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Platelet Reactivity (platelet + reactivity)
Selected AbstractsHeritability of platelet function in families with premature coronary artery diseaseJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2007P. F. BRAY Summary.,Background:,Variations in platelet function among individuals may be related to differences in platelet-related genes. The major goal of our study was to estimate the contribution of inheritance to the variability in platelet function in unaffected individuals from white and African American families with premature coronary artery disease.Methods:,Platelet reactivity, in the absence of antiplatelet agents, was assessed by in vitro aggregation and the platelet function analyzer closure time. Heritability was estimated using a variance components model.Results:,Both white (n = 687) and African American (n = 321) subjects exhibited moderate to strong heritability (h2) for epinephrine- and adenosine diphosphate-induced aggregation (0.36,0.42 for white and >0.71 for African American subjects), but heritability for collagen-induced platelet aggregation in platelet-rich plasma was prominent only in African American subjects. Platelet lag phase after collagen stimulation was heritable in both groups (0.47,0.50). A limited genotype analysis demonstrated that the C825T polymorphism of GNB3 was associated with the platelet aggregation response to 2 ,M epinephrine, but the effect differed by race.Conclusions:,Considering the few and modest genetic effects reported to affect platelet function, our findings suggest the likely existence of undiscovered important genes that modify platelet reactivity, some of which affect multiple aspects of platelet biology. [source] Does Bipolar Pacemaker Current Activate Blood Platelets?PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2009GRUNDE GJESDAL M.D. Objective: The aim of this study was to investigate whether bipolar pacemaker current lead can activate blood platelets. The null hypothesis was that 1 minute of electrical stimulation of platelets would not influence their subsequent reactivity to adenosine diphosphate (ADP). Background: Both platelets and muscle cells contain actin and myosin filaments, and both cells are activated following calcium influx. Muscle cells open their calcium channels and contract when exposed to an electric current. Current through a bipolar pacemaker lead will expose a small volume of blood, including platelets, to the depolarizing current. Platelet activation may ensue, resulting in aggregation, release reaction, and contraction. In contrast, a unipolar pacemaker system will not depolarize blood, but transmit current directly into the myocardium, and the current afterward passes through other tissues before returning to the pacemaker can. Methods: Platelet-rich plasma was prepared from two healthy subjects. Platelet reactivity to the agonist ADP was tested in paired samples in an aggregometer in a case/control setup. Results: Eighteen of 46 tested pairs of platelet-rich plasma showed increased reactivity in the paced sample; 26 were unchanged while two showed decreased reactivity in the paced sample. Using a two-sided sign test, the null hypothesis was rejected (P = 0.0004). Conclusions: The study demonstrates increased reactivity to ADP in platelets exposed in vitro to stimulation by pacemaker current. The clinical relevance of these findings remains to be investigated. [source] Platelet activation and secretion in patients with major depression, thoracic aortic atherosclerosis, or renal dialysis treatmentDEPRESSION AND ANXIETY, Issue 3 2002Dominique L. Musselman M.D., M.S. Abstract Relatively little is known concerning the magnitude of alterations of platelet activation and secretion markers of patients with major depression when compared to patients at increased risk for, or with current, clinically significant atherosclerosis. Markers of in vivo platelet stimulation and secretion were measured under basal conditions in normal comparison subjects (n = 12) and three patient groups: patients diagnosed with DSM-IV major depression (n = 15), dialysis-dependent patients (n = 12), and patients with severe thoracic aortic atherosclerosis (n = 10). In comparison to normal comparison subjects, depressed patients and patients with thoracic aortic atherosclerosis exhibited the greatest platelet stimulation as detected by increased anti-LIBS platelet binding. Dialysis-dependent patients exhibited the highest plasma concentrations of the renally-excreted platelet-specific secretion protein, ,-thromboglobulin. This study extends previous observations of increased platelet activation in patients