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Data are limited on the impact of commencing antiplatelet therapy on von Willebrand Factor Antigen (VWF:Ag) or von Willebrand Factor propeptide (VWFpp) levels and ADAMTS13 activity, and their relationship with platelet reactivity following TIA/ischaemic stroke. In this pilot, observational study, VWF:Ag and VWFpp levels and ADAMTS13 activity were quantified in 48 patients ≤4 weeks of TIA/ischaemic stroke (baseline), and 14 days (14d) and 90 days (90d) after commencing aspirin, clopidogrel or aspirin+dipyridamole. Platelet reactivity was assessed at moderately-high shear stress (PFA-100® Collagen-Epinephrine / Collagen-ADP / INNOVANCE PFA P2Y assays), and low shear stress (VerifyNow® Aspirin / P2Y12, and Multiplate® Aspirin / ADP assays). VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d in the overall population (P ≤ 0.03). In the clopidogrel subgroup, VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d (P ≤ 0.01), with an increase in ADAMTS13 activity between baseline vs. 90d (P ≤ 0.03). In the aspirin+dipyridamole subgroup, there was an inverse relationship between VWF:Ag and VWFpp levels with both PFA-100 C-ADP and INNOVANCE PFA P2Y closure times (CTs) at baseline (P ≤ 0.02), with PFA-100 C-ADP, INNOVANCE PFA P2Y and C-EPI CTs at 14d (P ≤ 0.05), and between VWF:Ag levels and PFA-100 INNOVANCE PFA P2Y CTs at 90d (P = 0.03). There was a positive relationship between ADAMTS13 activity and PFA-100 C-ADP CTs at baseline (R2 = 0.254; P = 0.04). Commencing/altering antiplatelet therapy, mainly attributed to commencing clopidogrel in this study, was associated with decreasing endothelial activation following TIA/ischaemic stroke. These data enhance our understanding of the impact of VWF:Ag and VWFpp especially on ex-vivo platelet reactivity status at high shear stress after TIA/ischaemic stroke.
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BACKGROUND: Data are limited on the ability of dipyridamole to additionally inhibit platelet function/reactivity in ischaemic cerebrovascular disease (CVD) patients on aspirin. AIMS: To assess inhibition of platelet function/reactivity and platelet activation with dipyridamole in CVD. METHODS: This prospective, observational study assessed TIA/ischaemic stroke patients before (baseline; N = 60), at 14 ±7 days (14d, N = 39) and ≥ 90 days (90d, N = 31) after adding dipyridamole to aspirin. Platelet function/reactivity at high shear stress (PFA-100® C-ADP) and low shear stress (VerifyNow® P2Y12 and Multiplate® ADP assays), and platelet activation status (% expression of CD62P, CD63 and leucocyte-platelet complexes on whole blood flow cytometry) were quantified. 'Dipyridamole-high on-treatment platelet reactivity (HTPR)' was defined as failure to inhibit ADP-induced platelet aggregation +/- adhesion compared with the patient's baseline on aspirin monotherapy by more than twice the coefficient-of-variation of the assay after adding dipyridamole to aspirin. RESULTS: Dipyridamole-HTPR was identified in 71.4-75% of patients on PFA-100 C-ADP, 83.9-86.8% of patients on VerifyNow P2Y12, and 81.5-83.3% of patients on Multiplate ADP assays. There were no changes in CD62P/CD63 expression (P ≥ 0.18), or consistent changes in leucocyte-platelet complexes in CVD patients overall at 14d or 90d vs. baseline after commencing dipyridamole. Monocyte-platelet complexes increased in the patient subgroup with dipyridamole-HTPR at 14d and 90d on PFA-100, and at 14d on VerifyNow (P ≤ 0.04), but not in those without dipyridamole-HTPR. DISCUSSION: Additional antiplatelet effects of dipyridamole are detectable under high and low shear stress conditions with user-friendly platelet function/reactivity tests ex vivo. Increasing circulating monocyte-platelet complexes over time are associated with dipyridamole-HTPR.
