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Platelet Activation (platelet + activation)
Kinds of Platelet Activation Terms modified by Platelet Activation Selected AbstractsEffects of Helicobacter pylori Eradication on Platelet Activation and Disease Recurrence in Patients with Acute Coronary SyndromesHELICOBACTER, Issue 6 2004J. Ignasi Elizalde ABSTRACT Background., Platelet activation is consistently observed in animal models of Helicobacter pylori infection and could help to explain the alleged epidemiological association between H. pylori and coronary heart disease. Materials and Methods., Ninety-two patients with recent acute coronary syndromes were enrolled. Helicobacter pylori -positive patients were randomized to receive a 7-day course of omeprazole, amoxycillin and metronidazole or placebos. Two months later, H. pylori status was reassessed and baseline parameters, including soluble P-selectin and platelet surface expression of CD62P, CD63 and CD41, were measured again. Patients were followed-up for 1 year or until death or readmission. Results., No baseline differences were observed between H. pylori -positive and -negative cases. Among H. pylori -positive patients, 18 received placebo and 31 received active medication resulting in eradication in 21 cases. No differences were observed in inflammatory parameters or platelet activation markers between patients with persistent or resolved H. pylori infection. However, coronary events recurred at 6 and 12 months, respectively, in 35% and 55% of patients with persisting H. pylori infection compared with 10% and 25% of patients in whom H. pylori was either absent or eradicated (p = .01). Only final H. pylori status [RR 3.07 (95% CI 1.35,98)] and number of coronary risk factors [RR 2.58 (95% CI 1.51,4.41)] were independent predictors of recurrence. Conclusions., Infection with H. pylori does not induce significant platelet activation in patients treated for coronary disease. Helicobacter pylori -infected patients, however, may have an increased risk of recurrence of coronary events. [source] Synthesis of Novel Peptide Inhibitors of Thrombin-induced Platelet ActivationCHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2006Fernanda M. Burke Inhibitors of the activation of platelet aggregation have promise as important therapeutic agents for the management of acute coronary syndrome (ACS). Platelet activation by thrombin, a serine protease, occurs by binding to and cleavage of the extracellular N-terminal domains of protease-activated receptors 1 and 4 (PAR1 and PAR4). The proteolysis of the PARs exposes new tethered ligands that then signal through transmembrane domains to initiate platelet activation as a downstream effect. A pentapeptide cleavage product of bradykinin with the sequence Arg-Pro-Pro-Gly-Phe serves as a thrombin inhibitor by blocking , - and , -thrombin-induced platelet aggregation. Analogs of RPPGF have been prepared that result in improved inhibition of thrombin activation of platelets. Specific amino acid residues required for activity against platelet aggregation have been identified, and a lead compound, rOicPaPhe(p -Me)-NH2 (FM19), has been developed. FM19, which completely inhibits threshold , -thrombin-induced platelet aggregation at a concentration of 16 ± 4 ,m, represents an important lead compound in the development of inhibitors of thrombin-mediated platelet aggregation for treatment of ACS. [source] Enhanced Prothrombin Formation and Platelet Activation in Chinese Patients After Transcatheter Closure of Atrial Septal DefectCLINICAL CARDIOLOGY, Issue 7 2010Xiao-Chun Zeng MD Background The objective of this study was to investigate changes in coagulation activation and platelet activation after transcatheter closure of atrial septal defect (ASD) by determining the levels of specific markers over time to provide insight into preventing postprocedural embolism. Hypothesis We hypothesis that the activation status of coagulation and the platelet would be changed after the closure of ASD. Methods Forty consecutive patients who underwent transcatheter closure of ASD with the Lifetech ASD occluder (Lifetech Scientific, Shenzhen, China) were included in this prospective study. The serum level of prothrombin fragment 1 + 2 (F1 + 2) and expressions of P-selectin (CD62P) and platelet glycoprotein IIb/IIIa receptor (CD41a) on the surface of platelets were evaluated at baseline and at 1 day, 1 month, and 3 months after the closure. Results The median F1 + 2 level was 0.96 nmol/L. This increased to a maximal value of 1.43 nmol/L at 1 day after closure, but gradually returned to the baseline level at 1 month after closure and remained there at 3 months after closure (medians were 0.98 nmol/L and 1.08 nmol/L, respectively). Platelet surface expression of CD62P and CD41a decreased at 1 day, 1 month, and 3 months after closure. For CD62P, average expressions were 8.21% ± 2.11%, 6.28% ± 1.72%, 5.29% ± 1.52%, and 4.41% ± 1.11%, respectively, for baseline and 1 day, 1 month, and 3 months after closure. For CD41a, average expressions were 79.37% ± 14.14%, 71.98% ± 13.77, 56.69% ± 13.05%, and 54.88% ± 11.62%, respectively. Conclusions Transcatheter closure of ASD with the Lifetech ASD occluder was associated with significantly increased coagulation activation and decreased platelet activation. No evidence supporting the use of aspirin to prevent thrombus formation after closure was found. Copyright © 2008 Wiley Periodicals, Inc. This work was supported by Guangxi Key Technologies R&D Programme, 0472002-30, China. The authors have no other funding, financial relationships, or conflicts of interest to disclose. [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] Effects of Helicobacter pylori Eradication on Platelet Activation and Disease Recurrence in Patients with