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Thrombus Formation (thrombus + formation)

Distribution by Scientific Domains

Medical Sciences	88%
Chemistry	6%
Life Sciences	4%

Distribution within Medical Sciences

Cardiovascular Disease	28%
General & Internal Medicine	6%
General & Introductory Veterinary Medicine	2%

Selected Abstracts

Evaluation of Atrial Thrombus Formation and Atrial Appendage Function in Patients with Pacemaker by Transesophageal Echocardiography

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 11 2006
ABOLFATH ALIZADEH M.D.
Background: Physiologic pacing is claimed to be superior to ventricular pacing in as much as it entails lower risk of atrial fibrillation, stroke, and atrial remodeling. There are few data on the relation between atrioventricular (AV) synchrony and atrial clot formation. Utilizing transesophageal echocardiography (TEE), this study sought to evaluate the effect of AV synchrony loss on left atrial physiology, atrial stasis, and clot formation. Methods: We conducted a cross-sectional study on patients with both AV and ventricular pacing with left ventricular ejection fraction (LVEF) >30%. TEE enabled us to explore atrial and pacing leads thrombi and measure left atrial appendage (LAA) flow velocity Results: A total 72 patients (mean age, 65 ± 11.7) were enrolled in the study. The pacing mode was VVI in 53% and AV sequential in 47% of patients. LVEF (mean ± SD; %) was 53.3 ± 6.2% in ventricular pacing mode and 52.2 ± 6.6 in physiologic pacing mode. Thrombus formation on pacing lead (<10 mm in 97% of patients) was observed in 32% of all the patients (23% in patients with AV sequential pacing mode and 39% with VVI mode). Left atrial appendage flow velocity (LAA-FV) was significantly higher among the patients with AV sequential pacing mode (49.44 ± 18 cm/s vs 40.94 ± 19.4 cm/s, P value = 0.02). LAA-FV >40 cm/s was detected in 60% of the patients, 60% of whom were in physiologic mode. Left atrial size was significantly larger among the patients with VVI pacing mode (42.3 ± 2.3 mm vs 37.79 ± 4.5 mm, P = 0.001). Multivariate analysis showed no relation between LAA-FV and age, hypertension, diabetes mellitus, left atrial size, and left ventricular function. Only one patient had right atrial clot. There was no thrombus in the ventricles and atrial appendage. Conclusion: Long-term loss of AV synchrony induced by VVI pacing is associated with the impairment of LAA contraction. Thrombus formation in the LAA is not increased by VVI pacing in patients with relatively good left ventricular (LV) function and sinus rhythm. [source]

High Incidence of Thrombus Formation Without Impedance Rise During Radiofrequency Ablation Using Electrode Temperature Control

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2003
KAGARI MATSUDAIRA
The authors hypothesized that during RF ablation, the electrode to tissue interface temperature may significantly exceed electrode temperature in the presence of cooling blood flow and produce thrombus. In 12 anesthetized dogs, the skin over the thigh muscle was incised and raised to form a cradle that was superfused with heparinized canine blood(ACT > 350 s)at 37°C. A 7 Fr, 4-mm or 8-mm ablation electrode containing a thermocouple was held perpendicular to the thigh muscle at 10-g contact weight. Interface temperature was measured at opposite sides of the electrode using tiny optical probes. RF applications(n = 157)were delivered at an electrode temperature of 45°C, 55°C, 65°C, and 75°C for 60 seconds, with or without pulsatile blood flow (150 mL/min). Without blood flow, the interface temperature was similar to the electrode temperature. With blood flow, the interface temperature (side opposite blood flow) was up to 36°C and 57°C higher than the electrode temperature using the 4- and 8-mm electrodes, respectively. After each RF, the cradle was emptied and the electrode and interface were examined. Thrombus developed without impedance rise at an interface temperature as low as 73°C without blood flow and 80°C with blood flow (11/16 RFs at 65°C electrode temperature using 4 mm and 13/13 RFs at an electrode temperature of 55°C using an 8-mm electrode with blood flow). With blood flow, interface temperature markedly exceeded the electrode temperature and the difference was greater with an 8-mm electrode (due to greater electrode cooling). In the presence of blood flow, thrombus occurred without an impedance rise at an electrode temperature as low as 65°C with a 4-mm electrode and 55°C with an 8-mm electrode. (PACE 2003; 26:1227,1237) [source]

Simulation of Thrombus Formation in Shear Flows Using Lattice Boltzmann Method

ARTIFICIAL ORGANS, Issue 8 2009
Masaaki Tamagawa
Abstract This article describes the prediction of index of thrombus formation in shear blood flow by computational fluid dynamics with the Lattice Boltzmann Method (LBM), applying to backward-facing step flow, which is a simple model of shear flow in the rotary blood pumps and complicated geometry of medical fluid devices. Assuming that the blood flow is a multiphase flow composed of blood plasma and activated fibrinogen, the effects of surface tension and adhesion force to the wall were added to the LBM computational model. It was found that the thrombus formation in the backward-facing step flow occurred just after the reattachment point and behind the step. These results corresponded to our observation results of thrombus formation. For the thrombus formation in every case of blood flow to be predicted, effects of threshold level of physical parameters such as shear rate and adhesion force (effective distance from the wall) were estimated. Moreover, it was also found that the predicted adhesion point on the wall agrees with the visualization of thrombus formation by predicting proper thresholds. [source]