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Isquemia Encefálica , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adenosina Difosfato/metabolismo , Adenosina Difosfato/farmacología , Aspirina/farmacología , Aspirina/uso terapéutico , Plaquetas , Isquemia Encefálica/metabolismo , Dipiridamol/metabolismo , Dipiridamol/farmacología , Dipiridamol/uso terapéutico , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Activación Plaquetaria , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios ProspectivosRESUMEN
Information regarding the profile of reticulated platelets (RP) in ischemic cerebrovascular disease (CVD) patients is limited. Data from two prospective, observational, case-control studies were combined to compare the %RP using whole blood flow cytometry in patients ≤ 4 weeks of TIA/stroke onset (baseline, N = 210), and 14 ±7 days (14d, N = 182) and ≥ 90 days (90d, N = 145) after starting or changing antiplatelet therapy with healthy controls (N = 34). There were no differences in median %RP between the overall CVD patient population at baseline or 14d vs. controls (P ≥ 0.2). However, the median %RP was significantly higher in CVD patients overall at 90d (P = .036), and in the subgroup of patients with "lacunar" TIA/ischemic stroke at baseline (P = .04) and at 90d (P = .01), but not at 14d (P = .06) vs. controls. There were no significant differences in the median %RP between other TIA/stroke subgroups and controls (P ≥ 0.05). Elevated circulating reticulated platelets, as a marker of increased platelet production/turnover, may occur following an ischemic event in a well-phenotyped TIA/ischemic stroke population overall, but may precede symptom onset at least in the subgroup with small vessel occlusion. These data improve our understanding of the profile of reticulated platelets in CVD patients.
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Plaquetas/metabolismo , Ataque Isquémico Transitorio/sangre , Estudios de Casos y Controles , Humanos , Estudios ProspectivosRESUMEN
BACKGROUND: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. METHODS: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup. DISCUSSION: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.
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Aspirina/farmacología , Plaquetas , Estenosis Carotídea/tratamiento farmacológico , Embolia Intracraneal/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/farmacología , Anciano , Aspirina/administración & dosificación , Plaquetas/efectos de los fármacos , Plaquetas/fisiología , Isquemia Encefálica/tratamiento farmacológico , Estenosis Carotídea/diagnóstico por imagen , Femenino , Humanos , Embolia Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/diagnóstico por imagen , Inhibidores de Agregación Plaquetaria/administración & dosificación , Estudios Prospectivos , Accidente Cerebrovascular/tratamiento farmacológico , Ultrasonografía Doppler TranscranealRESUMEN
INTRODUCTION: Cerebral micro-embolic signals (MES) predict risk of stroke in carotid stenosis patients. However, MES-negative 'recently symptomatic patients' also have a higher stroke risk than 'asymptomatic patients'. Differences in platelet activation status may contribute to this disparity in risk. METHODS: This prospective, observational study assessed platelet biomarkers and their relationship with MES in asymptomatic versus symptomatic moderate (≥50-69%) or severe (≥70-99%) carotid stenosis patients. Full blood count parameters were measured and whole-blood flow cytometry was used to quantify platelet surface CD62P and CD63 expression and leucocyte-platelet complex formation. Bilateral simultaneous transcranial Doppler ultrasound of the middle cerebral arteries classified patients as 'MES positive' or 'MES negative'. RESULTS: Data from 34 asymptomatic patients were compared with those from 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 of these symptomatic patients in the 'late phase' (≥ 3 months) after transient ischaemic attack/ischaemic stroke. There were no differences in %CD62P or %CD63 expression between early or late symptomatic and asymptomatic patients overall (p > 0.05). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients (2.8 vs. 2.16%; p < 0.001). MES were more commonly observed in early symptomatic (31.4%; p = 0.027) but not in late symptomatic (6.7%; p = 0.996) versus asymptomatic patients (7.1%). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic MES-negative patients (2.7 vs. 2.17%; p = 0.02). CONCLUSION: These data add to the evidence that leucocyte-platelet complex formation/platelet activation is increased in recently symptomatic versus asymptomatic patients, and may contribute to the pathogenesis of first and subsequent strokes in carotid stenosis patients, including those who are MES negative.