Acute Coronary SyndromesHELICOBACTER, Issue 6 2004J. Ignasi Elizalde ABSTRACT Background., Platelet activation is consistently observed in animal models of Helicobacter pylori infection and could help to explain the alleged epidemiological association between H. pylori and coronary heart disease. Materials and Methods., Ninety-two patients with recent acute coronary syndromes were enrolled. Helicobacter pylori -positive patients were randomized to receive a 7-day course of omeprazole, amoxycillin and metronidazole or placebos. Two months later, H. pylori status was reassessed and baseline parameters, including soluble P-selectin and platelet surface expression of CD62P, CD63 and CD41, were measured again. Patients were followed-up for 1 year or until death or readmission. Results., No baseline differences were observed between H. pylori -positive and -negative cases. Among H. pylori -positive patients, 18 received placebo and 31 received active medication resulting in eradication in 21 cases. No differences were observed in inflammatory parameters or platelet activation markers between patients with persistent or resolved H. pylori infection. However, coronary events recurred at 6 and 12 months, respectively, in 35% and 55% of patients with persisting H. pylori infection compared with 10% and 25% of patients in whom H. pylori was either absent or eradicated (p = .01). Only final H. pylori status [RR 3.07 (95% CI 1.35,98)] and number of coronary risk factors [RR 2.58 (95% CI 1.51,4.41)] were independent predictors of recurrence. Conclusions., Infection with H. pylori does not induce significant platelet activation in patients treated for coronary disease. Helicobacter pylori -infected patients, however, may have an increased risk of recurrence of coronary events. [source] Antiplatelet Effect of Marchantinquinone, Isolated from Reboulia hemisphaerica, in Rabbit Washed PlateletsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2000CHANG-HUI LIAO Platelet activation is involved in serious pathological situations, including atherosclerosis and restenosis. It is important to find efficient antiplatelet medicines to prevent fatal thrombous formation during the course of these diseases. Marchantinquinone, a natural compound isolated from Reboulia hemisphaerica, inhibited platelet aggregation and ATP release stimulated by thrombin (0.1 units mL,1), platelet-activating factor (PAF; 2 ng mL,1), collagen (10 ,g mL,1), arachidonic acid (100 ,m), or U46619 (1 ,m) in rabbit washed platelets. The IC50 values of marchantinquinone on the inhibition of platelet aggregation induced by these five agonists were 62.0 ± 9.0, 86.0 ± 7.8, 13.6 ± 4.7, 20.9 ± 3.1 and 13.4 ± 5.3 ,m, respectively. Marchantinquinone inhibited thromboxane B2 (TxB2) formation induced by thrombin, PAF or collagen. However, marchantinquinone did not inhibit TxB2 formation induced by arachidonic acid, indicating that marchantinquinone did not affect the activity of cyclooxygenase and thromboxane synthase. Marchantinquinone did inhibit the rising intracellular Ca2+ concentration stimulated by the five platelet-aggregation inducers. The formation of inositol monophosphate induced by thrombin was inhibited by marchantinquinone. Platelet cAMP and cGMP levels were unchanged by marchantinquinone. The results indicate that marchantinquinone exerts antiplatelet effects by inhibiting phosphoinositide turnover. [source] The effects of vasoactive agents, platelet agonists and anticoagulation on thrombelastographyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2007J. Kawasaki Background:, Platelet activation is a critical step in primary hemostasis and clot formation. We tested a hypothesis that platelet stimulating effects of vasoactive agents or platelet agonists could be shown using thrombelastography (TEG®) as faster onset or increased clot strength. We further examined if TEG® could be modified to evaluate activated platelets as a reversal of anticoagulation in the presence of partial thrombin inhibition. Methods:, Blood samples were obtained from 126 non-cardiac surgical patients. Effects of vasoactive agents on TEG® and aggregometry were examined using epinephrine, norepinephrine, vasopressin, desmopressin acetate, milrinone and olprinone (Experiment I). Platelet agonists (epinephrine, ADP and collagen) were separately tested on TEG® (Experiment II). Effects of platelet agonists (ADP and collagen) on TEG® under anticoagulation in the absence or presence of abciximab were studied (Experiment III). We also tested antiplatelet effects of milrinone and olprinone in the presence of anticoagulants on TEG® (Experiment IV). Results:, Neither vasoactive agents nor platelet agonists affected TEG® or aggregometry results except for milrinone and olprinone on aggregometry (Experiment I, II). Platelet agonists facilitated clotting in the presence of anticoagulants (Experiment III). Abciximab-treated platelets still exhibited procoagulant effects in the presence of heparin, while not in the presence of argatroban (Experiment III). Platelet inhibition on the modified TEG® was more extensive with milrinone than olprinone, and it was dose dependent (Experiment IV). Conclusion:, Modified TEG® using heparin or argatroban might delineate the procoagulant effects of platelets by adding platelet specific agonist. [source] Platelet activation, myocardial ischemic events and postoperative non-response to aspirin in patients undergoing major vascular surgeryJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2007S. RAJAGOPALAN Summary.,Objectives:,Myocardial ischemia is the leading cause of postoperative mortality and morbidity in patients undergoing major vascular surgery. Platelets have been implicated in the pathogenesis of acute thrombotic events. We hypothesized that platelet activity is increased