Platelet Activation In Patients Research Articles

Iron Deficiency Generates Secondary Thrombocytosis and Platelet Activation in IBD

Secondary thrombocytosis is a common clinical feature. In patients with cancer, it is a risk factor for venous thromboembolic events. In inflammatory bowel disease (IBD), thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population. Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis. Here, we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis. We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L). Changes in platelet counts, hemoglobin, iron parameters, disease activity, megakaryopoietic growth factors, erythropoietin, and platelet activity were assessed. Patients received placebo or up to 1500 mg iron as FCM. Endpoints were evaluated at week 6. A total of 26 patients were included in the study, 15 patients were available for the per protocol analysis. A drop in platelets >25% (primary endpoint) was observed in 4 of 8 (50%, iron group) and 1 of 7 patients (14%, placebo group, P = 0.143). Mean platelet counts dropped on FCM but not on placebo (536 G/L to 411 G/L versus 580 G/L to 559 G/L; P = 0.002). Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM. The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression. FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.

AB0218 Plasma heparanase levels are elevated in patients with antiphospholipid syndrome and correlate with platelet activation

BackgroundOverexpression of tissue factor (TF) and activation of the coagulation system are characteristic pathophysiology of antiphospholipid syndrome (APS). Heparanase (HPSE) is an endo-b-D-glucuronidase that cleaves heparan sulfate chains on cell...

OC-024 Prolonged Platelet Activation in Patients with Acute Upper Gastrointestinal Bleeding: Abstract OC-024 Table 1

Introduction Acute upper gastrointestinal bleeding (AUGIB) is a common reason for hospital admission and is associated with significant cardiovascular (CVS) morbidity and mortality. Patients who have aspirin withheld for 8 weeks following AUGIB have significantly higher rates of CVS events. 1 We previously demonstrated that patients with AUGIB have significantly higher levels of platelet activation during the index hospital admission. 2 This study aimed to assess the level of platelet activation and reactivity 12 weeks following admission for AUGIB. Methods Patients admitted to SWBH NHS Trust with AUGIB were recruited. Dyspeptic patients attending for diagnostic OGD were used as controls. To assess platelet activation citrated whole blood was incubated at room temperature with monoclonal mouse antibodies against constitutively expressed platelet marker CD42a-PerCP, and markers of platelet activation PAC1-FITC, and CD62P-APC. Incubation was terminated after 15 minutes. Samples were analysed using a FACSCalibur flow cytometer. Platelets were identified on the basis of their forward and side scatter properties and the presence of the CD42a platelet-specific marker. CD62P and PAC1 expression were measured by the percentage of platelets expressing these markers. Data are expressed as mean±SD for normally distributed parameters and median (interquartile range) for non-normally distributed parameters. Statistical analysis was performed using SPSS 18.0 software. Results A total of 24 patients with AUGIB and 18 controls were recruited. Patients were age and gender matched. The mean age of the AUGIB group is 66.4 ± 18.2 years, and the control group 62.8 ± 6.1years. Significant differences were seen in all markers of platelet activation (table 1). Conclusion Patients presenting with AUGIB have prolonged levels of platelet activation for at least 12 weeks following the index event. This phenomenon may be further prolonged and further studies are required. This may explain the excess of CVS events in AUGIB patients. In patients with high cardiovascular risk early re-introduction of aspirin should be considered. Disclosure of Interest None Declared References Sung JJ, Lau JY, Ching JY, Wu JC, Lee YT, Chiu PW, Leung VK, Wong VW, Chan FK. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomised trial. Ann Intern Med. 2010 Jan 5; 152(1):1–9. Disney BR, Watson R, Blann A, Lip G, Tselepis C, Anderson M. Platelet activation in acute upper gastrointestinal bleeding. Gut 2012; 61 (Suppl 2): A361.

