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Platelet Function (platelet + function)
Terms modified by Platelet Function Selected AbstractsASSESSMENT OF PLATELET FUNCTION IN HAEMODIALYSIS PATIENTSNEPHROLOGY, Issue 1 2002Duy Nguyen [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] Endogenous Mechanisms of Inhibition of Platelet FunctionMICROCIRCULATION, Issue 3 2005RICHARD C. JIN MA ABSTRACT Platelets play an important role in coagulation, in maintenance of hemostasis, and in the pathophysiology of thrombotic diseases. In response to blood vessel injury, platelets accumulate at the site, recruit other platelets, promote clotting, and form a hemostatic plug to prevent hemorrhage. By contrast, several inhibitory mechanisms modulate platelet function and act in a synergistic manner to prevent pathologic thrombus formation. This review focuses on the principal endogenous inhibitors of platelet function and the central role of the normal endothelium in these inhibitory processes. The main endothelium-derived platelet inhibitors include nitric oxide, prostacyclin, and Ecto-ADPase/CD39/NTPDase. Each of these factors is discussed in turn, and the specific mechanisms by which they inhibit platelet function are reviewed. [source] Casual Chocolate Consumption and Inhibition of Platelet FunctionPREVENTIVE CARDIOLOGY, Issue 4 2007Bryan Bordeaux DO Observational studies have associated reduced cardiovascular mortality with chocolate consumption. Feeding studies of high-dose, flavanol-rich chocolate show antiplatelet effects, but the effect of casual chocolate consumption on platelet function is unknown. Healthy adults (N=1535) were proscribed from consuming foods affecting platelet function, including chocolate, for 48 hours and completed a 24-hour dietary recall before ex vivo platelet testing with the Platelet Function Analyzer (PFA)-100 (Dade Behring, Inc, Deerfield, IL) test and in vivo testing with urinary 11-dehydro thromboxane B2 (Tx-M) measurements. Some participants (n=141) reported ignoring the prohibition of consuming chocolate before platelet testing. Despite having similar baseline characteristics, chocolate consumers had longer PFA closure times (130 vs 123 seconds, P=.005) and decreased Tx-M levels (175 vs 290 ng/mol creatinine, P=.03). Chocolate remained a significant independent predictor of both ex vivo and in vivo platelet function testing after adjusting for confounders. The authors concluded that even consuming modest amounts of commercial chocolate has important antiplatelet effects. [source] Platelet function and coronary artery diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2001R. J. G. Peters No abstract is available for this article. [source] The PFA-100Ô system for the assessment of platelet function in normotensive and hypertensive pregnanciesINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2001Marco Marietta Platelet function was studied in 30 pregnant women: 14 normotensive (C), and 16 affected by pregnancy-induced hypertension (PIH). Platelet aggregometry (PA) on platelet-rich plasma according to Born was compared with the new PFA-100Ô System (Dade International Inc, Miami, USA). This device evaluates platelet function (expressed in seconds as closure time, CT) in anticoagulated whole blood ex vivo at high shear rates. PA (expressed as percentage of light transmission) and CT were measured at baseline and after incubation with L-Arginine (L-Arg). MANOVA for repeated measures showed that L-Arg incubation significantly decreased PA (F=7.2, P < 0.05) and increased CT (F=6.05, P < 0.05) in the whole population of pregnant women. Moreover, we analysed separately both parameters in C and in PIH subjects. No differences in PA were found in both groups, neither at baseline nor after L-Arginine incubation. In contrast, CT was significantly longer in PIH in comparison to C before (95.9 s vs. 84 s, P < 0.05) as well after (115 s vs. 92 s, P < 0.05) L-Arginine incubation. Data from PFA-100Ô confirm our previous reports that during pregnancy the L-Arginine: Nitric Oxide pathway regulates platelet function. In hypertensive patients a significant decrease in platelet function was found by using the PFA-100Ô system. [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] Platelet function in sepsisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2004A. YAGUCHI Summary.,Background: Coagulation abnormalities and thrombocytopenia are common in severe sepsis, but sepsis-related alterations in platelet function are ill-defined. Objectives: The purpose of this study was to elucidate the effect of sepsis on platelet aggregation, adhesiveness, and growth factor release. Patients and methods: Agonist-induced platelet aggregation was measured in platelet-rich plasma separated from blood samples collected from 47 critically ill patients with sepsis of recent onset. Expression of platelet adhesion molecules was measured by flow cytometry and the release