with major depression and documents similar alterations in patients with transesophageal echocardiography (TEE)-documented thoracic aortic atherosclerosis. Future studies will determine whether the magnitude of platelet stimulation and secretion in patients with comorbid depression and atherosclerotic aortic disease is greater than that observed in nondepressed patients with atherosclerotic aortic disease or major depression alone. These findings provide further evidence for either increased platelet activation and/or intrinsic heightened platelet reactivity as one of the biological substrates underlying the increased risk of depressed patients for cardiovascular disease. Depression and Anxiety 15:91,101, 2002. © 2002 Wiley-Liss, Inc. [source] The Rationale for and Comparisons of Different Antiplatelet Treatments in Acute Coronary SyndromeJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2008PAUL A. GURBEL M.D. Fundamentally, acute coronary syndromes are platelet-centric diseases, resulting from platelet-rich thrombi that develop at the site of vessel wall injury. In addition to aggregation, platelets modulate a plethora of other important pathophysiologic processes, including inflammation and coagulation. Therefore, a primary goal of therapy in the acute setting should be treatment with agents that provide predictable and superior platelet inhibition to prevent further ischemic events that develop from unchecked high platelet reactivity. Translational research studies of patients undergoing percutaneous revascularization have clearly demonstrated that adverse thrombotic outcomes are associated with high platelet reactivity and the latter is now emerging as a potent measurable cardiovascular risk factor. The intensity of antithrombotic therapy is influenced by patient risk. In the highest risk patients with elevated cardiac biomarkers indicative of myonecrosis, current guidelines support the use of early therapy with glycoprotein IIb/IIIa inhibition, aspirin, and clopidogrel. [source] Heritability of platelet function in families with premature coronary artery diseaseJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2007P. F. BRAY Summary.,Background:,Variations in platelet function among individuals may be related to differences in platelet-related genes. The major goal of our study was to estimate the contribution of inheritance to the variability in platelet function in unaffected individuals from white and African American families with premature coronary artery disease.Methods:,Platelet reactivity, in the absence of antiplatelet agents, was assessed by in vitro aggregation and the platelet function analyzer closure time. Heritability was estimated using a variance components model.Results:,Both white (n = 687) and African American (n = 321) subjects exhibited moderate to strong heritability (h2) for epinephrine- and adenosine diphosphate-induced aggregation (0.36,0.42 for white and >0.71 for African American subjects), but heritability for collagen-induced platelet aggregation in platelet-rich plasma was prominent only in African American subjects. Platelet lag phase after collagen stimulation was heritable in both groups (0.47,0.50). A limited genotype analysis demonstrated that the C825T polymorphism of GNB3 was associated with the platelet aggregation response to 2 ,M epinephrine, but the effect differed by race.Conclusions:,Considering the few and modest genetic effects reported to affect platelet function, our findings suggest the likely existence of undiscovered important genes that modify platelet reactivity, some of which affect multiple aspects of platelet biology. [source] Platelet hyperreactivity generalizes to multiple forms of stimulationJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2006D. L. YEE Summary.,Background:,Although platelet hyperreactivity constitutes an important cardiovascular risk factor, standardized methods for its measurement are lacking. We recently reported that aggregometry using a submaximal concentration of epinephrine identifies individuals with in vitro platelet hyperreactivity; this hyperreactivity was reproducible on multiple occasions over long periods of time. Objective and methods:,To better understand this aberrant reactivity, we studied in a large group of subjects (n = 386) the relationship between healthy individuals' platelet reactivity to epinephrine and their platelet phenotype as measured by other functional assays. Results:,Subjects with hyperreactivity to epinephrine were more likely to exhibit hyperfunction in each major aspect of platelet activity, including adhesion (response to low-dose ristocetin; P < 0.001), activation (surface P-selectin