following major vascular surgery and that this may predispose patients to myocardial ischemia.Methods:,Platelet function in 136 patients undergoing elective surgery for subcritical limb ischemia or infrarenal abdominal aortic aneurysm repair was assessed by P-selectin expression and fibrinogen binding with and without adenosine diphosphate (ADP) stimulation, and aggregation mediated by thrombin receptor-activating peptide and arachidonic acid (AA). Cardiac troponin-I (cTnI) was performed.Results:,P-selectin expression increased from days 1 to 3 after surgery [median increase from baseline on day 3: 53% (range: ,28% to 212%, P < 0.01) for unstimulated and 12% (range: ,9% to 45%, P < 0.01) for stimulated]. Fibrinogen binding increased in the immediate postoperative period [median increase from baseline: 34% (range: ,46% to 155%, P < 0.05)] and decreased on postoperative day 3 (P < 0.05). ADP-stimulated fibrinogen binding increased on day1 (P < 0.05) and thereafter decreased. Platelet aggregation increased on days 1,5 (P < 0.05). Twenty-eight (21%) patients had a postoperative elevation (> 0.1 ng mL,1) of cTnI. They had significantly increased AA-stimulated platelet aggregation in the immediate postoperative period and on day 2 (P < 0.05), and non-response to aspirin (48% vs. 26%, P = 0.036).Conclusions:,This study has shown increased platelet activity and the existence of non-response to aspirin following major vascular surgery. Patients with elevated postoperative cTnI had significantly increased AA-mediated platelet aggregation and a higher incidence of non-response to aspirin compared with patients who did not. [source] Distribution and dynamic changes of sphingolipids in blood in response to platelet activationJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2006F. DAHM Summary.,Background:,Sphingolipids are signaling molecules in a range of biological processes. While sphingosine-1-phosphate (S1P) is thought to be abundantly stored in platelets and released upon stimulation, knowledge about the distribution and function of other sphingolipids in blood is lacking. Objectives:,To analyze the sphingolipid content of blood components with special emphasis on dynamic changes in platelets. Methods:,Blood components from mice and humans were prepared by gradient centrifugation and analyzed by liquid chromatography,mass spectrometry. Additionally, murine platelets were activated in vitro and in vivo. Results:,Isolated non-activated platelets of mice were devoid of S1P, but instead contained dihydrosphingosine-1-phosphate (dhS1P), along with a high concentration of ceramide. Activation of platelets in vitro led to a loss of dhS1P and an increase in sphingosine, accompanied by a reduction of ceramide content. Platelet activation in vivo led to an immediate and continuous rise of dhS1P in plasma, while S1P remained stable. The sphingolipid distribution of human blood was markedly different from mice. Human platelets contained dhS1P in addition to S1P. Conclusions:,Mouse platelets contain dhS1P instead of S1P. Platelet activation causes loss of dhS1P and breakdown of ceramide, implying ceramidase activation. Release of dhS1P from activated platelets might be a novel signaling pathway. Finally, the sphingolipid composition of mouse and human blood shows large differences, which must be considered when studying sphingolipid biology. [source] Platelet activation in type 2 diabetes mellitusJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2004P. Ferroni Summary., The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets. In particular, an altered platelet metabolism and changes in intraplatelet signaling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. A variety of mechanisms may be responsible for enhanced platelet aggregation. Among them, hyperglycemia may represent a causal factor for in vivo platelet activation, and may be responsible for nonenzymatic glycation of platelet glycoproteins, causing changes in their structure and conformation, as well as alterations of membrane lipid dynamics. Furthermore, hyperglycemia-induced oxidative stress is responsible for enhanced peroxidation of arachidonic acid to form biologically active isoprostanes, which represents an important biochemical link between impaired glycemic control and persistent platelet activation. Finally, increased oxidative stress is responsible for activation of transcription factors and expression of redox-sensitive genes leading to a phenotypic switch of endothelium toward an adhesive, pro-thrombotic condition, initial platelet activation, adhesion and subsequent platelet aggregate formation. All this evidence is strengthened by the results of clinical trials documenting the beneficial effects of metabolic control on platelet function, and by the finding that aspirin treatment may even be more beneficial in diabetic than in high-risk non-diabetic patients. Attention to appropriate medical management of diabetic patients will have great impact on long-term outcome in this high-risk population. [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] Fluorescence spectroscopic analysis of circulating platelet activation during coronary angioplastyLASERS IN SURGERY AND MEDICINE, Issue 5 2001Alexander Christov PhD Abstract Background and Objective Platelet activation during percutaneous transluminal coronary angioplasty (PTCA) initiates thrombus formation and plaque regrowth at sites of arterial injury, limiting procedure efficacy. We have developed a simple assay for circulating platelet activation based on fluorescence analysis of membrane fluidity and intracellular calcium concentration and light scattering analysis of platelet aggregation. Study Design/Materials and Methods Platelet activation state was measured in 45 patients undergoing angioplasty, before and after treatment with platelet inhibitors. Results PTCA alone produced a decrease in pyrene dimer formation (P0.0083) and an increase in light scattering at 650 nm (P0.0128). Treatment with ADP and GPIIb/IIIa receptor antagonists reduced PTCA induced changes in pyrene dimer formation. An unexpected decrease in pyrene dimer formation (P0.05) was detected when the GPIIb/IIIa receptor antagonist was given together with an ADP receptor antagonist. Conclusions 1) Analysis of membrane fluidity provides a sensitive marker for platelet activation state. 