of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) was measured by ELISA in the supernatant of platelet aggregation. Results: Septic patients had consistently decreased platelet aggregation compared with controls, regardless of the platelet count, thrombin generation, or overt disseminated intravascular coagulation (DIC) status. The severity of sepsis correlated to the platelet aggregation defect. Adhesion molecules, receptor expression (CD42a, CD42b, CD36, CD29, PAR-1), and ,-granule secretion detected by P-selectin expression remained unchanged but the release of growth factors was differentially regulated with increased VEGF and unchanged PDGF after agonist activation even in uncomplicated sepsis. Conclusions: Sepsis decreases circulating platelets' hemostatic function, maintains adhesion molecule expression and secretion capability, and modulates growth factor production. These results suggest that sepsis alters the hemostatic function of the platelets and increases VEGF release in a thrombin-independent manner. [source] Etomidate and thiopental inhibit platelet function in patients undergoing infrainguinal vascular surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2001A. Gries Background: Postoperative platelet hyperaggregability following general anesthesia has been reported in patients undergoing major vascular surgery. In contrast, since anesthetic agents inhibited platelet function both in vitro and in vivo, an increased risk for postoperative bleedings due to prolonged platelet dysfunction has been discussed. Nevertheless, data describing platelet-affecting properties of induction agents such as etomidate and thiopental in patients undergoing major vascular surgery are lacking. Methods: Platelet function was determined at 0, 2, 20, and 200 ,g/ml thiopental and at 0, 0.2, 2, 20 ,g/ml etomidate in vitro in blood samples drawn from 16 patients suffering from severe occlusive arterial disease. In addition, 30 patients undergoing vascular surgery were investigated before (PRE) and after anesthesia induction (T0) either with etomidate (ETO group, n=16) or thiopental (THIO group, n=14), and 2 h after the beginning of surgery (T2). Platelet function was determined according to platelet aggregation, in vitro bleeding time, and flow cytometric measurements. Results:In vitro, P-selectin expression was inhibited by etomidate at 2 and 20 ,g/ml (,28% and ,38%, respectively) and also by thiopental at 200 ,g/ml (,27%). In patients undergoing vascular surgery, anesthesia induction in the ETO group resulted in a 31% prolongation of the in vitro bleeding time and an inhibition of ADP- and collagen-induced platelet aggregation (,30% and ,17%, respectively) and of P-selectin expression (,25%) at T0. In the THIO group, only ADP-induced platelet aggregation was affected (,16%). At T2, all parameters had reached PRE level again in both groups. Furthermore, in comparison with the THIO group, operation time was significantly prolonged and transfusion volume was significantly increased in the ETO group. In addition, platelet count and hematocrit significantly decreased at T2, whereas levels of tPA, PAI-1, fibrinogen and antithrombin III and partial thromboplastin time remained unchanged in both groups during the study period. Conclusions: In the present study, etomidate and, to a minor extent, thiopental offered significant platelet inhibitory properties. Anesthetic-induced platelet inhibition may lead to higher transfusion rates and prolonged operation times. Therefore, anesthetic-related platelet inhibitory properties should be considered when searching for the anesthetic agent of choice, especially in patients with compromised hemostasis and co-existing bleeding disorders. [source] Platelet function analyser-100 testing and primary haemostasis analysisBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2006I. Elalamy No abstract is available for this article. [source] Platelet functions beyond hemostasisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2009S. S. SMYTH Summary., Although their central role is in the prevention of bleeding, platelets probably contribute to diverse processes that extend beyond hemostasis and thrombosis. For example, platelets can recruit leukocytes and progenitor cells to sites of vascular injury and inflammation; they release proinflammatory and anti-inflammatory and angiogenic factors and microparticles into the circulation; and they spur thrombin generation. Data from animal models suggest that these functions may contribute to atherosclerosis, sepsis, hepatitis, vascular restenosis, acute lung injury, and transplant rejection. This article represents an integrated summary of presentations given at the Fourth Annual Platelet Colloquium in January 2009. The process of and factors mediating platelet,platelet and platelet,leukocyte interactions in inflammatory and immune responses are discussed, with the roles of P-selectin, chemokines and Src family kinases being highlighted. Also