global scale. Over the years, this severe condition has been widely studied and while many alternatives have been utilized, platelet-rich plasma (PRP) remains one of the most popular solutions among researchers and clinicians alike. While there are different formulations and techniques involved in the preparation of PRP, produced either manually or via the use of commercial kits, the presence of leukocytes in a PRP mixture is a factor that raises concern due to their well-known proinflammatory activity. Although it is reasonable to worry about this, it should be taken into consideration that in order for the healing process to occur, the inflammatory phase is necessary. Leukocytes present in the inflammatory phase release both pro and anti-inflammatory molecules and, when combined with activated platelets, their potential increases. Additionally, due to the macrophage's plasticity to switch from the subtype 1 to subtype 2, it is suggested that the inclusion of the components from the buffy coat layer in a PRP mixture, classifying it as leukocyte-rich platelet-rich plasma or L-PRP, may provide benefits instead of detriments, from a standpoint of the regenerative potential of PRP.

The mechanism of action of Platelet Rich Plasma (PRP) is thought to be related to the biomolecules present in a-granules. However, for the healing process to occur, an inflammatory phase is also deemed necessary. Leukocytes present in the inflammatory phase release both pro-and anti-inflammatory molecules. The latter may play an important role in the process of "inflammatory regeneration". Thus, we propose that in the context of healing, both platelets and leukocytes play an important role, specifically due to the macrophage's plasticity to switch from the M1 to M2 fraction. Therefore, we propose that PRP products derived from the buffy coat may be more beneficial than detrimental from a standpoint of the regenerative potential of PRP.

Metabolic syndrome (MS) has become one of the top major health burdens for over three decades not only due to its effects on cardiovascular health but also its implications in orthopedics. Extensive research has shown that MS is tightly linked to osteoarthritis and inflammation, a process which appears to primarily occur in the subchondral bone via the incidence of bone-marrow lesions (BMLs). Numerous studies identify obesity, dyslipidemia, insulin resistance and hypertension as the top metabolic risk factors, the so-called "deadly quartet". These factors are responsible for the disruptive physiological processes that culminate in detrimental alterations within the subchondral bone, cartilage damage and, overall, the predominant pro-inflammatory joint microenvironment. Although it has long been thought that osteoarthritis was limited to the cartilage component of the joint, other studies indicate that the disease may originate from the harmful alterations that occur primarily in the subchondral bone, especially via means of vascular pathology. Since metabolic risk factors are manageable to a certain extent, it is therefore possible to decelerate the progression of OA and mitigate its devastating effects on the subchondral bone and subsequent articular cartilage damage. Methods: Literature was reviewed using PubMed and Google Scholar in order to find a correlation between metabolic syndrome and osteoarthritic progression. The investigation included a combination of nomenclature such as: "metabolic syndrome", "obesity", "insulin resistance", "hypertension", "dyslipidemia", "low-grade systemic inflammation", "osteoarthritis", "subchondral bone", "cartilage" and "inflammatory biomarkers". Conclusion: Based on several studies, there seems to be a significant association between The Deadly Quartet (metabolic syndrome), dysregulation of both pro-and anti-inflammatory biomarkers, and osteoarthritic progression arising from unbridled systemic inflammation.

Aims: To compare levels and activity of the growth factors between fresh and lyophilized platelet-rich plasma (PRP). Methods: Analysis of platelet concentration using fibroblast and human umbilical vein endothelial cell cultures were compared between fresh and lyophilized PRP obtained from peripheral blood. Results: After lyophilization, 54% of platelets were intact whereas the fresh showed no aggregation with agonists (levels under 20%). The concentration of growth factors (VEGF, EGF, TGF-β and PDGF) in both products were similar. Fresh and lyophilized PRPs induced proliferation in the fibroblasts at 24 h (0.303 vs 0.300, respectively). Conclusion: Lyophilized PRP appears to be an alternative to fresh PRP and the results evidenced the role of growth factors as a key element in the activity of this product.

This study aims at evaluating the clinical effects of Platelet Rich Plasma (PRP) and Hyaluronic Acid (HA) as individual treatments for mild to moderate Osteoarthritis (OA) and it also examines 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 multi-center, 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 intra-articular 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. the extracellular matrix [4] , providing increased joint lubrication. Studies have demonstrated that HA has positive therapeutic efficacy for knee osteoarthritis with initial efficacy at 4 weeks, and peak effectiveness at 8 weeks which lasts for up to 6 months [5]. When compared to continuous oral NSAIDS or other anti-inflammatory medications, HA has illustrated comparable, if not greater, therapeutic effects on knee OA with a better safety profile [5,6]. Autologous platelet rich plasma (PRP) has also emerged as an alternative in the context of injectable treatment for OA. PRP is comprised of a potent cellular milieu containing platelet concentrations above baseline, as well as an undifferentiated mixture of anti-inflammatory, pro-inflammatory, anabolic and catabolic mediators in an attempt to stimulate a supra-physiologic response and elicit the body's natur...

Coagulation activation is a prominent feature of SARS-CoV-2 infection (COVID-19). Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We thus sought to assess activation of the contact system and intrinsic pathway in subjects with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by ELISA, while extrinsic pathway activation was assessed by microvesicle tissue factor-mediated factor Xa generation (MVTF). Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and thirty age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 were demonstrated by increased plasma levels of factor XIIa:C1 esterase inhibitor (FXIIa:C1), kallikrein:C1, FXIa:C1, FXIa:1antitrypsin, and FIXa:antithrombin (FIXa:AT). MVTF levels were also increased in COVID-19 subjects. Since FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both the contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically the total length of hospitalization, length of ICU stay, and extent of lung CT changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.