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Sample records for acute thrombus formation

  1. Factors influencing acute thrombus formation on carotid artery vascular grafts

    SciTech Connect

    Torem, S.; Schneider, P.A.; Paxton, L.D.; Yasuda, H.; Hanson, S.R.

    1988-10-01

    Scintillation camera imaging of 111Indium-labeled platelets has been used to measure acute thrombus formation on modified expanded Teflon (ePTFE) vascular grafts placed in the carotid arteries of normal baboons. Platelet deposition plateaued over 2 hr postoperatively and occurred primarily at the graft-vessel anastomoses. A positive correlation was found between the circulating platelet count in individual animals and the extent of early platelet thrombus deposition. Unmodified ePTFE grafts accumulated 4.6 +/- 1.2 x 10(9) platelets per graft, or 2.3 +/- 0.71 x 10(9) platelets per anastomosis. Acutely, platelet accumulation was reduced versus control graft results by coating the graft lumenal surfaces with a smooth layer of silicone rubber polymer (0.60 +/- 0.19 x 10(9) platelets per anastomosis; P less than 0.02) but not by coating the grafts using a plasma polymer based on methane, which did not modify graft texture (8.2 +/- 1.7 x 10(9) platelets per graft; P greater than 0.10). The benefit of the silicone rubber coating persisted for at least 48 hr. However, longer term patency was not preserved because 10 of 12 grafts placed had failed within 1 to 2 months.

  2. Thrombus formation in vivo

    PubMed Central

    Furie, Bruce; Furie, Barbara C.

    2005-01-01

    To examine thrombus formation in a living mouse, new technologies involving intravital videomicroscopy have been applied to the analysis of vascular windows to directly visualize arterioles and venules. After vessel wall injury in the microcirculation, thrombus development can be imaged in real time. These systems have been used to explore the role of platelets, blood coagulation proteins, endothelium, and the vessel wall during thrombus formation. The study of biochemistry and cell biology in a living animal offers new understanding of physiology and pathology in complex biologic systems. PMID:16322780

  3. Early thrombus formation in patient with HeartWare left ventricular assist device presenting with acute heart failure

    PubMed Central

    Ucar, Mustafa; Karakas, Mustafa Serkan; Bayrak, Murat; Altekin, Refik Emre; Koksel, Umut; Bayezid, Omer

    2015-01-01

    Heart failure is one of the leading causes of mortality and morbidity in the world. Heart transplantation is still the gold standard therapy despite emerging treatment options. Due to the limited number of available donors, the use of ventricular assist devices has increased. However, increasing incidences of complications are observed with using these devices. In this article, surgical treatment of a huge mobile thrombus formation in an inflow cannula due to ineffective anticoagulation in a 59 year-old man who received a HeartWare ventricular assist device because of ischemic cardiomyopathy is presented. PMID:26778905

  4. Early thrombus formation in patient with HeartWare left ventricular assist device presenting with acute heart failure.

    PubMed

    Ucar, Mustafa; Karakas, Mustafa Serkan; Bayrak, Murat; Altekin, Refik Emre; Koksel, Umut; Bayezid, Omer

    2016-01-01

    Heart failure is one of the leading causes of mortality and morbidity in the world. Heart transplantation is still the gold standard therapy despite emerging treatment options. Due to the limited number of available donors, the use of ventricular assist devices has increased. However, increasing incidences of complications are observed with using these devices. In this article, surgical treatment of a huge mobile thrombus formation in an inflow cannula due to ineffective anticoagulation in a 59 year-old man who received a HeartWare ventricular assist device because of ischemic cardiomyopathy is presented. PMID:26778905

  5. Thrombus aspiration in acute myocardial infarction: concepts, clinical trials, and current guidelines.

    PubMed

    Vandermolen, Sebastian; Marciniak, Maciej; Byrne, Jonathan; De Silva, Kalpa

    2016-05-01

    The pathogenesis that underlies acute myocardial infarction is complex and multifactorial. One of the most important components, however, is the role of thrombus formation following atherosclerotic plaque rupture, leading to sudden coronary occlusion and subsequent ischemia and infarction. Thrombus aspiration provides the opportunity of intracoronary clot extraction with the aim to improve coronary and myocardial perfusion, by reducing the risk of no-reflow secondary to distal embolization of thrombus. The utility of thrombus aspiration during primary percutaneous coronary intervention has been assessed in an increasing number of observational and randomized studies. This article reviews the contemporary data and provides insights into the validity of thrombus aspiration in the setting of acute myocardial infarction. PMID:26751424

  6. Management of Vertebral Stenosis Complicated by Presence of Acute Thrombus

    SciTech Connect

    Canyigit, Murat; Arat, Anil Cil, Barbaros E.; Sahin, Gurdal; Turkbey, Baris; Elibol, Bulent

    2007-04-15

    A 44-year-old male presented with multiple punctate acute infarcts of the vertebrobasilar circulation and a computed tomographic angiogram showing stenosis of the right vertebral origin. A digital subtraction angiogram demonstrated a new intraluminal filling defect at the origin of the stenotic vertebral artery where antegrade flow was maintained. This filling defect was accepted to be an acute thrombus of the vertebral origin, most likely due to rupture of a vulnerable plaque. The patient was treated with intravenous heparin. A control angiogram revealed dissolution of the acute thrombus under anticoagulation and the patient was treated with stenting with distal protection. Diffusion-weighted magnetic resonance imaging demonstrated no additional acute ischemic lesions. We were unable to find a similar report in the English literature documenting successful management of an acute vertebral ostial thrombus with anticoagulation. Anticoagulation might be considered prior to endovascular treatment of symptomatic vertebral stenoses complicated by the presence of acute thrombus.

  7. Thrombus aspiration in acute myocardial infarction.

    PubMed

    Mahmoud, Karim D; Zijlstra, Felix

    2016-07-01

    The success of primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is often hampered by incomplete microvascular myocardial reperfusion owing to distal embolization of thrombus resulting in microvascular obstruction. To address this problem, thrombus aspiration devices have been developed that can be used to evacuate coronary thrombus either manually or mechanically. Thrombus aspiration has the potential to reduce the local thrombus load, minimize the need for balloon predilatation, facilitate direct stenting, prevent distal embolization, and ultimately improve myocardial reperfusion. Furthermore, thrombus aspiration has enabled us to study coronary thrombus in vivo, and has facilitated recognition of distinct mechanisms of coronary thrombosis. Clinical trials focusing on manual thrombus aspiration in primary PCI have generally shown improved myocardial reperfusion. However, in two large trials powered for clinical end points, no reduction in 1-year mortality or other adverse clinical events was observed with the use of this strategy. Moreover, one of these trials showed a marginally increased risk of stroke. Consequently, current guidelines do not recommend routine use of thrombus aspiration. Future studies should focus on the identification of subgroups of patients with STEMI who might derive benefit from manual thrombus aspiration, and establish the effect of operator performance on the efficacy and safety of the procedure. PMID:26961064

  8. Relation between early mitral regurgitation and left ventricular thrombus formation after acute myocardial infarction: results of the GISSI-3 echo substudy

    PubMed Central

    Ascione, L; Antonini-Canterin, F; Macor, F; Cervesato, E; Chiarella, F; Giannuzzi, P; Temporelli, P L; Gentile, F; Lucci, D; Maggioni, A P; Tavazzi, L; Badano, L; Stoian, I; Piazza, R; Bosimini, E; Pavan, D; Nicolosi, G L

    2002-01-01

    Objective: To evaluate the prevalence and correlates of left ventricular thrombosis in patients with acute myocardial infarction, and whether the occurrence of early mitral regurgitation has a protective effect against the formation of left ventricular thrombus. Design and setting: Multicentre clinical trial carried out in 47 Italian coronary care units. Patients and methods: 757 patients from the GISSI-3 echo substudy population with their first acute myocardial infarct were studied by echocardiography at 24–48 hours from symptom onset (S1), at discharge (S2), at six weeks (S3), and at six months (S4). The diagnosis of left ventricular thrombosis was based on the detection of an echo dense mass with defined margins visible throughout the cardiac cycle in at least two orthogonal views. Results: In 64 patients (8%), left ventricular thrombosis was detected in one or more examinations. Compared with the remaining 693 patients, subjects with left ventricular thrombosis were older (mean (SD) age: 64.6 (13.0) v 59.8 (11.7) years, p < 0.005), and had larger infarcts (extent of wall motion asynergy: 40.9 (11.5)% v 24.9 (14)%, p < 0.001), greater depression of left ventricular ejection fraction at S1 (43.3 (6.9)% v 48.1 (6.8)%, p < 0.001), and greater left ventricular volumes at S1 (end diastolic volume: 87 (22) v 78 (18) ml/m2, p < 0.001; end systolic volume: 50 (17) v 41 (14) ml/m2, p < 0.001). The prevalence of moderate to severe mitral regurgitation on colour Doppler at S1 was greater in patients who had left ventricular thrombosis at any time (10.2% v 4.2%, p < 0.05). On stepwise multiple logistic regression analysis the only independent variables related to the presence of left ventricular thrombosis were the extent of wall motion asynergy and anterior site of infarction. Conclusions: Left ventricular thrombosis is not reduced, and may even be increased, by early moderate to severe mitral regurgitation after acute myocardial infarction. The only independent

  9. The fluid mechanics of thrombus formation

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Experimental data are presented for the growth of thrombi (blood clots) in a stagnation point flow of fresh blood. Thrombus shape, size and structure are shown to depend on local flow conditions. The evolution of a thrombus is described in terms of a physical model that includes platelet diffusion, a platelet aggregation mechanism, and diffusion and convection of the chemical species responsible for aggregation. Diffusion-controlled and convection-controlled regimes are defined by flow parameters and thrombus location, and the characteristic growth pattern in each regime is explained. Quantitative comparisons with an approximate theoretical model are presented, and a more general model is formulated.

  10. Extracellular Thiol Isomerases and Their Role in Thrombus Formation

    PubMed Central

    Schulman, Sol; Bendapudi, Pavan; Sharda, Anish; Chen, Vivien; Bellido-Martin, Lola; Jasuja, Reema; Furie, Barbara C.; Flaumenhaft, Robert

    2016-01-01

    Abstract Significance: The mammalian endoplasmic reticulum (ER) houses a large family of twenty thioredoxin-like proteins of which protein disulfide isomerase (PDI) is the archetypal member. Although the PDI family is best known for its role in oxidative protein folding of secretory proteins in the ER, these thioredoxin-like proteins fulfill ever-expanding roles, both within the secretory pathway and beyond. Recent Advances: Secreted PDI family proteins have now been shown to serve a critical role in platelet thrombus formation and fibrin generation. Utilizing intravital microscopy to visualize thrombus formation in mice, we have demonstrated the presence of extracellular PDI antigen during thrombus formation following injury of the vascular wall. Inhibition of PDI abrogates thrombus formation in vivo (16, 26, 46, 55). These observations have been extended to other PDI family members, including ERp57 (39, 116, 118, 123) and ERp5 (77). The vascular thiol isomerases are those PDI family members secreted from platelets and/or endothelium (40): PDI, ERp57, ERp5, ERp72, ERp44, ERp29, and TMX3. We focus here on PDI (16, 46, 55), ERp57 (39, 116, 118, 123), and ERp5 (77), which have been implicated in thrombus formation in vivo. Critical Issues: It would appear that a system of thiol isomerase redox catalysts has been hijacked from the ER to regulate thrombus formation in the vasculature. Future Directions: How this redox system is trafficked to and regulated at the cell surface, the identity of extracellular substrates, why so many thiol isomerases are required, and which thiol isomerase functions are necessary are critical unanswered questions in understanding the role of thiol isomerases in thrombus formation. Antioxid. Redox Signal. 24, 1–15. PMID:26467859

  11. Automated Entire Thrombus Density Measurements for Robust and Comprehensive Thrombus Characterization in Patients with Acute Ischemic Stroke

    PubMed Central

    Santos, Emilie M. M.; Niessen, Wiro J.; Yoo, Albert J.; Berkhemer, Olvert A.; Beenen, Ludo F.

    2016-01-01

    Background and Purpose In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. Materials and Method In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described using medians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between the median of entire thrombus measurements and commonly applied manual measurements using 3 regions of interest were determined using linear regression. Results Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density. Conclusions Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, discrimination of low and high density thrombi is improved with the automated method. PMID:26765847

  12. Left atrial thrombus formation after brief interruption of rivaroxaban.

    PubMed

    Turner, Matthew; Solarz, David

    2016-01-01

    Every year, nearly 250000 atrial fibrillation patients require temporary interruption of anticoagulation therapy for invasive procedures, acute illness, or bleeding events. Rivaroxaban is an oral anticoagulant that works by inhibiting factor Xa leading to a blockage of thrombin production, which inhibits platelet aggregation and thrombus formation. As with other anticoagulants, there is an increased risk of a thrombotic event occurring when rivaroxaban therapy is temporarily interrupted (TI) or prematurely discontinued. The 30-day rate of stroke or systemic embolism for rivaroxaban TI is 0.36%. Possible factors for higher than expected rates of embolic events include a prothrombotic perioperative environment among patients having TI for surgery and a prothrombotic environment associated with TI due to bleeding. The ROCKET AF study showed that there was no detectable difference in the risk of stroke and systemic embolism for participants treated with rivaroxaban vs warfarin undergoing TI. Another analysis suggested that the risk for stroke from TI is probably higher in the rivaroxaban group with 3 to 30 days discontinuation. Alternative anticoagulation therapy such as bridging should always be considered when stopping rivaroxaban. PMID:26081413

  13. Coagulation activity and white thrombus formation in the microminipig.

    PubMed

    Miura, Naoki; Kawaguchi, Hiroaki; Nagasato, Tomoka; Yamada, Tomonobu; Ito, Takashi; Izumi, Hiroyuki; Shameshima, Hisayo; Miyoshi, Noriaki; Tanimoto, Akihide; Maruyama, Ikuro

    2013-01-01

    Swine are becoming increasingly attractive as animal models for clinical research and the recently developed Microminipig (MMPig) has emerged as a possible experimental animal model. In this study, we demonstrated age-dependent changes in hematological parameters and coagulation activity in healthy MMPigs (58 male and 67 females, aged 0-34 months), and investigated white thrombus formation (WTF) using an in vitro microchip flow-chamber system (four males and four females, aged 22-23 months). There was no clear sex or age-dependent differences in any hematological parameters. While activated partial thromboplastin time (APTT) was shorter than prothrombin time (PT), with APTT:PT of 0.88:1, microchip flow-chamber system analysis showed that WTF time was shorter than that in humans, suggesting a possible thrombotic tendency in the MMPig. These results could be useful to life science researchers in the use of the MMPig as an experimental model animal for thrombus formation. PMID:23606691

  14. Platelet PECAM-1 inhibits thrombus formation in vivo.

    PubMed

    Falati, Shahrokh; Patil, Sonali; Gross, Peter L; Stapleton, Michelle; Merrill-Skoloff, Glenn; Barrett, Natasha E; Pixton, Katherine L; Weiler, Harmut; Cooley, Brian; Newman, Debra K; Newman, Peter J; Furie, Barbara C; Furie, Bruce; Gibbins, Jonathan M

    2006-01-15

    Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell surface glycoprotein receptor expressed on a range of blood cells, including platelets, and on vascular endothelial cells. PECAM-1 possesses adhesive and signaling properties, the latter being mediated by immunoreceptor tyrosine-based inhibitory motifs present on the cytoplasmic tail of the protein. Recent studies in vitro have demonstrated that PECAM-1 signaling inhibits the aggregation of platelets. In the present study we have used PECAM-1-deficient mice and radiation chimeras to investigate the function of this receptor in the regulation of thrombus formation. Using intravital microscopy and laser-induced injury to cremaster muscle arterioles, we show that thrombi formed in PECAM-1-deficient mice were larger, formed more rapidly than in control mice, and were more stable. Larger thrombi were also formed in control mice that received transplants of PECAM-1-deficient bone marrow, in comparison to mice that received control transplants. A ferric chloride model of thrombosis was used to investigate thrombus formation in carotid arteries. In PECAM-1-deficient mice the time to 75% vessel occlusion was significantly shorter than in control mice. These data provide evidence for the involvement of platelet PECAM-1 in the negative regulation of thrombus formation. PMID:16166583

  15. Left ventricular apical thrombus after systemic thrombolysis with recombinant tissue plasminogen activator in a patient with acute ischemic stroke

    PubMed Central

    Doepp, Florian; Sanad, Wasiem; Schreiber, Stephan J; Baumann, Gert; Borges, Adrian C

    2005-01-01

    Background Thrombolysis with recombinant tissue plasminogen activator (rtPA) is an established treatment in acute stroke. To prevent rethrombosis after rtPA therapy, secondary anticoagulation with heparin is commonly performed. However, the recommended time-point and extent of heparin treatment vary and are not well investigated. Case presentation We report a 61-year-old man who developed an acute global aphasia and right-sided hemiparesis. Cranial CT was normal and systemic thrombolytic therapy with tPA was started 120 minutes after symptom onset. Low-dose subcutaneous heparin treatment was initiated 24 hours later. Transthoracic echocardiography (TTE) 12 hours after admission showed slightly reduced left ventricular ejection fraction (LVEF) but was otherwise normal. 48 hours later the patient suddenly deteriorated with clinical signs of dyspnea and tachycardia. TTE revelead a large left ventricular apical thrombus as well as a reduction of LVEF to 20 %. Serial further TTE investigations demonstrated a complete resolution of the thrombus and normalisation of LVEF within two days. Conclusion Our case demonstrates an intracardiac thrombus formation following rtPA treatment of acute stroke, probably caused by secondary hypercoagulability. Rethrombosis or new thrombus formation might be an underestimated complication of rtPA therapy and potentially explain cases of secondary stroke progression. PMID:15918893

  16. Platelet receptors and signaling in the dynamics of thrombus formation

    PubMed Central

    Rivera, José; Lozano, María Luisa; Navarro-Núñez, Leyre; Vicente, Vicente

    2009-01-01

    Hemostasis and pathological thrombus formation are dynamic processes that require a co-ordinated series of events involving platelet membrane receptors, bidirectional intracellular signals, and release of platelet proteins and inflammatory substances. This review aims to summarize current knowledge in the key steps in the dynamics of thrombus formation, with special emphasis on the crucial participation of platelet receptors and signaling in this process. Initial tethering and firm adhesion of platelets to the exposed subendothelium is mediated by glycoprotein (GP) Ib/IX/V complex and collagen receptors, GP VI and α2β1 integrin, in the platelet surface, and by VWF and fibrillar collagen in the vascular site. Interactions between these elements are largely influenced by flow and trigger signaling events that reinforce adhesion and promote platelet activation. Thereafter, soluble agonists, ADP, thrombin, TxA2, produced/released at the site of vascular injury act in autocrine and paracrine mode to amplify platelet activation and to recruit circulating platelets to the developing thrombus. Specific interactions of these agonists with their G-protein coupled receptors generate inside-out signaling leading to conformational activation of integrins, in particular αIIbβ3, increasing their ligand affinity. Binding of αIIbβ3 to its ligands, mainly fibrinogen, supports processes such as clot retraction and platelet aggregation. Stabilization of thrombi is supported by the late wave of signaling events promoted by close contact between aggregated platelets. The best known contact-dependent signaling is outside-in signaling through αIb β3, but new ones are being clarified such as those mediated by interaction of Eph receptors with ephrins, or by Sema 4D and Gas-6 binding to their receptors. Finally, newly identified mechanisms appear to control thrombus growth, including back-shifting of activated integrins and actuation of compensatory molecules such as ESAM or PECAM-1

  17. Multiscale Simulation for the Initial Stage of Thrombus Formation

    NASA Astrophysics Data System (ADS)

    Takagi, Shu; , Satoshi, II; Shiozaki, Seiji; Shimamoto, Norio; Sugiyama, Kazuyasu; Matsumoto, Yoichiro

    2012-11-01

    Thrombosis is regarded as one of the most important diseases, which cause the myocardial and cerebral infarctions. The thrombus formation is strongly related to the multiscale coupling phenomena from molecular scale protein-protein interaction to continuum scale in blood flow. Initially, platelets start aggregate at the injured vessel wall, where von Willebrand Factor (vWF) is attached. The Glycoprotein, GPIb- α, on platelet membrane starts showing ligand-receptor interaction with this vWF and platelets start aggregating around this spot. In the present study, multiscale coupling method is developed to simulate the initial stage of thrombus formation. In this method, the molecular scale interactions between vWF and GPIb- α is solve using the stochastic Monte Carlo simulations and the binding force at each computational cell is calculated. Then the force is directly coupled with the continuum scale simulation using finite different method. The results illustrate that fluctuation given by the motion of red blood cells plays an important role for the platelets to adhere to the injured vessel walls.