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Plaquetas/fisiología , Estenosis Carotídea/diagnóstico , Embolia Intracraneal/diagnóstico , Leucocitos/fisiología , Anciano , Enfermedades Asintomáticas , Comunicación Celular , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Activación Plaquetaria , Pronóstico , Estudios ProspectivosRESUMEN
A large fraction of atmospheric organic aerosol (OA) originates from natural emissions that are oxidized in the atmosphere to form secondary organic aerosol (SOA). Isoprene (IP) and monoterpenes (MT) are the most important precursors of SOA originating from forests. The climate impacts from OA are currently estimated through parameterizations of water uptake that drastically simplify the complexity of OA. We combine laboratory experiments, thermodynamic modeling, field observations, and climate modeling to (1) explain the molecular mechanisms behind RH-dependent SOA water-uptake with solubility and phase separation; (2) show that laboratory data on IP- and MT-SOA hygroscopicity are representative of ambient data with corresponding OA source profiles; and (3) demonstrate the sensitivity of the modeled aerosol climate effect to assumed OA water affinity. We conclude that the commonly used single-parameter hygroscopicity framework can introduce significant error when quantifying the climate effects of organic aerosol. The results highlight the need for better constraints on the overall global OA mass loadings and its molecular composition, including currently underexplored anthropogenic and marine OA sources.
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Several commonly completed tests have low diagnostic yield in the setting of transient loss of consciousness (T-LOC). We estimated the use and cost of inappropriate investigations in patients admitted with T-LOC and assessed if these patients were given a definitive diagnosis for their presentation. We identified 80 consecutive patients admitted with T-LOC to a university teaching hospital. Eighty-eight percent (70/80) had a computerized topography (CT) brain scan and 49% (34/70) of these scans were inappropriate based on standard guidelines. Almost half (17/80) of electroencephalograms (EEG) and 82% (9/11) of carotid doppler ultrasound performed were not based on clinical evidence of seizure or stroke respectively. Forty-four percent (35/80) of patients had no formal diagnosis documented for their presentation. Inappropriate investigation in T-LOC is very prevalent in the acute hospital, increasing cost of patient care. In addition, there is poor diagnostic formulation for T-LOC making recurrent events more likely in the absence of definitive diagnoses.
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Electroencefalografía/estadística & datos numéricos , Hospitalización , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Inconsciencia/etiología , Mal Uso de los Servicios de Salud/estadística & datos numéricos , Humanos , Prevalencia , Convulsiones/diagnóstico por imagen , Inconsciencia/diagnóstico por imagenRESUMEN
INTRODUCTION: Von Willebrand factor propeptide (VWF:Ag II) is proposed to be a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). Simultaneous data on VWF:Ag and VWF:Ag II profiles are very limited following TIA and ischaemic stroke. METHODS: In this prospective, observational, case-control study, plasma VWF:Ag and VWF:Ag II levels were quantified in 164 patients≤4weeks of TIA or ischaemic stroke (baseline), and then ≥14days (14d) and ≥90days (90d) later, and compared with those from 27 healthy controls. TIA and stroke subtyping was performed according to the TOAST classification. The relationship between VWF:Ag and VWF:Ag II levels and platelet activation status was assessed. RESULTS: 'Unadjusted' VWF:Ag and VWF:Ag II levels were higher in patients at baseline, 14d and 90d than in controls (p≤0.03). VWF:Ag levels remained higher in patients than controls at baseline (p≤0.03), but not at 14d or 90d after controlling for differences in age or hypertension, and were higher in patients at baseline and 90d after controlling for smoking status (p≤0.04). 'Adjusted' VWF:Ag II levels were not higher in patients than controls after controlling for age, hypertension or smoking (p≥0.1). Patients with symptomatic carotid stenosis (N=46) had higher VWF:Ag and VWF:Ag II levels than controls at all time-points (p≤0.002). There was no significant correlation between platelet activation status and VWF:Ag or VWF:Ag II levels. CONCLUSIONS: VWF:Ag and VWF:Ag II levels are increased in an overall TIA and ischaemic stroke population, especially in patients with recently symptomatic carotid stenosis. VWF:Ag II was not superior to VWF:Ag at detecting acute endothelial activation in this cohort and might reflect timing of blood sampling in our study.
