Background-Apoptotic microparticles are responsible for almost all tissue factor activity of the plaque lipid core. We hypothesized that elevated levels of procoagulant microparticles could also circulate in the peripheral blood of patients with recent clinical signs of plaque disruption and thrombosis. Methods and Results-We studied 39 patients with coronary heart disease, including 12 patients with stable angina and 27 patients with acute coronary syndromes (ACS), and 12 patients with noncoronary heart disease. We isolated the circulating microparticles by capture with annexin V and determined their procoagulant potential with a prothrombinase assay. The cell origins of microparticles were determined in an additional 22 patients by antigenic capture with specific antibodies. A cute coronary syndromes (ACS) are severe clinical manifestations of coronary artery lumen occlusion by a thrombus formed on the contact of a ruptured or eroded atherosclerotic plaque. 1,2 Tissue factor (TF) is highly expressed in atherosclerotic plaques, 3 and TF activity of plaques retrieved from patients with unstable angina (UA) is significantly higher than that found in the plaques of patients with stable angina (SA), 4 which suggests that it may significantly determine thrombus formation after plaque disruption. TF activity is highly dependent on the presence of phosphatidylserine (PS), 5 and it has been shown that this anionic phospholipid is redistributed on the cell surface during apoptotic death, 6 conferring to the cell a potent procoagulant activity. 7,8 Interestingly, shed membrane apoptotic microparticles rich in PS are produced in considerable amounts within human atherosclerotic plaques and carry almost all TF activity of the plaque lipid core, 9 indicating that they may largely determine plaque thrombogenicity. In the present study, we hypothesized that high levels of cell-derived microparticles with procoagulant potential could also be detectable in the circulating blood of patients with recent clinical signs of plaque disruption and thrombosis and may therefore contribute to the initiation and perpetuation of the thrombotic process. Methods Patient SelectionTo isolate the circulating microparticles and determine their procoagulant potential, we prospectively included 39 patients with angina and angiographic documentation of coronary artery disease (CAD) and 12 controls. Among patients with CAD, 12 (9 men; mean age 62Ϯ3 years) had SA with no signs of myocardial ischemia at rest, and 27 had ACS: 13 (8 men; mean age 62Ϯ4 years) had UA (Braunwald class III) with documented signs of recent myocardial ischemia at rest, and 14 (10 men; mean age 61Ϯ4 years) had acute myocardial infarction (MI). Cardiovascular risk factors were not significantly different between the 3 groups of patients with CAD, except for hypercholesterolemia, which was more prevalent in patients with SA (PϽ0.02).All coronary patients were receiving aspirin. Patients with ACS received additional standard antithrombotic therapy before blood sampling. Anti-isch...

IntroductionCell stimulation leads to the shedding of phosphatidylserine (PS)-rich microparticles (MPs). Because autoimmune diseases (AIDs) are characterized by cell activation, we investigated level of circulating MPs as a possible biomarker in primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).MethodsWe measured plasma levels of total, platelet and leukocyte MPs by prothrombinase capture assay and flow cytometry in 43 patients with pSS, 20 with SLE and 24 with RA and in 44 healthy controls (HCs). Secretory phospholipase A2 (sPLA2) activity was assessed by fluorometry. Soluble CD40 ligand (sCD40L) and soluble P-selectin (sCD62P), reflecting platelet activation, were measured by ELISA.ResultsPatients with pSS showed increased plasma level of total MPs (mean ± SEM 8.49 ± 1.14 nM PS equivalent (Eq), P < 0.0001), as did patients with RA (7.23 ± 1.05 n PS Eq, P = 0.004) and SLE (7.3 ± 1.25 nM PS Eq, P = 0.0004), as compared with HCs (4.13 ± 0.2 nM PS Eq). Patients with AIDs all showed increased level of platelet MPs (P < 0.0001), but only those with pSS showed increased level of leukocyte MPs (P < 0.0001). Results by capture assay and flow cytometry were correlated. In patients with high disease activity according to extra-glandular complications (pSS), DAS28 (RA) or SLEDAI (SLE) compared with low-activity patients, the MP level was only slightly increased in comparison with those having a low disease activity. Platelet MP level was inversely correlated with anti-DNA antibody level in SLE (r = -0.65; P = 0.003) and serum β2 microglobulin level in pSS (r = -0.37; P < 0.03). The levels of total and platelet MPs were inversely correlated with sPLA2 activity (r = -0.37, P = 0.0007; r = -0.36, P = 0.002, respectively). sCD40L and sCD62P concentrations were significantly higher in pSS than in HC (P ≤ 0.006).ConclusionsPlasma MP level is elevated in pSS, as well as in SLE and RA, and could be used as a biomarker reflecting systemic cell activation. Level of leukocyte-derived MPs is increased in pSS only. The MP level is low in case of more severe AID, probably because of high secretory phospholipase A2 (sPLA2) activity, which leads to consumption of MPs. Increase of platelet-derived MPs, sCD40L and sCD62P, highlights platelet activation in pSS.

clinicaltrials.gov Identifier: NCT00632866.