Platelet-derived Microparticles Research Articles

Association between arginase-containing platelet-derived microparticles and altered plasma arginine metabolism in polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine and metabolic disease associated with insulin resistance and increased risk of cardiovascular diseases. However, a biomarker for potential cardiovascular disease in PCOS patients is not available. Materials and MethodsTwenty-two patients with PCOS and 22 healthy controls were included in the present study and amino acid profiling was performed on fasting plasma samples. Circulating microparticles were characterized by FACS analysis and complemented with enzyme activity assays. ResultsThe ratio of ornithine to arginine was significantly increased in plasma form PCOS patients and was associated with a significant increase in plasma arginase levels and activity. Platelet-derived microparticles were identified to be the main sources of the increased plasma arginase activity. ConclusionsIncreased levels of arginase-bearing platelet-derived microparticles contribute to the alteration of the arginine metabolism in patients with polycystic ovary syndrome. Moreover, ornithine and arginine levels represent early biomarkers of potential cardiovascular disease in PCOS patients.

Platelet-Derived Microparticles Increase Expression of hTERT in Umbilical Cord Mesenchymal Stem Cells

Introduction: Mesenchymal stem cells (MSCs) are widely studied due to their self- renewal potential and capacity to differentiate into multiple tissues. However, they have a limited life span of several divisions in vitro, which alters various cellular characteristics and reduces their application. Aim: We evaluated the effect of platelet-derived microparticles on gene expression of hTERT, one of the main factors involved in aging and cell longevity. Materials and methods: Umbilical cord MSCs were used for this study. Cells were characterized by evaluating morphology via inverted microscope and identifying associated surface markers using flow cytometry. Platelet-derived microparticles were prepared by centrifuging platelet bags at varying speeds, and their concen- trations were determined by Bradford assay. At 30% confluency, MSCs were treated with 50 μg/mL of microparticles for five days. Then, RNA was extracted and cDNA was synthesized. Quantitative expression of hTERT was assessed using real-time polymerase chain reaction (PCR). Results: Fibroblast-like cells were isolated from umbilical cord tissue and MSCs were identified by the presence of mesenchymal surface markers via flow cytometry. Real- time PCR showed that gene expression of hTERT increased by more than three times when treated with platelet-derived microparticles, in comparison to expression of the control group. Conclusion: We concluded that platelet-derived microparticles may be a potentially safe and effective method to increase hTERT gene expression in MSCs, ultimately prolonging their life span in vitro.

Platelet communication with the vascular wall: role of platelet-derived microparticles and non-coding RNAs.

Platelets play an important role in vascular homeostasis through their interaction with circulating blood cells as well as the vascular wall. Platelet-mediated communication with other cells can take the form of direct cell-cell interactions via membrane receptors or indirectly through the release of different soluble factors stored in their granules as well as through the release of microparticles. The latter carry different proteins and RNAs which are transferred to the target cells. The aim of this review is to discuss the role of platelet-derived factors, adhesion molecules as well as RNAs as mediators of the cross-talk between platelets and the vessel wall.

Nanofiltration of extracellular vesicles from human plasma & their on-chip qualification and quantification with a NanoBioAnalytical platform

One complication of plasma transfusion is non-immune transfusion related acute lung injury (TRALI), which is associated with the formation of neutrophil extracellular traps (NETs) resulting from polymorphonuclear neutrophil (PMN) activation. Activated platelets have recently been shown to trigger NETs formation. We hypothesized that (a) NETs could be promoted by platelet derived microparticles (PMPs) and (b) that 75 nm-nanofiltration of plasma, by removing parts of PMPs, could avoid NETs formation. To better characterize the large spectrum of size and concentration of PMPs in complex media, we combined conventional approaches (Flow Cytometry, TRPS) with an original nanobioanalytical (NBA) platform based on Surface Plasmon Resonance imaging (SPRi) and Atomic Force Microscopy (AFM) techniques. We will demonstrate that this new analytic solution allows:•a label-free follow-up of PMPs capture in real time from various complex media,•a multiplex detection of different PMPs subpopulations,•the determination of the size and morphology of captured PMPs in a range of 20 nm to 1 μm their proteomic studies.We expect that such platform will contribute to (i) a better understanding of the physiological function of Evs subpopulations, (ii) the discovery of specific biomarkers and (iii) to therapeutic follow-up.

Examination of biomarker expressions in sepsis-related DIC patients.