Intracardiac Ultrasound Detection of Thrombus on Transseptal Sheath: Incidence, Treatment, and Prevention

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2005
KATANEH MALEKI M.D.
Background: Transseptal (TS) catheterization is used for left atrial (LA) ablation procedures and a major risk is thromboembolism. The purpose of this study was to assess (1) the value of intracardiac ultrasound (ICUS) monitoring during LA ablation procedures, and (2) a new technique to reduce the risk of thrombus formation. Methods and Results: One hundred and eighty consecutive patients underwent TS catheterization under ICUS guidance with two sheaths for atrial fibrillation ablation and one for other LA procedures. Group I included the initial 90 patients in whom TS sheaths were flushed with a standard 2 U/cc concentration of heparin; group II consisted of the next 90 patients in whom sheaths were flushed with 1,000 U/cc concentration. All patients received bolus and infusion of heparin to maintain ACT between 250,300 seconds. ICUS was monitored throughout. In group I, echodense material at the tip of the sheath consistent with thrombus was observed on ICUS in 8 of 90 patients (9%) within 5,15 minutes of entering the LA. In group II, only 1 of 90 patient (1%) demonstrated thrombus (P < 0.001). There were no significant clinical differences in group I patients with and without thrombus. In all nine patients, the clot was removed with vigorous aspiration. No patients suffered a neurological event. Conclusion: Thrombus formation on TS sheath, detected by ICUS, may be more common than expected despite adequate anticoagulation. Using a higher concentration of heparin for the TS system before deployment reduced the risk. The thrombus was retrieved with aspiration without the need to abort the procedure. [source]

Ex vivo inhibition of thrombus formation by an anti-glycoprotein VI Fab fragment in non-human primates without modification of glycoprotein VI expression

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2008
P. OHLMANN
Summary.,Objectives:,Glycoprotein (GP)VI is an attractive target for the development of new antithrombotic drugs. Its deficiency protects animals in several models of thrombosis, arterial stenosis and ischemia-,reperfusion while inducing no major bleeding tendency. The Fab fragment of one anti-GPVI monoclonal antibody (9O12.2) inhibits all GPVI functions in vitro. The aim of this study was to determine the ex vivo effects of 9O12.2 Fab on hemostasis, coagulation and thrombosis in non-human primates. Methods and results:,Blood samples were collected from cynomolgus monkeys before and after (30, 90 and 150 min, 1 and 7 days) a bolus injection of 9O12.2 Fab (4 mg kg,1) or vehicle. Platelet counts and coagulation tests (prothrombin time, activated partial thromboplastin time) were not modified following Fab injection. The PFA-100 closure time increased during the first hours and returned to initial values on day + 1. Platelet-bound Fab was detected from 30 min to 24 h after Fab injection without GPVI depletion at any time. Collagen-induced platelet aggregation was selectively and fully inhibited at 30 min. Thrombus formation on collagen in flowing whole blood (1500 s,1) was delayed and decreased, and collagen-induced or tissue factor-induced thrombin generation in platelet-rich plasma was profoundly inhibited. Conclusion:,The anti-GPVI 9O12.2 Fab inhibits thrombus formation ex vivo in non-human primates with a composite effect on platelet activation and thrombin generation in the absence of GPVI depletion. [source]

Orbofiban: An orally active GPIIb/IIIa platelet receptor antagonist

MEDICINAL RESEARCH REVIEWS, Issue 3 2001
Nancy S. Nicholson
Abstract A key role has been established for platelet activation and thrombus formation in the pathogenesis of acute coronary syndromes, and restenosis after percutaneous interventions. Antiplatelet agents that have a wider spectrum of activity than aspirin, and clopidogrel would be expected to provide improved antithrombotic protection. Preclinical studies were used to predict clinical efficacy of orally active GPIIb/IIIa antagonists such as xemilofiban, sibrafiban, lefradafiban, and orbofiban. While clinical trials have shown potent and sustained platelet inhibition, outcomes of trials with these first generation GPIIb/IIIa compounds have been disappointing. The active moiety of orbofiban is a potent and specific inhibitor of fibrinogen binding to GPIIb/IIIa, leading to inhibition of platelet aggregation to a wide variety of agonists. Studies comparing inhibition of aggregation and bleeding suggest that chronic inhibition of platelet aggregation can be achieved without major bleeding side effects. Thrombus formation is prevented in canine models of thrombosis. Orbofiban is approximately 28% bioavailable with a t1/2 of 18,hr. The high bioavailability, long half-life, and potential safety suggest orbofiban would be suitable for chronic oral administration. Clinical data demonstrate that orally administered orbofiban has the desired pharmacodynamic effect of inhibiting platelet aggregation but does not demonstrate clinical benefit when examined in large-scale trials. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 3, 211,226, 2001 [source]

Evaluation of Atrial Thrombus Formation and Atrial Appendage Function in Patients with Pacemaker by Transesophageal Echocardiography