THU0053 Anti-TNF Treatment Results in a Lower Activation State and Prothrombotic Profile of Platelets from Patients with Rheumatoid Arthritis

BackgroundCardiovascular disease is the major cause of mortality in patients with rheumatoid arthritis (RA) and it is not fully explained by traditional risk factors. Some evidence exists that RA treatment,...

Impact of diabetes on platelet activation in different manifestations of atherosclerosis

Atherosclerosis affects many patients with type 2 diabetes. Both are associated with platelet activation, but it remains unclear how diabetes contributes to, or even enhances, platelet activation in patients with atherosclerosis. We therefore investigated the impact of diabetes on platelet activation and protease activated receptor-1 (PAR-1) mediated platelet response in patients with symptomatic coronary artery disease (CAD), as compared with other manifestations of atherosclerosis. Baseline P-selectin expression, thrombin receptor activating peptide-6 (TRAP-6) inducible P-selectin, and relative increase of platelet P-selectin after activation with TRAP-6 were measured using flow cytometry in platelets from 317 patients after angioplasty and stenting for symptomatic atherosclerotic disease, and from 50 healthy controls. Patients with symptomatic atherosclerosis exhibited significantly higher levels of baseline P-selectin expression, TRAP-6-inducible P-selectin and relative increase of platelet P-selectin after stimulation with TRAP-6 than healthy controls. Patients with symptomatic peripheral artery disease or cerebrovascular disease (PAD/CVD) had higher levels of platelet activation and PAR-1-mediated platelet reactivity than patients with symptomatic CAD. Of interest, CAD patients with diabetes responded more strongly to TRAP-6 than those without diabetes, and their platelet activation and PAR-1-mediated platelet reactivity resembled those from PAD/CVD patients. Compared with healthy controls, platelets from patients with symptomatic atherosclerotic disease are activated and susceptible to PAR-1-mediated activation. Diabetes affects platelet reactivity only in patients with symptomatic CAD, while other manifestations of atherosclerosis may have an overwhelming effect on platelet reactivity that is not further enhanced by diabetes.

Platelet activation in chronic urticaria and its correlation with disease severity

Chronic urticaria (CU) is characterized by the occurrence of wheals lasting for more than 6 weeks. The role of platelet activation in the pathophysiology of this condition has not been clearly studied. We undertook a cross-sectional study among 45 patients with CU and 45 age- and gender-matched healthy controls. The severity of the disease was assessed using the urticaria severity score. The autologous plasma skin test (APST) was done in all cases of CU. The platelet count and indices were estimated by an automated haematological laser optical analyzer. Platelet aggregation and soluble P-selectin levels were estimated in all study participants. It was observed that there was a significantly higher mean platelet volume (MPV) and platelet distribution width (PDW) in patients with CU when compared to controls. Platelet aggregation and soluble P-selectin levels were significantly higher in patients with CU, as compared to controls. Urticaria severity score correlated positively with platelet aggregability and soluble P-selectin levels. APST-positive patients had significantly higher platelet aggregation and higher soluble P-selectin levels, when compared to the APST-negative patients, indicating more platelet activation in the autoimmune group. There is significant platelet activation in patients with CU, especially in those with autoreactivity.

Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study

ObjectiveThe inflammatory cytokine, tumour necrosis factor α (TNF-α), exerts deleterious cardiovascular effects. We wished to determine the effects of TNF-α antagonism on endothelial function and platelet activation in patients with...