BackgroundDisseminated avascular coagulation (DIC) is the main cause of death among patients with sepsis. In particular, low platelet count is predictive of poor outcome. However, the significance of platelet activation in patients with sepsis-related DIC is poorly understood. To determine the characteristics of platelet-related abnormality in patients with sepsis-related DIC, we assessed the expression levels of several biomarkers.MethodsPlasma levels of biomarkers, including cytokines, chemokines, soluble selectins, platelet-derived microparticles (PDMPs), soluble vascular adhesion molecule 1, and high mobility group box protein 1 were measured by enzyme-linked immunosorbent assay at baseline and after 4, 7, 14, and 21 days of DIC treatment.ResultsDifferences in platelet activation and in the elevation of activated platelet-related PDMPs and of soluble P-selectin were seen between patients suffering from sepsis and hematologic malignancy with DIC. In addition, the elevation of interleukin (IL)-6 and thrombopoietin (TPO) was significant in sepsis patients with DIC. Furthermore, IL-6 and TPO promoted platelet activation in vitro.ConclusionAssessment of PDMPs, sP-selectin, IL-6, and TPO may be beneficial in the primary prevention of multi-organ failure in sepsis patients with DIC.

Platelet-Derived Microparticles: A New Index of Monitoring Platelet Activation and Inflammation in Kawasaki Disease.

To investigate the dynamic changes of platelet-derived microparticles (PDMP) in Kawasaki disease (KD) and its clinical significance and to study its relationship with intravenous immunoglobulin (IVIG) resistance, inflammatory indicators and aspirin treatment in children with KD. Twenty children with KD were enrolled as the experimental group, while 20 age- and gender-matched children with common febrile disease were included in the control group. Blood samples were drawn before and 7-10 d after IVIG infusion and thereafter at 1, 2, and 3 mo after the onset of KD to estimate the PDMP concentrations by enzyme linked immunosorbent assay (ELISA). C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and cytokines [Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), and Soluble interleukin-2 (sIL-2R)] were also measured. The level of PDMP in KD children before IVIG was significantly higher than that in controls (P < 0.0001). The PDMP level in KD children decreased significantly at 7 to 10 d after IVIG (P < 0.0001) and then decreased to the lowest level in the course of 1 to 2 mo. Some children's PDMP level rebounded in the course of 3 mo (P = 0.047). In addition, the mean level of PDMP in IVIG-resistant children was higher than that in IVIG-effective children; however, there was no significant difference between the two groups (P = 0.1945). Furthermore, PDMP was positively correlated with hs-CRP, IL-6, and sIL-2R levels, but no correlation was observed with ESR, PCT, and TNF-α levels. PDMP can be used as an index to monitor inflammation in children at the acute stage of KD. And the duration of platelet activation in KD is individualized.

Surface modification of metallic materials designed for a new generation of artificial heart valves.

The main goal of this work was to develop haemocompatibile thin film materials dedicated to novel flexible mechanical heart valves intended for pulsatile ventricle assist devices. The studies performed have led to the selection of a material for the surface modification of the metallic scaffold. Haemocompatible, biofunctional, ultra-elastic, thin carbon-based coatings were proposed. The surface was designed to eliminate thrombogenic and microbial construction by a reduction in turbulence and sufficient washing of the biofunctional-adapted surfaces, thus allowing for extended use for temporary heart support. The article presents the influence of the mechanical properties of coatings and their influence on the haemocompatibility. In this study, we investigated a simplified model of the whole blood shear stress based on a cone and plate rotational viscometer. Several indices of platelet activation were analysed, including platelet and granulocyte-platelet aggregates, platelet activation markers and platelet-derived microparticles. The shear stress induced a platelet aggregate count in the range from 2% to 30% of the CD61 positive cells. For polyurethane (PU), the average value of platelet aggregates was on the level of 7%. The analyses have demonstrated that the cytometric methods of the direct determination of platelet-derived microparticles in plasma are reproducible and reliable. Considering the generation of microparticles on the tested coatings under hydrodynamic conditions, the best properties were observed for the coating a-C:H,N. The results indicate that a-C:H-based coatings with the thickness of 110 nm do not induce an immune response and do not influence the origin of platelet microparticle formation; thus, these type of coatings are the most promising for the parts which are planned to withstand blood contact under the high value of shear stress.