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Ataque Isquémico Transitorio/sangre , Precursores de Proteínas/sangre , Accidente Cerebrovascular/sangre , Factor de von Willebrand/metabolismo , Anciano , Antígenos CD/sangre , Biomarcadores/sangre , Isquemia Encefálica/complicaciones , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria , Estudios Prospectivos , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiologíaAsunto(s)
Medicina Basada en la Evidencia/economía , Medicina Basada en la Evidencia/legislación & jurisprudencia , Infertilidad/economía , Infertilidad/terapia , Técnicas Reproductivas Asistidas/economía , Técnicas Reproductivas Asistidas/legislación & jurisprudencia , Instituciones de Atención Ambulatoria/economía , Instituciones de Atención Ambulatoria/legislación & jurisprudencia , Análisis Costo-Beneficio/legislación & jurisprudencia , Femenino , Humanos , Recién Nacido , Estudios Observacionales como Asunto , Embarazo , Resultado del Embarazo/epidemiología , Garantía de la Calidad de Atención de Salud/economía , Garantía de la Calidad de Atención de Salud/legislación & jurisprudencia , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Técnicas Reproductivas Asistidas/efectos adversos , Reino UnidoRESUMEN
The care of older persons accounts for an increasing proportion of the unscheduled care workload for acute hospitals. The recent development of acute medical assessment units (AMAU) has provided an alternative model for acute unscheduled care for all medical patients. Screening instruments have been developed to capture the higher levels of clinical complexity and medical comorbidities that older patients present with. The aim of this study was to report on the characteristics and outcomes for older patients reviewed in the AMAU of a tertiary referral university teaching hospital. Data on 3071 patients attending the unit over one year was prospectively collected and information on characteristics and outcomes for older patients retrieved. Older patients represented over one third (1066/3071, 35%) of those attending AMAU, and had an admission rate of nearly twice that of younger patients (60.5% vs 32%), highlighting the increased complexity of this group. Gerontologically attuned AMAUs have great potential to enhance care for frail older patients from the time of their acute presentation to hospital.