discussed are specific disorders characterized by local or systemic platelet activation, including coronary artery restenosis after percutaneous intervention, alloantibody-mediated transplant rejection, wound healing, and heparin-induced thrombocytopenia. [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] Gestational diabetes affects platelet behaviour through modified oxidative radical metabolismDIABETIC MEDICINE, Issue 1 2004L. Mazzanti Abstract Aims Patients with Type 1 and Type 2 diabetes mellitus show altered platelet function including decreased nitric oxide synthase (NOS) activity and increased peroxynitrite production. Gestational diabetes mellitus (GDM) is a clinical condition which is ideal for evaluating short-term effects of impaired glucose metabolism, ruling out the possibility that the platelet abnormalities are a consequence of diabetic complications. The aim of the present work was to study NO metabolism in platelets from pregnant women with GDM. The production of peroxides was also studied as it is strongly involved in peroxynitrite formation. Methods Platelet NOS activity and peroxynitrite production, levels of hydroperoxides and thiobarbituric acid reactive substances (TBARS) in platelet membranes in the basal state and after in vitro peroxidative stress with phenylhydrazine were determined in 40 pregnant women with GDM, 40 healthy pregnant women (pregnant controls) of comparable age and gestational age, and 15 healthy non-pregnant women (controls). Results NOS activity was significantly increased in both groups of pregnant women compared with non-pregnant ones, and in GDM women compared with pregnant controls. Production of peroxynitrite was higher in GDM women than in pregnant controls, who also had significantly reduced production compared with non-pregnant women. Basal levels of peroxidation of the platelet membranes evaluated either by hydroperoxide content and TBARS levels or the susceptibility to peroxidation were increased in GDM patients in comparison with both control groups. Conclusions We have shown a modification in platelet NO and peroxynitrite production and an increase in platelet indicators of oxidative stress in GDM women compared with healthy pregnant women which might be at the basis of a cellular dysfunction. [source] Discovery and recognition of purine receptor subtypes on plateletsDRUG DEVELOPMENT RESEARCH, Issue 1-2 2001Susanna M.O. HouraniArticle first published online: 9 MAY 200 Abstract The effects of purines on platelets have been known since the 1960s, when Born demonstrated aggregation induced by ADP and its inhibition by adenosine and by ATP. The inhibition by adenosine is not specific for ADP, and adenosine acts at a separate receptor to stimulate adenylate cyclase, which has an inhibitory effect on platelet function. Studies using selective agonists and antagonists have shown that the platelet receptor is of the A2A subtype and this has been confirmed using A2A knockout mice. The situation with ADP is more complex, and there has been controversy about the number of ADP receptors on platelets. ADP causes shape change, aggregation, mobilisation of calcium from intracellular stores, rapid calcium influx, and inhibition of adenylate cyclase, and the relationship between these is becoming clearer. Two cloned P2 receptors have been detected on platelets, P2X1 and P2Y1, and a third P2Y receptor is thought to exist. The P2X1 receptor is responsible for the rapid calcium influx and can be activated by ATP as well as by ADP, but is likely to be desensitised under normal experimental conditions and its pathophysiological role is uncertain. The P2Y1 receptor is responsible for calcium mobilisation, shape change, and the initiation of aggregation, and these responses are abolished in P2Y1 knockout mice, while the other P2Y receptor is responsible for inhibition of adenylate cyclase and is required for full aggregation. ATP is a competitive antagonist at both these P2Y receptors, while some nucleotide analogues can discriminate between them. Drug Dev. Res. 52:140,149, 2001. © 2001 Wiley-Liss, Inc. [source] Evaluation of effects of rofecoxib on platelet function in an in vitro model of thrombosis with circulating human bloodEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2004M. R. Hernandez Abstract Background, Cyclooxygenase (COX)-2-selective non-steroidal anti-inflammatory drugs have been used for anti-inflammatory therapy. However, it has also been described that they may increase risk of cardiovascular events. Objectives, To study the effects of COX2 inhibitor rofecoxib on platelet function using in vitro tests. Results were compared with those obtained in a parallel experiment with acetyl salicylic acid (ASA). Methods, Studies of platelet aggregation, using different agonists, were performed by a turbidimetric method. Adhesive and cohesive function of platelets were analyzed by perfusion techniques, treated blood was exposed to