Levels Of Platelet-derived Microparticles Research Articles

The Comparison of Platelet-Derived Microparticles between Ambulatory Cancer Patients and Controls

Background: Elevated levels of microparticles in cancer have been associated with hypercoagulability; however, the specific subtypes of microparticles are still unclear. We hypothesize that active cancer may increase the level of platelet-derived microparticles from platelet activation and play a role in cancer-associated thrombosis. Moreover, chemotherapy is also an important factor playing a role in platelet activation which may affect the levels of platelet-derived microparticles in ambulatory cancer patients. Objectives: To evaluate the hypothesis that platelet-derived microparticles will increase in cancer patients compared with non-cancer patients. To extrapolate the hypothesis that levels of platelet-derived microparticles will increase after receiving chemotherapy. Methods: This was a prospective, cross-sectional study, where, we enrolled ambulatory cancer patients who were about to receive the first cycle (pre-chemotherapy) and those who already received a cycle of chemotherapy (post-chemotherapy). Controls were age- and sex- matched healthy individuals. Patients who had venous thrombosis or who were currently receiving anticoagulants were excluded. Flow cytometry was used to detect, quantify and specify platelet-derived microparticles using the co-expression of both Annexin V for phosphatidylserine and CD41a for platelet marker, and then reported as the unit of event/mL. All outcomes were compared among three groups. Results: A total of 45 patients and 15 controls were enrolled with a mean age of 58.09 years; of which, most patients were female. There was not any significant difference in age, sex, BMI, and platelet count among these groups. Gynecologic malignancy and lymphoma covered almost three-fourths of all patients, which were 51.11% and 24.44% of the total cancer patients, respectively. There was no significant difference in platelet-derived microparticles between cancer patients and controls [411,600 events/mL (331,200-722,400 events/mL) versus 563,640 events/mL (273,720-1,625,580 events/mL), p=0.3179]. Platelet-derived microparticles were significantly higher in cancer patients who had already received chemotherapy (post-chemotherapy) in comparison to cancer patients in the pre-chemotherapy group [582,000 events/mL (346,500-149,3220 events/mL) versus 402,300 events/mL (141,000 - 624,600 events/mL), p=0.0391], Figure 2. There was no significant difference in platelet-derived microparticles between hematologic and non-hematologic malignancy; however, the levels tend to be higher in the non-hematologic malignancy group. Conclusions: Platelet-derived microparticles were not significantly higher among cancer patients who have not received their first cycle of chemotherapy as compared to controls. However, after receiving chemotherapy, cancer patients exhibited significantly higher levels of platelet-derived microparticles. Chemotherapy is an important factor in platelet activation in cancer patients which may increase the levels of platelet-derived microparticles and play a role in cancer-associated thrombosis.

Presurgical circulating platelet-derived microparticles level as a risk factor of blood transfusion in patients with valve heart disease undergoing cardiac surgery

BackgroundCell-derived microparticles (MPs) are membrane vesicles that have emerged as a potential biomarker for various diseases and their clinical complications. This study investigates the role of MPs as a risk factor for blood transfusion in patients with valve heart disease undergoing cardiac surgery. MethodsForty adult patients undergoing heart valve surgery with cardiopulmonary bypass (CPB) were enrolled, and venous blood samples were collected prior to surgical incision. Plasma rich in MPs was prepared by double centrifugation, and the concentration of MPs was determined using the Bradford method. Flow cytometry analysis was performed to determine MPs count and phenotype. Patients were divided into “with transfusion” (n = 18) and “without transfusion” (n = 22) groups based on red blood cell (RBC) transfusion. ResultsThere was no significant difference in MPs concentration between the “with transfusion” and “without transfusion” groups. Although the count of preoperative platelet-derived MPs (PMPs), monocyte-derived MPs (MMPs), and red cell-derived MPs (RMPs) was higher in “without transfusion” group, these differences were not statistically significant. The preoperative PMPs count was negatively correlated with RBC transfusion (P = 0.005, r = -0.65). Multivariate logistic regression analysis revealed that the count of CD41+ PMPs, Hemoglobin (Hb), and RBC count were risk factors for RBC transfusion. ConclusionThis study suggests that the presurgical levels of PMPs, Hb, and RBC count can serve as risk factors of RBC transfusion in patients with valve heart disease undergoing cardiac surgery. The findings provide insights into the potential use of MPs as biomarkers for blood transfusion prediction in cardiac surgery.

Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer.

Aside from their key protective roles in hemostasis and innate immunity, platelets are now recognized as having multifaceted, adverse roles in the pathogenesis, progression and outcome of many types of human malignancy. The most consistent and compelling evidence in this context has been derived from the notable association of elevated circulating platelet counts with the onset and prognosis of various human malignancies, particularly lung cancer, which represents the primary focus of the current review. Key topics include an overview of the association of lung cancer with the circulating platelet count, as well as the mechanisms of platelet-mediated, pro-tumorigenic immunosuppression, particularly the role of transforming growth factor beta 1. These issues are followed by a discussion regarding the pro-tumorigenic role of platelet-derived microparticles (PMPs), the most abundant type of microparticles (MPs) in human blood. In this context, the presence of increased levels of PMPs in the blood of lung cancer patients has been associated with tumor growth, invasion, angiogenesis and metastasis, which correlate with disease progression and decreased survival times. The final section of the review addresses, firstly, the role of cancer-related platelet activation and thrombosis in the pathogenesis of secondary cardiovascular disorders and the associated mortality, particularly in lung cancer, which is second only to disease progression; secondly, the review addresses the potential role of antiplatelet agents in the adjunctive therapy of cancer.

Microparticles: potential new contributors to the pathogenesis of systemic sclerosis?

BackgroundMicroparticles (MPs) are membrane-derived vesicles released from cells undergoing activation or apoptosis with diverse proinflammatory and prothrombotic activities, that have been implicated in the pathogenesis of systemic sclerosis (SSc). We aimed to evaluate the plasma levels of platelet-derived microparticles (PMPs), endothelial cell-derived microparticles (EMPs), and monocyte-derived microparticles (MMPs) in SSc patients, and the association between MPs and the clinical features of SSc.MethodsIn this cross-sectional study, 70 patients with SSc and 35 age- and sex-matched healthy controls were evaluated. Clinical and nailfold capillaroscopy (NFC) data were obtained from all patients. Plasma levels of PMPs (CD42+/31+), EMPs (CD105+), and MMPs (CD14+) were quantified by flow cytometry.ResultsPatients were mainly females (90%), with a mean age of 48.9 years old. PMP, EMP, and MMP levels were significantly increased in SSc patients compared to controls (79.2% ± 17.3% vs. 71.0% ± 19.8%, p = 0.033; 43.5% ± 8.7% vs. 37.8% ± 10.4%, p = 0.004; and 3.5% ± 1.3% vs. 1.1% ± 0.5%, p < 0.0001, respectively). PMP levels were significantly higher in patients with positive anti-topoisomerase-I antibodies (p = 0.030) and in patients with a disease duration > 3 years (p = 0.038). EMP levels were lower in patients with a higher modified Rodnan skin score (p = 0.015), and in those with an avascular score > 1.5 in NFC (p = 0.042).ConclusionThe increased levels of PMPs, EMPs and MMPs in scleroderma patients might indicate a possible role for these agents in the pathogenesis of this challenging disease.

Annexin V− and tissue factor+ microparticles as biomarkers for predicting deep vein thrombosis in patients after joint arthroplasty

ObjectiveVenous thromboembolism (VTE) is a common and severe complication of joint arthroplasty. Microparticles (MPs) containing phosphatidylserine (PS) and tissue factor (TF) can trigger coagulation in VTE. This study aims to measure and compare MP levels in joint arthroplasty patients with and without VTE. MethodsThis prospective cohort study enrolled 181 patients who underwent joint arthroplasty. Ultrasound examination was used to diagnose VTE on preoperative day 0 and postoperative day 6. MPs were analysed using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. The levels of platelet-derived microparticles (PMPs), endothelial cell-derived microparticles (EMPs), granulocyte-derived microparticles (GMPs), red cell-derived microparticles (RMPs), monocyte-derived microparticles (MMPs), Annexin V+ MPs (AV+ MPs), and tissue factor+ MPs (TF+ MPs) derived from five kinds of MPs were measured on day 0 (before surgery), 1, 2, 3, 4, 5, and 6 after surgery. ResultsThe levels of AV-TF+ EMPs and AV-TF+ MMPs were significantly increased in patients with VTE on postoperative day 5 compared to those without VTE (P = 0.031 and P = 0.031, respectively). ConclusionAV-TF+ MPs may indicate the development of VTE and serve as predictive markers in joint arthroplasty patients.

