Evaluation of Factors Associated With Elevated Levels of Platelet-Derived Microparticles in the Acute Phase of Cerebral Infarction (original) (raw)
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Cerebrovascular Diseases, 2013
Background and purpose: The endothelium is crucial in maintaining the haemostatic balance between pro-and anti-thrombotic factors. In this pilot study, the association of endothelial biomarkers with arterial recanalization and clinical outcome in the setting of acute ischaemic stroke (AIS) was evaluated amongst patients treated with recombinant tissue plasminogen activator (rt-PA). Methods: Sixty-four AIS patients treated with rt-PA were prospectively recruited. Blood was collected before thrombolysis and analysed for von Willebrand factor (vWF), soluble thrombomodulin (sTM) and soluble endothelial protein C receptor (sEPCR). Complete recanalization was defined by a Thrombolysis in Myocardial Infarction Score of 3. Favourable clinical outcome was defined by a modified Rankin Score of 0-2 at 90 days. Results: Amongst the 64 patients, 31 had no documented occlusion, 19 had persistent occlusion and 14 had complete recanalization. After adjustment for confounding factors, these patients presented lower sTM and sEPCR levels than patients with persistent occlusion (median sTM, 21 vs. 48 ng/ml, P = 0.008; median sEPCR, 78 vs. 114 ng/ml, P = 0.018), but similar levels compared with patients without occlusion. vWF levels did not differ between groups. None of these biomarkers was significantly associated with favourable outcome. Conclusions: Recanalization after thrombolytic therapy is associated with low sTM and sEPCR levels but not with vWF levels. If corroborated in further larger studies, these findings could be helpful in the identification of patients resistant to rt-PA thrombolysis who could benefit from a modified recanalization therapy.
Neurological Research, 2009
Background: The in vivo correlates of microembolic signals (MES) are still unknown. Platelet-associates (PA) with monocytes or granulocytes or platelet aggregates only may represent these correlates. Methods: Thirty patients with asymptomatic carotid stenosis .50% and 16 patients with acute (,4 days) atherothrombotic stroke were investigated. PA, P-selectin and thrombospondin expressions on platelets were assessed by flow cytometry. Soluble P-selectin (sPS) levels were assessed. MES detections were performed by transcranial Doppler sonography for 1 hour. PA, Pselectin and thrombospondin expressions on platelets and sPS levels were compared between MES-positive (MESz) and MES-negative (MES2) patients. Results: Eight patients (27%) with asymptomatic carotid stenosis had 1-26 MES/h. Degree of stenosis was 78 ¡ 10% in MES2 and 88 ¡ 8% in the MESz (p50.01). There were no differences in percentages of PA. P-selectin and thrombospondin surface expression was lower in MESz, but this was not significant. sPS levels were higher in MESz (122 ¡ 27 ng/ml versus 80 ¡ 25 ng/ml in MES2, p50.01). Seven (44%) patients with stroke had 1-39 MES/h. There were no differences in percentages of PA. MESz had higher sPS levels (178 ¡ 43 versus 121 ¡ 44 ng/ml, p50.02) and less P-selectin surface expression than MES2 (9.0 ¡ 3.4 versus 4.5 ¡ 1.6%, p50.004). Conclusion: High levels of sPS in MESz and lower expression of platelet activation markers on platelets' surface suggest shedding of activation markers from the platelets' surface and thus enhanced activation of platelets of MESz compared with MES2. PA are probably not the clinical correlates of MES, but platelets seem to be the main cellular element of solid cerebral microemboli.
Journal of Thrombosis and Thrombolysis, 2009
Background Studies have shown that plateletleukocyte aggregates (PLA) are sensitive to platelet activation which might exist before the onset of cerebral infarction. In this study, we investigated the formation of PLA in patients with cerebral infarction and the effects of antiplatelet agents on PLA. Methods The level of soluble P-selectin, C-reaction protein, platelet aggregation rate and leukocyte-platelet aggregations were measured in 40 patients with acute cerebral infarction and 20 normal controls. The 40 patients were randomly assigned to two treatment groups: aspirin group (n = 20) and clopidogrel group (n = 20). Both groups were monitored for Scandinavian stroke scale (SNSS), soluble P-selectin, serum C-reaction protein, platelet aggregation rate and PLA before and after the treatment. Flow cytometry was used to detect the levels of PLA in the blood. Results The percentage of platelet-monocyte aggregates (PMA) in patients with cerebral infarction was significantly increased compared with the controls (P \ 0.001), which was positively correlated to soluble P-selectin, C-reaction protein and platelet aggregation rate (P \ 0.05). After the treatment, the levels of PMA and platelet aggregation rate were decreased in both groups (P \ 0.05). The level of PMA and platelet aggregation rate in the clopidogrel group was significantly lower than that in the aspirin group (P \ 0.05). Conclusions PMA are a sensitive biomarker to platelet activation in patients with cerebral infarction. In addition, although both aspirin and clopidogrel lowered the level of PMA, clopidogrel is a more effective treatment than aspirin in inhibiting platelet activation.