Thrombin activation of proteinase-activated receptor 1 potentiates the myofilament Ca2+ sensitivity and induces vasoconstriction in porcine pulmonary arteries

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2010
Jun Maki
Background and purpose:, Thrombus formation is commonly associated with pulmonary arterial hypertension (PAH). Thrombin may thus play an important role in the pathogenesis and pathophysiology of PAH. Hence, we investigated the contractile effects of thrombin and its mechanism in pulmonary artery. Experimental approach:, The cytosolic Ca2+ concentrations ([Ca2+]i), 20 kDa myosin light chain (MLC20) phosphorylation and tension development were evaluated using the isolated porcine pulmonary artery. Key results:, Thrombin induced a sustained contraction in endothelium-denuded strips obtained from different sites of a pulmonary artery, ranging from the main pulmonary artery to the intrapulmonary artery. In the presence of endothelium, thrombin induced a transient relaxation. The contractile effect of thrombin was abolished by either a protease inhibitor or a proteinase-activated receptor 1 (PAR1) antagonist, while it was mimicked by PAR1 -activating peptide (PAR1AP), but not PAR4AP. The thrombin-induced contraction was associated with a small elevation of [Ca2+]i and an increase in MLC20 phosphorylation. Thrombin and PAR1AP induced a greater increase in tension for a given [Ca2+]i elevation than that obtained with high K+ -depolarization. They also induced a contraction at a fixed Ca2+ concentration in ,-toxin-permeabilized preparations. Conclusions and implications:, The present study revealed a unique property of the pulmonary artery. In contrast to normal arteries of the systemic circulation, thrombin induces a sustained contraction in the normal pulmonary artery, by activating PAR1 and thereby increasing the sensitivity of the myofilament to Ca2+. This responsiveness of the pulmonary artery to thrombin may therefore contribute to the pathogenesis and pathophysiology of PAH. [source]

ORIGINAL INVESTIGATIONS: Potential Faces of Patent Foramen Ovale (PFO PFO)

ECHOCARDIOGRAPHY, Issue 8 2010
F.R.C.P., Tasneem Z Naqvi M.D.
Background: Patent foramen ovale (PFO) is diagnosed on echocardiography by saline contrast study with or without color Doppler evidence of shunting. PFO is benign except when it causes embolic events. Methods and Results: In this report, we describe unique additional manifestations related to the diagnosis and presentation of PFO. These include demonstration of PFO during the release phase of "sigh" on the ventilator in the operating room, use of a separate venipuncture to allow preparation of blood-saline-air mixture after multiple failed saline bubble injections, resting and stress hypoxemia related to left to right shunting across a PFO in the absence of pulmonary hypertension, presentation of quadriperesis secondary to an embolic event from a PFO and development of a thrombus on the left atrial aspect of PFO in a patient with atrial fibrillation, and on the right atrial aspect of PFO in a patient who had undergone repair of a flail mitral valve. Finally, in one patient with end-stage renal disease, aortic valve endocarditis and periaortic abscess, PFO acted as a vent valve relieving right atrial pressure following development of aortoatrial fistula. Conclusion: PFO diagnosis can be elusive if appropriate techniques are not used during saline contrast administration. PFO can present as hypoxemia in the absence of pulmonary hypertension, can be a rare cause of quadriperesis, and can be associated with thrombus formation on either side of interatrial septum. Finally, PFO presence can be lifesaving in those with sudden increase in right atrial pressure such as with aortoatrial fistula. (Echocardiography 2010;27:897-907) [source]

Clinical and Echocardiographic Risk Factors for Embolization in the Presence of Left Atrial Thrombus

ECHOCARDIOGRAPHY, Issue 5 2007
Ela Sahinbas Kavlak
Aims: The aim of our study was to evaluate the factors leading to embolization in patients with left atrial thrombi (LAT). With this purpose, we retrospectively analyzed clinical, transthoracic, transesophageal echocardiographic data of patients with LAT in the transesophageal echocardiographic evaluation. Methods and Results: One hundred ninety-two patients with LAT not on anticoagulant therapy were divided into two groups according to the presence of prior ischemic stroke. The group with ischemic stroke included more patients with sinus rhythm and less patients with mitral stenosis. They had smaller left atrial diameter, more left atrial appendage spontaneous echo-contrast, higher appendage ejection fraction, and emptying velocity. Conclusion: Once the thrombus has been formed, cerebral embolization seems to be higher in patients with relatively preserved appendage ejection fraction and emptying velocity. Presence of atrial appendage spontaneous echo-contrast also favor embolization. Factors leading to embolization seem to differ in some respects from the causes of thrombus formation. [source]

The Use of Anatomic M-Mode Echocardiography to Determine the Left Atrial Appendage Functions in Patients with Sinus Rhythm