Upregulation of cytokine signalling in platelets increases risk of thrombophilia in severe COVID-19 patients

Abnormal coagulation dynamics, including disseminated intravascular coagulopathy, pulmonary embolism, venous thromboembolism and risk of thrombosis are often associated with the severity of COVID-19. However, very little is known about the contribution of platelets in above pathogenesis. In order to decipher the pathophysiology of thrombophilia in COVID-19, we recruited severely ill patients from ICU, based on the above symptoms and higher D-dimer levels, and compared these parameters with their asymptomatic counterparts. Elevated levels of platelet-derived microparticles and platelet-leukocyte aggregates suggested the hyperactivation of platelets in ICU patients. Strikingly, platelet transcriptome analysis showed a greater association of IL-6 and TNF signalling pathways in ICU patients along with higher plasma levels of IL-6 and TNFα. In addition, upregulation of pathways like blood coagulation and hemostasis, as well as inflammation coexisted in platelets of these patients. Further, the increment of necrotic pathway and ROS-metabolic processes in platelets was suggestive of its procoagulant phenotype in ICU patients. This study suggests that higher plasma IL-6 and TNFα may trigger platelet activation and coagulation, and in turn aggravate thrombosis and hypercoagulation in severe COVID-19 patients. Therefore, the elevated IL-6 and TNFα, may serve as potential risk factors for platelet activation and thrombophilia in these patients.

Platelets Derived Microparticles in COVID-19

BACKGROUND: Evidences indicate that COVID-19 infection causes hypercoagulable state with micro and macrovascular thrombosis. Platelet-derived microparticles (PDMPs) have inflammatory and diverse coagulant roles. AIM: The aim of the study was to assess PDMPs in patients with active and convalescent post COVID-19 infection and correlate PDMPs with clinical, radiological and laboratory findings used in follow up. PATIENTS AND METHODS: The study enrolled 25 patients during active COVID-19 (Group A), of them five patients had thromboembolic events (TEE); and Group B including 32 patients during post COVID-19 stages. Clinical and radiological assessment, routine biomarkers, and detection of PDMPs levels, using enzyme-linked immunosorbent assay method, were done for all patients. RESULTS: In addition to significant differences detected regarding hemoglobin level, total leukocyte count, absolute neutrophil count, absolute lymphocyte count, C-reactive protein level, D-dimer, and serum ferritin, and high significant differences in PDMPs levels were elicited between groups A and B (mean ± standard deviation: 38.7 ± 10.6 IU/mL, and 18.9 ± 15.3 IU/mL) respectively, with discriminative level at 20.5 IU/mL. PDMPs showed nonsignificant difference between patients with and without TEE and no correlation was detected between PDMPs and clinical or radiological severity in post-COVID-19 patients. CONCLUSION: In COVID-19 infection, PDMPs are related to viral activity, and their major role is inflammatory associated.

Platelet-Derived Procoagulant Microparticles as Blood-based Biomarker of Breast Cancer.