expression and PAC-1 binding after stimulation; P , 0.003) and aggregation to other agonists [no agonist, adenosine diphosphate (ADP), arachidonic acid, collagen, collagen-related peptide and ristocetin; P , 0.025] and to applied shear stress (PFA-100 and cone-and-plate viscometer; P < 0.05). These differences persisted after adjusting for demographic and hematologic differences between groups. We studied candidate genes relevant to epinephrine-mediated platelet activation and found that hyperreactivity to epinephrine was associated with a polymorphism on the gene (GNB3) encoding the beta-3 subunit of G proteins (P = 0.03). Conclusions:,Robust aggregation to a submaximal concentration of epinephrine establishes a true hyperreactive platelet phenotype that is ,global' as opposed to agonist specific; detection of this phenotype could be useful for studying patients at risk for arterial thrombosis. The mechanisms underlying hyperreactivity to different types of platelet stimulation may share common signaling pathways, some of which may involve specific G protein subunits. [source] High postclopidogrel platelet reactivity in non-ST-elevation acute coronary syndrome treated with stenting: a clue for adverse prognosis?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2006M. GALVANI [source] Antistreptokinase platelet-activating antibodies are common and heterogeneousJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2003V. Regnault Summary.,Background:,Platelet activation by antistreptokinase (SK) antibodies could impair the clinical effect of SK administration. Objective:,To better describe anti-SK antibodies with particular emphasis on procoagulant activities as a result of platelet activation. Patients and methods:,Sera were collected from 146 patients with coronary artery disease: non-SK-treated, 95 from mainland France, 31 from French Polynesia; 20 patients from mainland in year 2 after SK treatment. Serum-induced SK-dependent platelet activation resulting in procoagulant activities was assessed with washed platelets from five donors representative of the known patterns of reactivities to IgG. Results:,Concentrations (2,5252 µg mL,1) and fibrinolytic neutralization titres (< 10 to >,1280) were found in the expected wide range and correlated (, = 0.66, P < 0.0001). Platelet activation was detected with 145 samples, but varied in intensity and pattern (depending on the donors), although there was no systematic hierarchy; it was presumably due to IgG (inhibited by an IgG Fc receptor-blocking antibody and recovered in the IgG fraction) and only partially affected by aspirin. Marked platelet activation could be detected in samples with concentration as low as 2 µg mL,1, and/or no detectable neutralizing titers. The way of immunization to SK was not found to influence the functional profile of antibodies. Conclusion:,Anti-SK platelet-activating antibodies are widespread, heterogeneous, poorly predictable on the basis of their antifibrinolytic effect and strong enough to trigger procoagulant activities. Their clinical relevance should be formally assessed, using patients' own platelets for detection owing to the variation of platelet reactivity. [source] Decreased Platelet Function in Cavalier King Charles Spaniels with Mitral Valve RegurgitationJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2003Inge Tarnow With aggregometry, increased platelet activity has been reported in Cavalier King Charles Spaniels (CKCS) without mitral regurgitation (MR). In contrast, dogs with MR have been found to have decreased platelet activity. The purpose of this study was to test an easy bedside test of platelet function (the Platelet Function Analyzer [PFA-100]) to see if it could detect an increase in platelet activity in CKCS without MR and a decrease in platelet activity in CKCS with MR. This study included 101 clinically healthy dogs 1 year of age: 15 control dogs of different breeds and 86 CKCS. None of the dogs received medication or had a history of bleeding. The PFA-100 evaluates platelet function in anticoagulated whole blood under high shear stress. Results are given as closure times (CT): the time it takes before a platelet plug occludes a hole in a membrane coated by agonists. The CT with collagen and adenosine-diphosphate as agonists was similar in control dogs (median 62 seconds; interquartile interval 55,66 seconds) and CKCS with no or minimal MR (55; 52,64 seconds). The CT was higher in CKCS with mild MR (regurgitant jet occupying 15,50% of the left atrial area) (75; 60,84 seconds; P= .0007) and in CKCS with moderate to severe MR (jet 50%) (87; 66,102 seconds; P < .0001). CKCS with mild, moderate, and severe, clinically