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Servicio de Urgencia en Hospital/organización & administración , Anciano Frágil/estadística & datos numéricos , Evaluación Geriátrica , Admisión del Paciente/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Evaluación Geriátrica/métodos , Evaluación Geriátrica/estadística & datos numéricos , Servicios de Salud para Ancianos/organización & administración , Hospitales Universitarios/estadística & datos numéricos , Humanos , Irlanda , Masculino , Modelos Organizacionales , Evaluación de Resultado en la Atención de Salud , Gravedad del Paciente , Centros de Atención Terciaria/estadística & datos numéricosRESUMEN
INTRODUCTION: The importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively assessed. METHODS: Plasma thrombin generation parameters from patients with moderate or severe (≥ 50%) asymptomatic carotid stenosis were compared with those from patients with symptomatic carotid stenosis in the early (≤ 4 weeks) and late phases (≥ 3 months) after TIA or stroke in this prospective, pilot observational study. Thrombin generation profile was longitudinally assessed in symptomatic patients with data at each time point. Bilateral transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed whenever possible to classify patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic, 46 'early symptomatic' and 35 'late symptomatic' patients were analysed. Peak thrombin (344.2 nM vs 305.3 nM; p = 0.01) and endogenous thrombin potential (1772.4 vs 1589.7; p = 0.047) were higher in early symptomatic than asymptomatic patients. Peak thrombin production decreased in symptomatic patients followed up from the early to late phase after TIA or stroke (339.7 nM vs 308.6 nM; p = 0.02). Transcranial Doppler ultrasound data were available in 25 asymptomatic, 31 early symptomatic and 27 late symptomatic patients. Early symptomatic MES-positive patients had a shorter 'time-to-peak thrombin' than asymptomatic MES-positive patients (p=0.04), suggesting a more procoagulant state in this early symptomatic subgroup. DISCUSSION: Thrombin generation potential is greater in patients with recently symptomatic than asymptomatic carotid stenosis, and decreases over time following TIA or stroke associated with carotid stenosis. These data improve our understanding of the haemostatic/thrombotic biomarker profile in moderate-severe carotid stenosis.
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Estenosis Carotídea/metabolismo , Embolia Intracraneal/metabolismo , Trombina/biosíntesis , Anciano , Estenosis Carotídea/tratamiento farmacológico , Femenino , Humanos , Embolia Intracraneal/diagnóstico por imagen , Embolia Intracraneal/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores de Riesgo , Ultrasonografía Doppler TranscranealRESUMEN
The Irish Health Information and Quality Authority (HIQA) published National Quality Standards for Residential Care Settings for Older People in 2009. We reported on experiences of general practitioners (GPs) in Dublin caring for nursing home patients (NHPs) in 2006. We revisit these experiences following publication of HIQA's standards. 400 GPs received an anonymous postal survey. Of 204 respondents, 145 (71%) felt NHPs required more contact time and 124 (61%) reported more complex consultations compared to other patients. Only 131 (64%) felt adequately trained in gerontology. 143 (70%) reported access to specialist advice, but only 6 (3%) reported a change in this following HIOA standards. 65 (32%) had witnessed substandard care in a NH, of which 16 (25%) made no report, similar figures to 2006. There remains similar levels of concern regarding patient complexity, substandard care, access to specialist support and training in the care of NHPs. Many GPs expressed uncertainty regarding their role in implementing HIQA standards.
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Médicos Generales/psicología , Médicos Generales/estadística & datos numéricos , Casas de Salud/normas , Atención Primaria de Salud/normas , Actitud del Personal de Salud , Humanos , Irlanda , Encuestas y CuestionariosRESUMEN
The impact of commencing or changing antiplatelet therapy on von Willebrand factor antigen (VWF:Ag) and von Willebrand factor propeptide (VWF:Ag II) levels has not been comprehensively assessed following TIA or ischaemic stroke. In this pilot, longitudinal, observational analytical study, VWF:Ag and VWF:Ag II levels were simultaneously quantified in platelet poor plasma by ELISA in patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Ninety-one patients were recruited. Eighteen were initially assessed on no antiplatelet therapy, and then after 14d (N = 17) and 90d (N = 8) on aspirin monotherapy; 21 patients were assessed on aspirin and after 14d and 90d on clopidogrel; 52 were assessed on aspirin monotherapy, and after 14d and 90d on aspirin and dipyridamole combination therapy. VWF:Ag, VWF:Ag II levels and VWF:Ag/VWF:Ag II ratio were unchanged at 14d and 90d in the overall study population (p ≥ 0.1). VWF:Ag and VWF:Ag II levels remained stable at 14d and 90d after commencing aspirin (p ≥ 0.054), and after changing from aspirin to clopidogrel (p ≥ 0.2). Following the addition of dipyridamole MR to aspirin, there was a significant reduction in VWF:Ag levels at 14d (p = 0.03) and 90d (p = 0.005), but not in VWF:Ag II levels (p ≥ 0.3). The addition of dipyridamole to aspirin led to a persistent reduction in VWF:Ag but not in VWF:Ag II levels, suggesting that dipyridamole may inhibit release of platelet-derived VWF:Ag following TIA or ischaemic stroke.