Objective:Breast cancer is the main cause of cancer death in women worldwide. Elevated plasma levels of circulating cell-derived microparticles (MPs) have been reported in various types of cancer, including breast cancer, with the ability to mediate inflammation and thrombosis. Microparticles are bioactive agents, and it has been suggested that MPs can be used as a diagnostic, prognostic, or therapeutic biomarker in various diseases. The aim of this study was to investigate the levels of platelet-derived MPs (PMPs) in breast cancer patients. Materials and Methods:In this case-control study, 30 patients with breast cancer and 20 normal subjects were sampled after obtaining written consent. MPs were isolated from blood samples by centrifugation technique. CD42b and annexin V markers were used respectively for counting PMPs and procoagulant MPs with flow cytometry. Results:Flow cytometry results showed that the number of PMPs and procoagulant annexin V positive MPs was significantly higher in the breast cancer patients than normal subjects (p<0.001). The number of the annexin V MPs differed significantly in patients with high tumor size (T2) compared to the patients with low tumor size (T1) and controls (p<0.001). Significant and positive correlations were found between PMP levels and tissue-based biomarkers, tumor grading, and distant metastasis (P<0.05). Tumor histological type did not correlate with the numbers of PMPs (p=0.065). Conclusion:Increased levels of PMPs and activity in terms of hemostasis and having a positive and significant relationship with tumor grading and metastasis may indicate the effective role of PMPs in the pathogenesis and prognosis of breast cancer.

Impact of anemia on platelet production and function in acute coronary syndrome: results of long-term single-center registry

Abstract Funding Acknowledgements Type of funding sources: None. Anemia is the most common clinical condition known to increase both ischemic and hemorrhagic risks in patients with acute coronary syndrome (ACS). Despite it"s high frequency there are certain gaps in evidence on how to choose appropriate antiplatelet regimen in anemia, for anemia was among exclusion criteria in almost all randomized clinical trials on efficacy and safety of antiplatelet agents. Purpose of the study to evaluate prevalence of anemia and it"s impact on platelet production and function in patients admitted to ICU with ACS. Methods. To determine the prevalence and characteristics of anemia we analyzed data from the local single-center long-term registry of coronary heart disease (n total= 4776, n ACS = 765). To evaluate platelet production and function we used data obtained from those patients with ACS in whom platelet function, immature platelet fraction (IPF), thrombopoietin (TPO), stromal cell-derived factor 1 (SDF1), TPO receptors (MPL) and platelet derived microparticles (PDMP) were measured serially at admission, on the second and on the 7th day since ACS manifestation (n = 321). Results. Anemia on admission was verified in 12.5% of ACS, and there were no significant differences in antiplatelet therapy at first medical contact and on admission. Anemia in patients with ACS was accompanied with decreased platelet count, therefore TPO level at admission was higher: 336.23 (141.35; 429.85) ng/mL vs 266.04 (199.16; 341.20) pg/mL, p = 0.050. PDMP level at admission was minimal in anemic patients: 6.75 (5.31; 7.81) vs 26.45 (16.05; 39.35) ng/mL (p = 0.027). There were no significant differences in TPO levels measured on the 2nd and the 7th days, as well as SDF and MPL. IPF was also comparable in anemic patients and those with normal Hb levels. Despite similar platelet function on admission in patients with anemia there was significant increase in platelet ADP-induced aggregation and secretion with maximal level at the 7th day since ACS manifestation: 2 (1; 4) vs 0 (0; 1) Ohm, p = 0.02. Anemia in ACS was characterized with unfavorable myocardial stress and injury biomarkers dynamics: BNP at the 7th day – 1155 (867; 2251) vs 73.4 (40.3; 148.5) pg/mL, and with increase in risk of early adverse (ischemic, but not hemorrhagic) events OR 8.6 CI 1.1; 19.4, p = 0.038. Conclusion. Anemia is a common comorbidity in acute coronary syndrome increasing risk of early complications. Anemia on admission in ACS is characterized by increase of platelet aggregation and secretion despite antiplatelet therapy, and this activation does not result from possible associated changes in platelet production and turnover. Received results underline the risk of early discontinuation of antiplatelet therapy in ACS with anemia, and possible benefits of platelet function monitoring in these patients.