ECHOCARDIOGRAPHY, Issue 2 2005
Yekta Gurlertop M.D.
Left atrial appendage (LAA) contractile dysfunction is associated with thrombus formation and systemic embolism. LAA function is determined by its flow velocities and fractional area change. This study was performed in order to determine the LAA functions with the anatomic M-mode echocardiography (AMME). Our study comprised 74 patients who had sinus rhythm and underwent transesophageal echocardiography (TEE) for various reasons. LAA fractional change (LAAFAC) was measured by manual planimetry in a transverse basal short-axis approach and LAA emptying and filling velocities also were measured. The AMME values were determined by an M-mode cross section from a cursor placed beneath the orifice of the LAA in transverse basal short-axis imaging. From these values LAA fractional shortening (LAAFS) and ejection fraction (LAAEF) were calculated. LAAEF was calculated by the Teicholz method. The comparisons were conducted, and no correlations between the LAA late filling and the anatomic M-mode values were found (for LAAFS r = 0.18; P > 0.05 and for LAAEF r = 0.19; P > 0.05). There were significant but poor correlations among the LAA late emptying with the anatomic M-mode measurements (for LAAFS r = 0.26; P < 0.05 and for LAAEF r = 0.30; P < 0.01), whereas, there were significant and good correlations between the LAAFAC and the anatomic M-mode values (for LAAFS r = 0.75; P < 0.01 and for LAAEF r = 0.78; P < 0.01). There were significant differences between the valvular heart disease group and the normal group, and between the valvular heart disease group and the ASD group (for LAAFAC P < 0.01, for LAAEF P < 0.01, for LAAFS P < 0.01). There was no difference between the normal group and the ASD group. Our study showed that the LAAEF and LAAFS in patients with sinus rhythm obtained via anatomical M-mode echocardiography is a new method, which can be used instead of left atrial appendage area change. [source]

Effect of Inotropic Stimulation on Left Atrial Appendage Function in Atrial Myopathy of Chronic Atrial Fibrillation

ECHOCARDIOGRAPHY, Issue 4 2000
MASOOR KAMALESH M.D.
Atrial fibrillation (AF) leads to remodeling of the left atrium (LA) and left atrial appendage (LAA), resulting in atrial myopathy. Reduced LA and LAA function in chronic AF leads to thrombus formation and spontaneous echo contrast (SEC). The effect of inotropic stimulation on LAA function in patients with chronic AF is unknown. LAA emptying velocity (LAAEV) and maximal LAA area at baseline and after dobutamine were measured by transesophageal echocardiography in 14 subjects in normal sinus rhythm (NSR) and 6 subjects in AF. SEC in the LA was assessed before and after dobutamine. LAAEV increased significantly in both groups. However, the LAAEV at peak dobutamine in patients with AF remained significantly lower than the baseline LAAEV in patients who were in NSR (P= 0.009). Maximal LAA area decreased significantly with dobutamine in both groups, but LAA area at peak dose of dobutamine inpatients with AF remained greater than baseline area in those in NSR (P= 0.01). Despite the increase in LAAEV, SEC improved in only two of five patients. We conclude that during AF, the LAA responds to inotropic stimulation with only a modest improvement in function. [source]

Evaluation of effects of rofecoxib on platelet function in an in vitro model of thrombosis with circulating human blood

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2004
M. 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]

The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P- and l -selectin function in vivo

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2000
Thorlacius
Background Adhesion molecules of the selectin family (mainly P- and L-selectin) have been suggested to mediate interactions between platelets, leukocytes and endothelial cells in thrombus formation. The polysaccharide fucoidan has anticoagulative properties, but is also able to bind and block the function of the selectins. Here, we investigated in vivo (i) if fucoidan can prevent microvascular thrombus formation, and (ii) whether this is potentially mediated by the inhibition of P-and/or L-selectin. Materials and Methods For this purpose, we used intravital microscopy in the mouse cremaster microcirculation in which thrombosis was induced photochemically by light exposure to individual arterioles and venules after intravenous (i.v.) injection of FITC-dextran. Results We found that intravenous administration of fucoidan significantly prolonged the time required for complete occlusion in arterioles and venules by almost seven- and nine-fold, respectively. In contrast, treatment with monoclonal antibodies against P- and L-selectin had no effect on the development of microvascular thrombosis. Fucoidan and also the anti-P-selectin antibody completely inhibited baseline venular leukocyte rolling in the cremaster muscle, indicating that these treatment regimes abolished P-selectin function. Importantly, fucoidan and the anti-P-selectin antibody had no effect on systemic platelet and leukocyte counts. On the other hand, we found that fucoidan treatment significantly altered coagulation parameters, including prothrombin time (Quick percentage), activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), which may explain the potent in vivo anticoagulative effect of fucoidan observed here. Conclusions Taken together, our novel findings suggest that fucoidan effectively prevents microvascular thrombus formation induced by endothelial damage in arterioles and venules in vivo. This protective effect of fucoidan is not attributable to inhibition of P- and L -selectin function but may instead be related to the anticoagulative capacity of fucoidan. [source]

Aegyptin displays high-affinity for the von Willebrand factor binding site (RGQOGVMGF) in collagen and inhibits carotid thrombus formation in vivo