2) Reduced membrane fluidity after combined platelet inhibitor treatments suggests reduced antiplatelet efficacy. Lasers Surg. Med. 39:414,426, 2001. © 2001 Wiley-Liss, Inc. [source] Ridogrel, a dual thromboxane synthase inhibitor and receptor antagonist: anti-inflammatory profile in inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2000Carty Background: Thromboxanes, prostaglandins, reactive oxygen metabolites and pro-inflammatory cytokines are produced in excess in inflammatory bowel disease. Preliminary reports suggest that ridogrel, a thromboxane synthesis inhibitor and receptor blocker, may have therapeutic benefits in ulcerative colitis. Aims: To investigate the anti-inflammatory profile of ridogrel. Methods: The effects of ridogrel on the production of eicosanoids, reactive oxygen metabolites and cytokines by cultured inflamed colorectal mucosal biopsies were made using ELISA and chemiluminescence, reactive oxygen metabolite generation in a cell-free system, and platelet activation using flow cytometry. The effects of oral ridogrel on mucosal release of eicosanoids in two patients with active ulcerative colitis were assessed using rectal dialysis. Results: Ridogrel significantly reduced the release of thromboxane B2, but not prostaglandin E2 or tumour necrosis factor-,, from biopsies (P < 0.01 for 10 ,M ridogrel). Ridogrel showed no direct antioxidant activity but significantly reduced reactive oxygen metabolite production from cultured biopsies (P < 0.01 for 10 ,M ridogrel). Platelet activation in vitro was inhibited by ridogrel (P , 0.05 for , 10 ,M ridogrel). Mean rectal mucosal thromboxane B2 release was reduced to 86% of pre-treatment levels in two patients treated with oral ridogrel. Conclusions: Its inhibition of mucosal production of thromboxane B2, reactive oxygen metabolites, and of platelet activation, suggests that ridogrel could have a therapeutic role in inflammatory bowel disease. [source] Fibronectin-binding proteins of Staphylococcus aureus mediate activation of human platelets via fibrinogen and fibronectin bridges to integrin GPIIb/IIIa and IgG binding to the Fc,RIIa receptorMOLECULAR MICROBIOLOGY, Issue 1 2006J. Ross Fitzgerald Summary Staphylococcus aureus is a leading cause of infective endocarditis (IE). Platelet activation promoted by S. aureus resulting in aggregation and thrombus formation is an important step in the pathogenesis of IE. Here, we report that the fibrinogen/fibronectin-binding proteins FnBPA and FnBPB are major platelet-activating factors on the surface of S. aureus from the exponential phase of growth. Truncated derivatives of FnBPA, presenting either the fibrinogen-binding A domain or the fibronectin-binding BCD region, each promoted platelet activation when expressed on the surface of S. aureus or Lactococcus lactis, indicating two distinct mechanisms of activation. FnBPA-promoted platelet activation is mediated by fibrinogen and fibronectin bridges between the A domain and the BCD domains, respectively, to the low affinity form of the integrin GPIIb/IIIa on resting platelets. Antibodies recognizing the FnBPA A domain or the complex between the FnBPA BCD domains and fibronectin were essential for activation promoted by bacteria expressing the A domain or the BCD domain respectively. Activation was inhibited by a monoclonal antibody (IV-3) specific for the Fc,RIIa IgG receptor on platelets. We propose that the activation of quiescent platelets by bacteria expressing FnBPs involves the formation of a bridge between the bacterial cell and the platelet surface by (i) fibronectin and fibrinogen interacting with the low affinity form of GPIIb/IIIa and (ii) by antibodies specific to FnBPs that engage the platelet Fc receptor Fc,RIIa. Platelet activation by S. aureus clinical IE isolates from both the exponential and stationary phases of growth was completely inhibited by monoclonal antibody IV-3 suggesting that the IgG,Fc,RIIa interaction is of fundamental importance for platelet activation mediated by this organism. This suggests new avenues for development of therapeutics against vascular infections. [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] Platelets Influence Vascularized Organ Transplants from Start to FinishAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009A. D. Kirk This review relates the basic functions of platelets to specific aspects of organ allograft rejection. Platelet activation can occur in the donor or recipient before transplantation as well as during antibody- and cell-mediated rejection. Biopsies taken during organ procurement from cadaver donors have documented that activated platelets are attached to vascular endothelial cells or leukocytes. In addition, many patients waiting for transplants have activated platelets due to the diseases that lead to organ failure or as a result of interventions used to support patients before and during transplantation. The contribution of platelets to hyperacute rejection of both allografts and xenografts is well recognized. Intravascular aggregates of platelets can also be prominent in experimental and clinical transplants that undergo acute antibody or cell-mediated rejection. In acute rejection, platelets can recruit mononuclear cells by secretion of chemokines. After