Platelet-derived microparticles induce the formation of neutrophil extracellular traps

Platelet-derived microparticles induce the formation of neutrophil extracellular traps

Platelets and extracellular vesicles in cancer: diagnostic and therapeutic implications

Several pieces of evidence support the role of activated platelets in the development of the chronic inflammation-related diseases, such as atherothrombosis and cancer, mainly via the release of soluble factors and microparticles (MPs). Platelets and MPs contain a repertoire of proteins and genetic material (i.e., mRNAs and microRNAs) which may be influenced by the clinical condition of the individuals. In fact, platelets are capable of up-taking proteins and genetic material during their lifespan. Moreover, the content of platelet-derived MPs can be delivered to other cells, including stromal, immune, epithelial, and cancer cells, to change their phenotype and functions, thus contributing to cancer promotion and its metastasization. Platelets and MPs can play an indirect role in the metastatic process by helping malignant cells to escape from immunological surveillance. Furthermore, platelets and their derived MPs represent a potential source for blood biomarker development in oncology. This review provides an updated overview of the roles played by platelets and MPs in cancer and metastasis formation. The possible analysis of platelet and MP molecular signatures for the detection of cancer and monitoring of anticancer treatments is discussed. Finally, the potential use of MPs as vectors for drug delivery systems to cancer cells is put forward.

Platelets activated by the anti-\u03b22GPI/\u03b22GPI complex release microRNAs to inhibit migration and tube formation of human umbilical vein endothelial cells

BackgroundPatients with anti-β2GPI antibodies display significantly higher platelet activation/aggregation and vascular endothelial cell damage. The mechanism underlying the correlation between platelet activation, vascular endothelial cell dysfunctions and anti-β2GPI antibodies remains unknown.MethodsIn this study, we derived miR-96 and -26a from platelets activated by the anti-β2GPI/β2GPI complex and explored their role in modulating human umbilical vein endothelial cell (HUVEC) migration and tube formation.ResultsAnti-β2GPI/β2GPI complex induces the release of platelet-derived microparticles (p-MPs). The amounts of miR-96 and -26a in these p-MPs were also higher than for the control group. Co-incubation of HUVECs with p-MPs resulted in the transfer of miR-96 and -26a into HUVECs, where they inhibited migration and tube formation. The targeting role of these miRNAs was further validated by directly downregulating targeted selectin-P (SELP) and platelet-derived growth factor receptor alpha (PDGFRA) via luciferase activity assay.ConclusionOur study suggests that miR-96 and -26a in p-MPs can inhibit HUVEC behavior by targeting SELP and PDGFRA.

Circulating microparticles in patients after ischemic stroke: a systematic review and meta-analysis.

Microparticles (MPs), a class of cell products with biological activities, have been found to participate in a series of vascular activities. The aim of this article is to investigate the changes in the concentrations of MPs after ischemic stroke by meta-analysis. According to pre-established criteria, a strict screening of articles was performed through the Medline and Embase databases. Subsequently, the included studies were subjected to quality assessment and data extraction. Finally, a meta-analysis was performed on seven major outcomes from 985 noncerebrovascular disease controls and 988 ischemic stroke patients. The pooled concentrations of total MPs (TMPs), endotheliocyte-derived MPs (EMPs), platelet-derived MPs (PMPs), erythrocyte-derived MPs (RMPs), leukocyte-derived MPs (LMPs), and monocyte-derived MPs (MMPs) were significantly increased in the ischemic stroke patients compared to the noncerebrovascular disease controls, with the results as follows: TMPs [standardized mean difference (SMD), 1.12; 95% confidence interval (CI), 0.26-1.97; p=0.01], EMPs (SMD, 0.90; 95% CI, 0.67-1.13; p<0.00001), PMPs (SMD, 1.15; 95% CI, 0.69-1.60; p<0.00001), RMPs (SMD, 1.14; 95% CI, 0.57-1.71; p<0.0001), LMPs (SMD, 1.42; 95% CI, 0.74-2.10; p<0.0001), and MMPs (SMD, 1.09; 95% CI, 0.59-1.60; p<0.0001). However, the pooled concentration of lymphocyte-derived MPs (LyMPs) demonstrated no significant difference between the patients and the controls (SMD, 0.22; 95% CI, -0.19 to 0.63; p=0.29). The available data indicated that the circulating MPs, except for LyMPs, play an important role in the development and prognosis of ischemic stroke.

Influence of Diabetes on Circulating Apoptotic Microparticles in Patients with Chronic Hepatitis C.