thrombogenic surfaces and platelet interaction was morphometrically evaluated. Results, Twenty-five µM of rofecoxib induced a prolonged lag time and a reduction in the percentage of aggregation when arachidonic acid, ADP or collagen were used as agonists. In perfusion studies with parallel chamber rofecoxib 50 µM and ASA 500 µM reduced overall platelet interaction with the collagen surface (17·4 ± 3·7, P < 0·05; vs. 32·1 ± 2·6%P < 0·05 and 17·9 ± 2·4, vs. 31·9 ± 3·24, P < 0·05, respectively). In studies performed on annular chambers, 25 µM of rofecoxib reduced platelet interaction; values of the thrombus and covered surface were 17·4 ± 4·5%; P < 0·05 and 21·1 ± 4·1%; P < 0·05, respectively, vs. 30·4 ± 7·5% and 33·5 ± 6·5 in the control. ASA did also impair thrombus formation but differences did not reach the levels of statistical significance. Moreover, rofecoxib but not ASA reduced significantly thrombus height and thrombus area (7·4 ± 0·5 µM; P < 0·005 and 96·0 ± 21·2 µM2; P < 0·05 vs. control 11·2 ± 0·9 µM and 220·0 ± 47·7µM2, respectively). Conclusion, We conclude that under our experimental conditions, rofecoxib diminished platelet aggregation induced by different agonists and inhibited platelet-mediated thrombogenesis in an in vitro model of thrombosis. [source] A 4-trifluoromethyl derivative of salicylate, triflusal, stimulates nitric oxide production by human neutrophils: role in platelet functionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2000De Miguel Background The thrombotic process is a multicellular phenomenon in which not only platelets but also neutrophils are involved. Recent in vitro studies performed in our laboratory have demonstrated that triflusal, a 4-trifluoromethyl derivative of salicylate, reduced platelet aggregation not only by inhibiting thromboxane A2 production but also by stimulating nitric oxide (NO) generation by neutrophils. The aim of the present study was to evaluate whether oral treatment of healthy volunteers with triflusal could modify the ability of their neutrophils to produce NO and to test the role of the NO released by neutrophils in the modulation of ADP-induced platelet aggregation and ,-granule secretion. Methods The study was performed in 12 healthy volunteers who were orally treated with triflusal (600 mg day,1) for 5 days. Flow cytometric detection of platelet surface expression of P-selectin was used as a measure of the ability of platelets to release the contents of their ,-granules. Results After treatment with triflusal, there was an increase in NO production by neutrophils and an increase in endothelial nitric oxide synthase (eNOS) protein expression in neutrophils. A potentiation of the inhibition of platelet aggregation by neutrophils was reversed by incubating neutrophils with both an l -arginine antagonist, NG -nitro- l -arginine methyl ester ( l -NAME) and an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline 1-oxyl 3-oxide (C-PTIO). A slight decrease in P-selectin surface expression on platelets was found which was not modified by the presence of neutrophils and therefore by the neutrophil-derived NO. Exogenous NO released by sodium nitroprusside dose-dependently inhibited both ADP-stimulated ,-granule secretion and platelet aggregation. Therefore, platelet aggregation showed a greater sensitivity to be inhibited by exogenous NO than P-selectin expression. Conclusion Oral treatment of healthy volunteers with triflusal stimulated NO production and eNOS protein expression in their neutrophils. After triflusal treatment, the neutrophils demonstrated a higher ability to prevent ADP-induced platelet aggregation. However, the neutrophils and the endogenous NO generated by them failed to modify P-selectin expression in ADP-activated platelets. [source] Patterned Hydrogels for Controlled Platelet Adhesion from Whole Blood and PlasmaADVANCED FUNCTIONAL MATERIALS, Issue 15 2010Tobias Ekblad Abstract This work describes the preparation and properties of hydrogel surface chemistries enabling controlled and well-defined cell adhesion. The hydrogels may be prepared directly on plastic substrates, such as polystyrene slides or dishes, using a quick and experimentally simple photopolymerization process, compatible with photolithographic and microfluidic patterning methods. The intended application for these materials is as substrates for diagnostic cell adhesion assays, particularly for the analysis of human platelet function. The non-specific adsorption of fibrinogen, a platelet adhesion promoting protein, is shown to be completely inhibited by the hydrogel, provided that the film thickness is sufficient (>5,nm). This allows the hydrogel to be used as a matrix for presenting selected bioactive ligands without risking interference from non-specifically adsorbed platelet adhesion factors, even in undiluted whole blood and blood plasma. This concept is demonstrated by preparing patterns of proteins on hydrogel surfaces, resulting in