inapparent MR have decreased platelet function. The previous finding of increased platelet reactivity in nonthrombocytopenic CKCS without MR could not be reproduced with the PFA-100 device. [source] Relationship of serum interleukin-7 concentration and the coagulation state in children with nephrotic syndromePEDIATRICS INTERNATIONAL, Issue 4 2005Anna Wasilewska Abstract, Background:,Enhanced platelet reactivity may play a significant role in the hypercoagulable state of nephrotic syndrome (NS). Thrombocytosis with platelet aggregation cause the release of some cytokines, among them interleukin-7 (IL-7). The aim of the study was to evaluate serum IL-7 levels in children with the symptoms of NS and to determine a correlation between its concentration and platelet count, other hemostatic factors, and NS intensity. Methods:,The study was performed in two groups. I , the examined group of 26 children with NS (12 boys, 14 girls) aged 6.8 ± 2.1 years, subjected to two examinations: A , before treatment, B , during treatment with prednisone (60 mg/kg 24 h after albuminuria regression); and II , the control group (C) of 20 healthy children. Serum IL-7 level was assayed by enzyme-linked immunosorbent assay method using a R & D Quantikine set. Results:,In group I, IL-7 level in examination A (33.33 ± 33.24 pg/mL) was higher than in the control subjects (P < 0.01). In examination B, IL-7 concentration was reduced to the level of 10.86 ± 5.22 pg/mL and did not differ from the controls (P > 0.05). A positive correlation was observed between IL-7 and platelet count and serum fibrinogen level. A negative correlation was noted with antithrombin III concentration. No correlation was found with serum levels of albumin and cholesterol or urine protein. Conclusion:,In children with NS, serum IL-7 level increases proportionally to the elevated platelet count and other hemostatic components, but shows no correlation with serum albumin or urine protein. [source] Reduced Blood Platelet Sensitivity to Aspirin in Coronary Artery Disease: Are Dyslipidaemia and Inflammatory States Possible Factors Predisposing to Sub-optimal Platelet Response to Aspirin?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2006Leszek Markuszewski Platelet non-responsiveness to aspirin is associated with an increased risk of serious cardiovascular events. Several environmental and hereditary factors are reportedly involved in sub-optimal acetylsalicylic acid response. Forty-five coronary artery disease patients and 45 non-coronary artery disease controls received acetylsalicylic acid at a daily dose of 75,150 mg. Controls were examined twice: on the day of entering the study and 10 days later. Urinary 11-dehydrothromboxane B2 was assessed as the marker of platelet thromboxane generation. Aggregation was studied in platelet-rich plasma using turbidimetric aggregometry with collagen and arachidonic acid. Fifty to seventy percent of coronary artery disease patients showed an extent of collagen-induced aggregation above the upper quartile of the reference range compared with 8,15% in controls (P<0.003). For arachidonic acid-activated aggregation these proportions were 45,50% in coronary artery disease versus 7% in controls (P<0.007). In coronary artery disease patients, the acetylsalicylic acid-mediated platelet inhibition positively correlated with increased triglycerides (in arachidonic acid-stimulated platelets, r=0.30, P=0.0018), total cholesterol (r=0.33, P<0.0001 in coll and arachidonic acid-activated platelets) and elevated serum C-reactive protein (CRP) (r=0.27, P=0.0024). In coronary artery disease patients urine 11-dehydrothromboxane B2 concentrations were significantly increased compared to controls after 10 day acetylsalicylic acid intake (563; 313,728 pg/mg creatinine versus 321; 246,488 pg/mg creatinine, P=0.04). The incidence of suboptimal acetylsalicylic acid response incidence was more common in patients with coronary artery disease. Acetylsalicylic acid inhibition of blood platelet reactivity and thromboxane generation was less effective in these patients. Dyslipidaemia and chronic inflammatory states may promote suboptimal acetylsalicylic acid response in coronary artery disease patients. [source] High glucose levels enhance platelet activation: involvement of multiple mechanismsBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2006Dzana Sudic Summary Diabetes mellitus (DM) and hyperglycaemia are associated with platelet activation. The present study was designed to investigate how high glucose levels influence platelet function. Fasting human blood was incubated with different concentrations of d -glucose (5, 15 and 30 mmol/l) and other sugars without