Type 2 diabetes mellitus (DM) frequently occurs in patients with chronic hepatitis C (CHC) and is associated with atherosclerosis, in which circulating microparticles (MPs) play an important role. We asked whether the presence of DM affects endothelial-derived (EMPs) and platelet-derived microparticles (PMPs) levels; and whether MPs levels associate with biomarkers of inflammation and oxidative stress in patients with CHC. Overall, 136 patients were enrolled in the study, 86 CHC patients (41 with DM with moderate glycemic control), 20 outpatients with DM and 30 controls. Circulating MPs were phenotyped by flow cytometry. When the MPs levels were analyzed individually in CHC patients, there was a positive association of plasma apoptotic MPs with oxidative stress markers. We report a hitherto undescribed relationship between diabetes prevalence and apoptotic MPs-associated inflammation in patients with CHC. The presence of apoptotic MPs in the plasma of CHC patients, with increased levels being found in patients with DM and moderate glycemic control was herein demonstrated. The simultaneous monitoring of plasma apoptotic MPs, oxidative stress markers and inflammatory biomarkers can be helpful for the cardiovascular disease control in diabetic patients with CHC.

In vitro quality of apheresis platelets divided into paediatric-sized units and stored in PVC bags plasticised with TOTM, BTHC or DINCH.

Two of the predictive factors of the quality of small volumes of platelets suitable for paediatric use are bag size and material. This study evaluated the storage properties of paediatric platelet aliquots in TOTM-, BTHC- or DINCH-PVC bags. (i) Three apheresis platelet concentrates (PC) were pooled and split into three units. One was retained as an adult unit (control; polyolefin bag). The second and third units were split into four MacoPharma TOTM-PVC and BTHC-PVC paediatric bags, respectively. (ii) Two apheresis PC were pooled and split into two units. One PC was retained as an adult unit, and the other was split into four Fresenius DINCH-PVC paediatric bags. Testing was performed on storage for pH, blood gases, hypotonic shock response, soluble CD62P, LDH, glucose and lactate, ATP, CD62P, CD63, platelet-derived microparticles and annexin V. The volumes, platelet yields and pH of all paediatric units met local specifications. The TOTM-PVC bag showed no worse quality than the adult bag up to day 7 for all parameters studied, and it maintained pH higher than BTHC-PVC and DINCH-PVC over storage. The BTHC-PVC bag was shown to be the most gas permeable; however, it had the highest glucose consumption rates and the highest platelet activation. All bags showed an acceptable in vitro quality. Overall, the TOTM-PVC paediatric bag showed better platelet quality compared to the other storage bags, whereas storage in the BTHC-PVC bag resulted in poorer platelet quality.

Potential Involvement of Platelet-Derived Microparticles and Microparticles Forming Immune Complexes during Monocyte Activation in Patients with Systemic Lupus Erythematosus

Microparticles (MPs) are vesicles derived from the plasma membrane of different cells, are considered a source of circulating autoantigens, and can form immune complexes (MPs-ICs). The number of MPs and MPs-ICs increases in patients with systemic lupus erythematosus (SLE). MPs activate myeloid cells by inducing IL-6 and TNF-α in both SLE and other diseases. Therefore, we propose that the recognition of MPs-ICs by monocytes rather that MPs may define their phenotype and contribute to the inflammatory process in patients with SLE. Thus, the aims of this study were to evaluate the association among circulating MPs-ICs from different cell sources, alterations observed in monocyte subsets, and disease activity in patients with SLE and to establish whether monocytes bind and respond to MPs-ICs in vitro. Circulating MPs and monocyte subsets were characterized in 60 patients with SLE and 60 healthy controls (HCs) using multiparametric flow cytometry. Patients had higher MP counts and frequencies of MPs-CD41a + (platelet-derived) compared with HCs, regardless of disease activity. MPs from patients with SLE were C1q + and formed ICs with IgM and IgG. MPs-IgG + were positively correlated with active SLE (aSLE), whereas MPs-IgM + were negatively correlated. Most of the circulating total ICs-IgG + were located on MPs. The proportion and number of non-classical monocytes were significantly decreased in patients with SLE compared with HCs and in patients with aSLE compared with patients with the inactive disease. Non-classical monocytes obtained from patients with SLE exhibited increased levels of CD64 associated with MPs-IgG +, MPs-C1q +, total circulating ICs-IgG +, and disease activity. The direct effects of MPs and MPs-IgG + on monocytes were evaluated in cell culture. Monocytes from both HCs and patients bound to and internalized MPs and MPs-IgG + independent of CD64. These vesicles derived from platelets (PMPs), mainly PMPs-IgG +, activated monocytes in vitro and increased the expression of CD69, CD64, and pro-inflammatory cytokines such as IL-1β, TNF-α, and IFN-α. Therefore, MPs are one of the most representative sources of the total amount of circulating ICs-IgG + in patients with SLE. MPs-IgG + are associated with SLE activity, and PMPs-IgG + stimulate monocytes, changing their phenotype and promoting pro-inflammatory responses related to disease activity.