highly controlled platelet adhesion. Further insights into the protein immobilization and platelet adhesion processes are provided by studies using imaging surface plasmon resonance. The hydrogel surfaces used in this work appear to provide an ideal platform for cell adhesion studies of platelets, and potentially also for other cell types. [source] Combination product containing Ginkgo biloba has no effect on cognitive function, quality of life or platelet function in the healthy elderlyFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 3 2007J Carlson [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] Platelet aggregation is significantly associated with cardiovascular mortality in elderly patientsGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 4 2004Kyoko Kin Background: The relationship between cardiovascular mortality and platelet function in elderly patients remains unclear. Methods: The outcomes for 347 consecutive patients aged 60 or older (mean age 77.5 years; 161 men and 186 women) who were treated without antiplatelet drugs on registration, were retrospectively studied after platelet aggregatability tests. The grading curve (GC) type, as an index of platelet aggregatability, was determined with an aggregometer and adenosine-5,-diphosphate as an agonist. Patients were classified into three groups according to GC type: Group I with suppressed aggregation (n = 40); Group II, normal aggregation (n = 208); and Group III, increased aggregation (n = 99). The mean follow-up was 3.9 years. Results: There were three deaths in Group I, 33 in Group II, and 30 in Group III. The mean annual mortality rate was 2.1% in Group I, 4.0% in Group II and 7.5% in Group III. Although the most common cause of death was pneumonia in all three groups, the annual mortality rates due to vascular events were 0.7% in Group I, 0.6% in Group II and 4.2% in Group III. Cox proportional hazards models for vascular death yielded a hazard ratio of 1.5 in the increased GC type. Conclusion: These findings indicated that elderly patients with accelerated aggregation had higher mortality rates due to vascular events. Therefore, accelerated aggregation in the elderly suggested not only the progress of arteriosclerosis, but indications of antiplatelet therapy to prevent vascular events. [source] Effect of recombinant factor VIIa variant (NN1731) on platelet function, clot structure and force onset time in whole blood from healthy volunteers and haemophilia patientsHAEMOPHILIA, Issue 5 2007D. F. BROPHY Summary., NN1731 is a novel variant of recombinant factor VIIa (rFVIIa) that binds to activated platelets, but has greater enzymatic activity than rFVIIa in generating FXa and thrombin. The effect of NN1731 on clot structure and platelet function was characterized ex vivo in whole blood from healthy volunteers and haemophilic patients. Blood samples from six healthy volunteers, nine haemophilia A patients with and without inhibitors and one acquired haemophilia A patient, were spiked with increasing concentrations (0.32, 0.64 and 1.28 ,g mL,1) of rFVIIa and NN1731. Platelet contractile force (PCF) or platelet function, clot elastic modulus (CEM) or clot structure, and force onset time (FOT) or the thrombin generation time (TGT) were determined using the Hemodyne Hemostasis Analysis System (HASÔ). Baseline PCF, CEM and FOT values in patients were abnormal compared to healthy volunteers' baseline values. Overall, haemophilia blood samples with or without inhibitors spiked with NN1731 had significantly greater PCF, CEM and shorter FOT values relative to samples spiked with corresponding doses of rFVIIa. The variability in response to treatment between patients was greater with rFVIIa compared to NN1731. At 1.28 ,g mL,1 (90 ,g kg,1), NN1731 normalized PCF, CEM and FOT in nine of 10 patients, while rFVIIa normalized these parameters in four of 10 patients. Increasing in vitro concentrations of NN1731 normalized platelet function, clot structure and thrombin generation consistently in haemophilia blood with or without inhibitors. NN1731 may be a promising haemostatic agent for patients with bleeding disorders. These results should be confirmed in an in vivo study. [source] Effect kinetics of desmopressin-induced platelet retention in healthy volunteers treated with aspirin or placeboHAEMOPHILIA, Issue 1 2000Lethagen Desmopressin is often used for haemostatic treatment in platelet dysfunction, but the effect kinetics of platelet responses and the mechanism of action are poorly known. This study aimed to determine the kinetics of platelet function responses induced by desmopressin in healthy volunteers treated with aspirin or placebo. Another aim was to correlate platelet responses to changes of von Willebrand factor (vWF) in plasma. We measured platelet function with a glass bead retention test, Ivy bleeding time, vWF:Ag and multimeric structure in plasma. Median baseline platelet retention was 12% (normal reference