FEBS JOURNAL, Issue 2 2010
Eric Calvo
Aegyptin is a 30 kDa mosquito salivary gland protein that binds to collagen and inhibits platelet aggregation. We have studied the biophysical properties of aegyptin and its mechanism of action. Light-scattering plot showed that aegyptin has an elongated monomeric form, which explains the apparent molecular mass of 110 kDa estimated by gel-filtration chromatography. Surface plasmon resonance identified the sequence RGQOGVMGF (where O is hydroxyproline) that mediates collagen interaction with von Willebrand factor (vWF) as a high-affinity binding site for aegyptin, with a KD of approximately 5 nm. Additionally, aegyptin interacts with the linear peptide RGQPGVMGF and heat-denatured collagen, indicating that the triple helix and hydroxyproline are not a prerequisite for binding. However, aegyptin does not interact with scrambled RGQPGVMGF peptide. Aegyptin also recognizes the peptides (GPO)10 and GFOGER with low affinity (,m range), which respectively represent glycoprotein VI and integrin ,2,1 binding sites in collagen. Truncated forms of aegyptin were engineered, and the C-terminus fragment was shown to interact with collagen and to attenuate platelet aggregation. In addition, aegyptin prevents laser-induced carotid thrombus formation in the presence of Rose Bengal in vivo, without significant bleeding in rats. In conclusion, aegyptin interacts with distinct binding sites in collagen, and is useful tool to inhibit platelet,collagen interaction in vitro and in vivo. Structured digital abstract ,,MINT-7299280, MINT-7299290: Collagen (uniprotkb:P02461) binds (MI:0407) to Aegyptin (uniprotkb:O01949) by enzyme linked immunosorbent assay (MI:0411) ,,MINT-7298991, MINT-7299153, MINT-7299208: Collagen (uniprotkb:P02452) binds (MI:0407) to Aegyptin (uniprotkb:O01949) by surface plasmon resonance (MI:0107) ,,MINT-7299266: Collagen (uniprotkb:P02452) binds (MI:0407) to Aegyptin (uniprotkb:O01949) by fluorescence microscopy (MI:0416) ,,MINT-7299256: Collagen (uniprotkb:P02452) binds (MI:0407) to Aegyptin (uniprotkb:O01949) by solid phase assay (MI:0892) [source]

Guidelines on the management of secondary prophylaxis of vascular events in stable patients in primary care

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2004
D.J. Betteridge
Summary Atherothrombosis, thrombus formation superimposed on an existing atherosclerotic plaque, is an acute process leading to ischaemic events such as myocardial infarction, stroke and critical limb ischaemia. Patients presenting with clinical conditions associated with atherothrombosis are at increased risk of subsequent vascular events. The beneficial effect of antiplatelet therapies for short-term and long-term secondary prevention of atherothrombotic events has been established. These guidelines aim to provide evidence-based recommendations that will assist in the antiplatelet-mediated secondary prophylaxis of vascular events in patients with stable cardiovascular disease treated in the primary healthcare setting. Medline and the Cochrane library were accessed using free-text strategies in the domains of antiplatelet agents and antithrombotics. Development of the guidelines was driven by a series of Steering Committee meetings, in which the quality of relevant studies was assessed and identified using narrative summary. These guidelines present evidence and recommendations for the treatment of numerous atherothrombotic indications depending on individual patient circumstances. [source]

Surgical Technique for Massive Mural Thrombus in the Left Atrium

JOURNAL OF CARDIAC SURGERY, Issue 5 2007
Masaru Yoshikai M.D.
The fresh autologous pericardium was used to cover the roughened left atrial endocardium after the removal of the mural thrombus. This procedure seems useful to prevent not only the perioperative thromboembolism caused by the dislodgement of the fragmented small thrombus but also any long-term future thrombus formation by creating a smooth surface layer with the autologous pericardium. [source]

Intracardiac Ultrasound Detection of Thrombus on Transseptal Sheath: Incidence, Treatment, and Prevention

Thrombogenic and atherogenic activities of lysophosphatidic acid

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2004
Wolfgang Siess
Abstract Lysophosphatidic acid (LPA) has been identified as a biologically active lipid in mildly-oxidized LDL, human atherosclerotic lesions, and the supernatant of activated platelets. The evidence that LPA has thrombogenic and atherogenic activities has increased substantially in recent years. Supporting the thrombogenic activity of LPA, analysis of the core region of human carotid plaques revealed recently the presence of alkyl- and acyl-molecular species from LPA with high platelet-activating potency (16:0 alkyl-LPA, 20:4 acyl-LPA). LPA, lipid extracts of atherosclerotic plaques, and the lipid-rich core elicited shape change and, in synergy with other platelet stimuli, aggregation of isolated platelets. This effect was completely abrogated by prior incubation of platelets with LPA receptor antagonists. Furthermore, LPA at concentrations approaching those found in vivo, induced platelet shape change, aggregation, and platelet-monocyte aggregate formation in blood. LPA-stimulated platelet aggregation was mediated by the ADP-stimulated activation of the P2Y1 and P2Y12 receptors. Supporting its atherogenic activity, LPA is a mitogen and motogen to vascular smooth muscle cells (VSMCs) and an activator of endothelial cells and macrophages. Recently, LPA has been identified as an agonist of the peroxisome proliferator activating receptor , (PPAR,), which is a key regulator of atherogenesis. LPA elicits progressive neointima formation, which is fully abolished by GW9662, an antagonist of PPAR,. We propose that LPA plays a central role in eliciting vascular remodeling and atherogenesis. Furthermore, upon rupture of lipid-rich atherosclerotic plaques, LPA may trigger platelet aggregation and intra-arterial thrombus formation. Antagonists of LPA receptors might be useful in preventing LPA-elicited thrombus formation and neointima formation in patients with cardiovascular diseases. © 2004 Wiley-Liss, Inc. [source]