or with in vitro stimuli. Platelet activation was monitored by whole blood flow cytometry. High glucose levels enhanced adenosine diphosphate (ADP)- and thrombin receptor-activating peptide (TRAP)-induced platelet P-selectin expression, and TRAP-induced platelet fibrinogen binding. Similar effects were seen with 30 mmol/l l -glucose, sucrose and galactose. Hyperglycaemia also increased TRAP-induced platelet-leucocyte aggregation. Protein kinase C (PKC) blockade did not counteract the enhancement of platelet P-selectin expression, but abolished the enhancement of TRAP-induced platelet fibrinogen binding by hyperglycaemia. Superoxide anion scavenging by superoxide dismutase (SOD) attenuated the hyperglycaemic enhancement of platelet P-selectin expression, but did not counteract the enhancement of TRAP-induced platelet fibrinogen binding. Hyperglycaemia did not alter platelet intracellular calcium responses to agonist stimulation. Blockade of cyclo-oxygenase (COX), phosphotidylinositol-3 (PI3) kinase, or nitric oxide synthase, or the addition of insulin did not influence the effect of hyperglycaemia. In conclusion, high glucose levels enhanced platelet reactivity to agonist stimulation through elevated osmolality. This occurred via superoxide anion production, which enhanced platelet P-selectin expression (secretion), and PKC signalling, which enhanced TRAP-induced fibrinogen binding (aggregablity). [source] Antiplatelet drug response variability and the role of platelet function testing: A practical guide for interventional cardiologists,CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 1 2009Dominick J. Angiolillo MD Abstract Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndrome and is also of particular importance in those who undergo percutaneous coronary intervention with stent implantation. Dual antiplatelet therapy with aspirin and clopidogrel is associated with improvement in long-term clinical outcomes in such patients and is presently the antiplatelet therapy of choice for secondary prevention of thrombotic events. However, a significant number of patients experience recurrent events despite antiplatelet therapy. Although poor patient compliance can account for some of these events, particularly in those patients who receive a drug-eluting stent, increasing evidence indicates that there is variability in response to antiplatelet therapy and patients who have higher levels of platelet reactivity are at increased risk for recurrent ischemic events. However, the lack of a consistent definition of inadequate platelet response, as well as the lack of a standardized measurement technique, has made it difficult to define how to treat these patients. To translate findings associated with variability in platelet response into improved patient care, it is necessary to gain a better understanding of what variable platelet response is, how it is measured, who it should be measured in, and what its clinical relevance is. The objective of this review is to evaluate the data regarding interindividual response variability to antiplatelet therapy with the aim of providing practical considerations and where possible, recommendations, regarding this topic for interventional cardiologists. © 2008 Wiley-Liss, Inc. [source] Resistance to thienopyridines: Clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylationCATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 3 2003Paul Barragan MD Abstract We carried out a prospective evaluation of a new vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay in order to detect patients with high-risk coronary subacute stent thrombosis (SAT) despite thienopyridine regimen. Twenty healthy donors (group 1) without any medication were compared to 16 stented patients (group 2) treated by ticlopidin or clopidogrel initiated 2 days before stenting and aspirin (250 mg/day). No difference in platelet reactivity was noted between group 1 and group 2 treated only with aspirin (72.00% ± 4.17% vs. 69.73% ± 5.62%, respectively; P = NS). Significant differences were found between patients of group 2 treated with aspirin alone (69.73% ± 5.62%), after 2.0 days (60.14% ± 9.60%; P < 0.05), and after 4.8 ± 1.3 days (48.37% ± 11.19%; P < 0.05) with thienopyridine-aspirin. Among 1,684 consecutive stented patients, 16 patients who presented an SAT (group 3) were compared with 30 other stented patients free of SAT (group 4). We found a significant difference between group 3 (63.28% ± 9.56%) and group 4 (39.80% ± 10.9%; P < 0.0001). VASP phosphorylation analysis may be useful for the detection of coronary SAT. Cathet Cardiovasc Intervent 2003;59:295,302. © 2003 Wiley-Liss, Inc. [source] | ||||||||||