  18. Incidence of post myocardial infarction left ventricular thrombus formation in the era of primary percutaneous intervention and glycoprotein IIb/IIIa inhibitors. A prospective observational study

    PubMed Central

    Rehan, Arshad; Kanwar, Manpreet; Rosman, Howard; Ahmed, Sujood; Ali, Arshad; Gardin, Julius; Cohen, Gerald

    2006-01-01

    Background Before the widespread use of primary percutaneous coronary intervention (PCI) and glycoprotein IIb/IIIa inhibitors (GP IIb/IIIa) left ventricular (LV) thrombus formation had been reported to complicate up to 20% of acute myocardial infarctions (AMI). The incidence of LV thrombus formation with these treatment modalities is not well known. Methods 92 consecutive patients with ST-elevation AMI treated with PCI and GP IIb/IIIa inhibitors underwent 2-D echocardiograms, with and without echo contrast agent, within 24–72 hours. Results Only 4/92 (4.3%) had an LV thrombus, representing a significantly lower incidence than that reported in the pre-PCI era. Use of contrast agents did not improve detection of LV thrombi in our study. Conclusion The incidence of LV thrombus formation after acute MI, in the current era of rapid reperfusion, is lower than what has been historically reported. PMID:16600036

  19. Platelet adhesion signalling and the regulation of thrombus formation.

    PubMed

    Gibbins, Jonathan M

    2004-07-15

    Platelets perform a central role in haemostasis and thrombosis. They adhere to subendothelial collagens exposed at sites of blood vessel injury via the glycoprotein (GP) Ib-V-IX receptor complex, GPVI and integrin alpha(2)beta(1). These receptors perform distinct functions in the regulation of cell signalling involving non-receptor tyrosine kinases (e.g. Src, Fyn, Lyn, Syk and Btk), adaptor proteins, phospholipase C and lipid kinases such as phosphoinositide 3-kinase. They are also coupled to an increase in cytosolic calcium levels and protein kinase C activation, leading to the secretion of paracrine/autocrine platelet factors and an increase in integrin receptor affinities. Through the binding of plasma fibrinogen and von Willebrand Factor to integrin alpha(IIb)beta(3), a platelet thrombus is formed. Although increasing evidence indicates that each of the adhesion receptors GPIb-V-IX and GPVI and integrins alpha(2)beta(1) and alpha(IIb)beta(3) contribute to the signalling that regulates this process, the individual roles of each are only beginning to be dissected. By contrast, adhesion receptor signalling through platelet endothelial cell adhesion molecule 1 (PECAM-1) is implicated in the inhibition of platelet function and thrombus formation in the healthy circulation. Recent studies indicate that understanding of platelet adhesion signalling mechanisms might enable the development of new strategies to treat and prevent thrombosis. PMID:15252124

  20. No-Reflow Phoenomenon by Intracoronary Thrombus in Acute Myocardial Infarction

    PubMed Central

    2016-01-01

    Recently, percutaneous coronary intervention has been the treatment of choice in most acute myocardial infarction cases. Although the results of percutaneous coronary interventions have ben good, the no-reflow phenomenon and distal embolization of intracoronary thrombus are still major problems even after successful interventions. In this article, we will briefly review the deleterious effects of no-reflow and distal embolization of intracoronary thrombus during percutaneous coronary interventions. The current trials focused on the prevention and treatment of the no-reflow phenomenon and intracoronary thrombus. PMID:26865998

  1. Counting the platelets: a robust and sensitive quantification method for thrombus formation.

    PubMed

    Claesson, Kjersti; Lindahl, Tomas L; Faxälv, Lars

    2016-06-01

    Flow chambers are common tools used for studying thrombus formation in vitro. However, the use of such devices is not standardised and there is a large diversity among the flow chamber systems currently used, and also in the methods used for quantifying the thrombus development. It was the study objective to evaluate a new method for analysis and quantification of platelet thrombus formation that can facilitate comparison of results between research groups. Whole blood was drawn over a collagen patch in commercial Ibid or in-house constructed PDMS flow chambers. Five percent of the platelets were fluorescently labelled and z-stack time-lapse images were captured during thrombus formation. Images were processed in a Python script in which the number of platelets and their respective x-, y- and z-positions were obtained. For comparison with existing methods the platelets were also labelled and quantified using fluorescence intensity and thrombus volume estimations by confocal microscopy. The presented method was found less sensitive to microscope and image adjustments and provides more details on thrombus development dynamics than the methods for measuring fluorescence intensity and thrombus volume estimation. The platelet count method produced comparable results with commercial and PDMS flow chambers, and could also obtain information regarding the stability of each detected platelet in the thrombus. In conclusion, quantification of thrombus formation by platelet count is a sensitive and robust method that enables measurement of platelet accumulation and platelet stability in an absolute scale that could be used for comparisons between research groups. PMID:26842994

  2. Continuous Modeling of Arterial Platelet Thrombus Formation Using a Spatial Adsorption Equation.

    PubMed

    Babushkina, Evgenia S; Bessonov, Nikolay M; Ataullakhanov, Fazoil I; Panteleev, Mikhail A

    2015-01-01

    In this study, we considered a continuous model of platelet thrombus growth in an arteriole. A special model describing the adhesion of platelets in terms of their concentration was derived. The applications of the derived model are not restricted to only describing arterial platelet thrombus formation; the model can also be applied to other similar adhesion processes. The model reproduces an auto-wave solution in the one-dimensional case; in the two-dimensional case, in which the surrounding flow is taken into account, the typical torch-like thrombus is reproduced. The thrombus shape and the growth velocity are determined by the model parameters. We demonstrate that the model captures the main properties of the thrombus growth behavior and provides us a better understanding of which mechanisms are important in the mechanical nature of the arterial thrombus growth. PMID:26517377

  3. A biologically active surface enzyme assembly that attenuates thrombus formation

    PubMed Central

    Qu, Zheng; Muthukrishnan, Sharmila; Urlam, Murali K.; Haller, Carolyn A.; Jordan, Sumanas W.; Kumar, Vivek A.; Marzec, Ulla M.; Elkasabi, Yaseen; Lahann, Joerg; Hanson, Stephen R.

    2013-01-01

    Activation of hemostatic pathways by blood-contacting materials remains a major hurdle in the development of clinically durable artificial organs and implantable devices. We postulate that surface-induced thrombosis may be attenuated by the reconstitution onto blood contacting surfaces of bioactive enzymes that regulate the production of thrombin, a central mediator of both clotting and platelet activation cascades. Thrombomodulin (TM), a transmembrane protein expressed by endothelial cells, is an established negative regulator of thrombin generation in the circulatory system. Traditional techniques to covalently immobilize enzymes on solid supports may modify residues contained within or near the catalytic site, thus reducing the bioactivity of surface enzyme assemblies. In this report, we present a molecular engineering and bioorthogonal chemistry approach to site-specifically immobilize a biologically active recombinant human TM fragment onto the luminal surface of small diameter prosthetic vascular grafts. Bioactivity and biostability of TM modified grafts is confirmed in vitro and the capacity of modified grafts to reduce platelet activation is demonstrated using a non-human primate model. These studies indicate that molecularly engineered interfaces that display TM actively limit surface-induced thrombus formation. PMID:23532366

  4. Chlorogenic Acid Inhibits Human Platelet Activation and Thrombus Formation

    PubMed Central

    Fuentes, Eduardo; Caballero, Julio; Alarcón, Marcelo; Rojas, Armando; Palomo, Iván

    2014-01-01

    Background Chlorogenic acid is a potent phenolic antioxidant. However, its effect on platelet aggregation, a critical factor in arterial thrombosis, remains unclear. Consequently, chlorogenic acid-action mechanisms in preventing platelet activation and thrombus formation were examined. Methods and Results Chlorogenic acid in a dose-dependent manner (0.1 to 1 mmol/L) inhibited platelet secretion and aggregation induced by ADP, collagen, arachidonic acid and TRAP-6, and diminished platelet firm adhesion/aggregation and platelet-leukocyte interactions under flow conditions. At these concentrations chlorogenic acid significantly decreased platelet inflammatory mediators (sP-selectin, sCD40L, CCL5 and IL-1β) and increased intraplatelet cAMP levels/PKA activation. Interestingly, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent A2A receptor antagonist) attenuated the antiplatelet effect of chlorogenic acid. Chlorogenic acid is compatible to the active site of the adenosine A2A receptor as revealed through molecular modeling. In addition, chlorogenic acid had a significantly lower effect on mouse bleeding time when compared to the same dose of aspirin. Conclusions Antiplatelet and antithrombotic effects of chlorogenic acid are associated with the A2A receptor/adenylate cyclase/cAMP/PKA signaling pathway. PMID:24598787

  5. Acute Bilateral Internal Carotid Occlusion from Embolization of Left Atrial Thrombus During Transesophageal Echocardiography: Case Report

    PubMed Central

    Mahmood, Syed Saad; Manjila, Sunil; Singh, Gagandeep; Xavier, Andrew R

    2016-01-01

    Background and purpose: Transesophageal echocardiography (TEE) is a relatively safe imaging modality used to visualize intracardiac thrombus. Summary of case: We report on a unique, fatal complication during TEE of embolization of a pre-existing “smoking” left atrial thrombus causing acute bilateral internal carotid occlusion, confirmed on angiogram. Conclusions: Patients with history of lung pathology, such as COPD, who experience retching and cough during transesophageal echocardiography may be more susceptible to embolization of pre-existing thrombi. A need exists to risk stratify such patients. PMID:27403219

  6. Role of intracoronary thrombus in acute complications during percutaneous transluminal coronary angioplasty.

    PubMed

    Arora, R R; Platko, W P; Bhadwar, K; Simpfendorfer, C

    1989-04-01

    Coronary angiograms from 2,372 consecutive patients who underwent percutaneous transluminal coronary angioplasty (PTCA) were retrospectively reviewed for the presence of intracoronary thrombus (ICT) before dilatation. Patients with evolving acute myocardial infarction and those receiving thrombolytic therapy were excluded from analysis. Coronary artery thrombus was present in 126 patients (6%) (group 1). When compared to 2,246 patients (group 2) without ICT, group 1 had a higher incidence of unstable angina, 74% vs. 66% (less than 0.06), previous myocardial infarction, 59% vs. 37% (P less than .0001), and history of a recent myocardial infarction, 28% vs. 9% (P less than .0001). Patients with predilatation intracoronary thrombus had a higher risk for acute occlusion, 6% vs. 2% (P less than .002); however, the incidence of emergency coronary bypass surgery and myocardial infarction was similar in both groups. Therefore, the presence of predilatation intracoronary thrombus heralds an increased risk of acute occlusion, but not myocardial infarction or emergency coronary artery bypass surgery. PMID:2523243

  7. Platelet size and density affect shear-induced thrombus formation in tortuous arterioles

    NASA Astrophysics Data System (ADS)

    Chesnutt, Jennifer K. W.; Han, Hai-Chao

    2013-10-01

    Thrombosis accounts for 80% of deaths in patients with diabetes mellitus. Diabetic patients demonstrate tortuous microvessels and larger than normal platelets. Large platelets are associated with increased platelet activation and thrombosis, but the physical effects of large platelets in the microscale processes of thrombus formation are not clear. Therefore, the objective of this study was to determine the physical effects of mean platelet volume (MPV), mean platelet density (MPD) and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A computational model of the transport, shear-induced activation, collision, adhesion and aggregation of individual platelets was used to simulate platelet interactions and thrombus formation in tortuous arterioles. Our results showed that an increase in MPV resulted in a larger number of activated platelets, though MPD and level of tortuosity made little difference on platelet activation. Platelets with normal MPD yielded the lowest amount of mural thrombus. With platelets of normal MPD, the amount of mural thrombus decreased with increasing level of tortuosity but did not have a simple monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD and arteriole tortuosity play important roles in platelet activation and thrombus formation.

  8. Numerical modeling of the flow in intracranial aneurysms: prediction of regions prone to thrombus formation

    PubMed Central

    Rayz, V.L.; Boussel, L.; Lawton, M.T.; Acevedo-Bolton, G.; Ge, L.; Young, W.L.; Higashida, R.T.; Saloner, D.

    2009-01-01

    The deposition of intralumenal thrombus in intracranial aneurysms adds a risk of thrombo-embolism over and above that posed by mass-effect and rupture. In addition to biochemical factors, hemodynamic factors that are governed by lumenal geometry and blood flow rates likely play an important role in the thrombus formation and deposition process. In this study, patient-specific computational fluid dynamics (CFD) models of blood flow were constructed from MRA data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intra-lumenal thrombus. In order to determine whether features of the flow fields could suggest which regions had an elevated potential for thrombus deposition, the flow was modeled in the baseline, thrombus-free geometries. Pulsatile flow simulations were carried out using patient-specific inlet flow conditions measured with MR velocimetry. Newtonian and non-Newtonian blood behavior was considered. A strong similarity was found between the intra-aneurysmal regions with CFD-predicted slow, recirculating flows and the regions of thrombus deposition observed in vivo in the follow-up MR studies. In two cases with larger aneurysms, the agreement between the low velocity zones and clotted off regions improved when non-Newtonian blood behavior was taken into account. A similarity was also found between the calculated low shear stress regions and the regions that were later observed to clot. PMID:18787954

  9. A spatio-temporal model for spontaneous thrombus formation in cerebral aneurysms.

    PubMed

    Malaspinas, O; Turjman, A; Ribeiro de Sousa, D; Garcia-Cardena, G; Raes, M; Nguyen, P-T T; Zhang, Y; Courbebaisse, G; Lelubre, C; Zouaoui Boudjeltia, K; Chopard, B

    2016-04-01

    We propose a new numerical model to describe thrombus formation in cerebral aneurysms. This model combines CFD simulations with a set of bio-mechanical processes identified as being the most important to describe the phenomena at a large space and time scales. The hypotheses of the model are based on in vitro experiments and clinical observations. We document that we can reproduce very well the shape and volume of patient specific thrombus segmented in giant aneurysms. PMID:26802480

  10. Platelet receptor interplay regulates collagen-induced thrombus formation in flowing human blood.

    PubMed

    Siljander, Pia R-M; Munnix, Imke C A; Smethurst, Peter A; Deckmyn, Hans; Lindhout, Theo; Ouwehand, Willem H; Farndale, Richard W; Heemskerk, Johan W M

    2004-02-15

    The platelet glycoproteins (GPs) Ib, integrin alpha(2)beta(1), and GPVI are considered central to thrombus formation. Recently, their relative importance has been re-evaluated based on data from murine knockout models. To examine their relationship during human thrombus formation on collagen type I fibers at high shear (1000 s(-1)), we tested a novel antibody against GPVI, an immunoglobulin single-chain variable fragment, 10B12, together with specific antagonists for GPIb alpha (12G1 Fab(2)) and alpha(2)beta(1) (6F1 mAb or GFOGER-GPP peptide). GPVI was found to be crucial for aggregate formation, Ca(2+) signaling, and phosphatidylserine (PS) exposure, but not for primary adhesion, even with more than 97% receptor blockade. Inhibiting alpha(2)beta(1) revealed its involvement in regulating Ca(2+) signaling, PS exposure, and aggregate size. Both GPIb alpha and alpha(2)beta(1) contributed to primary adhesion, showing overlapping function. The coinhibition of receptors revealed synergism in thrombus formation: the coinhibition of adenosine diphosphate (ADP) receptors with collagen receptors further decreased adhesion and aggregation, and, crucially, the complete eradication of thrombus formation required the coinhibition of GPVI with either GPIb alpha or alpha(2)beta(1). In summary, human platelet deposition on collagen depends on the concerted interplay of several receptors: GPIb in synergy with alpha(2)beta(1) mediating primary adhesion, reinforced by activation through GPVI, which further regulates the thrombus formation. PMID:14563646

  11. Computational Study of Thrombus Formation and Clotting Factor Effects under Venous Flow Conditions.

    PubMed

    Govindarajan, Vijay; Rakesh, Vineet; Reifman, Jaques; Mitrophanov, Alexander Y

    2016-04-26

    A comprehensive understanding of thrombus formation as a physicochemical process that has evolved to protect the integrity of the human vasculature is critical to our ability to predict and control pathological states caused by a malfunctioning blood coagulation system. Despite numerous investigations, the spatial and temporal details of thrombus growth as a multicomponent process are not fully understood. Here, we used computational modeling to investigate the temporal changes in the spatial distributions of the key enzymatic (i.e., thrombin) and structural (i.e., platelets and fibrin) components within a growing thrombus. Moreover, we investigated the interplay between clot structure and its mechanical properties, such as hydraulic resistance to flow. Our model relied on the coupling of computational fluid dynamics and biochemical kinetics, and was validated using flow-chamber data from a previous experimental study. The model allowed us to identify the distinct patterns characterizing the spatial distributions of thrombin, platelets, and fibrin accumulating within a thrombus. Our modeling results suggested that under the simulated conditions, thrombin kinetics was determined predominantly by prothrombinase. Furthermore, our simulations showed that thrombus resistance imparted by fibrin was ∼30-fold higher than that imparted by platelets. Yet, thrombus-mediated bloodflow occlusion was driven primarily by the platelet deposition process, because the height of the platelet accumulation domain was approximately twice that of the fibrin accumulation domain. Fibrinogen supplementation in normal blood resulted in a nonlinear increase in thrombus resistance, and for a supplemented fibrinogen level of 48%, the thrombus resistance increased by ∼2.7-fold. Finally, our model predicted that restoring the normal levels of clotting factors II, IX, and X while simultaneously restoring fibrinogen (to 88% of its normal level) in diluted blood can restore fibrin generation to

  12. Identification of platelet function defects by multi-parameter assessment of thrombus formation

    PubMed Central

    de Witt, Susanne M.; Swieringa, Frauke; Cavill, Rachel; Lamers, Moniek M. E.; van Kruchten, Roger; Mastenbroek, Tom; Baaten, Constance; Coort, Susan; Pugh, Nicholas; Schulz, Ansgar; Scharrer, Inge; Jurk, Kerstin; Zieger, Barbara; Clemetson, Kenneth J.; Farndale, Richard W.; Heemskerk, Johan W. M.; Cosemans, Judith M.E.M.