contact, monocytes, macrophages and T cells interact with platelets through receptor/ligand pairs, including P-selectin/PSGL-1 and CD40/CD154. There is a potential for therapy to inhibit platelet mediated immune stimulation, but it is counterbalanced by the need to maintain coagulation in the perioperative period. [source] The management of heparin-induced thrombocytopeniaBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2006David Keeling Abstract The Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology has produced a concise practical guideline to highlight the key issues in the management of heparin-induced thrombocytopenia (HIT) for the practicing physician in the UK. The guideline is evidence-based and levels of evidence are included in the body of the article. All patients who are to receive heparin of any sort should have a platelet count on the day of starting treatment. For patients who have been exposed to heparin in the last 100 d, a baseline platelet count and a platelet count 24 h after starting heparin should be obtained. For all patients receiving unfractionated heparin (UFH), alternate day platelet counts should be performed from days 4 to 14. For surgical and medical patients receiving low-molecular-weight heparin (LMWH) platelet counts should be performed every 2,4 d from days 4 to 14. Obstetric patients receiving treatment doses of LMWH should have platelet counts performed every 2,4 d from days 4 to 14. Obstetric patients receiving prophylactic LMWH are at low risk and do not need routine platelet monitoring. If the platelet count falls by 50% or more, or falls below the laboratory normal range and/or the patient develops new thrombosis or skin allergy between days 4 and 14 of heparin administration HIT should be considered and a clinical assessment made. If the pretest probability of HIT is high, heparin should be stopped and an alternative anticoagulant started at full dosage unless there are significant contraindications while laboratory tests are performed. Platelet activation assays using washed platelets have a higher sensitivity than platelet aggregation assays but are technically demanding and their use should be restricted to laboratories experienced in the technique. Non-expert laboratories should use an antigen-based assay of high sensitivity. Only IgG class antibodies need to be measured. Useful information is gained by reporting the actual optical density, inhibition by high concentrations of heparin, and the cut-off value for a positive test rather than simply reporting the test as positive or negative. In making a diagnosis of HIT the clinician's estimate of the pretest probability of HIT together with the type of assay used and its quantitative result (enzyme-linked immunosorbent assay, ELISA, only) should be used to determine the overall probability of HIT. Clinical decisions should be made following consideration of the risks and benefits of treatment with an alternative anticoagulant. For patients with strongly suspected or confirmed HIT, heparin should be stopped and full-dose anticoagulation with an alternative, such as lepirudin or danaparoid, commenced (in the absence of a significant contraindication). Warfarin should not be used until the platelet count has recovered. When introduced in combination with warfarin, an alternative anticoagulant must be continued until the International Normalised Ratio (INR) is therapeutic for two consecutive days. Platelets should not be given for prophylaxis. Lepirudin, at doses adjusted to achieve an activated partial thromboplastin time (APTT) ratio of 1·5,2·5, reduces the risk of reaching the composite endpoint of limb amputation, death or new thrombosis in patients with HIT and HIT with thrombosis (HITT). The risk of major haemorrhage is directly related to the APTT ratio, lepirudin levels and serum creatinine levels. The patient's renal function needs to be taken into careful consideration before treatment with lepirudin is commenced. Severe anaphylaxis occurs rarely in recipients of lepirudin and is more common in previously exposed patients. Danaparoid in a high-dose regimen is equivalent to lepirudin in the treatment of HIT and HITT. Danaparoid at prophylactic doses is not recommended for the treatment of HIT or HITT. Patients with previous HIT who are antibody negative (usually so after >100 d) who require cardiac surgery should receive intraoperative UFH in preference to other anticoagulants that are less validated for this purpose. Pre- and postoperative anticoagulation should be with an anticoagulant other than UFH or LMWH. Patients with recent or active HIT should have the need for surgery reviewed and delayed until the patient is antibody negative if possible. They should then proceed as above. If deemed appropriate early surgery should be carried out with an alternative anticoagulant. We recommend discussion of these complex cases requiring surgery with an experienced centre. The diagnosis must be clearly recorded in the patient's medical record. [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] Effects of warm-up on exercise capacity, platelet activation and platelet,leucocyte aggregation in patients with claudication ,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2005S. Pasupathy Background: The effects of exercise and warm-up were investigated in patients with claudication. Methods: This case,control crossover study involved two treadmill exercise tests, one preceded by a warm-up. Exercise continued until maximal leg pain (patients with claudication) or exhaustion (controls). Blood was taken before, and 5 and 60 min after exercise for flow cytometric analysis of platelet activation and platelet,leucocyte aggregation. Results: Both cohorts (eight patients with claudication of median age 63 years and eight healthy controls