Increased levels of platelet-derived microparticles in pulmonary hypertension

IntroductionThrombosis and coagulation abnormalities are thought to be involved in disease progression of pulmonary hypertension. Platelet-derived microparticles (PDMP) are released from platelets following stimulation and have recently been demonstrated to play an important role in pathogenesis of various diseases. This study aimed to evaluate PDMP levels in patients with pulmonary hypertension. Materials and methodsOur cross-sectional study enrolled a total of 113 participants including 73 patients with pulmonary hypertension and 40 participants to serve as a control group. PDMP levels were measured using a PDMP ELISA kit, which detects glycoproteins CD42a and CD42b. Clinical parameters, including exercise capacity and hemodynamic parameters, were collected, and the relationship to PDMP levels were evaluated. ResultsPDMP levels were significantly higher in patients than in participants in the control group (23.2 ± 39.4 U/mL and 7.8 ± 3.6 U/mL, respectively, P < 0.05). PDMP levels in patients with chronic thromboembolic pulmonary hypertension were correlated with right atrial pressure and cardiac index. PDMP levels were higher in male patients with idiopathic pulmonary arterial hypertension. Furthermore, patients administered a higher dose of epoprostenol had a tendency for lower PDMP levels. ConclusionsThe data suggest that PDMP levels are increased in patients with pulmonary hypertension. Further study is needed to understand the mechanism and impact of PDMP on disease progression.

Circulating Platelet-Derived Microparticles Associated with Postdischarge Major Adverse Cardiac Events in ST-Elevation Acute Myocardial Infarction.

Introduction Platelet-derived microparticles (PDMPs) measurement adds prognostic implication for ST-elevation acute myocardial infarction (STEMI). The long-term implication of PDMPs in STEMI needs to be corroborated. Methods The research design was a cohort study. Subjects were STEMI patients and were enrolled consecutively. The PDMPs were defined as microparticles bearing CD41(+) and CD62P(+) markers detected with flow cytometry. The PDMPs were measured on hospital admission and 30 days after discharge. The outcomes were major adverse cardiac events (MACE), i.e., a composite of cardiac death, heart failure, cardiogenic shock, reinfarction, and resuscitated ventricular arrhythmia, occurring from hospitalization until 1 year after discharge. Results We enrolled 101 subjects with STEMI. During hospitalization, 17 subjects (16.8%) developed MACE. The PDMPs were not different between subjects with MACE and those without (median (IQR): 3305.0/μL (2370.0–14690.5/μL) vs. 4452.0/μL (2024.3–14396.8/μL), p=0.874). Forty-five subjects had increased PDMPs in 30 days after discharge as compared with on-admission measurement. Subjects with increased PDMPs had significantly higher 30-day MACE as compared to subjects with decreased PDMPs 17 (37.8%) vs. 6 (16.7%, p=0.036). There was a trend toward higher MACE in subjects with increased PDMPs as compared to those with decreased PDMPs in 90 days after discharge (48.9% vs. 30.6%, p=0.095) and 1 year after discharge (48.9% vs. 36.1%, p=0.249). Conclusion The PDMPs level was increased from the day of admission to 30 days after discharge in patients with STEMI. The persistent increase in the PDMPs level in 30 days after the STEMI event was associated with the 30-day postdischarge MACE and trended toward increased MACE during the 90-day and 1-year follow-up.

Platelet factor 4 and β-thromboglobulin mRNAs in circulating microparticles of trauma patients as diagnostic markers for deep vein thrombosis.

Deep vein thrombosis (DVT) is a common complication after trauma. The development of markers to predict DVT in trauma patients is needed, and circulating microparticles (MPs) and their contents are possible candidates. In this study, we aimed to identify platelet factor 4 (PF4) and β-thromboglobulin (β-TG) mRNAs in circulating MPs as potential markers for DVT diagnosis in trauma patients. Fifteen trauma patients diagnosed with DVT and fifteen matched patients without DVT were included in this study. Fifteen healthy volunteers also were included as controls. Circulating MPs were obtained from the plasma of all study subjects. Annexin V+ MPs and platelet-derived MPs (PMPs) were quantified using flow cytometry. PF4 and β-TG mRNAs in MPs were determined by qPCR, and the common logarithm of relative quantitation (RQ) was calculated using the comparative Ct method. Receiver-operating characteristic (ROC) curves were performed to analyze the diagnostic value of PF4 and β-TG mRNAs. No significant differences were found in Annexin V+ MPs and PMPs levels between trauma patients with and without DVT. However, both PF4 and β-TG mRNAs in MPs from the DVT group were significantly higher than the non-DVT group and healthy controls (P = 0.014 for PF4, P = 0.010 for β-TG). The ROC curve analysis showed that both the PF4 mRNA (area-under curve (AUC) 0.756, P = 0.017) and the β-TG mRNA (AUC 0.751, P = 0.019) had a positive predictive value for DVT. This finding indicates that the PF4 and β-TG mRNAs in MPs may be used as potential biomarkers for DVT diagnosis in trauma patients.