    2014-01-01

    Assays measuring platelet aggregation (thrombus formation) at arterial shear rate mostly use collagen as only platelet-adhesive surface. Here we report a multi-surface and multi-parameter flow assay to characterize thrombus formation in whole blood from healthy subjects and patients with platelet function deficiencies. A systematic comparison is made of 52 adhesive surfaces with components activating the main platelet-adhesive receptors, and of eight output parameters reflecting distinct stages of thrombus formation. Three types of thrombus formation can be identified with a predicted hierarchy of the following receptors: glycoprotein (GP)VI, C-type lectin-like receptor-2 (CLEC-2)>GPIb>α6β1, αIIbβ3>α2β1>CD36, α5β1, αvβ3. Application with patient blood reveals distinct abnormalities in thrombus formation in patients with severe combined immune deficiency, Glanzmann’s thrombasthenia, Hermansky–Pudlak syndrome, May–Hegglin anomaly or grey platelet syndrome. We suggest this test may be useful for the diagnosis of patients with suspected bleeding disorders or a pro-thrombotic tendency. PMID:25027852

  13. Glaucocalyxin A inhibits platelet activation and thrombus formation preferentially via GPVI signaling pathway.

    PubMed

    Li, Wei; Tang, Xiaorong; Yi, Wenxiu; Li, Qiang; Ren, Lijie; Liu, Xiaohui; Chu, Chunjun; Ozaki, Yukio; Zhang, Jian; Zhu, Li

    2013-01-01

    Platelets play a pivotal role in atherothrombosis and the antiplatelet agents have been proved to be useful in preventing onset of acute clinical events including myocardial infarction and stroke. Increasing number of natural compounds has been identified to be potential antiplatelet agents. Here we report the antiplatelet effect of glaucocalyxin A (GLA), an ent-diterpenoid that we isolated and purified from the aerial parts of Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, and investigate the molecular mechanisms by which GLA inhibits platelet activation and thrombus formation. The effect of GLA on platelet activation was measured using platelets freshly isolated from peripheral blood of healthy donors. Results showed that pretreatment of human platelets with lower concentrations of GLA (0.01 μg/ml, 0.1 μg/ml) significantly inhibited platelet aggregation induced by collagen (P<0.001) and CRP (P<0.01), a synthetic GPVI ligand, but not by ADP and U46619. Accordingly, GLA inhibited collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GPⅥ pathway. GLA also inhibited platelet p-selectin secretion and integrin activation by convulxin, a GPVI selective ligand. Additionally, GLA was found to inhibit low-dose thrombin-induced platelet activation. Using a flow chamber device, GLA was found to attenuate platelet adhesion on collagen surfaces in high shear condition. In vivo studies showed that GLA administration increased the time for complete occlusion upon vascular injury in mice, but did not extend tail-bleeding time when mice were administered with relatively lower doses of GLA. Therefore, the present results provide the molecular basis for the inhibition effect of GLA on platelet activation and its in vivo effect on thrombus formation, suggesting that GLA could potentially be developed as an antiplatelet and antithrombotic agent. PMID:24386454

  14. Segregation of Platelet Aggregatory and Procoagulant Microdomains in Thrombus Formation Regulation by Transient Integrin Activation

    PubMed Central

    Munnix, Imke C.A.; Kuijpers, Marijke J.E.; Auger, Jocelyn; Thomassen, Christella M.L.G.D.; Panizzi, Peter; van Zandvoort, Marc A.M.; Rosing, Jan; Bock, Paul E.; Watson, Steve P.; Heemskerk, Johan W.M.

    2008-01-01

    Objective Platelets play a dual role in thrombosis by forming aggregates and stimulating coagulation. We investigated the commitment of platelets to these separate functions during collagen-induced thrombus formation in vitro and in vivo. Methods and Results High-resolution 2-photon fluorescence microscopy revealed that in thrombus formation under flow, fibrin(ogen)-binding platelets assembled into separate aggregates, whereas distinct patches of nonaggregated platelets exposed phosphatidylserine. The latter platelet population had inactivated αIibβ3 integrins and displayed increased binding of coagulation factors. Coated platelets, expressing serotonin binding sites, were not identified as a separate population. Thrombin generation and coagulation favored the transformation to phosphatidylserine-exposing platelets with inactivated integrins and reduced adhesion. Prolonged tyrosine phosphorylation in vitro resulted in secondary downregulation of active αIIbβ3. Conclusions These results lead to a new spatial model of thrombus formation, in which aggregated platelets ensure thrombus stability, whereas distinct patches of nonaggregated platelets effectuate procoagulant activity and generate thrombin and fibrin. Herein, the hemostatic activity of a developing thrombus is determined by the balance in formation of proaggregatory and procoagulant platelets. This balance is influenced by antiplatelet and anticoagulant medication. PMID:17761939

  15. A Case Report: An Acute Thrombus in the Femoral Artery following Total Hip Arthroplasty

    PubMed Central

    GBS, Varun; N, Muralidhar; Bharathidasan, Kavya

    2016-01-01

    Introduction: Vascular complications post-operative to a total hip arthroplasty are a very rare phenomenon. Only a few isolated cases have been reported to date. Diagnosis of such a case in a timely manner so as to preserve the limb is also difficult due to the subtle signs with which the patient presents. We report a case of complete occlusion of the common femoral artery following total hip arthroplasty due to acute thrombus formation. Case Presentation: A 56 year old Indian male patient underwent a cemented total hip replacement. Three hours post-operatively, the patient’s left lower limb was found to be pale and pulseless. Angiography showed complete occlusion of the left common femoral artery. Thrombectomy was carried out immediately and the patient recovered well. Conclusion: Vascular injuries are highly unusual findings following a total hip arthroplasty. Careful pre-operative and immediate post-operative monitoring of the patient is essential. Signs such as limb ischemia, absence of pulses, etc. must be recognized as early as possible and the necessary investigations and procedures should be carried out without any delay. PMID:27299128

  16. Effect of Red Blood Cells on Platelet Activation and Thrombus Formation in Tortuous Arterioles

    PubMed Central

    Chesnutt, Jennifer K. W.; Han, Hai-Chao

    2013-01-01

    Thrombosis is a major contributor to cardiovascular disease, which can lead to myocardial infarction and stroke. Thrombosis may form in tortuous microvessels, which are often seen throughout the human body, but the microscale mechanisms and processes are not well understood. In straight vessels, the presence of red blood cells (RBCs) is known to push platelets toward walls, which may affect platelet aggregation and thrombus formation. However in tortuous vessels, the effects of RBC interactions with platelets in thrombosis are largely unknown. Accordingly, the objective of this work was to determine the physical effects of RBCs, platelet size, and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A discrete element computational model was used to simulate the transport, collision, adhesion, aggregation, and shear-induced platelet activation of hundreds of individual platelets and RBCs in thrombus formation in tortuous arterioles. Results showed that high shear stress near the inner sides of curved arteriole walls activated platelets to initiate thrombosis. RBCs initially promoted platelet activation, but then collisions of RBCs with mural thrombi reduced the amount of mural thrombus and the size of emboli. In the absence of RBCs, mural thrombus mass was smaller in a highly tortuous arteriole compared to a less tortuous arteriole. In the presence of RBCs however, mural thrombus mass was larger in the highly tortuous arteriole compared to the less tortuous arteriole. As well, smaller platelet size yielded less mural thrombus mass and smaller emboli, either with or without RBCs. This study shed light on microscopic interactions of RBCs and platelets in tortuous microvessels, which have implications in various pathologies associated with thrombosis and bleeding. PMID:25022613

  17. Differences in thrombus structure and kinetics in patients with type 2 diabetes mellitus after non ST elevation acute coronary syndrome

    PubMed Central

    Viswanathan, Girish N.; Marshall, Sally M.; Balasubramaniam, Karthik; Badimon, Juan J.; Zaman, Azfar G.

    2014-01-01

    Introduction Despite optimal secondary prevention therapy following non-ST elevation acute coronary syndrome (NSTE-ACS), recurrent thrombotic events are more frequent in patients with type 2 diabetes mellitus (T2DM). Materials and Methods This exploratory study was aimed to evaluate quantitative and qualitative aspects of thrombus. In 28 patients with and without T2DM treated with aspirin and clopidogrel we assessed thrombus quantity using an ex-vivo chamber, platelet reactivity, thrombus ultrastructure and thrombus kinetics one week after NSTE-ACS. Results T2DM was associated with increased thrombus [14861 (8003 to 30161) vs 8908 (6812 to 11996), μ2/mm, median (IQR), p = 0.045] and platelet reactivity. In addition, diabetic thrombus showed lower visco-elastic tensile strength [(− 0.2(− 1.7 to 0.7) vs 1.0(− 0.9 to 3.3), p = 0.044)] and was more resistant to autolysis [(27.8(11.7 to 70.7) vs 78.8(68.5 to109.6) mm/min, p = 0.002)]. On SEM, fibrin fibres in diabetes were thinner, with higher lateral interlinkage and mesh-like organisation. Thrombus quantity correlated inversely with thrombus retraction (r = − 0.450 p = 0.016) but not with platelet reactivity (r = 0.153, p = 0.544). Conclusions Despite optimal antiplatelet therapy, T2DM patients after NSTE-ACS developed increased thrombus of lower tensile strength and slower retraction. SEM revealed loosely arranged fibrin fibres. Our data showed significant differences in the magnitude as well as structural and mechanistic characteristics of thrombus in patients with T2DM. PMID:24582462

  18. Platelets and coagulation in thrombus formation: aberrations in the Scott syndrome.

    PubMed

    van Geffen, Johanna P; Swieringa, Frauke; Heemskerk, Johan W M

    2016-05-01

    Platelets play key roles in thrombosis and hemostasis by forming aggregates and providing a procoagulant surface, at which thrombin is generated and fibrin fibers are formed. Here we present an overview of the different mechanisms how platelets orchestrate coagulation processes in thrombus formation in thrombosis and hemostasis. Parts of these are via Ca(2+)-dependent activation responses, leading to phosphatidylserine exposure; swelling to form balloons with increased binding of coagulation factors; and calpain-mediated integrin αIIbβ3 cleavage and inactivation. Other mechanisms are secretion of (anti) coagulation factors, and αIIbβ3-mediated thrombus retraction, and clot retraction. In a thrombus, coagulation factors are found at both platelets and fibrin fibers. Many of the procoagulant platelet activities are altered in the Scott syndrome. PMID:27207414

  19. Defective PDI release from platelets and endothelial cells impairs thrombus formation in Hermansky-Pudlak syndrome

    PubMed Central

    Sharda, Anish; Kim, Sarah H.; Jasuja, Reema; Gopal, Srila; Flaumenhaft, Robert; Furie, Barbara C.

    2015-01-01

    Protein disulfide isomerase (PDI), secreted from platelets and endothelial cells after injury, is required for thrombus formation. The effect of platelet and endothelial cell granule contents on PDI-mediated thrombus formation was studied by intravital microscopy using a mouse model of Hermansky-Pudlak syndrome in which platelet dense granules are absent. Platelet deposition and fibrin generation were nearly absent, and extracellular PDI was significantly reduced in HPS6−/− mice after vascular injury. HPS6−/− platelets displayed impaired PDI secretion and impaired exocytosis of α granules, lysosomes, and T granules due to decreased sensitivity to thrombin, but these defects could be corrected by addition of subthreshold amounts of adenosine 5′-diphosphate (ADP). Human Hermansky-Pudlak syndrome platelets demonstrated similar characteristics. Infusion of wild-type platelets rescued thrombus formation in HPS6−/− mice. Human umbilical vein endothelial cells in which the HPS6 gene was silenced displayed impaired PDI secretion and exocytosis of Weibel-Palade bodies. Defective thrombus formation in Hermansky-Pudlak syndrome, associated with impaired exocytosis of residual granules in endothelial cells and platelets, the latter due to deficiency of ADP, is characterized by a defect in T granule secretion, a deficiency in extracellular PDI secretion, and impaired fibrin generation and platelet aggregation. Hermansky-Pudlak syndrome is an example of a hereditary disease whereby impaired PDI secretion contributes to a bleeding phenotype. PMID:25593336

  20. Defective PDI release from platelets and endothelial cells impairs thrombus formation in Hermansky-Pudlak syndrome.

    PubMed

    Sharda, Anish; Kim, Sarah H; Jasuja, Reema; Gopal, Srila; Flaumenhaft, Robert; Furie, Barbara C; Furie, Bruce

    2015-03-01

    Protein disulfide isomerase (PDI), secreted from platelets and endothelial cells after injury, is required for thrombus formation. The effect of platelet and endothelial cell granule contents on PDI-mediated thrombus formation was studied by intravital microscopy using a mouse model of Hermansky-Pudlak syndrome in which platelet dense granules are absent. Platelet deposition and fibrin generation were nearly absent, and extracellular PDI was significantly reduced in HPS6(-/-) mice after vascular injury. HPS6(-/-) platelets displayed impaired PDI secretion and impaired exocytosis of α granules, lysosomes, and T granules due to decreased sensitivity to thrombin, but these defects could be corrected by addition of subthreshold amounts of adenosine 5'-diphosphate (ADP). Human Hermansky-Pudlak syndrome platelets demonstrated similar characteristics. Infusion of wild-type platelets rescued thrombus formation in HPS6(-/-) mice. Human umbilical vein endothelial cells in which the HPS6 gene was silenced displayed impaired PDI secretion and exocytosis of Weibel-Palade bodies. Defective thrombus formation in Hermansky-Pudlak syndrome, associated with impaired exocytosis of residual granules in endothelial cells and platelets, the latter due to deficiency of ADP, is characterized by a defect in T granule secretion, a deficiency in extracellular PDI secretion, and impaired fibrin generation and platelet aggregation. Hermansky-Pudlak syndrome is an example of a hereditary disease whereby impaired PDI secretion contributes to a bleeding phenotype. PMID:25593336

  1. Feasibility of the optical imaging of thrombus formation in a rotary blood pump by near-infrared light.

    PubMed

    Sakota, Daisuke; Murashige, Tomotaka; Kosaka, Ryo; Nishida, Masahiro; Maruyama, Osamu

    2014-09-01

    Blood coagulation is one of the primary concerns when using mechanical circulatory support devices such as blood pumps. Noninvasive detection and imaging of thrombus formation is useful not only for the development of more hemocompatible devices but also for the management of blood coagulation to avoid risk of infarction. The objective of this study is to investigate the use of near-infrared light for imaging of thrombus formation in a rotary blood pump. The optical properties of a thrombus at wavelengths ranging from 600 to 750 nm were analyzed using a hyperspectral imaging (HSI) system. A specially designed hydrodynamically levitated centrifugal blood pump with a visible bottom area was used. In vitro antithrombogenic testing was conducted five times with the pump using bovine whole blood in which the activated blood clotting time was adjusted to 200 s prior to the experiment. Two halogen lights were used for the light sources. The forward scattering through the pump and backward scattering on the pump bottom area were imaged using the HSI system. HSI showed an increase in forward scattering at wavelengths ranging from 670 to 750 nm in the location of thrombus formation. The time at which the thrombus began to form in the impeller rotating at 2780 rpm could be detected. The spectral difference between the whole blood and the thrombus was utilized to image thrombus formation. The results indicate the feasibility of dynamically detecting and imaging thrombus formation in a rotary blood pump. PMID:25234757

  2. Effects of Dabigatran on the Resolution of Left Ventricular Thrombus after Acute Myocardial Infarction.

    PubMed

    Ohashi, Norihiko; Okada, Takenori; Uchida, Mio; Amioka, Michitaka; Fujiwara, Mai; Kaseda, Shunichi

    2015-01-01

    Left ventricular thrombus (LVT) after acute myocardial infarction (AMI) is a risk factor for embolic complications. Although warfarin has traditionally been used to treat LVT, it has relevant disadvantages that limit its use. We herein describe the case of a 78-year-old man with AMI who had a history of paroxysmal atrial fibrillation. Following 10 days of urgent coronary reperfusion therapy, transthoracic echocardiography revealed a moderately sized LVT in the apex, which subsequently disappeared after 18 days of treatment with dabigatran. This case demonstrates that dabigatran may represent an alternative to warfarin as a therapeutic option in patients with LVT after AMI. PMID:26179532

  3. Role of 5-hydroxytryptamine in platelet thrombus formation and mechanisms of inhibition of thrombus formation by 5-hydroxytryptamine2A antagonists in rabbits.