Platelet Microparticles and miRNA Transfer in Cancer Progression: Many Targets, Modes of Action, and Effects Across Cancer Stages.

Platelet-derived microparticles (PMPs) have long been known to increase in circulation in the presence of cancer, and have been considered to be cancer promoting by multiple mechanisms including shrouding of circulating tumor cells allowing immune evasion, inducing a procoagulant state associated with increased risk for venous thromboembolic events in cancer patients, and supporting metastatic dissemination by establishment of niches for anchorage of circulating tumor cells. These modes of PMP-enhanced progression of late stage cancer are generally based on the adhesive and procoagulant surfaces of PMPs. However, it is now clear that PMPs can also act as intercellular signaling vesicles, by fusion with target cells and transfer of a broad array of platelet-derived molecular contents including growth factors, angiogenic modulators, second messengers, lipids, and nucleic acids. It is also now well established that PMPs are major repositories of microRNAs (miRNAs). In recent years, new roles of PMPs in cancer have begun emerging, primarily reflecting their ability to transfer miRNA contents and modulate gene expression in target cells, allowing PMPs to affect cancer development at many stages. PMPs have been shown to interact with and transfer miRNAs to various blood vascular cells including endothelium, macrophages and neutrophils. As each of these contributes to cancer progression, PMP-mediated miRNA transfer can affect immune response, NETosis, tumor angiogenesis, and likely other cancer-associated processes. Recently, PMP miRNA transfer was found to suppress primary tumor growth, via PMP infiltration in solid tumors, anchorage to tumor cells and direct miRNA transfer, resulting in tumor cell gene suppression and inhibition of tumor growth. This mini-review will summarize current knowledge of PMP-miRNA interactions with cancer-associated cells and effects in cancer progression, and will indicate new research directions for understanding platelet-cancer interactions.

Platelet-derived microparticles promote endothelial cell proliferation in hypertension via miR-142-3p.

Endothelial cells (ECs) are located at the interface between flowing blood and the vessel wall, and abnormal EC proliferation induced by pathologic environments plays an important role in vascular remodeling in hypertensive conditions. Exchanges of information between blood components and ECs are important for EC function. Hence, the present study sought to determine how platelets induce EC dysfunction under hypertensive conditions. EC proliferation was increased in renal hypertensive rats established by abdominal aortic coarctation compared with control rats and that elevated thrombin in plasma promoted platelet activation, which may induce the release of platelet-derived microparticles (PMPs). MicroRNA (MiR) array and qPCR revealed a higher level of miR-142-3p in platelets and PMPs. In vitro, PMPs delivered miR-142-3p into ECs and enhanced their proliferation via Bcl-2-associated transcription factor (BCLAF)1 and its downstream genes. These results indicate that PMPs deliver miR-142-3p from activated platelets into ECs and that miR-142-3p may play important roles in EC dysfunction in hypertensive conditions and may be a novel therapeutic target for maintaining EC homeostasis in hypertension.-Bao, H., Chen, Y.-X., Huang, K., Zhuang, F., Bao, M., Han, Y., Chen, X.-H., Shi, Q., Yao, Q.-P., Qi, Y.-X. Platelet-derived microparticles promote endothelial cell proliferation in hypertension via miR-142-3p.

Standardization of a fast and effective method for the generation and detection of platelet-derived microparticles by a flow cytometer

The Flow Cytometry is the principal method used to measure platelet-derived microparticles (PDMPs), by fluorescent properties analysis. PDMPs (0.1–1.0 μm) are abundant in circulation, accounting for approximately 90% of the microparticles and are associated with Cardiovascular Disease, the leading cause of death in the world.

Induction of Apoptosis in Cancer Cells of pre-B ALL Patients after Exposure to Platelets, Platelet-Derived Microparticles and Soluble CD40 Ligand.