range 16,27%) during aspirin treatment and 18% during placebo. Median peak platelet retention after desmopressin was 33% during aspirin treatment and 34% during placebo. After about 3 h platelet function had returned to baseline. A second desmopressin dose after 3 h stimulated platelet retention to a similar extent as the first dose. There was no correlation between platelet responses and quantitative or qualitative changes of vWF in plasma. Platelet count did not change significantly. Thus, desmopressin's effect on platelet function lasts for about 3 h, but may be prolonged by a second dose immediately thereafter. These findings may have important clinical implications for patients with aspirin-induced platelet dysfunction undergoing surgery. [source] Should we give thromboprophylaxis to patients with liver cirrhosis and coagulopathy?HPB, Issue 6 2009Marco Senzolo Abstract Patients with liver cirrhosis are characterized by decreased synthesis of both pro- and anticoagulant factors, and recently there has been evidence of normal generation of thrombin resulting in a near normal haemostatic balance. Although it is generally recognized that bleeding is the most common clinical manifestation as a result of decreased platelet function and number, diminished clotting factors and excessive fibrinolysis, hypercoagulability may play an under recognized but important role in many aspects of chronic liver disease. In fact, they can encounter thrombotic complications such as portal vein thrombosis, occlusion of small intrahepatic vein branches and deep vein thrombosis (DVT). In particular, patients with cirrhosis appear to have a higher incidence of unprovoked DVT and pulmonary embolism (PE) compared with the general population. In dedicated studies, the incidence of DVT/PE ranges from 0.5% to 1.9%, similar to patients without comorbidities, but lower than patients with other chronic diseases (i.e, renal or heart disease). Surprisingly, standard coagulation laboratory parameters are not associated with a risk of developing DVT/PE; however, with multivariate analysis, serum albumin level was independently associated with the occurrence of thrombosis. Moreover, patients with chronic liver disease share the same risk factors as the general population for DVT/PE, and specifically, liver resection can unbalance the haemostatic equilibrium towards a hypercoagulable state. Current guidelines on antithrombotic prophylaxis do not specifically comment on the cirrhotic population as a result of the perceived risk of bleeding complications but the cirrhotic patient should not be considered as an auto-anticoagulated patient. Therefore, thromboprophylaxis should be recommended in patients with liver cirrhosis at least when exposed to high-risk conditions for thrombotic complications. Low molecular weight heparins (LWMHs) seem to be relatively safe in this group of patients; however, when important risk factors for bleeding are present, graduated compression stockings or intermittent pneumatic compression should be considered. [source] Glanzmann thrombasthenia and Bernard,Soulier syndrome in south IranINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2005A. AFRABIASI Summary Glanzmann thrombasthenia (GT) and Bernard,Soulier syndrome (BSS) are two rare inherited disorders of platelet function. In this study, we report the demographic, clinical and biological characteristics of 23 patients with GT and of seven patients with BSS from southern Iran who had been followed for many years but fully characterized only recently, when platelet aggregation tests and flow cytometric studies became available for the first time in the country. We found a high prevalence of both diseases that can be explained by the high rate of consanguineous marriages in south Iran. Patients affected by GT and BSS suffer mainly from mucocutaneous bleedings causing anemia and transfusion requirements. [source] The PFA-100Ô system for the assessment of platelet function in normotensive and hypertensive pregnanciesINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2001Marco Marietta Platelet function was studied in 30 pregnant women: 14 normotensive (C), and 16 affected by pregnancy-induced hypertension (PIH). Platelet aggregometry (PA) on platelet-rich plasma according to Born was compared with the new PFA-100Ô System (Dade International Inc, Miami, USA). This device evaluates platelet function (expressed in seconds as closure time, CT) in anticoagulated whole blood ex vivo at high shear rates. PA (expressed as percentage of light transmission) and CT were measured at baseline and after incubation with L-Arginine (L-Arg). MANOVA for repeated measures showed that L-Arg incubation significantly decreased PA (F=7.2, P < 0.05) and increased CT (F=6.05, P < 0.05) in the whole population of pregnant women. Moreover, we analysed separately both parameters in C and in PIH subjects. No differences in PA were found in both groups, neither at baseline