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Ataque Isquémico Transitorio/sangre , Ataque Isquémico Transitorio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Precursores de Proteínas/sangre , Accidente Cerebrovascular/tratamiento farmacológico , Factor de von Willebrand/metabolismo , Adulto , Anciano , Aspirina/uso terapéutico , Clopidogrel , Dipiridamol/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estadísticas no Paramétricas , Accidente Cerebrovascular/metabolismo , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Factores de TiempoRESUMEN
BACKGROUND: Cerebral microembolic signals (MES) may predict increased stroke risk in carotid stenosis. However, the relationship between platelet counts or platelet activation status and MES in symptomatic vs. asymptomatic carotid stenosis has not been comprehensively assessed. SETTING: University teaching hospitals. METHODS: This prospective, pilot observational study assessed platelet counts and platelet activation status, and the relationship between platelet activation and MES in asymptomatic vs. early (≤ 4 weeks after TIA/stroke) and late phase (≥ 3 months) symptomatic moderate or severe (≥ 50%) carotid stenosis patients. Full blood count measurements were performed, and whole blood flow cytometry was used to quantify platelet surface activation marker expression (CD62P and CD63) and circulating leucocyte-platelet complexes. Bilateral simultaneous transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed for 1 h to classify patients as MES positive or MES negative. RESULTS: Data from 31 asymptomatic patients were compared with 46 symptomatic patients in the early phase, and 35 of these patients were followed up to the late phase after symptom onset. The median platelet count (211 vs. 200 × 10(9) L(-1) ; P = 0.03) and the median percentage of lymphocyte-platelet complexes was higher in early symptomatic than asymptomatic patients (2.8 vs. 2.4%; P = 0.001). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients with ≥ 70% carotid stenosis (P = 0.0005) and symptomatic patients recruited within 7 days of symptom onset (P = 0.028). Complete TCD data were available in 25 asymptomatic, 31 early phase symptomatic and 27 late phase symptomatic patients. Twelve per cent of asymptomatic vs. 32% of early phase symptomatic (P = 0.02) and 19% of late phase symptomatic patients (P = 0.2) were MES positive. Early symptomatic MES-negative patients had a higher percentage of lymphocyte-platelet complexes than asymptomatic MES-negative patients (2.8 vs. 2.3%; P = 0.0085). DISCUSSION: Recently, symptomatic carotid stenosis patients have had higher platelet counts (potentially reflecting increased platelet production, mobilization or reduced clearance) and platelet activation status than asymptomatic patients. MES were more frequently detected in early symptomatic than asymptomatic patients, but the differences between late symptomatic and asymptomatic groups were not significant. Increased lymphocyte-platelet complex formation in recently symptomatic vs. asymptomatic MES-negative patients indicates enhanced platelet activation in this early symptomatic subgroup. Platelet biomarkers, in combination with TCD, have the potential to aid risk-stratification in asymptomatic and symptomatic carotid stenosis patients.