Iliac vein compression syndrome: An underdiagnosed cause of lower extremity deep venous thrombosis,

JOURNAL OF HOSPITAL MEDICINE, Issue 7 2010
Ami Naik BS
Abstract Iliac vein compression syndrome (CS) is a rare cause of deep venous thrombosis. It is caused by an anatomic anomaly in which the right common iliac artery overlies the left common iliac vein causing mechanical compression. Subsequent endothelial changes within the vessels have the potential to spur thrombus formation. Aggressive diagnostic and therapeutic interventions must be implemented upon suspicion to avoid long-term complications. We report on a 19 year old male who presented with ICS. We discuss the clinical presentation, diagnosis, and current treatment options. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine. [source]

Role of a Streamer-like Coronary Thrombus in the Genesis of Unstable Angina

JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 3 2010
YASUMI UCHIDA M.D.
Introduction: It is generally believed that the coronary occlusion occurs at the site of plaque disruption in acute coronary syndromes. An exceptional mechanism of coronary occlusion, namely a streamer-like thrombus (SLT) originating in a nonstenotic lesion extended distally to obstruct a just distal nondisrupted stenotic segment, was found by angioscopy in patients with unstable angina (UA). This study was carried out to examine the incidence of this phenomenon and its relationship to the subtypes of UA. Methods: The culprit coronary artery was investigated by angioscopy in successive 48 patients (mean ± SE age, 61.0 ± 2.3 years; 10 females and 38 males) with UA. Results: SLT originating in a nonstenotic lesion extended distally, and obstructed the just distal most stenotic segment (DMSS) by its tail in 11 patients (eight with class III and three with class II according to Braunwald's classification). Recurrent anginal attacks were observed in all. The nonstenotic lesion in which the SLT originated was a disrupted yellow plaque in most cases. The SLT was frequently red and yellow in a mosaic pattern, indicating a mixture of fresh thrombus and plaque debris. The plaques that constructed the DMSS were not disrupted. Angiographically, the SLT was not detectable and the entry of the DMSS showed a "tapering" configuration. Conclusions: Obstruction of the DMSS by the tail of SLT originating in a nonstenotic lesion is another mechanism of UA. Therefore, treatment of both the nonstenotic lesion and DMSS is needed to prevent recurrent thrombus formation and consequent reattacks. (J Interven Cardiol 2010;23:216,222) [source]

The Short-Term Effect on Restenosis and Thrombosis of a Cobalt-Chromium Stent Eluting Two Drugs in a Porcine Coronary Artery Model

JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 5 2009
YINGYING HUANG Ph.D.
The aim of this article was to study the effect of dual drug-eluting stent (DES) on both restenosis and thrombosis in a porcine coronary artery model. This study reports on the use of two drugs coated on the stent to simultaneously minimize both restenosis and thrombosis. The DES was prepared by spray coating a bare metal stent with a biodegradable polymer loaded with sirolimus and triflusal, to treat against restenosis and thrombosis, respectively. The two-layered dual drug-coated stent was characterized in vitro for surface properties before and after expansion, as well as for possible delamination by cross-sectioning the stent in vitro. In vivo animal studies (in a pig model) were then performed for acute thrombosis, inflammation, and restenosis. The results show a significant reduction in restenosis with a stent coated with both drugs compared with the controls (a bare metal stent, a sirolimus-coated, and a pure polymer-coated stent). The reduction in restenosis with a sirolimus/triflusal-eluting stent is associated with an inhibition of inflammation and thrombus formation, suggesting that such dual DES have a role to play for the treatment of coronary artery diseases. [source]

Transcatheter Closure of Patent Foramen Ovale in Patients with Paradoxical Embolism.

JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2 2008
Follow-up Results after Implantation of the Starflex® Occluder Device with Conjunctive Intensified Anticoagulation Regimen, Procedural
Background:Prevalence of patent foramen ovale (PFO) is higher in patients with paradoxical embolism and associated with increased risk for recurrent thromboembolic events. By percutaneous closure of PFO, surgical closure or permanent oral anticoagulation can be avoided. So far, published series included different occluder systems and various indications and regimens of postprocedural anticoagulation. The aim of the present study was to evaluate the short- and long-term results after implantation of the Starflex® occluder in patients with PFO using an intensified anticoagulation regimen. Methods and Results:154 patients with PFO (94 men; age: 44 ± 13 years) and >1 thromboembolic event were included. Other causes for embolism were excluded. PFO closure was successful in 147 patients (95.5%). All patients were treated with phenprocoumon (INR 2.5) and aspirin (100 mg/die) for 6 months. Transesophageal echocardiography (TEE) was repeated at 6 months. Mean clinical follow-up period was 26 ± 18 months. After 6 months, five patients had a significant residual shunt, and five patients had suspected thrombus formation on the occluder. In three of these five patients, the occluder was surgically removed and foreign body reaction was noted. During follow-up, nine patients suffered from neurological events (two strokes, seven transient ischemic attacks [TIA]), though complete closure of the PFO was documented by TEE. Two patients died during follow-up; three patients had bleeding complications. Conclusion:Percutaneous closure of PFO in symptomatic patients by Starflex® occluder represents an effective therapy with a low incidence of periinterventional complications and recurrent thromboembolism. However, thrombus formation at the occluder system may occur in some patients despite an aggressive anticoagulation regimen. [source]