    PubMed

    Takano, S

    1995-01-01

    The role of 5-hydroxytryptamine (5-HT) in platelet thrombus formation and in the mechanisms of inhibition of thrombus formation by 5-HT2A antagonists was investigated using a turbidimetric method. Collagen-induced platelet aggregation occurred simultaneously with a release of 5-HT from the platelets. The supernatant of collagen-aggregated platelets induced a further aggregation volume-dependently. This supernatant-induced aggregation was inhibited by either 5-HT2A antagonists or adenosine-diphosphate (ADP) scavenging. 5-Hydroxytryptamine and a small amount of the supernatant shifted the dose-response curves of collagen to the left. The aggregation velocity and the onset of aggregation by collagen were significantly increased by the supernatant, but not by 5-HT. The 5-HT2A antagonists, ketanserin and MCI-9042, returned the dose-response curves of the maximum aggregation and of the aggregation velocity of collagen, which were already amplified by the supernatant, to the original values. The onset of aggregation was delayed by the antagonists, but was not completely returned to the original points. There were distinct differences between the effects of endogenous 5-HT, derived from platelets which were stimulated by collagen, and those of exogenous 5-HT on both extensive platelet activation and amplification of the collagen-induced aggregation. These findings suggest that endogenous 5-HT activates platelets in synergism with ADP. The 5-HT2A antagonists used, block the synergism via 5-HT2A receptors and lead to inhibition of a positive feedback loop of thrombus formation. PMID:8836449

  4. Acute Left Arm Ischemia Associated with Floating Thrombus in the Proximal Descending Aorta: Combined Endovascular and Surgical Therapy

    SciTech Connect

    Fanelli, F.; Gazzetti, M.; Boatta, E.; Ruggiero, M.; Lucatelli, P.; Speziale, F.

    2011-02-15

    Free floating thrombus in the proximal descending aorta is an uncommon and dangerous condition that can be associated with acute peripheral embolization. The few cases described were solved with surgical and/or medical therapy. We report the case of a patient with acute left arm ischemia secondary to the presence of floating thrombus in the proximal descending aorta extending into the left subclavian artery, solved with combined endovascular and surgical therapy. Treatment was successfully performed with thrombembolectomy combined with temporary deployment, into the descending aorta, of a Wallstent in a 'basket-fashion' to avoid distal embolization secondary to thrombus fragmentation. At 1 year follow-up the patient remained symptom-free.

  5. Paraphenylene diamine exacerbates platelet aggregation and thrombus formation in response to a low dose of collagen.

    PubMed

    Zaid, Younes; Marhoume, Fatimazahra; Senhaji, Nezha; Kojok, Kevin; Boufous, Hicham; Naya, Abdallah; Oudghiri, Mounia; Darif, Youssef; Habti, Norddine; Zouine, Soukaina; Mohamed, Fekhaoui; Chait, Abderahmane; Bagri, Abdellah

    2016-02-01

    Paraphenylene daimine (PPD) is an aromatic amine that is widely used in several industrial products; however, its toxicity has been reported in several cases of cardiac arrests. As platelets play a key role in cardiovascular diseases, we aimed to determine the impact of PPD in vitro and in vivo on platelet function. Our findings demonstrated that platelet activation and aggregation were strongly enhanced by PPD. Treatment with PPD primed human platelets that became more reactive in response to low doses of collagen. Furthermore, PPD exacerbated thrombus formation in rats in comparison with those untreated. Our results suggest that PPD is an important platelet primer predisposing platelets to promote thrombus formation in response to vascular injury. This should prompt the authorities to consider controlling the marketing of this product. PMID:26763399

  6. [THE THROMBUS FORMATION IN THE PROSTHESIS AS A REACTION OF ORGANISM ON ITS MATERIAL].

    PubMed

    Alekseyeva, T A; Gupalo, Yu M; Kolomoets, A M; Lazarenko, O N; Lazarenko, G O; Litvin, P M; Lohs, I V; Smorzhevskiy, V J; Stepkin, V I

    2016-04-01

    Abstract Vascular prostheses, excised because of their functional properties loss, were studied. Using different methods there was established, that this complication is caused by the thrombus formation as a reaction of organism on the prosthesis material. The testing procedure on compatibility was proposed, using atomic-power microscope. Components of a patient immunity may identify the prosthesis material and start the rejection mechanisms in case of negative reaction. PMID:27434951

  7. A Computational Model for Thrombus Formation in Response to Cardiovascular Implantable Devices

    NASA Astrophysics Data System (ADS)

    Horn, John; Ortega, Jason; Maitland, Duncan

    2014-11-01

    Cardiovascular implantable devices elicit complex physiological responses within blood. Notably, alterations in blood flow dynamics and interactions between blood proteins and biomaterial surface chemistry may lead to the formation of thrombus. For some devices, such as stents and heart valves, this is an adverse outcome. For other devices, such as embolic aneurysm treatments, efficient blood clot formation is desired. Thus a method to study how biomedical devices induce thrombosis is paramount to device development and optimization. A multiscale, multiphysics computational model is developed to predict thrombus formation within the vasculature. The model consists of a set of convection-diffusion-reaction partial differential equations for blood protein constituents involved in the progression of the clotting cascades. This model is used to study thrombus production from endovascular devices with the goal of optimizing the device design to generate the desired clotting response. This work was performed in part under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  8. Cathepsin G-Dependent Modulation of Platelet Thrombus Formation In Vivo by Blood Neutrophils

    PubMed Central

    Faraday, Nauder; Schunke, Kathryn; Saleem, Sofiyan; Fu, Juan; Wang, Bing; Zhang, Jian; Morrell, Craig; Dore, Sylvain

    2013-01-01

    Neutrophils are consistently associated with arterial thrombotic morbidity in human clinical studies but the causal basis for this association is unclear. We tested the hypothesis that neutrophils modulate platelet activation and thrombus formation in vivo in a cathepsin G-dependent manner. Neutrophils enhanced aggregation of human platelets in vitro in dose-dependent fashion and this effect was diminished by pharmacologic inhibition of cathepsin G activity and knockdown of cathepsin G expression. Tail bleeding time in the mouse was prolonged by a cathepsin G inhibitor and in cathepsin G knockout mice, and formation of neutrophil-platelet conjugates in blood that was shed from transected tails was reduced in the absence of cathepsin G. Bleeding time was highly correlated with blood neutrophil count in wildtype but not cathepsin G deficient mice. In the presence of elevated blood neutrophil counts, the anti-thrombotic effect of cathepsin G inhibition was greater than that of aspirin and additive to it when administered in combination. Both pharmacologic inhibition of cathepsin G and its congenital absence prolonged the time for platelet thrombus to form in ferric chloride-injured mouse mesenteric arterioles. In a vaso-occlusive model of ischemic stroke, inhibition of cathepsin G and its congenital absence improved cerebral blood flow, reduced histologic brain injury, and improved neurobehavioral outcome. These experiments demonstrate that neutrophil cathepsin G is a physiologic modulator of platelet thrombus formation in vivo and has potential as a target for novel anti-thrombotic therapies. PMID:23940756

  9. The EP3 Agonist Sulprostone Enhances Platelet Adhesion But Not Thrombus Formation Under Flow Conditions.

    PubMed

    Pasterk, Lisa; Philipose, Sonia; Eller, Kathrin; Marsche, Gunther; Heinemann, Akos; Schuligoi, Rufina

    2015-01-01

    Platelets express the EP2, EP3 and EP4 receptors. Prostaglandin (PG) E2 has a biphasic effect on platelets. Low concentrations of PGE2 enhance platelet aggregation through the activation of the EP3 receptors, while at high concentrations it attenuates aggregation via the EP4 receptor. Consequently, EP3 receptor inhibition was shown to inhibit artherothrombosis, but had no influence on bleeding time in vivo. In this study, we investigated the role of the EP3 receptor in adhesion and thrombus formation under flow conditions in vitro. The EP3 agonist sulprostone caused an increase in the adhesion of washed platelets to fibrinogen as well as to collagen under low shear stress, an effect that was blocked by the EP3 antagonist L-798106. In contrast, when whole blood was perfused over collagen-coated surfaces, sulprostone did not enhance binding and thrombus formation of platelets on collagen; at high concentrations it even attenuated this response. We conclude that in more physiological models of thrombus formation, the role for EP3 receptors is limited, indirectly suggesting that the primary action of PGE2 in haemostasis might be an inhibitory one. PMID:26228833

  10. A role for factor XIIa–mediated factor XI activation in thrombus formation in vivo

    PubMed Central

    Cheng, Qiufang; Tucker, Erik I.; Pine, Meghann S.; Sisler, India; Matafonov, Anton; Sun, Mao-fu; White-Adams, Tara C.; Smith, Stephanie A.; Hanson, Stephen R.; McCarty, Owen J. T.; Renné, Thomas; Gruber, András

    2010-01-01

    Mice lacking factor XII (fXII) or factor XI (fXI) are resistant to experimentally–induced thrombosis, suggesting fXIIa activation of fXI contributes to thrombus formation in vivo. It is not clear whether this reaction has relevance for thrombosis in pri mates. In 2 carotid artery injury models (FeCl3 and Rose Bengal/laser), fXII-deficient mice are more resistant to thrombosis than fXI- or factor IX (fIX)–deficient mice, raising the possibility that fXII and fXI function in distinct pathways. Antibody 14E11 binds fXI from a variety of mammals and interferes with fXI activation by fXIIa in vitro. In mice, 14E11 prevented arterial occlusion induced by FeCl3 to a similar degree to total fXI deficiency. 14E11 also had a modest beneficial effect in a tissue factor–induced pulmonary embolism model, indicating fXI and fXII contribute to thrombus formation even when factor VIIa/tissue factor initiates thrombosis. In baboons, 14E11 reduced platelet-rich thrombus growth in collagen-coated grafts inserted into an arteriovenous shunt. These data support the hypothesis that fXIIa-mediated fXI activation contributes to thrombus formation in rodents and primates. Since fXII deficiency does not impair hemostasis, targeted inhibition of fXI activation by fXIIa may be a useful antithrombotic strategy associated with a low risk of bleeding complications. PMID:20634381

  11. Thrombus Formation After Percutaneous Catheterization and Manual Compression of the Femoral Artery in Heparinized Sheep

    SciTech Connect

    Kim, Young Hwan; Pavcnik, Dusan Kakizawa, Hideyaki; Uchida, Barry T.; Burke, Allen; Loriaux, Marc; Keller, Frederick S.; Rosch, Josef

    2010-04-15

    The purpose of this study was to evaluate the angiographic and histopathologic changes in the superficial femoral artery (SFA) in heparinized sheep shortly after catheterization with an 8-Fr sheath and manual compression hemostasis either with standard manual compression (SMC) or with the use of a procoagulant chitosan-based HemCon Bandage. The evaluation was done in 38 SFAs of 19 heparinized (100 mg/kg) sheep. After a 5-min catheterization with an 8-Fr sheath, a 5-min compression was applied. Follow-up angiograms to evaluate hemostasis were done immediately after release of compression and then at 2.5-min intervals until no extravasation was present. Compression was reapplied between angiograms. Final angiograms were performed approximately 30 min after hemostasis and after 3 min of passive flexion and extension of sheep hind limbs. Sheep were then euthanized and SFA specimens with surrounding tissues excised for histopathologic evaluation. Both types of compression caused similar changes in the catheterized SFAs. Follow-up angiograms showed mild arterial narrowing in 14 SFAs and intraluminal clots in 9 SFAs. Histology revealed periarterial hematoma in all 38 specimens. Intraluminal thrombi consisting predominantly of platelets and fibrin were present in 32 SFAs. Their size varied from superficial elevations (8 arteries) to medium-sized, 1- to 2-mm, polypoid protrusions (15 arteries) to large polypoid clots, 3-4 mm long (9 arteries). In six SFAs, the arterial access sites were not included in the obtained specimens. In conclusion, hemostasis with manual compression is achieved in the acute phase by formation of a predominantly platelet-fibrin thrombus occluding the arterial wall access site and often extending significantly into the arterial lumen. The healing process of arterial access sites should be explored several days after catheterization.

  12. Biomechanical behaviour of cerebral aneurysm and its relation with the formation of intraluminal thrombus: a patient-specific modelling study.

    PubMed

    Wang, Xiaohong; Li, Xiaoyang

    2013-01-01

    Cerebral aneurysm is an irreversible dilatation causing intracranial haemorrhage with severe complications. It is assumed that the biomechanical factor plays a significant role in the development of cerebral aneurysm. However, reports on the correlations between the formation of intraluminal thrombus and the flow pattern, wall shear stress (WSS) distribution of the cerebral aneurysm as well as wall compliance are still limited. In this research, patient-specific numerical simulation was carried out for three cerebral aneurysms based on magnetic resonance imaging (MRI) data-sets. The interaction between pulsatile blood and aneurysm wall was taken into account. The biomechanical behaviour of cerebral aneurysm and its relation with the formation of intraluminal thrombus was studied systematically. The results of the numerical simulation indicated that the region of low blood flow velocity and the region of swirling recirculation were nearly coincident with each other. Besides, there was a significant correlation between the slow swirling flow and the location of thrombus deposition. Excessively low WSS was also found to have strong association with the regions of thrombus formation. Moreover, the relationship between cerebral aneurysm compliance and thrombus deposition was discovered. The patient-specific modelling study based on fluid-structure interaction) may provide a basis for future investigation on the prediction of thrombus formation in cerebral aneurysm. PMID:22292428

  13. Vascular wall hypoxia promotes arterial thrombus formation via augmentation of vascular thrombogenicity.

    PubMed

    Matsuura, Yunosuke; Yamashita, Atsushi; Iwakiri, Takashi; Sugita, Chihiro; Okuyama, Nozomi; Kitamura, Kazuo; Asada, Yujiro

    2015-07-01

    Atherosclerotic lesions represent a hypoxic milieu. However, the significance of this milieu in atherothrombosis has not been established. We aimed to assess the hypothesis that vascular wall hypoxia promotes arterial thrombus formation. We examined the relation between vascular wall hypoxia and arterial thrombus formation using a rabbit model in which arterial thrombosis was induced by 0.5 %-cholesterol diet and repeated balloon injury of femoral arteries. Vascular wall hypoxia was immunohistochemically detected by pimonidazole hydrochloride, a hypoxia marker. Rabbit neointima and THP-1 macrophages were cultured to analyse prothrombotic factor expression under hypoxic conditions (1 % O2). Prothrombotic factor expression and nuclear localisation of hypoxia-inducible factor (HIF)-1α and nuclear factor-kappa B (NF-κB) p65 were immunohistochemically assessed using human coronary atherectomy plaques. Hypoxic areas were localised in the macrophage-rich deep portion of rabbit neointima and positively correlated with the number of nuclei immunopositive for HIF-1α and NF-κB p65, and tissue factor (TF) expression. Immunopositive areas for glycoprotein IIb/IIIa and fibrin in thrombi were significantly correlated with hypoxic areas in arteries. TF and plasminogen activator inhibitor-1 (PAI-1) expression was increased in neointimal tissues and/or macrophages cultured under hypoxia, and both were suppressed by inhibitors of either HIF-1 or NF-κB. In human coronary plaques, the number of HIF-1α-immunopositive nuclei was positively correlated with that of NF-κB-immunopositive nuclei and TF-immunopositive and PAI-1-immunopositive area, and it was significantly higher in thrombotic plaques. Vascular wall hypoxia augments the thrombogenic potential of atherosclerotic plaque and thrombus formation on plaques via prothrombotic factor upregulation. PMID:25833755

  14. Misshapen/NIK-related kinase (MINK1) is involved in platelet function, hemostasis, and thrombus formation.

    PubMed

    Yue, Ming; Luo, Dongjiao; Yu, Shanshan; Liu, Pu; Zhou, Qi; Hu, Mengjiao; Liu, Yangyang; Wang, Shuai; Huang, Qian; Niu, Yuxi; Lu, Linrong; Hu, Hu

    2016-02-18

    The sterile-20 kinase misshapen/Nck-interacting kinase (NIK)-related kinase 1 (MINK1) is involved in many important cellular processes such as growth, cytoskeletal rearrangement, and motility. Here, with MINK1-deficient (MINK1(-/-)) mice, we showed that MINK1 plays an important role in hemostasis and thrombosis via the regulation of platelet functions. In the tail-bleeding assay, MINK1(-/-) mice exhibited a longer bleeding time than wild-type (WT) mice (575.2 ± 59.7 seconds vs 419.6 ± 66.9 seconds). In a model of ferric chloride-induced mesenteric arteriolar thrombosis, vessel occlusion times were twice as long in MINK1(-/-) mice as in WT mice. In an in vitro microfluidic whole-blood perfusion assay, thrombus formation on a collagen matrix under arterial shear conditions was significantly reduced in MINK1(-/-) platelets. Moreover, MINK1(-/-) platelets demonstrated impaired aggregation and secretion in response to low doses of thrombin and collagen. Furthermore, platelet spreading on fibrinogen was largely hampered in MINK1(-/-) platelets. The functional differences of MINK1(-/-) platelets could be attributed to impaired adenosine 5'-diphosphate secretion. Signaling events associated with MINK1 appeared to involve extracellular signal-regulated kinase, p38, and Akt. Hence, MINK1 may be an important signaling molecule that mediates mitogen-activated protein kinase signaling and participates in platelet activation and thrombus formation. PMID:26598717

  15. Protein kinase C mediates platelet secretion and thrombus formation through protein kinase D2

    PubMed Central

    Konopatskaya, Olga; Matthews, Sharon A.; Harper, Matthew T.; Gilio, Karen; Cosemans, Judith M. E. M.; Williams, Christopher M.; Navarro, Maria N.; Carter, Deborah A.; Heemskerk, Johan W. M.; Leitges, Michael; Cantrell, Doreen; Poole, Alastair W.