of median age 63·5 years) demonstrated improvement in exercise capacity after warm-up (13·1 per cent, P = 0·012 and 15·6 per cent, P = 0·008 respectively). Platelet activation increased after exercise in patients with claudication (fibrinogen binding: 1·11 per cent before exercise versus 2·63 per cent after exercise, P = 0·008; P-selectin: 0·68 versus 1·11 per cent, P = 0·028). Neither agonist stimulation nor warm-up altered this trend. Platelet,leucocyte (PLA) and platelet,neutrophil (PNA) aggregation were similarly increased immediately after exercise in patients with claudication (PLA: 7·6 versus 13·0 per cent, P = 0·004; PNA: 6·8 versus 10·2 per cent, P = 0·012). These remained high 60 min after exercise only in patients with claudication, but recovered to baseline levels when preceded by warm-up. Warm-up significantly desensitized PNA after stimulation with 10 µmol/l adenosine 5,-diphosphate at all time points. Conclusion: Warm-up increased the exercise capacity of patients with claudication. Exercise induced a thromboinflammatory response, with PLA and PNA persistently increased after 60 min in patients with claudication, an effect diminished after warm-up. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Synthesis of Novel Peptide Inhibitors of Thrombin-induced Platelet ActivationCHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2006Fernanda M. Burke Inhibitors of the activation of platelet aggregation have promise as important therapeutic agents for the management of acute coronary syndrome (ACS). Platelet activation by thrombin, a serine protease, occurs by binding to and cleavage of the extracellular N-terminal domains of protease-activated receptors 1 and 4 (PAR1 and PAR4). The proteolysis of the PARs exposes new tethered ligands that then signal through transmembrane domains to initiate platelet activation as a downstream effect. A pentapeptide cleavage product of bradykinin with the sequence Arg-Pro-Pro-Gly-Phe serves as a thrombin inhibitor by blocking , - and , -thrombin-induced platelet aggregation. Analogs of RPPGF have been prepared that result in improved inhibition of thrombin activation of platelets. Specific amino acid residues required for activity against platelet aggregation have been identified, and a lead compound, rOicPaPhe(p -Me)-NH2 (FM19), has been developed. FM19, which completely inhibits threshold , -thrombin-induced platelet aggregation at a concentration of 16 ± 4 ,m, represents an important lead compound in the development of inhibitors of thrombin-mediated platelet aggregation for treatment of ACS. [source] Platelet activation in asthma: integral to the inflammatory responseCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2006S. C. Pitchford No abstract is available for this article. [source] Modulation of platelet activation and initial cytokine release by alloplastic bone substitute materialsCLINICAL ORAL IMPLANTS RESEARCH, Issue 3 2010M. O. Klein Abstract Objectives: Platelet-derived cytokines play a crucial role in tissue regeneration. In regenerative dental medicine, bone substitute materials (BSM) are widely used. However, initial interactions of BSM and platelets are still unknown. The aim of this study was to evaluate the potential of platelet activation and subsequent initial cytokine release by different commercial alloplastic BSM. Material and methods: Eight commercial BSM of different origins and chemical compositions (tricalcium phosphate, hydroxyapatite, bioactive glass: SiO2 and mixtures) were incubated with a platelet concentrate (platelet-rich plasma, PRP) of three healthy volunteers at room temperature for 15 min. Platelet count, aggregation, degranulation (activated surface receptor CD62p) and cytokine release (Platelet-derived growth factor, Vascular endothelial growth factor) into the supernatant were quantified. Highly thrombogenic collagen served as a reference. Results: The investigated PRP samples revealed different activation patterns when incubated with different BSM. In general, SiO2 -containing BSM resulted in high platelet activation and cytokine release. In detail, pure bioactive glass promoted platelet activation most significantly, followed by hybrid BSM containing lower ratios of SiO2. Additionally, we found indications of cytokine retention by BSM of large specific surfaces. Conclusions: Platelet activation as well as consecutive storage and slow release of platelet-derived cytokines are desirable attributes of modern BSM. Within the limits of the study, SiO2 -containing BSM were identified as promising biomaterials. Further investigations on cytokine adsorption and cytokine release kinetics by the respective BSM have to be conducted. To cite this article: Klein MO, Kämmerer PW, Scholz T, Moergel M, Kirchmaier CM, Al-Nawas B. Modulation of platelet activation and initial cytokine release by alloplastic bone substitute materials. Clin. Oral Impl. Res. 21, 2010; 336,345 doi: 10.1111/j.1600-0501.2009.01830.x [source] Endothelin attenuates endothelium-dependent platelet inhibition in manACTA PHYSIOLOGICA, Issue 4 2010R. E. Malmström Abstract Aim:, The vascular endothelium produces several substances, including nitric oxide (NO) and endothelin-1 (ET-1), which participate in the regulation of vascular tone in humans. Both these substances may exert other actions of importance for cardiovascular disease, e.g. effects on vascular smooth muscle cell proliferation and inflammation, and NO inhibits platelet function. Experiments were designed to investigate the effect of ET-1 on endothelium-dependent vasodilatation and attenuation of platelet activation. Methods:, In 25 healthy male subjects (25 ± 1 years), forearm blood flow was measured by venous occlusion plethysmography, and platelet activity was assessed by whole blood flow cytometry (platelet fibrinogen