Increased Mean Platelet Volume in Hypertrophic Cardiomyopathy

Thromboembolic events may be seen in patients with hypertrophic cardiomyopathy (HCM). We investigated the mean platelet volume (MPV), an indicator of platelet activation in patients with HCM. This study included 112 patients with HCM, in which 40 were patients with hypertrophic obstructive cardiomyopathy (HOCM), and 106 were control participants. The MPV was significantly higher in patients with HCM than in controls (9.1 ± 0.3 vs 7.9 ± 0.3 fL, P = .01). In the subgroup analyses, MPV was also higher in patients with HOCM compared to those with hypertrophic nonobstructive cardiomyopathy (HNCM; 9.3 ± 0.3 vs 9.0 ± 0.2 fL, P = .01). Similarly, patients with HNCM had higher MPV values than controls (9.0 ± 0.2 vs 7.9 ± 0.3 fL, P = .01). The MPV was significantly and positively correlated with left ventricular outflow tract (LVOT) obstruction (r = .42, P = .001) and septal thickness (r =.62, P = .001). In linear regression analysis, MPV was independently associated only with septal thickness (β = .07, 95% confidence interval: 0.04-0.09, P = .001). The MPV can be elevated in patients with HCM regardless of the obstruction of LVOT and may be associated with the severity of septal thickness.

Platelet volume as a parameter for platelet activation in patients with endometrial cancer

The objective of this study was to use mean platelet volume (MPV) as a measure of platelet activation in patients with endometrial adenocarcinoma and healthy controls. There was a total of 310 patients with endometrial adenocarcinoma retrospectively evaluated and 250 healthy controls. Preoperative haemoglobin, platelet counts and mean platelet volume were evaluated and statistical tests were conducted to determine the differences among early and advanced disease groups and controls. Median haemoglobin (13.0 vs 13.3 g/dl) and platelet count (282,000 vs 280,000/μl) values were similar in patients with endometrial adenocarcinoma and healthy controls (p > 0.05). Subjects with endometrial cancer exhibited slightly higher MPV than the control group (8.4 fl vs 8.2 fl) (p = 0.048). In patients with advanced-stage endometrial cancer, haemoglobin was significantly lower (p < 0.05) and MPV was significantly higher (p < 0.05) than in either patients with early-stage endometrial cancer or the control group. It was concluded that MPV was found to be a marker for predicting advanced-stage endometrial cancers.

Advances in antiplatelet technologies to improve cardiovascular disease morbidity and mortality: a review of ticagrelor.

Antiplatelet therapy is widely used with proven benefit for the prevention of further ischemic cardiac complications in patients with acute coronary syndrome. Treatment guidelines for acute coronary syndrome and percutaneous coronary intervention now recommend the use of oral antiplatelet agents including ticagrelor, prasugrel, or clopidogrel in combination with aspirin to comprise dual antiplatelet therapy for the prevention of recurrent ischemic events. The limitations of conventional antiplatelet therapy with clopidogrel or prasugrel include the potential for low response to clopidogrel identified through platelet reactivity or genetic testing, increased risk of bleeding with prasugrel, or slower return to normal platelet activity in patients who received either prasugrel or clopidogrel prior to emergent or planned surgical procedures. This review will discuss the pharmacokinetic and pharmacodynamic properties of ticagrelor in comparison to conventional P2Y12 receptor inhibitors and its utility in patients identified as low responders to clopidogrel. Completed clinical studies and substudies comparing ticagrelor to clopidogrel and ongoing clinical trials evaluating ticagrelor in acute coronary syndrome patients will also be reviewed.

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Relationship between mean platelet volume and mitral annular calcification

Mitral annular calcification (MAC) is associated with several cardiovascular disorders including coronary artery disease (CAD), atherosclerosis, heart failure, and stroke. MAC and atherosclerosis share similar clinical risk factors for cardiovascular diseases, including age, obesity, hypertension, hyperlipidemia, and diabetes mellitus. The aim of this study was to assess the mean platelet volume (MPV), an indicator of platelet activation in patients with MAC. The study group consisted of 101 patients with MAC. An age, sex, and BMI matched control group was composed of 55 patients who were admitted to the echocardiography laboratory due to suspicion of organic heart disease and eventually found to be free of MAC. We measured platelet indices values in patients and controls. MPV was significantly higher in patients with MAC than in controls (8.9 ± 0.8 versus 8.0 ± 0.9 fl, respectively; P < 0.001) and platelet distribution width (PDW) was significantly higher in patients with MAC than in controls (15.8 ± 1.3 versus 15.0 ± 1.3%, respectively; P < 0.001). MPV was positively correlated with MAC (P < 0.001, r = 0.47), atrial fibrillation (P = 0.01, r = 0.19), left atrial (P = 0.02, r = 0.83) and negatively correlated with platelet count (P = 0.01, r = -0.20). MPV [odds ratio (OR) 3.89; 95% confidence interval (CI) 1.97-7.67; P < 0.0001], and PDW (OR 2.27; 95% CI 1.45-3.55; P < 0.0001) were independently associated with the MAC. We have shown that MPV and PDW were significantly elevated in patients with MAC. MPV was correlated with MAC, atrial fibrillation and left atrial and negatively correlated with platelet count. MPV and PDW were independently associated with MAC.