Platelet-Derived Microparticles are an Important Biomarker in Patients with Cancer-Associated Thrombosis.

BackgroundPlatelet-derived microparticles (PDMPs) that ultimately cause vascular complications might be used as a tool to assess thrombotic areas. We identified PDMPs, high-mobility group box-1 (HMGB1) and soluble endothelial protein C receptor (sEPCR) as useful prognosis indicators for cancer-related thrombosis (CAT) to evaluate the utility of PDMPs in cancer patients.MethodsWe investigated 232 cancer patients: 24 (10.3%) had thrombotic complications within 6 months after their first examination. Levels of PDMP and biomarkers were measured by enzyme-linked immunosorbent assay.ResultsThe levels of PDMPs, HMGB1 and sEPCR were higher in cancer patients compared with controls. In particular, these levels were significantly elevated in lung cancer patients compared with controls, and all were higher in CAT-positive patients compared with CAT-negative patients. In particular, PDMP levels in CAT-positive patients were significantly elevated compared with CAT-negative patients. PDMP levels were significantly lower in patients who lived for more than 901 days after their first examination compared with previous data. PDMP levels were positively correlated with HMGB1, and caused the dose-dependent elevation of PDMPs in vitro using platelet-rich plasma from healthy persons.ConclusionThe combined increase in PDMP and HMGB1 levels might be related to CAT in cancer patients. Therefore, coagulatory dysfunction may result from increased levels of these biomarkers and contribute to the poor prognosis of cancer patients.

IMPACT OF THE PLATELET WASHING PROCESS ON IN VITRO PLATELET PROPERTIES, AND THE LEVELS OF SOLUBLE CD40 LIGAND AND PLATELET-DERIVED MICROPARTICLES IN THE STORAGE MEDIA

Background A new platelet (PLT) additive solution, bicarbonated Ringer's solution supplemented with acid-citrate-dextrose Formula A, termed BRS-A, as well as a new automated closed system cell processor for washing PLTs have recently been developed. This study evaluated the in vitro properties of PLTs with the automated system versus the manual method, using the BRS-A additive solution for washing and storage. Methods ABO-identical apheresis PLTs in 100% plasma were pooled and split equally for control (in 100% plasma or a manual method) and test (ACP215 automated system) units. In vitro characteristics of PLTs washed with the automated system were compared to those of PLTs in 100% plasma (Study 1) or washed with a manual method (Study 2) during the 7-day storage. Results In Study 1, hypotonic shock response, aggregation response, mitochondrial membrane potential, adenosine triphosphate, and CD42b mean fluorescence intensity were comparable in the control and test groups during the 7-day storage. CD62P expression was lower in the test group than controls on Days 3 and 7. The level of platelet-derived microparticles (PDMPs) in the test group on Days 1 and 2 were higher than those in controls. In contrast, the levels of soluble CD40 ligand (sCD40L) and regulated upon activation of normal T-cell expressed and secreted (RANTES) in the test units were lower than controls. In Study 2, no significant differences were found in all in vitro properties except for PLT count and the levels of PDMPs in the test units were higher than controls during storage. Conclusion Apheresis PLTs washed with the automated system using BRS-A additive solution maintained in vitro properties during storage. Washing methods influenced PDMP levels but not sCD40L and RANTES.

Cell-derived microparticles and von Willebrand factor in Brazilian renal transplant recipients.