Activation of platelets and cellular coagulation in cerebral small-vessel disease
Blood Coagulation & Fibrinolysis, 2010
Platelets and monocytes play a pivotal role in the initiation and progression of large-vessel atherosclerosis. An upregulation of various platelet and coagulation activation markers has been described in cardiovascular diseases and in patients with acute cerebral ischemia. In the present study the role of platelets and cellular coagulation activation in cerebral small-vessel disease (cSVD) was assessed. In 24 patients with cSVD but without established large-vessel disease, whole blood samples were obtained. Patients were divided into three subgroups (Fazekas 1, 2 and 3) according to extent of cSVD based on morphological magnetic resonance imaging criteria. Surface expression of CD40L and CD62P on platelets, tissue-factor exposition on monocytes and platelet-monocyte aggregates were measured with flow cytometry. Plasma levels of soluble CD40L, interleukin (IL)-6 and IL-7 were assessed by ELISA. Patients with cSVD show a significantly elevated expression of platelet CD40L (P < 0.001) and CD62P (P < 0.023), significantly elevated amounts of platelet-monocyte aggregates (P < 0.004), a significantly enhanced tissuefactor exposition on monocytes (P < 0.019) and significantly lower plasma levels of IL-7 compared to 10 healthy controls. However, this platelet and monocyte activation did not correlate with the severity of cSVD. Patients with cSVD show an up-regulation of the platelet CD40L and CD62P system and an activation of cellular coagulation which might contribute to the initiation and progression of cSVD. Blood Coagul Fibrinolysis 21:729-735 ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Platelet activation and reactivity in the convalescent phase of ischaemic stroke
Thrombosis and Haemostasis, 2010
SummaryThe study was aimed at the evaluation of blood platelet activation and reactivity in patients in the convalescent phase of stroke (n=58) and controls matched in respect to risk factors of vascular pathology (n=55). Both groups were treated daily with acetylsalicylic acid (ASA), 150 mg/day. Using flow cytometry, the expressions of P-selectin and the active GP IIb/IIIa receptor, as well as the fraction of platelet-derived microparticles (PMPs) and total platelet aggregates (Ag), were evaluated in non-stimulated platelets and in platelets stimulated in vitro by thrombin, thrombin receptor activating peptide (TRAP) or ADP. The expression of P-selectin in non-stimulated platelets was found to be significantly (p=0.04) lower in stroke patients. In parallel, these patients manifested a significantly (p=0.0008) higher proportion of PMPs and a lowered (p=0.003) proportion of Ag, as compared to the controls. In the stroke patients the increased expressions of P-selectin and active GP I...
Potential roles of cell-derived microparticles in ischemic brain disease
Neurological Research, 2009
The objective of this study is to review the role of cell-derived microparticles in ischemic cerebrovascular diseases. Materials and methods: An extensive PubMed search of literature pertaining to this study was performed in April 2009 using specific keyword search terms related to cell-derived microparticles and ischemic stroke. Some references are not cited here as it is not possible to be all inclusive or due to space limitation. Discussion: Cell-derived microparticles are small membranous vesicles released from the plasma membranes of platelets, leukocytes, red cells and endothelial cells in response to diverse biochemical agents or mechanical stresses. They are the main carriers of circulating tissue factor, the principal initiator of intravascular thrombosis, and are implicated in a variety of thrombotic and inflammatory disorders. This review outlines evidence suggesting that cell-derived microparticles are involved predominantly with microvascular, as opposed to macrovascular, thrombosis. More specifically, cell-derived microparticles may substantially contribute to ischemic brain disease in several settings, as well as to neuroinflammatory conditions. Conclusion: If further work confirms this hypothesis, novel therapeutic strategies for minimizing cell-derived microparticles-mediated ischemia are available or can be developed, as discussed.
Brain Research, 2020
Limited lower detection ranges associated with traditional immunoassay techniques have prevented the use of brain-specific proteins as blood biomarkers of stroke in the acute phase of care, as these proteins are often only present in circulation at low concentrations. Digital ELISA is a newly developed technique with allows for quantification of proteins in biofluids with up to 1000 times greater sensitivity than conventional ELISA techniques. The purpose of this study was to determine whether the extended lower limits of detection associated with digital ELISA could enable the use of brain-specific proteins as blood biomarkers of ischemic stroke during triage. Blood was sampled from ischemic stroke patients (n=14) at emergency department admission, as well as from neurologically normal controls matched in terms of risk factors for cardiovascular disease (n=33). Plasma levels of two brain-specific axonal proteins, neurofilament light chain (NfL) and Tau, were measured via digital ELISA, and receiver-operator characteristic analysis was used to determine their ability to discriminate between groups. Plasma levels of NfL and Tau were both significantly elevated in stroke patients versus controls, and could respectively discriminate between groups with 92.9% sensitivity and 84.9% specificity, and 85.7% sensitivity and 54.6% specificity. Furthermore, adjustment of measured NfL and Tau levels according to the lower-limits of detection associated with commercially-available conventional ELISA assays resulted in a dramatic and statistically significant decrease in diagnostic performance. Collectively, our results #
Clinical and Applied Thrombosis/Hemostasis, 2011
An upregulation of platelet CD40 ligand (CD40L) and CD62P has been described in atherosclerotic cardiovascular diseases and among patients with acute cerebral ischemia. Correlation between platelet and monocyte activation and the etiology of ischemic stroke were examined in 41 patients with acute ischemic stroke. Compared to 10 controls, all patients with stroke showed a significantly elevated platelet expression of CD40L ( P < .001) and had significantly higher amounts of platelet–monocyte aggregates ( P = .002). Plasma levels of interleukin 7 were significantly lower in patients with stroke compared to controls ( P = .006). Patients with small artery disease had a significantly higher platelet CD40L expression than patients with cardioembolic stroke ( P = .029). Plasma levels of soluble CD40L were significantly higher in patients with large artery disease compared to patients with cardioembolic stroke ( P = .047). In conclusion, patients with acute ischemic stroke show an upreg...