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Estenosis Carotídea/sangre , Embolia Intracraneal/sangre , Activación Plaquetaria , Anciano , Enfermedades Asintomáticas , Biomarcadores/sangre , Estenosis Carotídea/complicaciones , Estenosis Carotídea/inmunología , Distribución de Chi-Cuadrado , Femenino , Citometría de Flujo , Hospitales de Enseñanza , Humanos , Embolia Intracraneal/diagnóstico por imagen , Embolia Intracraneal/inmunología , Ataque Isquémico Transitorio/sangre , Ataque Isquémico Transitorio/inmunología , Modelos Lineales , Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Selectina-P/sangre , Proyectos Piloto , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/etiología , Tetraspanina 30/sangre , Factores de Tiempo , Ultrasonografía Doppler en Color , Ultrasonografía Doppler TranscranealRESUMEN
BACKGROUND AND PURPOSE: Intracranial haemorrhage in neurosarcoidosis (NS-ICH) is rare, poorly understood and the diagnosis of NS may not be immediately apparent. METHODS: The clinical features of three new NS-ICH cases are described including new neuropathological findings and collated with cases from a systematic literature review. CASES: (i) A 41-year-old man with headaches, hypoandrogenism and encephalopathy developed a cerebellar haemorrhage. He had neuropathological confirmation of NS with biopsy-proven angiocentric granulomata and venous disruption. He responded to immunosuppressive therapy. (ii) A 41-year-old man with no history of hypertension was found unconscious. A subsequently fatal pontine haemorrhage was diagnosed. Liver biopsy revealed sarcoid granulomas. (iii) A 36-year-old man with raised intracranial pressure headaches presented with a seizure and a frontal haemorrhage. Hilar lymph node biopsy confirmed sarcoidosis, and he was treated successfully. Systematic review: Twelve other published cases were identified and collated with our cases. Average age was 36 years and M:F = 2.3:1; 46% presented with neurological symptoms and 31% had CNS-isolated disease. Immediate symptoms of ICH were acute/worsening headache or seizures (60%). ICH was supratentorial (62%), infratentorial (31%) or subarachnoid (7%). Forty percent had definite NS, 53% probable NS and 7% possible NS (Zajicek criteria). Antigranulomatous/immunosuppressive therapy regimens varied and 31% died. CONCLUSIONS: This series expands our knowledge of the pathology of NS-ICH, which may be of arterial or venous origin. One-third have isolated NS. Clinicians should consider NS in young-onset ICH because early aggressive antigranulomatous therapy may improve outcome.
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Enfermedades del Sistema Nervioso Central/complicaciones , Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/etiología , Sarcoidosis/complicaciones , Adulto , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND AND PURPOSE: The prevalence of ex vivo 'high on-treatment platelet reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain. METHODS: HTPR was assessed with PFA-100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet activation (CD62P, CD63 and leucocyte-platelet complex formation) was assessed with whole-blood flow cytometry. Patients were assessed at baseline [≤ 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and ≥ 90 days after changing treatment from (i) no medication to aspirin monotherapy (N = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a novel, 'longitudinal fashion' as failure to prolong relevant closure times compared with the patient's 'baseline value' before he/she underwent an antiplatelet change by more than twice the coefficient of variation of the assay. RESULTS: (i) C-EPI closure times increased at 14 days and 90 days after commencing aspirin (P = 0.002); 24% at 14 days and 18% at 90 days demonstrated HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41% at 14 days, and 35% at 90 days demonstrated HTPR on clopidogrel. Platelet activation was unaffected by aspirin (P = 0.09). The percentage neutrophil-platelet complexes decreased at 14 days (P = 0.02), but this reduction was not maintained 90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent vascular event during prospective follow-up. CONCLUSIONS: Longitudinal definitions of HTPR in patients with ischaemic CVD who are undergoing a change in antiplatelet therapy have the potential to provide more clinically meaningful information than traditional 'cross-sectional definitions' of HTPR which are usually based on the comparison of patients' values with those in healthy controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be used to monitor ex vivo responsiveness to aspirin, and larger, prospective studies are warranted to assess the clinical predictive value of this and other platelet function tests in patients with ischaemic CVD.