binding and P-selectin expression) in unstimulated and adenosine diphosphate (ADP)-stimulated samples during administration of ET-1, the endothelium-dependent vasodilator acetylcholine and the NO synthase inhibitor l -NMMA. Results:, Acetylcholine increased forearm blood flow and significantly inhibited platelet activation in both unstimulated and ADP-stimulated samples. In samples stimulated with 0.3 ,m ADP, fibrinogen binding decreased from 41 ± 4% to 31 ± 3% (P < 0.01, n = 11) after acetylcholine administration. The vasodilator response to acetylcholine was significantly impaired during infusions of ET-1 and l -NMMA. ET-1 did not affect platelet activity per se, whereas l -NMMA increased platelet P-selectin expression. Both ET-1 and l -NMMA attenuated the acetylcholine-induced inhibition of platelet activity. Conclusions:, Our study indicates that, further to inhibiting endothelium-dependent vasodilatation, ET-1 may also attenuate endothelium-dependent inhibition of platelet activation induced by acetylcholine. An enhanced ET-1 activity, as suggested in endothelial dysfunction, may affect endothelium-dependent platelet modulation and thereby have pathophysiological implications. [source] Vinculin is proteolyzed by calpain during platelet aggregation: 95 kDa cleavage fragment associates with the platelet cytoskeletonCYTOSKELETON, Issue 4 2004Katherine Serrano Abstract The focal adhesion protein vinculin contributes to cell attachment and spreading through strengthening of mechanical interactions between cell cytoskeletal proteins and surface membrane glycoproteins. To investigate whether vinculin proteolysis plays a role in the influence vinculin exerts on the cytoskeleton, we studied the fate of vinculin in activated and aggregating platelets by Western blot analysis of the platelet lysate and the cytoskeletal fractions of differentially activated platelets. Vinculin was proteolyzed into at least three fragments (the major one being ,95 kDa) within 5 min of platelet activation with thrombin or calcium ionophore. The 95 kDa vinculin fragment shifted cellular compartments from the membrane skeletal fraction to the cortical cytoskeletal fraction of lysed platelets in a platelet aggregation-dependent manner. Vinculin cleavage was inhibited by calpeptin and E64d, indicating that the enzyme responsible for vinculin proteolysis is calpain. These calpain inhibitors also inhibited the translocation of full-length vinculin to the cytoskeleton. We conclude that cleavage of vinculin and association of vinculin cleavage fragment(s) with the platelet cytoskeleton is an activation response that may be important in the cytoskeletal remodeling of aggregating platelets. Cell Motil. Cytoskeleton 58:242,252, 2004. © 2004 Wiley-Liss, Inc. [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] Genetic influence in antithrombotic actions of atorvastatin in hypercholesterolaemiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2008L. Puccetti ABSTRACT Background, Recent data indicate that statins could offer coronary artery disease (CAD) benefit even by mechanisms beyond lipid lowering. Genetic influence has been shown for some antithrombotic actions of statins via oxidized-low-density lipoprotein cholesterol (ox-LDL) receptors and nitric oxide synthase (NOS) activity modulation. The present study was designed to evaluate the influence of ox-LDL lectin-like receptor-1 (LOX-1) and NOS polymorphisms in the incidence of cardiovascular events in pure hypercholesterolaemic subjects during statin treatment. Materials and methods, A prospective 4-year study involving 1039 event-free subjects (643 males, 396 females) treated with atorvastatin (10,40 mg day,1) to reach the appropriate Adult Treatment Panel-III LDL target of 3·36 mmol L,1. Enrolled subjects were evaluated every 6 months or at a clinical event. LOX-1 3,UTR/T-C and NOS G894T polymorphisms were detected by allelic discrimination assays (polymerase chain reaction), lipid profile by enzymatic-colorimetric method, ox-LDL by enzyme linked immunosorbent assay, platelet activation by P-selectin (P-sel) expression (FACScan), NOS activity (by intracellular citrullin recovery) and homocysteine (high performance liquid chromatography), C-reactive protein (CRP) by sensitive nephelometric technique. Results, LOX-1 3,UTR/T showed the strongest association with events in the whole cohort with respect to each other variable including LDL reduction and NOS G894T (OR 4·90, 95% CI 3·19,6·98, P < 0·00001). Smoking influenced events in LDL-targeted subjects (P < 0·0001). Ox-LDL and P-sel were better indicators than LDL or other variables according to 3,UTR/C genotype regardless of the magnitude of LDL reduction (OR 4·21, 95% CI 2·29,6·70 P < 0·0001). Conclusions, LOX-1 polymorphisms could influence statin effectiveness in CAD prevention by induction of sensitivity to antithrombotic mechanisms such as antiplatelet activity. [source] Aldosterone antagonism in heart failure: improvement of cardiac remodelling, endothelial dysfunction and platelet activationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2004J. Bauersachs First page of article [source] Prognostic value of interleukin-6, plasma viscosity, fibrinogen, von Willebrand factor, tissue factor and vascular endothelial growth factor levels in congestive heart failureEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2003B. S. P. Chin Abstract Background, Congestive heart failure (CHF) carries a poor prognosis with a high mortality rate, frequent hospitalizations and increased risk of thrombotic complications such as stroke. Cytokines may contribute to the progression and prothrombotic state of CHF, including the pro-inflammatory interleukin-6 (IL-6) and the pro-angiogenic vascular endothelial growth factor (VEGF), both of which are raised in CHF. The procoagulant