The Effect of Perioperative Immunonutrition on the Phagocytic Activity of Blood Platelets in Advanced Gastric Cancer Patients

Background and Aims. Perioperative immunonutrition can influence the phagocytic activity of platelets in advanced gastric cancer. Methods. 51 patients with stage IV gastric cancer divided into four groups depending on the clinical status and 40 normal donors were analyzed. Patients of groups I and II underwent palliative gastrectomy. Patients of groups III and IV had exploratory laparotomy. Perioperative immunonutrition was administered as follows: group I—TPN, II—oral arginine, peripheral TPN, III—TPN preoperatively, and IV—without nutrition. The phagocytic activity of blood platelets was determined before and after nutritional therapy and was assessed by measuring the fraction of phagocytic thrombocytes (%phag) and the phagocytic index (Ixphag). Results. The percentage of phagocytizing platelets and the phagocytic index prior to and after the surgery amounted to the following: group I—1.136–1.237, P = NS, and 1.007–1.1, P = NS, respectively, II—1.111–1.25, P < 0.05, and 1.011–1.083, P < 0.05, III—1.112–1.186, P = NS, and 0.962–1.042, P = NS, and IV—1.085–0.96, P = NS, and 1.023–1.04, P = NS. Conclusions. The phagocytic activity of platelets in patients with advanced gastric cancer is significantly impaired. Perioperative immunonutrition with oral arginine-rich diet can partially improve the phagocytic activity of blood platelets. This trial is registred with Clinicaltrials.gov-NCT01704664.

A study of leukocyte and platelet activity in patients with suicide attempt related to acute stres reaction

Aim: Acute stress reaction (ASR) is often seen with depression, and stress-related hormones may play an important role in acute arterial thrombosis by increasing platelet aggregation. To the best of our knowledge, no study has examined leukocyte and platelet counts following a suicide attempt with ASR. Method: The present study examined blood leukocyte, platelet and mean platelet volume (MPV) levels. In addition, we examined the factors affecting these parameters. Data for patients who were admitted to the emergency room and evaluated by same psychiatrist after a suicide attempt were obtained from the health registries. Controls were selected from all residents living in the same area. Using a case-control design, we examined 30 suicide cases and 33 controls matched for gender and age. Results: The 30 subjects diagnosed with ASR related suicide showed increased white blood cell counts but similar platelet counts and mean platelet volume compared with controls. At follow-up, the platelet count was lower in patients than in controls (p= 0.001), which was related to suicide attempts by using anti-depressants (p= 0.003). Conclusion: ASR did not increase platelet count or MPV, but we found an increase in leukocyte counts following ASR. Additionally, our study supported the antiplatelet effect of antidepressant medications.