Asunto(s)
Plaquetas/efectos de los fármacos , Ataque Isquémico Transitorio/fisiopatología , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Accidente Cerebrovascular/fisiopatología , Anciano , Aspirina/farmacología , Aspirina/uso terapéutico , Plaquetas/fisiología , Clopidogrel , Estudios Cruzados , Femenino , Humanos , Ataque Isquémico Transitorio/sangre , Ataque Isquémico Transitorio/inmunología , Leucocitos/fisiología , Masculino , Persona de Mediana Edad , Selectina-P/metabolismo , Proyectos Piloto , Activación Plaquetaria/fisiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/tratamiento farmacológico , Tetraspanina 30/metabolismo , Ticlopidina/análogos & derivados , Ticlopidina/farmacología , Ticlopidina/uso terapéuticoRESUMEN
BACKGROUND: Stroke patients' involvement in the rehabilitation process including decision making has made significant advances clinically over the past two decades. However, development of patient-focused interventions in stroke rehabilitation is a relatively under developed area of research. The aim of this study was to interpret the explanations that patients gave of their experience after stroke and how these may validate an already established patient-focused intervention framework - the Quest for quality and improved performance (QQUIP) (2006) that includes seven quality improvement goals. METHODS: A random purposive sample of eight stroke patients was interviewed between 3 and 6 months following discharge. Patients' reports of their experience after stroke were obtained using in-dept semi-structured interviews and analysed using Qualitative Content Analysis. RESULTS: Explanations given by patients included both positive and negative reports of the stroke experience. Regardless of consequences as a result of physical, psychological and social impairments, there were other life style disruptions that were reported by all patients such as taking new medication and adverse effects of these, experiencing increasing fatigue, difficulties with social activities and situations and having to make changes in health behaviours and lifestyle. Some of the core themes that emerged reflected the aims of QQUIP improvement goals that include improving health literacy, clinical decision-making, self-care, patient safety, access to health advice, care experience and service development. DISCUSSION: Further recommendations based on the findings from this study would be to consider using the QQUIP framework for developing intervention studies in stroke rehabilitation care that are person-centred. This framework provides a template that is equipped to address some of the main concerns that people have following the experience of stroke and also focuses on improving quality of care.
Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Adaptación Psicológica , Adulto , Afecto , Anciano , Anciano de 80 o más Años , Toma de Decisiones , Femenino , Alfabetización en Salud , Investigación sobre Servicios de Salud , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Atención Dirigida al Paciente , Mejoramiento de la Calidad , Apoyo Social , Accidente Cerebrovascular/psicologíaRESUMEN
The impact of changing antiplatelet therapy on thrombin generation potential in patients with ischaemic cerebrovascular disease (CVD) is unclear. We assessed patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Thrombin generation was assessed in platelet poor plasma. Ninety-one patients were recruited. Twenty-four were initially assessed on no antiplatelet therapy, and then after 14d (N = 23) and 90d (N = 8) on aspirin monotherapy; 52 were assessed on aspirin monotherapy, and after 14 and 90 days on aspirin and dipyridamole combination therapy; 21 patients were assessed on aspirin and after 14 days (N = 21) and 90 days (N = 19) on clopidogrel. Peak thrombin generation and endogenous thrombin potential were reduced at 14 and 90 days (p ≤ 0.04) in the overall cohort. We assessed the impact of individual antiplatelet regimens on thrombin generation parameters to investigate the cause of this effect. Lag time and time-to-peak thrombin generation were unchanged at 14 days, but reduced 90 days after commencing aspirin (p ≤ 0.009). Lag time, peak thrombin generation and endogenous thrombin potential were reduced at both 14 and 90 days after adding dipyridamole to aspirin (p ≤ 0.01). Lag time was reduced 14 days after changing from aspirin to clopidogrel (p = 0.045), but this effect was not maintained at 90 days (p = 0.2). This pilot study did not show any consistent effects of commencing aspirin, or of changing from aspirin to clopidogrel on thrombin generation potential during follow-up. The addition of dipyridamole to aspirin led to a persistent reduction in peak and total thrombin generation ex vivo, and illustrates the diverse, potentially beneficial, newly recognised 'anti-coagulant' effects of dipyridamole in ischaemic CVD.