    2016-01-01

    Platelets are highly specialized blood cells critically involved in hemostasis and thrombosis. Members of the protein kinase C (PKC) family have established roles in regulating platelet function and thrombosis, but the molecular mechanisms are not clearly understood. In particular, the conventional PKC isoform, PKCα, is a major regulator of platelet granule secretion, but the molecular pathway from PKCα to secretion is not defined. Protein kinase D (PKD) is a family of 3 kinases activated by PKC, which may represent a step in the PKC signaling pathway to secretion. In the present study, we show that PKD2 is the sole PKD member regulated downstream of PKC in platelets, and that the conventional, but not novel, PKC isoforms provide the upstream signal. Platelets from a gene knock-in mouse in which 2 key phosphorylation sites in PKD2 have been mutated (Ser707Ala/Ser711Ala) show a significant reduction in agonist-induced dense granule secretion, but not in α-granule secretion. This deficiency in dense granule release was responsible for a reduced platelet aggregation and a marked reduction in thrombus formation. Our results show that in the molecular pathway to secretion, PKD2 is a key component of the PKC-mediated pathway to platelet activation and thrombus formation through its selective regulation of dense granule secretion. PMID:21527521

  16. Tripeptide SQL Inhibits Platelet Aggregation and Thrombus Formation by Affecting PI3K/Akt Signaling.

    PubMed

    Su, Xing-li; Su, Wen; He, Zhi-long; Ming, Xin; Kong, Yi

    2015-09-01

    Centipede has been prescribed for the treatment of cardiovascular diseases in Asian countries for several hundred years. Previously, a new antiplatelet tripeptide SQL (H-Ser-Gln-Leu-OH) was isolated and characterized from centipede. In this study, we investigated its antithrombotic activities in vivo and underlying mechanism. It was found that SQL inhibited platelet aggregation induced by adenosine diphosphate, thrombin, epinephrine, and collagen and attenuated thrombus formation in both the ferric chloride-induced arterial thrombosis model and arteriovenous shunt thrombosis model in rats. It did not prolong the bleeding time in mice even at the dose of 10 mg/kg that showed potent antithrombosis effects. Molecular docking revealed that SQL binds PI3Kβ with the binding free energy of -24.341 kcal/mol, which is close to that of cocrystallized ligand (-24.220 kcal/mol). Additionally, SQL displayed inhibition on the late (180 seconds) but did not influence the early (60 seconds) Akt Ser473 phosphorylation in the immunoblot assay. These results suggest that SQL inhibits thrombus formation in vivo and that SQL inhibits PI3K-mediated signaling or even the PI3K itself in platelets. This study may help elucidate the mechanism for centipede treating cardiovascular diseases. PMID:25923322

  17. Image-based characterization of thrombus formation in time-lapse DIC microscopy

    PubMed Central

    Brieu, Nicolas; Navab, Nassir; Serbanovic-Canic, Jovana; Ouwehand, Willem H.; Stemple, Derek L.; Cvejic, Ana; Groher, Martin

    2012-01-01

    The characterization of thrombus formation in time-lapse DIC microscopy is of increased interest for identifying genes which account for atherothrombosis and coronary artery diseases (CADs). In particular, we are interested in large-scale studies on zebrafish, which result in large amount of data, and require automatic processing. In this work, we present an image-based solution for the automatized extraction of parameters quantifying the temporal development of thrombotic plugs. Our system is based on the joint segmentation of thrombotic and aortic regions over time. This task is made difficult by the low contrast and the high dynamic conditions observed in vivo DIC microscopic scenes. Our key idea is to perform this segmentation by distinguishing the different motion patterns in image time series rather than by solving standard image segmentation tasks in each image frame. Thus, we are able to compensate for the poor imaging conditions. We model motion patterns by energies based on the idea of dynamic textures, and regularize the model by two prior energies on the shape of the aortic region and on the topological relationship between the thrombus and the aorta. We demonstrate the performance of our segmentation algorithm by qualitative and quantitative experiments on synthetic examples as well as on real in vivo microscopic sequences. PMID:22482997

  18. White Thrombus Formation in Blood Tubing Lines in a Chronic Hemodialysis Unit

    PubMed Central

    Watnick, Suzanne; Stooksbury, Michael; Winter, Rolf; Riscoe, Michael; Cohen, David M.

    2008-01-01

    Background and objectives: Previous reports have described white particulate matter in banked blood components, but no prior public reports describe such matter in blood tubing during the course of routine in-center hemodialysis. This report describes the events, investigations, and preliminary conclusions associated with the spontaneous formation of adherent white thrombus in the venous and arterial blood lines during routine in-center hemodialysis treatments. Design setting, participants, & measurements: This investigation occurred at the Portland Veterans Administration Medical Center (PVAMC) Hemodialysis Unit from October 2006 through April 2007. Sixty-eight variables regarding demographics, medical history and dialysis treatments were collected on our 34 chronic hemodialysis outpatients. Results: Over a 5-wk interval, 62% (21 of 34) of the chronic hemodialysis patients unexpectedly developed a white precipitate adhering to the lumenal surface of their dialysis blood tubing, with 73 of 580 chronic dialysis treatments exhibiting the phenomenon. Microscopic and biochemical analyses were consistent with white thrombus, formed by an aggregation of platelets and fibrin. An alert was issued and other in-center hemodialysis units noted similar findings. This was remedied by the removal of specific tubing. Conclusions: Both patient-specific and tubing-specific factors may have been operative. Although patient safety was not adversely affected, assessment of clinical and manufacturing variables potentially affecting platelet activation is warranted. PMID:18184880

  19. Thrombin-initiated platelet activation in vivo is vWF independent during thrombus formation in a laser injury model

    PubMed Central

    Dubois, Christophe; Panicot-Dubois, Laurence; Gainor, Justin F.; Furie, Barbara C.; Furie, Bruce

    2007-01-01

    Adhesion of platelets to an injured vessel wall and platelet activation are critical events in the formation of a thrombus. Of the agonists involved in platelet activation, thrombin, collagen, and vWF are known to induce in vitro calcium mobilization in platelets. Using a calcium-sensitive fluorochrome and digital multichannel intravital microscopy to image unstimulated and stimulated platelets, calcium mobilization was monitored as a reporter of platelet activation (as distinct from platelet accumulation) during thrombus formation in live mice. In the absence of vWF, platelet activation was normal, but platelet adherence and aggregation were attenuated during thrombus formation following laser-induced injury in the cremaster muscle microcirculation. In WT mice treated with lepirudin, platelet activation was blocked, and platelet adherence and aggregation were inhibited. The kinetics of platelet activation and platelet accumulation were similar in FcRγ–/– mice lacking glycoprotein VI (GPVI), GPVI-depleted mice, and WT mice. Our results indicate that the tissue factor–mediated pathway of thrombin generation, but not the collagen-induced GPVI-mediated pathway, is the major pathway leading to platelet activation after laser-induced injury under the conditions employed. In the tissue factor–mediated pathway, vWF plays a role in platelet accumulation during thrombus formation but is not required for platelet activation in vivo. PMID:17380206

  20. Cooperative integrin/ITAM signaling in platelets enhances thrombus formation in vitro and in vivo

    PubMed Central

    Zhi, Huiying; Rauova, Lubica; Hayes, Vincent; Gao, Cunji; Boylan, Brian; Newman, Debra K.; McKenzie, Steven E.; Cooley, Brian C.; Poncz, Mortimer; Newman, Peter J.

    2013-01-01

    The integrin family is composed of a series of 24 αβ heterodimer transmembrane adhesion receptors that mediate cell-cell and cell-extracellular matrix interactions. Adaptor molecules bearing immunoreceptor tyrosine-based activation motifs (ITAMs) have recently been shown to cooperate with specific integrins to increase the efficiency of transmitting ligand-binding–induced signals into cells. In human platelets, Fc receptor γ-chain IIa (FcγRIIa) has been identified as an ITAM-bearing transmembrane receptor responsible for mediating “outside-in” signaling through αIIbβ3, the major adhesion receptor on the platelet surface. To explore the importance of FcγRIIa in thrombosis and hemostasis, we subjected FcγRIIa-negative and FcγRIIa-positive murine platelets to a number of well-accepted models of platelet function. Compared with their FcγRIIa-negative counterparts, FcγRIIa-positive platelets exhibited increased tyrosine phosphorylation of Syk and phospholipase Cγ2 and increased spreading upon interaction with immobilized fibrinogen, retracted a fibrin clot faster, and showed markedly enhanced thrombus formation when perfused over a collagen-coated flow chamber under conditions of arterial and venous shear. They also displayed increased thrombus formation and fibrin deposition in in vivo models of vascular injury. Taken together, these data establish FcγRIIa as a physiologically important functional conduit for αIIbβ3-mediated outside-in signaling, and suggest that modulating the activity of this novel integrin/ITAM pair might be effective in controlling thrombosis. PMID:23264598

  1. Relative permittivity measurement during the thrombus formation process using the dielectric relaxation method for various hematocrit values.

    PubMed

    Asakura, Yuta; Sapkota, Achyut; Maruyama, Osamu; Kosaka, Ryo; Yamane, Takashi; Takei, Masahiro

    2015-12-01

    The relative permittivity ε' and the dielectric loss ε″ for various hematocrit values H for static bovine blood condition have been measured using the dielectric relaxation method to detect thrombosis in real time. The suitable measurement frequency f m ranged within 60 kHz to 1 MHz, and the relaxation frequency of red blood cells (RBCs) f rc was observed to be 2 MHz. In the f m, the temporal change of normalized ε' exhibited a minimum (called as bottom point). The bottom point was observed to be exponentially shortened as H increased. This characteristic of the ε'* minimum is discussed from three viewpoints: during fibrin formation, direct thrombus formation, and rouleaux formation processes. ε'* during the fibrin formation process decreased over time, irrespective of f. However, ε'* in f m during the direct thrombus formation process and during the aggregation formation process increased immediately and rapidly over time. Therefore, the ε'* bottom point in f m might be the indication of micrometer-scale thrombus formation by RBC aggregation due to fibrin formation. PMID:26058831

  2. Coupled Hemodynamic-Biochemical Modeling of Thrombus Formation in Infarcted Left Ventricles

    NASA Astrophysics Data System (ADS)

    Seo, Jung Hee; Vedula, Vijay; George, Richard; Mittal, Rajat

    2013-11-01

    Patients with heart failure (HF) and left ventricular (LV) systolic dysfunction have higher rates of thromboembolic events including embolic stroke and peripheral arterial thrombi. A common cause of arterial emboli in HF patients is myocardial infarction (MI) and subsequent left ventricular thrombus (LVT) formation. Stagnation of blood and endocardial injury are hypothesized to promote the development of LVT. The identification of high risk patients and the pharmacologic prevention of LVT formation are the keys to preventing embolic events. Stratification of patients at risk for LVT formation is currently limited, and primarily based on global assessment of ventricular function and image based assessment of ventricular wall motion. In this study, we explore a method to predict LVT risk using a multi-physics computational model. The blood flow in the left ventricle is simulated by solving the incompressible Navier-Stokes equation using an immersed boundary method and this is coupled to a convection-diffusion-reaction equation based model of platelet activation and coagulation. The results are then correlated with the other hemodynamic metrics such as wall shear stress and residence time to develop quantitative metrics for the LVT risk prediction. Supported by NSF CDI-Type II grant IOS-1124804, Computational resource by XSEDE NSF grant TG-CTS100002.

  3. Quantification of volume, mass, and density of thrombus formation using brightfield and differential interference contrast microscopy

    NASA Astrophysics Data System (ADS)

    Baker-Groberg, Sandra M.; Phillips, Kevin G.; McCarty, Owen J. T.

    2013-01-01

    Flow chamber assays, in which blood is perfused over surfaces of immobilized extracellular matrix proteins, are used to investigate the formation of platelet thrombi and aggregates under shear flow conditions. Elucidating the dynamic response of thrombi/aggregate formation to different coagulation pathway perturbations in vitro has been used to develop an understanding of normal and pathological cardiovascular states. Current microscopy techniques, such as differential interference contrast (DIC) or fluorescent confocal imaging, respectively, do not provide a simple, quantitative understanding of the basic physical features (volume, mass, and density) of platelet thrombi/aggregate structures. The use of two label-free imaging techniques applied, for the first time, to platelet aggregate and thrombus formation are introduced: noninterferometric quantitative phase microscopy, to determine mass, and Hilbert transform DIC microscopy, to perform volume measurements. Together these techniques enable a quantitative biophysical characterization of platelet aggregates and thrombi formed on three surfaces: fibrillar collagen, fibrillar collagen +0.1 nM tissue factor (TF), and fibrillar collagen +1 nM TF. It is demonstrated that label-free imaging techniques provide quantitative insight into the mechanisms by which thrombi and aggregates are formed in response to exposure to different combinations of procoagulant agonists under shear flow.

  4. Quantification of volume, mass, and density of thrombus formation using brightfield and differential interference contrast microscopy.

    PubMed

    Baker-Groberg, Sandra M; Phillips, Kevin G; McCarty, Owen J T

    2013-01-01

    Flow chamber assays, in which blood is perfused over surfaces of immobilized extracellular matrix proteins, are used to investigate the formation of platelet thrombi and aggregates under shear flow conditions. Elucidating the dynamic response of thrombi/aggregate formation to different coagulation pathway perturbations in vitro has been used to develop an understanding of normal and pathological cardiovascular states. Current microscopy techniques, such as differential interference contrast (DIC) or fluorescent confocal imaging, respectively, do not provide a simple, quantitative understanding of the basic physical features (volume, mass, and density) of platelet thrombi/aggregate structures. The use of two label-free imaging techniques applied, for the first time, to platelet aggregate and thrombus formation are introduced: noninterferometric quantitative phase microscopy, to determine mass, and Hilbert transform DIC microscopy, to perform volume measurements. Together these techniques enable a quantitative biophysical characterization of platelet aggregates and thrombi formed on three surfaces: fibrillar collagen, fibrillar collagen +0.1  nM tissue factor (TF), and fibrillar collagen +1  nM TF. It is demonstrated that label-free imaging techniques provide quantitative insight into the mechanisms by which thrombi and aggregates are formed in response to exposure to different combinations of procoagulant agonists under shear flow. PMID:23348747

  5. Mesoscopic Modeling of Thrombus Formation and Growth: Platelet Deposition in Complex Geometries

    NASA Astrophysics Data System (ADS)

    Yazdani, Alireza; Karniadakis, George

    2014-11-01

    Haemodynamics and blood rheology are important contributing factors to thrombus formation at a vulnerable vessel wall, and adhesion of platelets to a vascular surface, particularly in regions of flow stagnation, recirculation and reattachment is significantly important in formation of thrombi. For example, haemodynamic micro-environment can have effects on thrombosis inside the atherosclerotic plaques and aneurysms. To study these effects, we have developed and validated a model for platelet aggregation in blood flow using Dissipative Particle Dynamics (DPD) method. In this model platelets are considered as single DPD particles interacting with each other via Morse potential once activated. We assign an activation delay time to each platelet such that they remain passive during that time. We investigate the effect of different geometries on platelet aggregation by considering arterial stenosis at different levels of occlusion, and aneurysms of different shapes and sizes. The results show a marked increase in platelet aggregation within the boundaries of deceleration zone by increasing the degree of stenosis. Further, we observe enhanced platelet margination and wall deposition in the presence of red blood cells.

  6. Eyelid varix with phlebolith formation, thrombus recanalization, and early intravascular papillary endothelial hyperplasia.

    PubMed

    Zakka, Fouad R; Jakobiec, Frederick A; Thakker, Manoj M

    2011-01-01

    An asymptomatic, bluish-gray, movable, raised, and firm left upper eyelid mass had been present for 8 months in an 82-year-old woman. Histopathologic examination revealed a lesion restricted to the dermis and composed in part of a calcific nodule that was circumscribed by an acellular fibrous capsule. An adjacent nodule exhibited proliferating endothelial cells invading a fresh thrombus. Immunohistochemical staining revealed positivity for CD31, CD34, and CD68; D2-40 was negative, ruling out a lymphatic origin. Masson trichrome and elastic staining of deeper sections revealed recanalization of an earlier thrombus; surviving elastic fibers were discovered in the outer wall, establishing a venous source. This is the first reported case of 3 microscopically discernible events (old phlebolith, fresh intravascular endothelial hyperplasia invading a thrombus, and labyrinthine recanalization of a temporally more remote thrombus) in an eyelid varix. The clinical differential diagnosis is reviewed. PMID:20724862

  7. Thrombus formation patterns in the HeartMate II ventricular assist device: clinical observations can be predicted by numerical simulations.

    PubMed

    Chiu, Wei-Che; Slepian, Marvin J; Bluestein, Danny

    2014-01-01

    Postimplant device thrombosis remains a life-threatening complication and limitation of continuous-flow ventricular assist devices (VADs). Using advanced computational fluid dynamic (CFD) simulations, we successfully depicted various flow patterns, recirculation zones, and stagnant platelet trajectories which promote thrombus formation and observed that they matched actual thrombus formation patterns observed in Thoratec HeartMate II VADs explanted from patients with pump thrombosis. Previously, these small eddies could not be captured by either digital particle image velocimetry or CFD due to insufficient resolution. Our study successfully demonstrated the potential capability of advanced CFD to be adopted for device optimization, leading to enhanced safety and efficacy of VADs for long-term destination therapy. PMID:24399065

  8. Plasma fibrin clot phenotype independently affects intracoronary thrombus ultrastructure in patients with acute myocardial infarction.