This study was aimed at investigating platelet-derived microparticles (PMP), endothelium cell-derived microparticles (EMP) and von Willebrand factor (VWF) according to renal function and time post-transplant. We found this study relevant because unusual biomarkers seem to be a promising tool to evaluate chronic renal disease and post-transplant monitoring. Ninety-one renal transplant recipients (RTx) were allocated into groups according to creatinine plasma levels (C1 < 1.4 and C2 ≥ 1.4 mg/dL), estimated glomerular filtration rates (R1 < 60 and R2 ≥ 60 mL/min per 1.73 m2 ) and time post-transplant (T1: 3-24; T2: 25-60; T3: 61-120; and T4 > 120 months). EMP and PMP levels were assessed by flow cytometry and VWF levels were evaluated by enzyme-linked immunosorbent assay. Platelet-derived microparticle levels were higher in C1 group compared with C2 (P = 0.00). According to diameter, small PMP and EMP (≤0.7 μm) were also higher in C1 group, all values of P less than 0.05. T1 and T2 groups have shown high EMP levels and a predominance of big microparticle (>0.7 μm) compared with T4 group, all values of P less than 0.05. Higher VWF levels were observed among RTx with creatinine ≥1.4 mg/dL compared with other RTx, P = 0.01. The results showed that PMP, EMP and VWF are promising markers to evaluate endothelial function in RTx. These biomarkers could play a major role in monitoring patients after renal transplant.

Circulating microparticles as biomarkers of stroke: A focus on the value of endothelial- and platelet-derived microparticles.

Stroke is one of the leading causes of mortality anddisability worldwide. Numerouspathophysiological mechanisms involving blood vessels, coagulation and inflammation contribute to the vascular occlusion. Perturbations in these pathways can be detected by numerous methods including changes in endoplasmic membrane remodeling and rearrangement leading to the shedding of microparticles (MPs) from various cellular origins in the blood. MPs are small membrane-derived vesicles that are shed from nearly all cells in the body in resting state or upon stimulation. MPs act as biological messengers to transfer information to adjacent and distant cells thus regulating various biological processes. MPs may be important biomarkers and tools for the identification of the risk and diagnosis of cerebrovascular diseases. Endothelial activation and dysfunction and altered thrombotic responses are two of the main features predisposing to stroke. Endothelial MPs (EMPs) have been recognized as both biomarkers and effectors of endothelial cell activation and injury while platelet-derived MPs (PMPs) carry a strong procoagulant potential and are activated in thrombotic states. Therefore, we reviewed here the role of EMPs and PMPs as biomarkers of stroke. Most studies reported high circulating levels of EMPs and PMPs in addition to other cell origins in stroke patients and have been linked to stroke severity, the size of infarction, and prognosis. The identification and quantification of EMPs and PMPs may thus be useful for the diagnosis and management of stroke.

Platelets release proinflammatory microparticles in anti-neutrophil cytoplasmic antibody-associated vasculitis.

The biological functions of the platelets contributing to ANCA-associated vasculitis (AAV) are largely unclear. The current study aimed to investigate the potential role of platelet-derived microparticles (PMPs) in AAV. In the current study, microparticles in AAV patients were analysed by flow cytometry, and PMPs were probed for relative levels of 640 bioactive proteins secreted from patients' platelets using antibody microarrays. These data were then correlated with clinical and pathological parameters. PMPs were significantly increased in 69 AAV patients, predominantly MPO-ANCA positive patients in active stage compared with in remission [4406.8/μl (2135.4, 5485.0) vs 549.7/μl (350, 708.5), P < 0.0001], and 43% of microparticles in active AAV were PMPs. Compared with 15 patients in remission, highly expressed proinflammatory molecules in the microparticles from platelets in 15 AAV patients in active stage revealed that potential functions of PMPs were promotion of the effect of chemotaxis, adhesion, growth and apoptosis (all the patients for array analysis were MPO-ANCA positive). The level of PMPs had a significant association with disease activity, inflammation, and renal damage. PMPs may serve as inflammatory propagators through their wide production of proinflammatory cytokines in AAV, potentially providing a novel therapeutic target.