Aspergillus fumigatus Activates Thrombocytes by Secretion of Soluble Compounds

During invasive aspergillosis, platelets might be involved in immune defense, but they also might contribute to the pathology of the disease. We tested the hypothesis that Aspergillus secretes factors that influence the activity and functionality of thrombocytes. Platelets were incubated with medium wherein Aspergillus fumigatus was grown. This fungal culture supernatant potently stimulated thrombocytes in a time- and dose-dependent fashion, inducing release of alpha and dense granules, membrane alterations, aggregation, and formation of microparticles. Fungus-induced platelet activation could be confirmed in vivo: thrombocytes from mice infected with A. fumigatus showed a higher activation level than platelets from noninfected animals. Two stimulating components in the fungal culture supernatant were identified: a fungal serine protease and the mycotoxin gliotoxin. Activation of platelets by fungal factors stimulates antifungal functions: platelets gain the capacity to interact with foreign particles, and they become able to inhibit fungal growth, thus supporting the host immune network. However, some consequences of platelet activation might also be harmful, including excessive inflammation and induction of thrombosis. These findings imply that measuring platelet activation in patients might be an interesting diagnostic parameter.

Mean Platelet Volume Is Increased in Infective Endocarditis and Decreases after Treatment

Objectives: The aim of this study was to assess the mean platelet volume (MPV), an indicator of platelet activation in patients with infective endocarditis. Subjects and Methods: Twenty-nine patients with infective endocarditis and 29 healthy subjects were studied. Plasma MPV values in patients and control subjects were measured on admission and after 2 weeks of specific treatment of infective endocarditis. Results: The MPV was significantly higher among patients with infective endocarditis when compared with the control group (9.86 ± 1.1 vs. 8.0 ± 1.0 fl, respectively; p < 0.01). The MPV values of patients with infective endocarditis decreased significantly after treatment from 9.86 ± 1.1 to 7.86 ± 1.0 fl (p < 0.01). Total platelet counts increased significantly after treatment from 193.4 ± 96.5 × 10⁹ to 243.7 ± 92.4 × 10⁹ (p = 0.04). Conclusion: MPV values were higher in patients with infective endocarditis and decreased significantly after treatment. Elevated MPV values indicate that patients with infective endocarditis have increased platelet activation and infective endocarditis treatment decreases this platelet activation by decreasing MPV.

Abstract 18765: PAR-1 Contributes to the Innate Immune Response to Viral Infection

Objective: Viral infections activate the blood coagulation cascade as part of the host defense response. Coagulation proteases, such as thrombin, induce cellular responses by cleaving protease-activated receptors (PARs). It has been proposed that infections are detected by a dual-sensor system consisting of PARs and Toll-like receptors (TLRs). In this study, we analyzed the role of PAR-1 in host defense against infection with coxsackievirus B3 (CVB3) and influenza A virus. Methods: Wild-type (WT) and PAR-1 deficient (PAR-1 -/- ) mice were infected with either CVB3 or influenza A (H1N1/PR8). The innate immune response, viral load and inflammation were was analyzed. Bone-marrow transplantation experiments were performed to identify the cellular source of PAR-1 contributing to the innate immune response to CVB3. In addition, we analyzed the effect of PAR-1 activation on TLR3-dependent induction of interferon-β and CXCL10 expression in culture cardiac fibroblasts. Results: PAR-1 -/- mice exhibited a reduced innate immune response to both viral infections that led to higher viral titers and inflammation compared to WT mice. PAR-1 -/- mice also exhibited increased CVB3-induced myocarditis. Bone marrow transplantation experiments demonstrated that PAR-1 on non-hematopoietic cells played a role in CVB3 infection, and mice overexpressing PAR-1 on cardiomyocytes had reduced myocarditis. Stimulation of PAR-1 on mouse cardiac fibroblasts enhanced p38 activation and TLR3-dependent induction of interferon-β and CXCL10. Conclusion: Our results indicate that activation of PAR-1 contributes in a p38-dependent manner to the innate immune response to viral infection. The use of PAR-1 inhibitors to reduce platelet activation in patients with cardiovascular disease may increase their susceptibility to virus infections.