Patent Foramen Ovale Using the Premere Device: The Results of the CLOSEUP Trial

JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 4 2006
FRANZISKA BÜSCHECK M.D.
Objectives: The CLOSEUP trial was conducted to determine the safety and effectiveness of the Premere closure device in closure of patent foramen ovale (PFO). Background: PFO is a relatively common congenital condition, associated with cryptogenic stroke and migraine with aura. The Premere device is specifically designed to close PFO of variable size and length, with right and left anchor arms connected by a flexible tether. The device has an open architecture, a low profile, and a small surface area on the left atrial side which may discourage thrombus formation. Methods: Patients between 18 and 65 years of age who had a cryptogenic ischemic stroke or a transient ischemic attack and a PFO underwent percutaneous PFO closure using the Premere device. Results: Of the 73 enrolled patients, six patients had atrial anatomy not appropriate for the Premere; 27 patients received the 15 mm and 40 patients received the 20 mm device. Implantation was successful in all patients. At 6 months of follow-up, 86% of patients had no shunt that could be provoked with Valsalva as assessed during contrast echocardiography. Closure rates were better with the 20 mm versus the 15 mm device, and three patients with residual shunt had atrial septal aneurysms at baseline. One patient had transient atrial fibrillation which resolved by 3 months. There were no instances of thrombus, death, or stroke. Conclusions: These data demonstrate that the Premere device can safely and effectively close PFO. Additional studies should be undertaken to demonstrate the effectiveness of PFO closure in reducing thrombo-embolic events such as stroke. [source]

Effect of the small molecule plasminogen activator inhibitor-1 (PAI-1) inhibitor, PAI-749, in clinical models of fibrinolysis

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2010
A. J. LUCKING
Summary.,Background:,The principal inhibitor of fibrinolysis in vivo is plasminogen activator inhibitor-1 (PAI-1). PAI-749 is a small molecule inhibitor of PAI-1 with proven antithrombotic efficacy in several preclinical models. Objective:,To assess the effect of PAI-749, by using an established ex vivo clinical model of thrombosis and a range of complementary in vitro human plasma-based and whole blood-based models of fibrinolysis. Methods:,In a double-blind, randomized, crossover study, ex vivo thrombus formation was assessed using the Badimon chamber in 12 healthy volunteers during extracorporeal administration of tissue-type plasminogen activator (t-PA) in the presence of PAI-749 or control. t-PA-mediated lysis of plasma clots and of whole blood model thrombi were assessed in vitro. The role of vitronectin was examined by assessing lysis of fibrin clots generated from purified plasma proteins. Results:,There was a dose-dependent reduction in ex vivo thrombus formation by t-PA (P < 0.0001). PAI-749 had no effect on in vitro or ex vivo thrombus formation or fibrinolysis in the presence or absence of t-PA. Inhibition of PAI-1 with a blocking antibody enhanced fibrinolysis in vitro (P < 0.05). Conclusions: Despite its efficacy in a purified human system and in preclinical models of thrombosis, the current study suggests that PAI-749 does not affect thrombus formation or fibrinolysis in a range of established human plasma and whole blood-based systems. [source]

The glycoprotein Ib,,von Willebrand factor interaction induces platelet apoptosis

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2010
S. LI
Summary.,Background: The interaction of glycoprotein (GP) Ib, with von Willebrand factor (VWF) initiates platelet adhesion, and simultaneously triggers intracellular signaling cascades leading to platelet aggregation and thrombus formation. Some of the signaling events are similar to those occurring during apoptosis, however, it is still unclear whether platelet apoptosis is induced by the GPIb,,VWF interaction. Objectives: To investigate whether the GPIb,,VWF interaction induces platelet apoptosis and the role of 14-3-3, in apoptotic signaling. Methods: Apoptotic events were assessed in platelets or Chinese hamster ovary (CHO) cells expressing wild-type (1b9) or mutant GPIb,IX interacting with VWF by flow cytometry or western blotting. Results: Ristocetin-induced GPIb,,VWF interaction elicited apoptotic events in platelets, including phosphatidylserine exposure, elevations of Bax and Bak, gelsolin cleavage, and depolarization of mitochondrial inner transmembrane potential. Apoptotic events were also elicited in platelets exposed to pathologic shear stresses in the presence of VWF; however, the shear-induced apoptosis was eliminated by the anti-GPIb, antibody AK2. Furthermore, apoptotic events occurred in 1b9 cells stimulated with VWF and ristocetin, but were significantly diminished in two CHO cell lines expressing mutant GPIb,IX with GPIb, truncated at residue 551 or a serine-to-alanine mutation at the 14-3-3,-binding site in GPIb,. Conclusions: This study demonstrates that the GPIb,,VWF interaction induces apoptotic events in platelets, and that the association of 14-3-3, with the cytoplasmic domain of GPIb, is essential for apoptotic signaling. This finding may suggest a novel mechanism for platelet clearance or some thrombocytopenic diseases. [source]