Platelet microparticles level in juvenile idiopathic arthritis: A pediatric population-based cross-sectional study in a tertiary care center

Background: Platelet-derived microparticles (PMPs) are small vesicles that are released from the plasma membrane upon platelet activation, which are then involved in haemostasis, vascular health, and have recently been shown to be intimately involved in immune responses. Aims and Objectives: We aimed to evaluate the level of plasma Platelet-derived micro particles in children with JIA and to assess the relationship between PMP levels and disease activity in JIA. Materials and Methods: Children with JIA who fulfilled the International League of Associations for Rheumatology (ILAR) classification criteria for juvenile idiopathic arthritis were included. They were categorised into active disease group and inactive disease as assessed by Wallace criteria. Samples were run in Navios flow cytometer (Beckman Coulter). Platelet microparticles were identified by MPs positive for both Annexin V and CD41 antibodies. Results: Out of 26 children with JIA, 12 had active disease group and 14 had inactive disease as assessed by Wallace criteria. Mean PMP level was 83507 cells/μl and 34904 cells/μl in active and inactive disease respectively (P = 0.06). There was no significant correlation between PMP and CRP levels (P = 0.75 and r = 0 .102) or PMP and ESR levels (P = 0.56 and r = -0.186) in JIA children with active disease. Conclusion: PMP levels were significantly elevated in disease activity of JIA and could represent a new biomarker reflecting the state of cell activation in JIA. PMP role in the inflammatory processes needs to be further elucidated.

Impact of the platelet washing process on in vitro platelet properties, and the levels of soluble CD40 ligand and platelet-derived microparticles in the storage media.

A new platelet (PLT) additive solution, bicarbonated Ringer's solution supplemented with acid-citrate-dextrose Formula A, termed BRS-A, as well as a new automated closed system cell processor for washing PLTs have recently been developed. This study evaluated the in vitro properties of PLTs with the automated system versus the manual method, using the BRS-A additive solution for washing and storage. ABO-identical apheresis PLTs in 100% plasma were pooled and split equally for control (in 100% plasma or a manual method) and test (ACP215 automated system) units. In vitro characteristics of PLTs washed with the automated system were compared to those of PLTs in 100% plasma (Study 1) or washed with a manual method (Study 2) during the 7-day storage. In Study 1, hypotonic shock response, aggregation response, mitochondrial membrane potential, adenosine triphosphate, and CD42b mean fluorescence intensity were comparable in the control and test groups during the 7-day storage. CD62P expression was lower in the test group than controls on Days 3 and 7. The level of platelet-derived microparticles (PDMPs) in the test group on Days 1 and 2 were higher than those in controls. In contrast, the levels of soluble CD40 ligand (sCD40L) and regulated upon activation of normal T-cell expressed and secreted (RANTES) in the test units were lower than controls. In Study 2, no significant differences were found in all in vitro properties except for PLT count and the levels of PDMPs in the test units were higher than controls during storage. Apheresis PLTs washed with the automated system using BRS-A additive solution maintained in vitro properties during storage. Washing methods influenced PDMP levels but not sCD40L and RANTES.

Assessment of soluble cytotoxic T lymphocyte-associated antigen-4, transforming growth factor β1, and platelet-derived microparticles during dasatinib therapy for patients with chronic myelogenous leukemia.

BackgroundThe outcome for chronic myelogenous leukemia (CML) patients presented in the chronic phase has changed dramatically since the introduction of tyrosine kinase inhibitor (TKI) therapy. Notably, an increased incidence of large granular lymphocytes (LGLs), which is related to immunological conditions, appears to be predictive of a favorable outcome for dasatinib therapy. We therefore examined the immunological characteristics of CML patients during dasatinib therapy by determining the plasma concentrations of five different biomarkers.MethodsThe plasma levels of biomarkers, specifically interleukin-6, platelet-derived microparticles (PDMPs), soluble vascular cell adhesion molecule 1 (sVCAM-1), transforming growth factor (TGF) β1, and soluble cytotoxic T lymphocyte-associated antigen-4 (sCTLA-4), were measured by ELISA at baseline and after 2 and 6 months of TKI treatment. The incidence of LGLs was estimated by microscopic examination.ResultsThe levels of PDMPs, sVCAM-1, and TGFβ1 were significantly elevated in patients with CML. Dasatinib treatment was associated with a significant reduction in the levels of these markers and with an increased incidence of LGLs compared with imatinib or nilotinib treatment. In addition, an increased incidence of LGLs was significantly correlated with a decreased sCTLA-4 level during dasatinib therapy.ConclusionThe assessment of the levels of specific biomarkers may be beneficial to understand the immunological conditions of patients with CML during dasatinib treatment.