    PubMed

    Zalewski, Jaroslaw; Bogaert, Jan; Sadowski, Marcin; Woznicka, Olga; Doulaptsis, Konstantinos; Ntoumpanaki, Maria; Ząbczyk, Michal; Nessler, Jadwiga; Undas, Anetta

    2015-06-01

    Determinants of intracoronary thrombus (ICT) composition in patients with ST-elevation myocardial infarction (STEMI) are largely unknown. We sought to investigate whether plasma fibrin phenotype and platelet reactivity affect ICT ultrastructure. We assessed the content of fibrin, platelets and erythrocytes including polyhedrocytes by scanning electron microscopy on the surface and inside ICT aspirated from 80 STEMI patients within 12 hours since chest pain onset. Plasma fibrin clot permeability (Ks), which indicates the average pore size, lysis time (t50 %), platelet reactivity index (PRI) and ADP-induced platelet aggregation (ADP5, 20µM) were evaluated on admission. All patients received aspirin and 45 (56.3 %) 600 mg of clopidogrel, 80 (60-120) min prior to aspiration. Higher content of fibrin (61.6 vs 34.3 %, P< 0.0001) and platelets (8.2 vs 4.8 %, P=0.018) and lower erythrocyte content (15.8 vs 42.9 %, P< 0.0001) were found on ICT surface compared with its inner part. After adjustment for fibrinogen, in both ICT parts fibrin content was correlated with Ks (r≤-0.55, P< 0.0001) and t50 % (r≥ 0.29, P≤ 0.02) but not with PRI and ADP5,20µM. Polyhedrocytes were observed in 16 (20 %) patients and their large amount expressed as ≥ 50 % fields of view covered by polyhedrocytes was associated with the lower PRI values (40 vs 69 %, P=0.015), but not Ks or t50 %. By multivariate regression, Ks (β=-0.62, P< 0.0001), clopidogrel pretreatment (β=-0.36, P< 0.001), ischemia time (β=0.19, P=0.044) and family history (β=0.18, P=0.049) independently predicted fibrin content in the whole ICT (R²=0.65, P< 0.0001). Formation of denser plasma fibrin clots is independently associated with high fibrin content within the ICT in STEMI. PMID:25739375

  9. Facile Fabrication of Lubricant-Infused Wrinkling Surface for Preventing Thrombus Formation and Infection.

    PubMed

    Yuan, Shuaishuai; Luan, Shifang; Yan, Shunjie; Shi, Hengchong; Yin, Jinghua

    2015-09-01

    Despite the advanced modern biotechniques, thrombosis and bacterial infection of biomedical devices remain common complications that are associated with morbidity and mortality. Most antifouling surfaces are in solid form and cannot simultaneously fulfill the requirements for antithrombosis and antibacterial efficacy. In this work, we present a facile strategy to fabricate a slippery surface. This surface is created by combining photografting polymerization with osmotically driven wrinkling that can generate a coarse morphology, and followed by infusing with fluorocarbon liquid. The lubricant-infused wrinkling slippery surface can greatly prevent protein attachment, reduce platelet adhesion, and suppress thrombus formation in vitro. Furthermore, E. coli and S. aureus attachment on the slippery surfaces is reduced by ∼98.8% and ∼96.9% after 24 h incubation, relative to poly(styrene-b-isobutylene-b-styrene) (SIBS) references. This slippery surface is biocompatible and has no toxicity to L929 cells. This surface-coating strategy that effectively reduces thrombosis and the incidence of infection will greatly decrease healthcare costs. PMID:26268298

  10. RhoG protein regulates platelet granule secretion and thrombus formation in mice.

    PubMed

    Goggs, Robert; Harper, Matthew T; Pope, Robert J; Savage, Joshua S; Williams, Christopher M; Mundell, Stuart J; Heesom, Kate J; Bass, Mark; Mellor, Harry; Poole, Alastair W

    2013-11-22

    Rho GTPases such as Rac, RhoA, and Cdc42 are vital for normal platelet function, but the role of RhoG in platelets has not been studied. In other cells, RhoG orchestrates processes integral to platelet function, including actin cytoskeletal rearrangement and membrane trafficking. We therefore hypothesized that RhoG would play a critical role in platelets. Here, we show that RhoG is expressed in human and mouse platelets and is activated by both collagen-related peptide (CRP) and thrombin stimulation. We used RhoG(-/-) mice to study the function of RhoG in platelets. Integrin activation and aggregation were reduced in RhoG(-/-) platelets stimulated by CRP, but responses to thrombin were normal. The central defect in RhoG(-/-) platelets was reduced secretion from α-granules, dense granules, and lysosomes following CRP stimulation. The integrin activation and aggregation defects could be rescued by ADP co-stimulation, indicating that they are a consequence of diminished dense granule secretion. Defective dense granule secretion in RhoG(-/-) platelets limited recruitment of additional platelets to growing thrombi in flowing blood in vitro and translated into reduced thrombus formation in vivo. Interestingly, tail bleeding times were normal in RhoG(-/-) mice, suggesting that the functions of RhoG in platelets are particularly relevant to thrombotic disorders. PMID:24106270

  11. RhoG Protein Regulates Platelet Granule Secretion and Thrombus Formation in Mice*

    PubMed Central

    Goggs, Robert; Harper, Matthew T.; Pope, Robert J.; Savage, Joshua S.; Williams, Christopher M.; Mundell, Stuart J.; Heesom, Kate J.; Bass, Mark; Mellor, Harry; Poole, Alastair W.

    2013-01-01

    Rho GTPases such as Rac, RhoA, and Cdc42 are vital for normal platelet function, but the role of RhoG in platelets has not been studied. In other cells, RhoG orchestrates processes integral to platelet function, including actin cytoskeletal rearrangement and membrane trafficking. We therefore hypothesized that RhoG would play a critical role in platelets. Here, we show that RhoG is expressed in human and mouse platelets and is activated by both collagen-related peptide (CRP) and thrombin stimulation. We used RhoG−/− mice to study the function of RhoG in platelets. Integrin activation and aggregation were reduced in RhoG−/− platelets stimulated by CRP, but responses to thrombin were normal. The central defect in RhoG−/− platelets was reduced secretion from α-granules, dense granules, and lysosomes following CRP stimulation. The integrin activation and aggregation defects could be rescued by ADP co-stimulation, indicating that they are a consequence of diminished dense granule secretion. Defective dense granule secretion in RhoG−/− platelets limited recruitment of additional platelets to growing thrombi in flowing blood in vitro and translated into reduced thrombus formation in vivo. Interestingly, tail bleeding times were normal in RhoG−/− mice, suggesting that the functions of RhoG in platelets are particularly relevant to thrombotic disorders. PMID:24106270

  12. Vascular Smooth Muscle Cells Stimulate Platelets and Facilitate Thrombus Formation through Platelet CLEC-2: Implications in Atherothrombosis

    PubMed Central

    Inoue, Osamu; Hokamura, Kazuya; Shirai, Toshiaki; Osada, Makoto; Tsukiji, Nagaharu; Hatakeyama, Kinta; Umemura, Kazuo; Asada, Yujiro; Suzuki-Inoue, Katsue; Ozaki, Yukio

    2015-01-01

    The platelet receptor CLEC-2 is involved in thrombosis/hemostasis, but its ligand, podoplanin, is expressed only in advanced atherosclerotic lesions. We investigated CLEC-2 ligands in vessel walls. Recombinant CLEC-2 bound to early atherosclerotic lesions and normal arterial walls, co-localizing with vascular smooth muscle cells (VSMCs). Flow cytometry and immunocytochemistry showed that recombinant CLEC-2, but not an anti-podoplanin antibody, bound to VSMCs, suggesting that CLEC-2 ligands other than podoplanin are present in VSMCs. VSMCs stimulated platelet granule release and supported thrombus formation under flow, dependent on CLEC-2. The time to occlusion in a FeCl3-induced animal thrombosis model was significantly prolonged in the absence of CLEC-2. Because the internal elastic lamina was lacerated in our FeCl3-induced model, we assume that the interaction between CLEC-2 and its ligands in VSMCs induces thrombus formation. Protein arrays and Biacore analysis were used to identify S100A13 as a CLEC-2 ligand in VSMCs. However, S100A13 is not responsible for the above-described VSMC-induced platelet activation, because S100A13 is not expressed on the surface of normal VSMCs. S100A13 was released upon oxidative stress and expressed in the luminal area of atherosclerotic lesions. Suspended S100A13 did not activate platelets, but immobilized S100A13 significantly increased thrombus formation on collagen-coated surfaces. Taken together, we proposed that VSMCs stimulate platelets through CLEC-2, possibly leading to thrombus formation after plaque erosion and stent implantation, where VSMCs are exposed to blood flow. Furthermore, we identified S100A13 as one of the ligands on VSMCs. PMID:26418160

  13. Vascular Smooth Muscle Cells Stimulate Platelets and Facilitate Thrombus Formation through Platelet CLEC-2: Implications in Atherothrombosis.

    PubMed

    Inoue, Osamu; Hokamura, Kazuya; Shirai, Toshiaki; Osada, Makoto; Tsukiji, Nagaharu; Hatakeyama, Kinta; Umemura, Kazuo; Asada, Yujiro; Suzuki-Inoue, Katsue; Ozaki, Yukio

    2015-01-01

    The platelet receptor CLEC-2 is involved in thrombosis/hemostasis, but its ligand, podoplanin, is expressed only in advanced atherosclerotic lesions. We investigated CLEC-2 ligands in vessel walls. Recombinant CLEC-2 bound to early atherosclerotic lesions and normal arterial walls, co-localizing with vascular smooth muscle cells (VSMCs). Flow cytometry and immunocytochemistry showed that recombinant CLEC-2, but not an anti-podoplanin antibody, bound to VSMCs, suggesting that CLEC-2 ligands other than podoplanin are present in VSMCs. VSMCs stimulated platelet granule release and supported thrombus formation under flow, dependent on CLEC-2. The time to occlusion in a FeCl3-induced animal thrombosis model was significantly prolonged in the absence of CLEC-2. Because the internal elastic lamina was lacerated in our FeCl3-induced model, we assume that the interaction between CLEC-2 and its ligands in VSMCs induces thrombus formation. Protein arrays and Biacore analysis were used to identify S100A13 as a CLEC-2 ligand in VSMCs. However, S100A13 is not responsible for the above-described VSMC-induced platelet activation, because S100A13 is not expressed on the surface of normal VSMCs. S100A13 was released upon oxidative stress and expressed in the luminal area of atherosclerotic lesions. Suspended S100A13 did not activate platelets, but immobilized S100A13 significantly increased thrombus formation on collagen-coated surfaces. Taken together, we proposed that VSMCs stimulate platelets through CLEC-2, possibly leading to thrombus formation after plaque erosion and stent implantation, where VSMCs are exposed to blood flow. Furthermore, we identified S100A13 as one of the ligands on VSMCs. PMID:26418160

  14. Promotion of experimental thrombus formation by the procoagulant activity of breast cancer cells

    NASA Astrophysics Data System (ADS)

    Berny-Lang, M. A.; Aslan, J. E.; Tormoen, G. W.; Patel, I. A.; Bock, P. E.; Gruber, A.; McCarty, O. J. T.

    2011-02-01

    The routine observation of tumor emboli in the peripheral blood of patients with carcinomas raises questions about the clinical relevance of these circulating tumor cells. Thrombosis is a common clinical manifestation of cancer, and circulating tumor cells may play a pathogenetic role in this process. The presence of coagulation-associated molecules on cancer cells has been described, but the mechanisms by which circulating tumor cells augment or alter coagulation remains unclear. In this study we utilized suspensions of a metastatic adenocarcinoma cell line, MDA-MB-231, and a non-metastatic breast epithelial cell line, MCF-10A, as models of circulating tumor cells to determine the thromobogenic activity of these blood-foreign cells. In human plasma, both metastatic MDA-MB-231 cells and non-metastatic MCF-10A cells significantly enhanced clotting kinetics. The effect of MDA-MB-231 and MCF-10A cells on clotting times was cell number-dependent and inhibited by a neutralizing antibody to tissue factor (TF) as well as inhibitors of activated factor X and thrombin. Using fluorescence microscopy, we found that both MDA-MB-231 and MCF-10A cells supported the binding of fluorescently labeled thrombin. Furthermore, in a model of thrombus formation under pressure-driven flow, MDA-MB-231 and MCF-10A cells significantly decreased the time to occlusion. Our findings indicate that the presence of breast epithelial cells in blood can stimulate coagulation in a TF-dependent manner, suggesting that tumor cells that enter the circulation may promote the formation of occlusive thrombi under shear flow conditions.

  15. A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation

    PubMed Central

    Fuentes, Rudy E.; Zaitsev, Sergei; Ahn, Hyun Sook; Hayes, Vincent; Kowalska, M. Anna; Lambert, Michele P.; Wang, Yuhuan; Siegel, Donald L.; Bougie, Daniel W.; Aster, Richard H.; Myers, Daniel D.; Stepanova, Victoria; Cines, Douglas B.; Muzykantov, Vladimir R.; Poncz, Mortimer

    2015-01-01

    The use of fibrinolytic agents to prevent new thrombus formation is limited by an increased risk of bleeding due to lysis of hemostatic clots that prevent hemorrhage in damaged blood vessels. We sought to develop an agent that provides thromboprophylaxis without carrying a significant risk of causing systemic fibrinolysis or disrupting hemostatic clots. We previously showed that platelet (PLT) α granule–delivered urokinase plasminogen activator (uPA) is highly effective in preventing thrombosis, while being associated with little systemic fibrinolysis or bleeding. Here, we generated a chimeric prodrug composed of a single-chain version of the variable region of an anti-αIIbβ3 mAb fused to a thrombin-activatable, low-molecular-weight pro-uPA (PLT/uPA-T). PLT/uPA-T recognizes human αIIbβ3 on both quiescent and activated platelets and is enzymatically activated specifically by thrombin. We found that this prodrug binds tightly to human platelets even after gel filtration, has a prolonged half-life in mice transgenic for human αIIb compared with that of uPA-T, and prevents clot formation in a microfluidic system. Importantly, in two murine injury models, PLT/uPA-T did not lyse preexisting clots, even when administration was delayed by as little as 10 minutes, while it concurrently prevented the development of nascent thrombi. Thus, PLT/uPA-T represents the prototype of a platelet-targeted thromboprophylactic agent that selectively targets nascent over preexisting thrombi. PMID:26690701

  16. Promotion of experimental thrombus formation by the procoagulant activity of breast cancer cells

    PubMed Central

    Berny-Lang, MA; Aslan, JE; Tormoen, GW; Patel, IA; Bock, PE; Gruber, A

    2011-01-01

    The routine observation of tumor emboli in the peripheral blood of patients with carcinomas raises questions about the clinical relevance of these circulating tumor cells. Thrombosis is a common clinical manifestation of cancer and circulating tumor cells may play a pathogenetic role in this process. The presence of coagulation-associated molecules on cancer cells has been described, but the mechanisms by which circulating tumor cells augment or alter coagulation remains unclear. In this study we utilized suspensions of a metastatic adenocarcinoma cell line, MDA-MB-231, and a non-metastatic breast epithelial cell line, MCF-10A, as models of circulating tumor cells to determine the thromobogenic activity of these blood-foreign cells. In human plasma, both metastatic MDA-MB-231 cells and non-metastatic MCF-10A cells significantly enhanced clotting kinetics. The effect of MDA-MB-231 and MCF-10A cells on clotting times was cell number-dependent and inhibited by a neutralizing antibody to tissue factor (TF) as well as inhibitors of activated factor X and thrombin. Using fluorescence microscopy, we found that both MDA-MB-231 and MCF-10A cells supported the binding of fluorescently-labeled thrombin. Furthermore, in a model of thrombus formation under pressure-driven flow, MDA-MB-231 and MCF-10A cells significantly decreased the time to occlusion. Our findings indicate that the presence of breast epithelial cells in blood can stimulate coagulation in a TF-dependent manner, suggesting that tumor cells that enter the circulation may promote the formation of occlusive thrombi under shear flow conditions. PMID:21301066

  17. Patterns of ST segment resolution after guidewire passage and thrombus aspiration in primary percutaneous coronary intervention (PPCI) for acute myocardial infarction

    PubMed Central

    Russhard, Paul; Al Janabi, Firas; Parker, Michael; Clesham, Gerald J

    2016-01-01

    Background ST segment elevation allows the rapid identification of patients with acute myocardial infarction who benefit from emergency reperfusion. Primary percutaneous coronary intervention (PPCI) has emerged as the preferred perfusion strategy for patients presenting with ST segment elevation myocardial infarction (STEMI). Methods and results We studied the effects of the simple passage of an angioplasty guidewire followed by mechanical thrombus aspiration on the ST segment displacement in 289 patients presenting with acute STEMI. Simple guidewire passage led to a statistically significant fall in the mean ST elevation from 5.9 to 4.9 mm (p<0.001), but the mean ST displacement after subsequent mechanical thrombus aspiration was 4.8 mm, not statistically significantly different from guidewire passage. When compared with simple guidewire passage, thrombus aspiration resulted in more patients achieving more than 50% ST resolution (21.8% vs 15.2%, p=0.009), but a higher proportion had a worsening of ST elevation compared to baseline (19.7% vs 13.5%, p=0.041). Conclusions Mechanical thrombus aspiration in acute STEMI did not improve the mean ST resolution compared with simple guidewire passage. Thrombus aspiration increased the proportion achieving 50% resolution but also increased the proportion who had a worsening of ST elevation. These data may help explain some of the uncertainties surrounding the routine use of thrombus aspiration in STEMI and potentially supports the use of ‘time to angioplasty guidewire passage’ as one of the ways to judge the promptness of PPCI services. PMID:27335657

  18. Visualization and analysis of biomaterial-centered thrombus formation within a defined crevice under flow.

    PubMed

    Jamiolkowski, Megan A; Pedersen, Drake D; Wu, Wei-Tao; Antaki, James F; Wagner, William R

    2016-07-01

    The blood flow pathway within a device, together with the biomaterial surfaces and status of the patient's blood, are well-recognized factors in the development of thrombotic deposition and subsequent embolization. Blood flow patterns are of particular concern for devices such as blood pumps (i.e. ventricular assist devices, VADs) where shearing forces can be high, volumes are relatively large, and the flow fields can be complex. However, few studies have examined the effect of geometric irregularities on thrombus formation on clinically relevant opaque materials under flow. The objective of this study was to quantify human platelet deposition onto Ti6Al4V alloys, as well as positive and negative control surfaces, in the region of defined crevices (∼50-150 μm in width) that might be encountered in many VADs or other cardiovascular devices. To achieve this, reconstituted fresh human blood with hemoglobin-depleted red blood cells (to achieve optical clarity while maintaining relevant rheology), long working optics, and a custom designed parallel plate flow chamber were employed. The results showed that the least amount of platelet deposition occurred in the largest crevice size examined, which was counterintuitive. The greatest levels of deposition occurred in the 90 μm and 53 μm crevices at the lower wall shear rate. The results suggest that while crevices may be unavoidable in device manufacturing, the crevice size might be tailored, depending on the flow conditions, to reduce the risk of thromboembolic events. Further, these data might be used to improve the accuracy of predictive models of thrombotic deposition in cardiovascular devices to help optimize the blood flow path and reduce device thrombogenicity. PMID:27156141

  19. Acute free-floating carotid artery thrombus causing stroke in a young patient: unique etiology and management using endovascular approach.

    PubMed

    Tan, Ai Peng; Taneja, Manish; Seah, Boon Heng; Leong, Hoe Nam; Venketasubramanian, Narayanaswamy

    2014-01-01

    Atherosclerotic disease accounts for 20%-30% of strokes in the general population. In young adults, it is an unexpected event and its causes involve diverse pathologies. Herein, we describe a unique case of acute embolic stroke in a young adult patient due to the presence of a large clot in the right common and internal carotid arteries, as a result of an extrinsic cause. Surgical clot retrieval was considered unsafe at that point in time in view of the active inflammatory changes surrounding the affected vessels. This was eventually treated with a novel endovascular technique, a unique alternative to open surgery, with excellent clinical outcome. To our knowledge, the penumbra system has never been used for thrombus removal in a nonacute setting. PMID:25440371

  20. Anti-oxidant ebselen delays microvascular thrombus formation in the rat cremaster muscle by inhibiting platelet P-selectin expression.