A platelet tetraspanin superfamily member, CD151, is required for regulation of thrombus growth and stability in vivo

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2009
E. ORLOWSKI
Summary.,Background:,This study was designed to determine the role of CD151 in platelet thrombus formation in vivo and define the contribution of platelet vs. endothelial CD151 in regulating platelet thrombus formation in vivo. Methods and Results: Using intravital microscopy and ferric chloride (FeCl3) injury of mesenteric arterioles, we found that thrombi formed in CD151+/, and CD151,/, mice were smaller and less stable, than those formed in CD151+/+ mice, with a tendency for embolization. Similarly, in Folt's FeCl3,induced carotid injury model, both CD151+/, and CD151,/, mice showed more prolonged times to 95% vessel occlusion than CD151+/+ mice. In addition, laser-induced injury of cremaster muscle arterioles showed that thrombi formed in CD151+/, and CD151,/, mice were smaller and less stable than those formed in CD151+/+ mice. Following platelet depletion/reconstitution with ex vivo -labeled donor platelets, platelet-depleted CD151+/+ mice that received reconstitution with CD151,/, platelets had smaller thrombi that were unstable and embolized. In contrast, platelet-depleted CD151,/, mice that received reconstitution with CD151+/+ platelets had normal thrombi that were stable. Conclusions: These data provide evidence that platelet CD151 is required for regulating thrombus formation in vivo. [source]

Factor XI deficiency in animal models

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009
T. RENNÉ
Summary., The blood coagulation system forms fibrin to limit blood loss from sites of injury, but also contributes to occlusive diseases such as deep vein thrombosis, myocardial infarction, and stroke. In the current model of a coagulation balance, normal hemostasis and thrombosis represent two sides of the same coin; however, data from coagulation factor XI-deficient animal models have challenged this dogma. Gene targeting of factor XI, a serine protease of the intrinsic pathway of coagulation, severely impairs arterial thrombus formation but is not associated with excessive bleeding. Mechanistically, factor XI may be activated by factor XII following contact activation or by thrombin in a feedback activation loop. This review focuses on the role of factor XI, and its deficiency states as novel target for prevention of thrombosis with low bleeding risk in animal models. [source]

The ,3 integrin cytoplasmic tail: protein scaffold and control freak

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009
S. J. SHATTIL
Summary., Platelet integrin ,IIb,3 plays an essential role in thrombus formation through interactions with adhesive ligands. Successful parenteral blockade of these interactions has validated ,IIb,3 as a therapeutic target in cardiovascular medicine. However, oral ,IIb,3 antagonists have not been successful and there is an unmet need for more effective anti-platelet drugs. Growing evidence points to the cytoplasmic tails of ,IIb and ,3, and the ,3 tail in particular, as scaffolds for intracellular proteins that mediate inside-out signaling and regulate ,IIb,3 affinity for ligands. Intracellular protein interactions with the integrin cytoplasmic tails also regulate outside-in signals to the actin cytoskeleton. Here we focus on recent studies that illustrate the relevance of the ,3 cytoplasmic tail as a regulatory scaffold in vivo. We speculate that this scaffold or its interacting proteins may serve as therapeutic targets for the development of future anti-thrombotic drugs. [source]

Complementary roles of platelets and coagulation in thrombus formation on plaques acutely ruptured by targeted ultrasound treatment: a novel intravital model

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2009
M. J. E. KUIJPERS
Summary.,Background:,Atherothrombosis is a major cause of cardiovascular events. However, animal models to study this process are scarce. Objectives:,We describe the first murine model of acute thrombus formation upon plaque rupture to study atherothrombosis by intravital fluorescence microscopy. Methods:,Localized rupture of an atherosclerotic plaque in a carotid artery from Apoe,/, mice was induced in vivo using ultrasound. Rupture of the plaque and formation of localized thrombi were verified by two-photon laser scanning microscopy (TPLSM) in isolated arteries, and by immunohistochemistry. The thrombotic reaction was quantified by intravital fluorescence microscopy. Results:,Inspection of the ultrasound-treated plaques by histochemistry and TPLSM demonstrated local damage, collagen exposure, luminal thrombus formation as well as intra-plaque intrusion of erythrocytes and fibrin. Ultrasound treatment of healthy carotid arteries resulted in endothelial damage and limited platelet adhesion. Real-time intravital fluorescence microscopy demonstrated rapid platelet deposition on plaques and formation of a single thrombus that remained subocclusive. The thrombotic process was antagonized by thrombin inhibition, or by blocking of collagen or adenosine diphosphate receptor pathways. Multiple thrombi were formed in 70% of mice lacking CD40L. Conclusions:,Targeted rupture of murine plaques results in collagen exposure and non-occlusive thrombus formation. The thrombotic process relies on platelet activation as well as on thrombin generation and coagulation, and is sensitive to established and novel antithrombotic medication. This model provides new possibilities to study atherothrombosis in vivo. [source]