Objective The in vitro treatment of tumor cells with platelet (Plt) causes inhibition of tumor cell growth, although mechanism of this effect is not clear yet. Induction of apoptosis has been proposed as a mechanism of Plt effects on tumor cells. The purpose of this study was to clarify the role of Plts and Plt-derived components in the induction of apoptosis in the blood mononuclear cells of patients with leukemia. Materials and Methods In this experimental study, peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of five patients with childhood B-precursor acute lymphoblastic leukemia (pre-B ALL) and encountered with Plts, Plt-derived microparticles (Plt-MPs) as well as purified soluble CD40L (sCD40L). After 48 hours of co-culture, the anti-cancer activity of the aforementioned factors was surveyed using examination of apoptosis markers of the cells including active caspase-3 and CD95 using ELISA and flow cytometer techniques, respectively. Additionally, staining of the cells with 7-Aminoactinomycin D (7-AAD) was evaluated by flow cytometer technique. Trypan blue exclusion test and WST-1 method were also used to compare the death/survival status of the cells. Results Levels of CD95 and caspase-3 were significantly increased in the all treated groups (P<0.05). On the other hand, trypan blue, 7-AAD and WST-1 methods showed significantly lower number of the live cells in the treated groups (P<0.05). ConclusionThis study can show the ability of Plts, Plt-MPs and sCD40L for the induction of apoptosis in PBMCs of pre-B-ALL patients. Further studies are necessary to elucidate the different effects of platelets on cancer cells in vitro and in vivo.

Evaluation of thrombosis-related biomarkers before and after therapy in patients with multiple myeloma.

BackgroundThrombosis is one of the complications in the clinical course of multiple myeloma (MM). Vascular endothelial cells and/or the hemostatic-coagulatory system are thought to play an important role in thrombosis of MM. In addition to melphalan-prednisone (Mel-P) therapy, several new therapeutic drugs such as lenalidomide or bortezomib have been developed and show effectiveness against MM. However, these new drugs also have risk of therapy-related thrombosis.MethodsWe assessed 103 MM patients and 30 healthy controls, using enzyme-linked immunosorbent assays to evaluate five biomarkers: platelet-derived microparticles (PDMP), plasminogen activator inhibitor-1 (PAI-1), high mobility group box protein-1 (HMGB1), endothelial protein C receptor (EPCR), and soluble vascular cell adhesion molecule-1 (sVCAM-1). The effects of Mel-P, bortezomib, and lenalidomide on the plasma concentrations of these biomarkers were investigated.ResultsThe plasma concentrations of PDMP, PAI-1, HMGB1, EPCR, and sVCAM-1 were higher in MM patients than in healthy controls. Mel-P, bortezomib, and lenalidomide therapies all reduced biomarker levels after treatment. However, when only patients with higher levels of EPCR were compared, differences were seen between the three therapies in the elevation of PDMP, HMGB1, and PAI-1.ConclusionThese results suggest that both MM and therapies for MM can induce a hypercoagulable state. The elevated risk of thrombosis conferred by hypercoagulability increases patient morbidity and mortality. Attention should be paid to therapy-related thrombosis when new therapeutic regimens are selected for MM patients.

Relevance of elevated microparticles in peripheral blood and synovial fluid of patients with rheumatoid arthritis

Introduction: Microparticles (MPs) are submicron sized heterogeneous membrane-bound vesicles released from cells undergoing cell activation or apoptosis. Elevated platelet-derived MPs (PMPs) are reported in rheumatic diseases. We profiled Annexin-V+ MPs and CD61+ MPs in plasma and synovial fluid of patients with rheumatoid arthritis (RA) and their clinical correlates. Methods: Twenty-three newly diagnosed disease-modifying anti-rheumatic drug naive patients with RA, 17 with osteoarthritis (OA) and 22 healthy controls (HC) were enrolled. Five milliliters of synovial fluid from the knee joint of patients with RA and OA was collected; 5 ml of peripheral blood was collected from patients with RA, OA, and HC. Cell-free synovial fluid and platelet poor plasma samples were stained with Annexin-V-APC and Anti-CD61-BV510 antibodies followed by flow cytometry analysis (FACSAria III) (results expressed as the mean ± standard deviation of % population). Results: Significantly greater levels of synovial fluid MPs (Annexin-V+ MPs) were observed in RA versus OA (P Conclusions: Higher levels of Annexin-V+ MPs in both plasma and synovial fluid of RA suggest a role for MPs in the pathogenesis of RA. Elevated plasma PMPs (Annexin V+ CD61+ MPs) in RA may suggest their role in systemic involvement. Furthermore, increased levels of MPs other than those of platelet origin (Annexin V+ CD61− MPs) indicate the necessity to study the MPs from other cell lineages.