nor after L-Arginine incubation. In contrast, CT was significantly longer in PIH in comparison to C before (95.9 s vs. 84 s, P < 0.05) as well after (115 s vs. 92 s, P < 0.05) L-Arginine incubation. Data from PFA-100Ô confirm our previous reports that during pregnancy the L-Arginine: Nitric Oxide pathway regulates platelet function. In hypertensive patients a significant decrease in platelet function was found by using the PFA-100Ô system. [source] Clinical approach to the patient with unexpected bleedingINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2000J. M. Teitel Bleeding can be considered unexpected if it is disproportionate to the intensity of the haemostatic stress in a patient with no known haemorrhagic disorder or if it occurs in a patient in whom a bleeding disorder has been characterized but is adequately treated. A thorough history usually allows the clinician to predict reasonably accurately whether the patient is likely to have a systemic haemostatic defect (and if so whether it is congenital or acquired), or whether the bleeding likely has a purely anatomical basis. The nature of bleeding is instructive with respect to preliminary categorization. Thus, mucocutaneous bleeding suggests defects of primary haemostasis (disordered platelet,vascular interactions). Bleeding into deeper structures is more suggestive of coagulation defects leading to impaired fibrin clot formation, and delayed bleeding after primary haemostasis is characteristic of hyperfibrinolysis. Localized bleeding suggests an anatomical cause, although an underlying haemostatic defect may coexist. Where bleeding is so acutely threatening as to require urgent intervention, diagnosis and treatment must proceed simultaneously. In the case of minor haemorrhage (not threatening to life or limb) it may be preferable to defer therapy while the nature of the bleeding disorder is methodically investigated. Initial laboratory evaluation is guided by the preliminary clinical impression. The amount of blood loss can be inferred from the haematocrit or haemoglobin concentration, and the platelet count will quickly identify cases in which thrombocytopenia is the likely cause of bleeding. In the latter instance, examination of the red cell morphology, leucocyte differential, and mean platelet volume may allow the aetiological mechanism to be presumptively identified as hypoproliferative or consumptive. With regard to coagulation testing, the activated PTT, prothrombin time, and thrombin time usually constitute an adequate battery of screening tests, unless the clinical picture is sufficiently distinctive to indicate the immediate need for more focused testing. In any event, sufficient blood should be taken to allow more detailed studies to be done based on the results of these screening tests. These results will direct the need for further assays, such as specific clotting factor activity levels, von Willebrand factor assays, tests for coagulation inhibitors, platelet function assays, and markers of primary or secondary fibrinolytic activity. [source] Phosphorylcholine-Coated Circuits Improve Preservation of Platelet Count and Reduce Expression of Proinflammatory Cytokines in CABG: A Prospective Randomized TrialJOURNAL OF CARDIAC SURGERY, Issue 4 2009Costas J. Schulze M.D. Phosphorylcholine (PC) is a new-generation coating material designed to ameliorate biocompatibility and thereby to reduce the detrimental interactions of CPB. We studied the effects of PC-coated perfusion circuits on platelet function and the humoral and cellular response to CPB. Methods: Thirty patients undergoing coronary artery bypass grafting were randomized to PC-coated (PC group, n = 15) and noncoated (control group, n = 15) circuit groups. Clinical data, total blood loss, and pre- and postoperative platelet counts were recorded and IL-6 and TNF-,, CD41a, CD42b, and CD62p were measured at induction of anesthesia, after the initiation of CPB and at termination of CPB. Results: There was a significantly improved preservation of platelet count following CPB in the PC group (p = 0.028), which was sustained over a period of 72 hours. The use of PC-coated circuits further resulted in a significant attenuation of TNF-, and IL-6 expression (p < 0.05 and p < 0.01); however, we were unable to detect any differences in clinical outcomes. Conclusions: Despite similar clinical outcome, the obvious reduction of cytokine expression and improved preservation of platelet count suggest superior biocompatibility of PC-coated circuits. [source] Paired comparison of apheresis platelet function after storage in two containersJOURNAL OF CLINICAL APHERESIS, Issue 1 2001Jürgen Zingsem Abstract Platelet quality after storage strongly depends on the pre-storage quality as well as on the storage conditions determined by the storage container. In this paired study, we evaluated two different containers (MedSep CLXÔ and Delmed DPL-110). The Fresenius AS104 cell separator was