properties of both cytokines may be mediated via tissue factor (TF), a potent clotting activator. We hypothesized that plasma levels of these markers, as well as levels of plasma viscosity, fibrinogen, soluble P-selectin and von Willebrand factor (markers of abnormal rheology, clotting, platelet activation, and endothelial damage, respectively) will be useful in predicting morbidity and mortality in chronic stable CHF. Methods and results, One hundred and twenty consecutive out-patients with chronic stable CHF (92 males; mean [SD] age 64 [11] years, mean [SD] left ventricular ejection fraction of 29 [6]%) were recruited and followed for 2 years during which 42 patients reached a clinical end-point of all-cause mortality and cardiovascular hospitalizations, including stroke and myocardial infarction. Plasma IL-6 (P = 0·003) and TF (P = 0·013) levels, but not other research indices, were higher in those who suffered events compared with those without events. Predictors of end-points were high (, median) TF (P = 0·011), and IL-6 (P = 0·023) levels, as well as the lowest quartile of a left ventricular ejection fraction (P = 0·007). A strong correlation was present between TF and IL-6 levels (r = 0·59; P < 0·0001) and with VEGF levels (r = 0·43; P < 0·0001). Conclusion, IL-6 and TF are predictors of poor prognosis in chronic CHF, raising the hypothesis that IL-6 may contribute to the progression and thrombotic complications of CHF via its actions on TF expression. Although VEGF did not independently predict outcome in chronic CHF, the possibility arises that it may act with IL-6 to induce TF expression. [source] Increased circulating platelet,leukocyte aggregates in myeloproliferative disorders is correlated to previous thrombosis, platelet activation and platelet countEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2001Morten Krogh Jensen Abstract: Platelet,leukocyte adhesion may occur as a consequence of platelet activation and possibly plays a key role in the deposition of activated platelets and fibrin in the thrombotic plug. The aim of the present study was to assess by whole blood flow cytometry the presence of circulating platelet,leukocyte aggregates (PLA) and the platelet,leukocyte response to platelet agonist stimulation (ADP and TRAP) in 50 patients with chronic myeloproliferative disorders (MPD) and 30 controls. PLA were identified as platelet,granulocyte/monocyte aggregates (PGMA), platelet,monocyte aggregates (PMA) and defined as the percentage of leukocytes coexpressing the platelet-specific marker glycoprotein Ib. Compared to controls the mean percentage of PGMA and PMA was increased in unstimulated whole blood from patients with MPD (7.98 vs. 1.76%; p<0.001 and 12.34 vs. 3.2%; p<0.001, respectively). The percentage of PGMA was correlated to the platelet count (r=0.46; p<0.001), percentage of P-selectin (r=0.69; p<0.001) and thrombospondin (r=0.58; p<0.001) positive platelets and platelet expression of GPIV (r=0.33; p=0.02). The mean percentage of PGMA and PMA was significantly increased in ADP-stimulated whole blood of patients (57.14 vs. 47.92%; p=0.009 and 54.91 vs. 45.89%; p<0.001, respectively). Compared to patients without a history of thrombosis, patients having experienced microvascular disturbances or a thrombotic event had a higher mean percentage of PGMA and PMA in non-stimulated whole blood (10.07 vs. 6.34%; p=0.025 and 14.81 vs. 10.48%; p=0.021, respectively) and a higher percentage of PGMA in ADP stimulated whole blood (64.32 vs. 51.50%; p<0.01). These data document an increased frequency of PLA in non-stimulated whole blood in MPD associated with a previous history of thrombosis or microvascular disturbances. [source] Antiplatelet ,resistance' and ,non-responders': what do these terms really mean?FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2009Victor L. Serebruany Abstract The term ,resistance' should be restricted to very specialized physiologic circumstances, if not abandoned altogether. The term ,non-responder' needs to be placed in the context of the question: ,Non-responder to what?' Even if we would somehow magically know what an optimal response to antiplatelet therapy was, it will still be challenging to demonstrate an ,inadequate' response to antiplatelet therapy. At present there are two alternatives , give more drug or give additional drugs. Both strategies may work in further inhibiting platelet function, but both strategies can also be associated with an increased risk of bleeding. The trick, for the future, much as with our antihypertensive and lipid-lowering armamentaria, will be to know in whom to do what with which drug, and why. Single isolated measurements are not useful , if you don't know where you started, how we would know that antiplatelet drug is producing an ,adequate' clinical effect? There is no evidence of any sort of absolute ,threshold' that must be exceeded for treatment to be effective, and in the absence of this, if we are to evaluate the effect of a given drug, we have to have baseline values (off drug), therapeutic values (on drug), and some sort of assessment of both resting (unstimulated) and agonist-provoked (stimulated) platelet function. Moreover, given all of the different things that platelets do, the ideal assessment of platelet function and drug responsiveness will need to incorporate more than one agonist and some sort of assessment of both platelet activation and platelet aggregation. No one man (or test) tells us everything; it is the totality of the information that gives us the most complete picture. And, ultimately, we need to more firmly establish how the variability in platelet function and drug-associated changes in that function correlates with long-term, hard-endpoint clinical events. [source] | |||||||||||||||||||||||||||||||||||||