The levels of β-thromboglobulin in female rheumatoid arthritis patients as activation criteria

The activation of the platelets plays a key role in the formation of thrombosis. The variables such as mean platelet volume, platelet factor 4 and β-thromboglobulin have been used in the demonstration of the platelet activation. However, when the literature was reviewed, there was not found any study investigating the level of β-thromboglobulin in patients with rheumatoid arthritis. Our goal is to evaluate the β-thromboglobulin levels together with mean platelet volume in patients with arthritis. This study is a clinical study which has a control group that has been designed prospectively, and in this study, Rheumatology Outpatient Clinic follow-up patients with rheumatoid arthritis and healthy control group were studied. All patients and healthy volunteers were examined β-thromboglobulin and mean platelet volume. Twenty-two patients with rheumatoid arthritis and 21 healthy volunteers participated in the study. β-Thromboglobulin mean was found as 98.00 ± 60.49 ng/mL in rheumatoid arthritis group and it was 62.38 ± 30.41 ng/mL in healthy control group. The differences between these groups were significant in terms of the levels of β-thromboglobulin (p = 0.02). We found significant differences between the groups in terms of mean platelet volume (p = 0.049). In this study, the level of β-thromboglobulin was found significantly higher in patients with rheumatoid arthritis, which is a chronic inflammatory disease. This result could be an indicator, such as platelet activation in patients with rheumatoid arthritis, or it may be a helper marker in the follow-up and treatment of developing cardiovascular risk.

Platelet Activation, Function, and Reactivity in Atherosclerotic Carotid Artery Stenosis: A Systematic Review of the Literature

An important proportion of transient ischemic attack or ischemic stroke is attributable to moderate or severe (50-99%) atherosclerotic carotid stenosis or occlusion. Platelet biomarkers have the potential to improve our understanding of the pathogenesis of vascular events in this patient population. A detailed systematic review was performed to collate all available data on ex vivo platelet activation and platelet function/reactivity in patients with carotid stenosis. Two hundred thirteen potentially relevant articles were initially identified; 26 manuscripts met criteria for inclusion in this systematic review. There was no consistent evidence of clinically informative data from urinary or soluble blood markers of platelet activation in patients with symptomatic moderate or severe carotid stenosis who might be considered suitable for carotid intervention. Data from flow cytometry studies revealed evidence of excessive platelet activation in patients in the early, sub-acute, or late phases after transient ischemic attack or stroke in association with moderate or severe carotid stenosis and in asymptomatic moderate or severe carotid stenosis compared with controls. Furthermore, pilot data suggest that platelet activation may be increased in recently symptomatic than in asymptomatic severe carotid stenosis. Excessive platelet activation and platelet hyperreactivity may play a role in the pathogenesis of first or subsequent transient ischemic attack or stroke in patients with moderate or severe carotid stenosis. Larger longitudinal studies assessing platelet activation status with flow cytometry and platelet function/reactivity in symptomatic vs. asymptomatic carotid stenosis are warranted to improve our understanding of the mechanisms responsible for transient ischemic attack or stroke.

Impact of exercise trainting on inflammation and platelet activation in patients with intermittent claudication

Serum markers of inflammation and platelet activation are related to cardiovascular risk. Cardiovascular risk reduction is a major treatment goal in patients with peripheral arterial disease (PAD). Although current guidelines recommend supervised exercise training (SET) for PAD patients with intermittent claudication, its contribution to risk reduction remains unclear. Aim of the present study was to assess the impact of SET on inflammation and platelet activation as surrogates for cardiovascular risk. Fifty-three patients with intermittent claudication were randomly assigned to SET on top of best medical treatment (BMT) for 6 months (SET-group) or to BMT only (BMT-group). High sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and fibrinogen as well as soluble P-selectin (sP-sel), prothrombin fragment 1+2 (F1.2) and monocyte-platelet aggregates (MPA) were determined at study entry, after 3, 6 and 12 months. While clinical improvement, reflected by an increase of walking capacity, was observed upon SET, no lasting changes of markers of inflammation and platelet activation were found within the SET-group during the training period. Compared to the BMT-group no improvements of these markers were observed in response to training at any time point (all p >0.05). Regular SET added no further anti-inflammatory effect and had no effect on platelet activation when provided on top of BMT in PAD patients with intermittent claudication.