    PubMed

    Lindenblatt, Nicole; Schareck, Wolfgang; Belusa, Lorenz; Nickels, Ruth Maria; Menger, Michael Dieter; Vollmar, Brigitte

    2003-11-01

    Ebselen, a seleno-organic compound showing glutathione per-oxidase-like activity, has potent anti-inflammatory and anti-oxidant effects. Since selenium deficiency is thought to be associated with an increased incidence of vascular thrombosis, we studied the effect of ebselen on blood cell aggregate formation and vessel occlusion in vivo. In individual microvessels of rat cremaster muscle preparations, photochemically induced thrombus formation was analyzed in detail using intravital fluorescence microscopy. In ebselen-pretreated animals (30 mg/kg ip), venular thrombus formation was significantly delayed (50% vessel occlusion: 535+/-34 s; initial stasis: 872+/-82 s; complete occlusion: 908+/-87 s) as compared to vehicle-treated controls (416+/-42; 612+/-49; 647+/-51). Moreover, ebselen significantly prolonged the kinetics of arteriolar thrombus formation and even completely prevented blood cell aggregate and thrombus formation in 88.9% of all arterioles studied (p<0.05 vs controls: 37.5%). Anti-thrombotic properties of ebselen could also be observed in a model of ferric chloride-induced microvascular thrombosis, with a low dose (5 mg/kg ip) being as effective as a high dose pretreatment (30 mg/kg ip). As assessed by flow cytometry of platelet P-selectin immunfluorescence, whole blood isolated from ebselen-treated animals revealed a significantly lower fraction of P-selectin expressing platelets when compared with that of DMSO-treated controls. In addition, oxidant stress-induced upregulation of P-selectin on isolated platelets was found dose-dependently inhibited by increasing concentrations of ebselen (10-100 micro M). Moreover, ebselen dose-dependently inhibited H(2)O(2)-induced platelet-leukocyte aggregate formation in whole blood in vitro, suggesting that the anti-thrombotic effect of ebselen is achieved by attenuation of P-selectin dependent platelet-leukocyte aggregation. Thus, ebselen represents preventive and therapeutic value for disorders with increased

  1. Comparison of the usefulness of enoxaparin versus warfarin for prevention of left ventricular mural thrombus after anterior wall acute myocardial infarction.

    PubMed

    White, Derek C; Grines, Cindy L; Grines, Lorelei L; Marcovitz, Pamela; Messenger, John; Schreiber, Theodore

    2015-05-01

    Left ventricular (LV) thrombus is one of the most common complications in patients with anterior acute myocardial infarction (AMI) and LV dysfunction. Although anticoagulation is frequently prescribed, data regarding the appropriate drug, duration, risks, and effect on echocardiographic indices of thrombus are lacking. Moreover, given the difficulty in obtaining adequate anticoagulation with warfarin, it is possible that short-term treatment with a more predictable agent would be effective. We randomized 60 patients at high risk of developing LV mural thrombus (anterior acute myocardial infarction with Q waves and ejection fraction≤40%) to receive either enoxaparin 1 mg/kg (maximum 100 mg) subcutaneously every 12 hours for 30 days or traditional anticoagulation (intravenous heparin followed by oral warfarin for 3 months). Clinical evaluations and transthoracic echocardiograms were obtained at baseline, in-hospital, and at 3.5 months. There were no differences between the groups regarding baseline demographics, acute echocardiographic findings, and in-hospital outcomes. The length of hospital stay tended to be shorter for the enoxaparin group (4.6 vs 5.6; p=0.066) and the corresponding hospital costs ($25,837 vs $34,666; p=0.18). At 3 months, bleeding and thromboembolic events were rare and similar between enoxaparin and warfarin groups. Although more patients had probable mural thrombus in the enoxaparin group compared with warfarin at 3.5 months (15% vs 4%; p=0.35), this was not significantly different. In conclusion, the use of enoxaparin tends to shorten hospitalization and lower cost of care. However, at 3.5 months, there appears to be numerically higher (but statistically insignificant) rates of LV thrombus in the enoxaparin group. PMID:25765590

  2. The differential effects of aspirin on platelets, leucocytes and vascular endothelium in an in vivo model of thrombus formation.

    PubMed

    Nagamatsu, Y; Tsujioka, Y; Hashimoto, M; Giddings, J C; Yamamoto, J

    1999-02-01

    Unanswered questions remain with regard to the therapeutic use of aspirin and the selective inhibition of thromboxane A2 and prostacyclin in platelets and endothelial cells. In the present study, the effects of aspirin on platelets and endothelial cells in vivo were examined using a helium-neon (He-Ne) laser-induced thrombosis model. Single intravenous injections of aspirin at concentrations of more than 0.5 mg/kg body weight mediated a dose dependent inhibition of thrombus formation in arterioles but not in venules. This antithrombotic effect was optimum after 15 min and declined after 90 min. Potent antithrombotic activity in arterioles was manifest at doses of 2.5 mg/kg to 50 mg/kg, and initial inhibition of thrombogenesis in vivo was most pronounced at high doses. Oral aspirin also inhibited thrombus formation in arterioles but not in venules, although the antithrombotic effects were delayed and prolonged. Maximum inhibition of ex vivo, collagen induced platelet aggregation by aspirin was observed approximately 180 min after intravenous injection. The results demonstrated that, although aspirin might have differential effects on platelets and endothelial cells, potent antithrombotic activity was manifest in arterioles at all concentrations. The findings suggest that the concept of the aspirin dilemma might be ignored for therapeutic purposes in many clinical circumstances. The antithrombotic effects of aspirin were unchanged in granulocyte-depleted animals, indicating that leucocyte-related mechanisms including neutrophil superoxide anion production did not modulate the potency of aspirin in this model. PMID:10197261

  3. Inhibition of Hb Binding to GP1bα Abrogates Hb-Mediated Thrombus Formation on Immobilized VWF and Collagen under Physiological Shear Stress

    PubMed Central

    Peng, Yuandong; Guchhait, Prasenjit

    2016-01-01

    Background Reports including our own describe that intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our recent study shows that plasma Hb concentrations correlate directly with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). The binding of Hb to glycoprotein1bα (GP1bα) increases platelet activation. A peptide AA1-50, designed from N-terminal amino acid sequence of GP1bα significantly inhibits the Hb binding to GP1bα as well as Hb-induced platelet activation. This study further examined if the Hb-mediated platelet activation plays any significant role in thrombus formation on subendothelium matrix under physiological flow shear stresses and the inhibition of Hb-platelet interaction can abrogate the above effects of Hb. Methods and Results Study performed thrombus formation assay in vitro by perfusing whole blood over immobilized VWF or collagen type I in presence of Hb under shear stresses simulating arterial or venous flow. The Hb concentrations ranging from 5 to 10 μM, commonly observed level in plasma of the hemolytic patients including PNH, dose-dependently increased thrombus formation on immobilized VWF under higher shear stress of 25 dyne/cm2, but not at 5 dyne/cm2. The above Hb concentrations also increased thrombus formation on immobilized collagen under both shear stresses of 5 and 25 dyne/cm2. The peptide AA1-50 abrogated invariably the above effects of Hb on thrombus formation. Conclusions and Significance This study therefore indicates that the Hb-induced platelet activation plays a crucial role in thrombus formation on immobilized VWF or collagen under physiological flow shear stresses. Thus suggesting a probable role of this mechanism in facilitating thrombosis under hemolytic conditions. PMID:27105433

  4. Immunohistological assessment of fibrin deposition and thrombus formation in canine mammary neoplasia.

    PubMed

    Golombiewski, A; Gutberlet, K; Rudolph, R

    1997-08-01

    A commercially available monoclonal antibody against human fibrin was used to detect fibrin in canine formalin-fixed, paraffin wax-embedded tissue by applying a slightly modified alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Twenty-eight mammary tumours from six bitches were examined for the presence of fibrin. Thrombi and extravascular fibrin deposits were detected in 15 tumours (12 complex adenocarcinomas, one adenocarcinoma, two solid carcinomas), and a single thrombus was detected in one adenoma; 12 tumours (three adenomas, one complex adenoma, four complex adenocarcinomas and four adenocarcinomas) did not show any staining reaction. PMID:9352443

  5. A Collision Probability Model of Portal Vein Tumor Thrombus Formation in Hepatocellular Carcinoma

    PubMed Central

    Xiong, Fei

    2015-01-01

    Hepatocellular carcinoma is one of the most common malignancies worldwide, with a high risk of portal vein tumor thrombus (PVTT). Some promising results have been achieved for venous metastases of hepatocellular carcinoma; however, the etiology of PVTT is largely unknown, and it is unclear why the incidence of PVTT is not proportional to its distance from the carcinoma. We attempted to address this issue using physical concepts and mathematical tools. Finally, we discuss the relationship between the probability of a collision event and the microenvironment of the PVTT. Our formulae suggest that the collision probability can alter the tumor microenvironment by increasing the number of tumor cells. PMID:26131562

  6. Inhibitory effect of caffeic acid on ADP-induced thrombus formation and platelet activation involves mitogen-activated protein kinases

    PubMed Central

    Lu, Yu; Li, Quan; Liu, Yu-Ying; Sun, Kai; Fan, Jing-Yu; Wang, Chuan-She; Han, Jing-Yan

    2015-01-01

    Caffeic acid (CA), one of the active constituents of Radix Salvia miltiorrhizae, exhibits antioxidant and anti-inflammatory activities. However, few studies have assessed the ability of CA to inhibit platelet mediated thrombus generation in vivo. In this study, we investigated the antithrombotic effect of CA in mouse cerebral arterioles and venules using intravital microscopy. The antiplatelet activity of CA in ADP stimulated mouse platelets in vitro was also examined in attempt to explore the underlying mechanism. Our results demonstrated that CA (1.25–5 mg/kg) significantly inhibited thrombus formation in vivo. In vitro, CA (25–100 μM) inhibited ADP-induced platelet aggregation, P-selectin expression, ATP release, Ca2+ mobilization, and integrin αIIbβ3 activation. Additionally, CA attenuated p38, ERK, and JNK activation, and enhanced cAMP levels. Taken together, these data provide evidence for the inhibition of CA on platelet-mediated thrombosis in vivo, which is, at least partly, mediated by interference in phosphorylation of ERK, p38, and JNK leading to elevation of cAMP and down-regulation of P-selectin expression and αIIbβ3 activation. These results suggest that CA may have potential for the treatment of aberrant platelet activation-related diseases. PMID:26345207

  7. Cocaine-Induced Delayed Myocardial Infarction Complicated by Apical Thrombus.

    PubMed

    Khan, Rafay; Arshed, Sabrina; Jehangir, Waqas; Sen, Shuvendu; Yousif, Abdalla

    2016-01-01

    It is well demonstrated in the literature that cocaine use has been well linked to the formation of various forms of acute and chronic cardiovascular problems including but not limited to acute coronary syndromes. However, cocaine has been commonly associated with coronary vasospasms and less commonly with myocardial infarction and the formation of atrial thrombus. Through this case presentation, we illustrate the findings of a 35-year-old gentleman with history of cocaine use presenting with acute coronary syndrome and complicated by thrombus formation. Furthermore, through this report, we illustrate in a patient with no other risk factors and at a young age, how chronic cocaine use or even a history of usage may result in complications even weeks after its consumption. PMID:26668686

  8. Cocaine-Induced Delayed Myocardial Infarction Complicated by Apical Thrombus

    PubMed Central

    Khan, Rafay; Arshed, Sabrina; Jehangir, Waqas; Sen, Shuvendu; Yousif, Abdalla

    2016-01-01

    It is well demonstrated in the literature that cocaine use has been well linked to the formation of various forms of acute and chronic cardiovascular problems including but not limited to acute coronary syndromes. However, cocaine has been commonly associated with coronary vasospasms and less commonly with myocardial infarction and the formation of atrial thrombus. Through this case presentation, we illustrate the findings of a 35-year-old gentleman with history of cocaine use presenting with acute coronary syndrome and complicated by thrombus formation. Furthermore, through this report, we illustrate in a patient with no other risk factors and at a young age, how chronic cocaine use or even a history of usage may result in complications even weeks after its consumption. PMID:26668686

  9. The Use of Fluid Mechanics to Predict Regions of Microscopic Thrombus Formation in Pulsatile VADs.

    PubMed

    Topper, Stephen R; Navitsky, Michael A; Medvitz, Richard B; Paterson, Eric G; Siedlecki, Christopher A; Slattery, Margaret J; Deutsch, Steven; Rosenberg, Gerson; Manning, Keefe B

    2014-03-01

    We compare the velocity and shear obtained from particle image velocimetry (PIV) and computational fluid dynamics (CFD) in a pulsatile ventricular assist device (VAD) to further test our thrombus predictive methodology using microscopy data from an explanted VAD. To mimic physiological conditions in vitro, a mock circulatory loop is used with a blood analog that matched blood's viscoelastic behavior at 40% hematocrit. Under normal physiologic pressures and for a heart rate of 75 bpm, PIV data is acquired and wall shear maps are produced. The resolution of the PIV shear rate calculations are tested using the CFD and found to be in the same range. A bovine study, using a model of the 50 cc Penn State V-2 VAD, for 30 days at a constant beat rate of 75 beats per minute (bpm) provides the microscopic data whereby after the 30 days, the device is explanted and the sac surface analyzed using scanning electron microscopy (SEM) and, after immunofluorescent labeling for platelets and fibrin, confocal microscopy. Areas are examined based on PIV measurements and CFD, with special attention to low shear regions where platelet and fibrin deposition are most likely to occur. Data collected within the outlet port in a direction normal to the front wall of the VAD shows that some regions experience wall shear rates less than 500 s(-1), which increases the likelihood of platelet and fibrin deposition. Despite only one animal study, correlations between PIV, CFD, and in vivo data show promise. Deposition probability is quantified by the thrombus susceptibility potential, a calculation to correlate low shear and time of shear with deposition. PMID:24634700

  10. The Use of Fluid Mechanics to Predict Regions of Microscopic Thrombus Formation in Pulsatile VADs

    PubMed Central

    Topper, Stephen R.; Navitsky, Michael A.; Medvitz, Richard B.; Paterson, Eric G.; Siedlecki, Christopher A.; Slattery, Margaret J.; Deutsch, Steven; Rosenberg, Gerson; Manning, Keefe B.

    2014-01-01

    We compare the velocity and shear obtained from particle image velocimetry (PIV) and computational fluid dynamics (CFD) in a pulsatile ventricular assist device (VAD) to further test our thrombus predictive methodology using microscopy data from an explanted VAD. To mimic physiological conditions in vitro, a mock circulatory loop is used with a blood analog that matched blood’s viscoelastic behavior at 40% hematocrit. Under normal physiologic pressures and for a heart rate of 75 bpm, PIV data is acquired and wall shear maps are produced. The resolution of the PIV shear rate calculations are tested using the CFD and found to be in the same range. A bovine study, using a model of the 50 cc Penn State V-2 VAD, for 30 days at a constant beat rate of 75 beats per minute (bpm) provides the microscopic data whereby after the 30 days, the device is explanted and the sac surface analyzed using scanning electron microscopy (SEM) and, after immunofluorescent labeling for platelets and fibrin, confocal microscopy. Areas are examined based on PIV measurements and CFD, with special attention to low shear regions where platelet and fibrin deposition are most likely to occur. Data collected within the outlet port in a direction normal to the front wall of the VAD shows that some regions experience wall shear rates less than 500 s−1, which increases the likelihood of platelet and fibrin deposition. Despite only one animal study, correlations between PIV, CFD, and in vivo data show promise. Deposition probability is quantified by the thrombus susceptibility potential, a calculation to correlate low shear and time of shear with deposition. PMID:24634700

  11. Trivalent methylated arsenical-induced phosphatidylserine exposure and apoptosis in platelets may lead to increased thrombus formation

    SciTech Connect

    Bae, Ok-Nam; Lim, Kyung-Min; Chung, Jin-Ho

    2009-09-01

    Trivalent methylated metabolites of arsenic, monomethylarsonous acid (MMA{sup III}) and dimethylarsinous acid (DMA{sup III}), have been found highly reactive and toxic in various cells and in vivo animal models, suggesting their roles in the arsenic-associated toxicity. However, their effects on cardiovascular system including blood cells, one of the most important targets for arsenic toxicity, remain poorly understood. Here we found that MMA{sup III} and DMA{sup III} could induce procoagulant activity and apoptosis in platelets, which play key roles in the development of various cardiovascular diseases (CVDs) through excessive thrombus formation. In freshly isolated human platelets, treatment of MMA{sup III} resulted in phosphatidylserine (PS) exposure, a hallmark of procoagulant activation, accompanied by distinctive apoptotic features including mitochondrial membrane potential disruption, cytochrome c release, and caspase-3 activation. These procoagulant activation and apoptotic features were found to be mediated by the depletion of protein thiol and intracellular ATP, and flippase inhibition by MMA{sup III}, while the intracellular calcium increase or reactive oxygen species generation was not involved. Importantly, increased platelet procoagulant activity by MMA{sup III} resulted in enhanced blood coagulation and excessive thrombus formation in a rat in vivo venous thrombosis model. DMA{sup III} also induced PS-exposure with apoptotic features mediated by protein thiol depletion, which resulted in enhanced thrombin generation. In summary, we believe that this study provides an important evidence for the role of trivalent methylated arsenic metabolites in arsenic-associated CVDs, giving a novel insight into the role of platelet apoptosis in toxicant-induced cardiovascular toxicity.

  12. An Investigation on Platelet Transport during Thrombus Formation at Micro-Scale Stenosis

    PubMed Central

    Tovar-Lopez, Francisco Javier; Rosengarten, Gary; Nasabi, Mahyar; Sivan, Vijay; Khoshmanesh, Khashayar; Jackson, Shaun P.; Mitchell, Arnan; Nesbitt, Warwick S.

    2013-01-01

    This paper reports on an investigation of mass transport of blood cells at micro-scale stenosis where local strain-rate micro-gradients trigger platelet aggregation. Using a microfluidic flow focusing platform we investigate the blood flow streams that principally contribute to platelet aggregation under shear micro-gradient conditions. We demonstrate that relatively thin surface streams located at the channel wall are the primary contributor of platelets to the developing aggregate under shear gradient conditions. Furthermore we delineate a role for red blood cell hydrodynamic lift forces in driving enhanced advection of platelets to the stenosis wall and surface of developing aggregates. We show that this novel microfluidic platform can be effectively used to study the role of mass transport phenomena driving platelet recruitment and aggregate formation and believe that this approach will lead to a greater understanding of the mechanisms underlying shear-gradient dependent discoid platelet aggregation in the context of cardiovascular diseases such as acute coronary syndromes and ischemic stroke. PMID:24194822

  13. Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate.