used to prepare 17 platelet concentrates that were split and distributed into the containers to be compared. Cell counts, blood gas analysis, morphological scores, glucose and lactate levels, platelet activation, and platelet aggregation were measured before splitting at the day of preparation and after storage at day 3 and day 5. At day 3, there was no significant difference between the two bags apart from increased lactate and decreased pCO2 concentrations in the CLXÔ bags. At day 5 there were significantly higher lactate concentrations, pO2 levels, and aggregation after stimulation in the CLXÔ group, while the glucose and pCO2 concentrations were significantly lower in these platelet concentrates as compared to the DPL-110 group. However, these parameters did not influence the functional parameters tested. While the platelet quality decreased during storage in all bags, the functional changes were nearly identical in both bags tested. We conclude that both bags are equivalent for 5-day storage of platelet concentrates. J. Clin. Apheresis. 16:10,14, 2001. © 2001 Wiley-Liss, Inc. [source] Coagulation dynamics and platelet functions in obstructive jaundiced patientsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2009Tebessüm Çak Abstract Background:, All of the body systems are affected by increased levels of bilirubin. The aim of this study is to investigate the function of platelets and clotting dynamics in patients with obstructive jaundice. Methods:, Liver function tests, serum CRP, PT, PTT and hemogram were measured in 23 patients with obstructive jaundice. Thromboelastography (TEG) was done for the evaluation of coagulation dynamics, while platelet function assay (PFA 100) was used to evaluate platelet functions. Blood samples were obtained at two occasions, before the drainage and 3 weeks after the relief of the obstruction. Results:, Hypercoagulation was detected in 80% of patients. Maximum strength, elasticity, coagulation indices of the clot were correlated with increased concentrations of direct bilirubin. Although maximum strength of coagulum usually represents increased activity of platelet function, membrane closure times with PFA 100 were found to be prolonged in 30% of patients, reduced values were determined in 17% of patients. No demonstrable effect on coagulation parameters and platelet function were detected after drainage procedures regardless of modality. Conclusions:, Even though there is a general assumption about the increased bleeding tendency in obstructive jaundiced patients, we could not demonstrate reduced clotting activity by measuring with either PFA or TEG. On the contrary we observed tendency for hypercoagulation independent of increased prothrombin times. The most probable cause of this effect is the increased activity of fibrin polymers on platelet membrane. [source] Coagulation profile and platelet function in patients with extrahepatic portal vein obstruction and non-cirrhotic portal fibrosisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2001Jasmohan S Bajaj Abstract Background and Aims: Coagulation disorders commonly develop in patients with cirrhosis of the liver. They have also been reported in patients with non-cirrhotic portal fibrosis (NCPF) and extra-hepatic portal venous obstruction (EHPVO); the two conditions with portal hypertension and near-normal liver functions. The spectrum and prevalence of coagulation abnormalities and their association with the pathogenesis of these diseases and with hypersplenism was prospectively studied. Methods: Eighteen EHPVO patients that included an equal number of NCPF patients and 20 healthy controls were prospectively studied. The coagulation parameters assessed included: international normalized ratio, partial thromboplastin time, and fibrinogen and fibrinogen degradation products. Platelet aggregation and malondialdehyde levels were measured. Results: Both EHPVO (83%) and NCPF (78%) patients had a significantly prolonged international normalized ratio and a decrease in fibrinogen and platelet aggregation. The EHPVO patients had a significant prolongation in partial thromboplastin time (67% patients), with increased levels of fibrinogen degradation product levels occurring in all patients; these were normal in NCPF patients. Platelet malondialdehyde levels were normal in both groups. Hypersplenism was present in four EHPVO and seven NCPF patients. It did not significantly influence the coagulation profile in either NCPF or EHPVO patients. Conclusions: Coagulation anomalies are common and significant in both NCPF and EHPVO patients, suggestive of a mild disseminated intravascular coagulation disorder. These imbalances could be caused by chronic subclinical endotoxemia and cytokine activation after the initial portal thromboembolic event. The persistence of these abnormalities in adolescent patients indicates an ongoing coagulation derangement. [source] | ||||||||||||||||||||||||||||||||||||||||||||||