    PubMed Central

    Weiss, H J; Hawiger, J; Ruggeri, Z M; Turitto, V T; Thiagarajan, P; Hoffmann, T

    1989-01-01

    Platelet adhesion and thrombus formation on subendothelium, studied at a shear rate of 2,600 s-1, were inhibited by two synthetic peptides known to interact with GPIIb-IIIa. One peptide (HHLGGAKQAGDV) corresponds to the carboxyl terminal segment of the fibrinogen gamma-chain (gamma 400-411) and the other (RGDS) contains the amino acid sequence Arg-Gly-Asp (RGD) common to fibronectin, von Willebrand factor, vitronectin and the alpha-chain of fibrinogen. Neither platelet adhesion nor thrombus formation were decreased in a patient with severe congenital fibrinogen deficiency and this was equally true when his blood was further depleted of the small amounts of fibrinogen present utilizing an anti-fibrinogen antibody. In normal subjects, adhesion and thrombus formation were inhibited by the Fab' fragments of a monoclonal anti-GPIIb-IIIa antibody (LJ-CP8), which interferes with the interaction of platelets with all four adhesive proteins in both the fluid and solid phase. However, another anti-GPIIb-IIIa antibody (LJ-P5) that had minimal effects on the interaction of platelets with fibrinogen, but inhibited to varying degrees platelet interaction with other adhesive proteins, was equally effective. The findings demonstrate that, at a shear rate of 2,600 s-1, adhesive proteins other than fibrinogen are involved in GPIIb-IIIa-mediated platelet adhesion and thrombus formation on subendothelium. In addition, since LJ-P5 inhibited the binding of soluble von Willebrand factor and vitronectin, these adhesive proteins may be involved in platelet thrombus formation. In contrast to the results obtained at a shear rate of 2,600 s-1, fibrinogen could play a role in mediating platelet-platelet interactions with weak agonists or lower shear rates. PMID:2910912

  14. Effect of low dose acetylsalicylic acid on the frequency and hematologic activity of left ventricular thrombus in anterior wall acute myocardial infarction

    SciTech Connect

    Kuepper, A.J.V.; Verheugt, F.W.; Peels, C.H.; Galema, T.W.; den Hollander, W.; Roos, J.P.

    1989-04-15

    In this prospective, randomized, placebo-controlled trial the effect of 100 mg acetylsalicylic acid (ASA) once daily on the incidence, hematologic activity and embolic potential of left ventricular (LV) thrombosis was studied in 100 consecutive patients with a first anterior wall acute myocardial infarction (AMI). Patients were randomized to ASA or placebo less than 12 hours after onset of symptoms. Heparin, 5,000 IU subcutaneously twice daily, was given to all patients during immobilization. Echocardiography was performed less than 24 hours, 48 to 72 hours and 1, 2, and 12 weeks after AMI. LV thrombosis was detected by echocardiography in 30 (33%) of the 92 evaluable patients (15 patients given ASA and 15 given placebo). Indium-111 platelet scintigraphy was done in 17 of the 22 patients with an LV thrombus at the second week echocardiogram. Among 7 ASA-treated patients, 4 had positive images; among 10 placebo patients, 5 had positive images. LV thrombus resolution was noted in 3 of 9 patients with a positive scan and in 5 of 8 patients with a negative platelet scan. In 7 of 10 ASA-treated patients and 5 of 12 placebo-treated patients thrombus resolution was observed (difference not significant). Systemic embolism occurred in 2 patients, both given ASA, during the first week after AMI. Thus, low dose ASA has no effect on the incidence, hematologic activity and embolic potential of LV thrombosis in anterior wall AMI.

  15. Nanoliposomal Growth Hormone and Sodium Nitrite Release from Silicone Fibers Reduces Thrombus Formation Under Flow.

    PubMed

    Salehi-Nik, Nasim; Amoabediny, Ghassem; Banikarimi, Seyedeh Parnian; Pouran, Behdad; Malaie-Balasi, Zahra; Zandieh-Doulabi, Behrouz; Klein-Nulend, Jenneke

    2016-08-01

    Biocompatibility of artificial lungs can be improved by endothelialization of hollow fibers. Bioavailability of growth-inducing and anti-thrombotic agents on the hollow fiber-blood interface inhibits thrombosis. We investigated if nanoliposomal growth-inducing growth hormone (nGH) and anti-thrombotic sodium nitrite (nNitrite) incorporation into collagen-coating on silicone hollow fibers improves blood biocompatibility by increasing endothelial cell growth and nitrite bioavailability under flow. Nitrite production rate was assessed under varying flow conditions. Finite element (FE) modeling was used to simulate nitrite transport within the parallel-plate flow chamber, and nitrite bioavailability on the fiber-blood interface at 1-30 dyn/cm(2) shear stress. Endothelial cell number on fibers coated with nNitrite-nGH-collagen conjugate was 1.5-fold higher than on collagen-coated fibers. For collagen-coated fibers, nitrite production reached a maximum at 18 dyn/cm(2) shear stress. When fibers were coated with nNitrite-nGH-collagen conjugate, nitrite production increased continuously by increasing shear stress. FE modeling revealed that nitrite concentrations at the fiber-blood interface were affected by shear stress-induced nitrite production, and diffusion/convection-induced nitrite removal. Highest nitrite concentrations and lowest thrombus deposition were observed on fibers coated with nNitrite-nGH-collagen conjugate exposed to 6-12 dyn/cm(2) shear stress. In conclusion, our results suggest that nNitrite-nGH-Col conjugate coatings promote endothelialization of silicone hollow fibers in biohybrid artificial lungs. PMID:26762283

  16. Iliac artery mural thrombus formation. Effect of antiplatelet therapy on 111In-platelet deposition in baboons

    SciTech Connect

    Hanson, S.R.; Paxton, L.D.; Harker, L.A.

    1986-09-01

    To measure the rate, extent, and time course of arterial mural thrombus formation in vivo and to assess the effects of antiplatelet therapy in that setting, we have studied autologous /sup 111/In-platelet deposition induced by experimental iliac artery aneurysms in baboons. Scintillation camera imaging analyses were performed at 1, 24, 48, and 72 hours after implantation of the device. Correction for tissue attenuation was determined by using a small, comparably located /sup 111/In source implanted at the time of surgery. In five animals, /sup 111/In-platelet activity accumulated progressively after device implantation, reaching a maximum after the third day. Repeat image analysis carried out 2 weeks after the surgical procedure also showed progressive accumulation of /sup 111/In-platelets over 3 days but at markedly reduced amounts as compared with the initial study. In five additional animals, treatment with a combination of aspirin and dipyridamole begun 1 hour after surgical implantation reduced /sup 111/In-platelet deposition to negligible levels by the third day. Although platelet survival time was shortened and platelet turnover was reciprocally increased in all operated animals, platelet survival and turnover were not affected by antiplatelet therapy. We conclude that, in contrast to platelet survival and turnover measurements, /sup 111/In-platelet imaging is a reliable and sensitive method for localizing and quantifying focal arterial thrombi and for assessing the effects of antiplatelet therapy.

  17. An Integrated Fluid-Chemical Model Toward Modeling the Formation of Intra-Luminal Thrombus in Abdominal Aortic Aneurysms

    PubMed Central

    Biasetti, Jacopo; Spazzini, Pier Giorgio; Swedenborg, Jesper; Gasser, T. Christian

    2012-01-01

    Abdominal Aortic Aneurysms (AAAs) are frequently characterized by the presence of an Intra-Luminal Thrombus (ILT) known to influence their evolution biochemically and biomechanically. The ILT progression mechanism is still unclear and little is known regarding the impact of the chemical species transported by blood flow on this mechanism. Chemical agonists and antagonists of platelets activation, aggregation, and adhesion and the proteins involved in the coagulation cascade (CC) may play an important role in ILT development. Starting from this assumption, the evolution of chemical species involved in the CC, their relation to coherent vortical structures (VSs) and their possible effect on ILT evolution have been studied. To this end a fluid-chemical model that simulates the CC through a series of convection-diffusion-reaction (CDR) equations has been developed. The model involves plasma-phase and surface-bound enzymes and zymogens, and includes both plasma-phase and membrane-phase reactions. Blood is modeled as a non-Newtonian incompressible fluid. VSs convect thrombin in the domain and lead to the high concentration observed in the distal portion of the AAA. This finding is in line with the clinical observations showing that the thickest ILT is usually seen in the distal AAA region. The proposed model, due to its ability to couple the fluid and chemical domains, provides an integrated mechanochemical picture that potentially could help unveil mechanisms of ILT formation and development. PMID:22934022

  18. Effect of GABA derivatives on the rate of thrombus formation, platelet aggregation, and plasma coagulation capacity in rats with experimental gestosis.

    PubMed

    Tyurenkov, I N; Perfilova, V N; Karamysheva, V I; Reznikova, L B; Mokrousov, I S; Mikhailova, L I; Berestovitskaya, V M; Vasil'eva, O S

    2014-12-01

    Experimental gestosis induced by replacement of drinking water with 1.8% NaCl promoted hypercoagulation, increased the rate and degree of platelet aggregation, and reduced clotting time in pregnant females. GABA derivatives, compounds RGPU-151, RGPU-152, and phenibut normalized parameters of hemostasis and platelet aggregation and the rate of thrombus formation in the animals. The efficiency of the test substances did not significantly differ from that of the reference drug sulodexide. PMID:25432276

  19. Delayed formation of pulmonary artery stump thrombus: a case report and review of the literature.

    PubMed

    Joshi, Monika; Farooq, Umar; Mehrok, Sandeep; Srouji, Nadine

    2009-01-01

    Pulmonary artery stump thrombosis is a recognized complication after pneumonectomy. However, to our knowledge, there is only one case report of delayed development of this complication. We report the case of a 68 year-old man who presented with chest pain nearly ten years after undergoing a right pneumonectomy for lung cancer. Workup identified a pulmonary artery stump thrombosis. Due to the acute onset of his symptoms, the patient was anticoagulated, and his chest pain resolved. While the literature suggests that anticoagulation is not generally required for stump thromboses, we highlight features of this case that may indicate an increased risk of clinically important sequelae. Taking previous reports into account, we argue that a specific subset of patients with stump thrombosis may benefit from systemic anticoagulation. PMID:19515226

  20. Delayed formation of pulmonary artery stump thrombus: a case report and review of the literature

    PubMed Central

    Joshi, Monika; Farooq, Umar; Mehrok, Sandeep; Srouji, Nadine

    2009-01-01

    Pulmonary artery stump thrombosis is a recognized complication after pneumonectomy. However, to our knowledge, there is only one case report of delayed development of this complication. We report the case of a 68 year-old man who presented with chest pain nearly ten years after undergoing a right pneumonectomy for lung cancer. Workup identified a pulmonary artery stump thrombosis. Due to the acute onset of his symptoms, the patient was anticoagulated, and his chest pain resolved. While the literature suggests that anticoagulation is not generally required for stump thromboses, we highlight features of this case that may indicate an increased risk of clinically important sequelae. Taking previous reports into account, we argue that a specific subset of patients with stump thrombosis may benefit from systemic anticoagulation. PMID:19515226

  1. Discrimination between platelet-mediated and coagulation-mediated mechanisms in a model of complex thrombus formation in vivo

    SciTech Connect

    Cadroy, Y.; Horbett, T.A.; Hanson, S.R.

    1989-04-01

    To study mechanisms of complex thrombus formation in vivo, and to compare the relative antithrombotic effects of anticoagulants and antiplatelet agents, a model was developed in baboons. Segments of collagen-coated tubing followed by two sequentially placed expansion chambers exhibiting disturbed flow patterns were exposed to native blood under laminar flow conditions. The device was incorporated for 1 hour into an exteriorized arteriovenous shunt in baboons under controlled blood flow (20 ml/min). Morphologic evaluation by scanning electron microscopy showed that thrombi associated with collagen were relatively rich in platelets but thrombi in the chambers were rich in fibrin and red cells. Deposition of indium 111-labeled platelets was continuously measured with a scintillation camera. Platelet deposition increased in a linear (collagen-coated segment) or exponential (chambers 1 and 2) fashion over time, with values after 40 minutes averaging 24.1 +/- 3.3 x 10(8) platelets (collagen segment), 16.7 +/- 3.4 x 10(8) platelets (chamber 1), and 8.4 +/- 2.4 x 10(8) platelets (chamber 2). Total fibrinogen deposition after 40 minutes was determined by using iodine 125-labeled baboon fibrinogen and averaged 0.58 +/- 0.14 mg in the collagen segment, 1.51 +/- 0.27 mg in chamber 1, and 0.95 +/- 0.25 mg in chamber 2. Plasma levels of beta-thromboglobulin (beta TG), platelet-factor 4 (PF4), and fibrinopeptide A (FPA) increased fourfold to fivefold after 60 minutes of blood exposure to the thrombotic device. Platelet deposition onto the collagen segment, chamber 1, and chamber 2 was linearly dependent on the circulating platelet count. Platelet accumulation in chamber 1 and chamber 2 was also dependent on the presence of the proximal collagen segment.

  2. Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation.

    PubMed

    Jang, Ja-Young; Kim, Tae-Su; Cai, Jingmei; Kim, Jihyun; Kim, Youngeun; Shin, Kyungha; Kim, Kwang Sei; Park, Sung Kyeong; Lee, Sung-Pyo; Choi, Ehn-Kyoung; Rhee, Man Hee; Kim, Yun-Bae

    2013-12-01

    The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-dependent manner. Rats were orally administered with nattokinase for 1 week, and their carotid arteries were exposed. Arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Nattokinase delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 160 mg/kg. In addition, a high dose (500 mg/kg) of nattokinase fully prevented the occlusion, as achieved with aspirin (30 mg/kg). The results indicate that nattokinase extracted from fermented soybean inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is suggested that nattokinase could be a good candidate without adverse effects for the improvement of blood flow. PMID:24396387

  3. Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation

    PubMed Central

    Jang, Ja-Young; Kim, Tae-Su; Cai, Jingmei; Kim, Jihyun; Kim, Youngeun; Shin, Kyungha; Kim, Kwang Sei; Park, Sung Kyeong; Lee, Sung-Pyo; Choi, Ehn-Kyoung

    2013-01-01

    The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-dependent manner. Rats were orally administered with nattokinase for 1 week, and their carotid arteries were exposed. Arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Nattokinase delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 160 mg/kg. In addition, a high dose (500 mg/kg) of nattokinase fully prevented the occlusion, as achieved with aspirin (30 mg/kg). The results indicate that nattokinase extracted from fermented soybean inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is suggested that nattokinase could be a good candidate without adverse effects for the improvement of blood flow. PMID:24396387

  4. Perilla oil improves blood flow through inhibition of platelet aggregation and thrombus formation

    PubMed Central

    Jang, Ja-Young; Kim, Tae-Su; Cai, Jingmei; Kim, Jihyun; Kim, Youngeun; Shin, Kyungha; Kim, Kwang-Sei; Lee, Sung-Pyo; Kang, Myung-Hwa; Choi, Ehn-Kyoung

    2014-01-01

    The inhibitory effects of perilla oil on the platelet aggregation in vitro and thrombosis in vivo were investigated in comparison with aspirin, a well-known blood flow enhancer. Rabbit platelet-rich plasma was incubated with perilla oil and aggregation inducers collagen or thrombin, and the platelet aggregation rate was analyzed. Perilla oil significantly inhibited both the collagen- and thrombin-induced platelet aggregations, in which the thromboxane B2 formation from collagen-activated platelets were reduced in a concentration-dependent manner. Rats were administered once daily by gavage with perilla oil for 1 week, carotid arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Perilla oil delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 0.5 mL/kg. In addition, a high dose (2 mL/kg) of perilla oil greatly prevented the occlusion, comparable to the effect of aspirin (30 mg/kg). The results indicate that perilla oil inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is proposed that perilla oil could be a good candidate without adverse effects for the improvement of blood flow. PMID:24707301

  5. Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo.

    PubMed

    Lin, Kuan H; Kuo, Jinn R; Lu, Wan J; Chung, Chi L; Chou, Duen S; Huang, Shih Y; Lee, Hsiu C; Sheu, Joen R

    2013-05-15

    Hinokitiol is a tropolone-related bioactive compound that has been used in hair tonics, cosmetics, and food as an antimicrobial agent. Recently, hinokitiol has attracted considerable interest because of its anticancer activities. Platelet activation plays a crucial role in atherothrombotic processes. We examined the effects of hinokitiol treatment on platelet activation using human platelets. In the present study, hinokitiol (1 and 2 μM) inhibited the collagen-induced aggregation of human platelets, but did not inhibit the activation of platelets by other agonists, including thrombin, arachidonic acid, and ADP. Hinokitiol inhibited the phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and Akt in collagen-activated human platelets, and significantly reduced intracellular calcium mobilization and hydroxyl radical (OH·) formation. Hinokitiol also reduced the PKC activation and platelet aggregation stimulated by PDBu. In addition, hinokitiol significantly prolonged thrombogenesis in mice. Hinokitiol did not influence the binding of a fluorescent triflavin probe to the αIIbβ3 integrin on platelet membrane, and neither ODQ nor SQ22536 significantly reversed the hinokitiol-mediated inhibition of platelet aggregation. In conclusion, hinokitiol may inhibit platelet activation by inhibiting the PLCγ2-PKC cascade and hydroxyl radical formation, followed by suppressing the activation of MAPKs and Akt. Our study suggests that hinokitiol may represent a potential therapeutic agent for the prevention or treatment of thromboembolic disorders. PMID:23473801

  6. A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models.

    PubMed

    Huang, Shiu-Wen; Kuo, Heng-Lan; Hsu, Ming-Tsung; Tseng, Yufeng Jane; Lin, Shu-Wha; Kuo, Sheng-Chu; Peng, Hui-Chin; Lien, Jin-Cherng; Huang, Tur-Fu

    2016-08-01

    A novel benzimidazole derivative, nstpbp5185, was discovered through in vitro and in vivo evaluations for antiplatelet activity. Thromaboxane receptor (TP) is important in vascular physiology, haemostasis and pathophysiological thrombosis. Nstpbp5185 concentration-dependently inhibited human platelet aggregation caused by collagen, arachidonic acid and U46619. Nstpbp5185 caused a right-shift of the concentration-response curve of U46619 and competitively inhibited the binding of 3H-SQ-29548 to TP receptor expressed on HEK-293 cells, with an IC50 of 0.1 µM, indicating that nstpbp5185 is a TP antagonist. In murine thrombosis models, nstpbp5185 significantly prolonged the latent period in triggering platelet plug formation in mesenteric and FeCl3-induced thrombi formation, and increased the survival rate in pulmonary embolism model with less bleeding than aspirin. This study suggests nstpbp5185, an orally selective anti-thrombotic agent, acting through blockade of TXA2 receptor, may be efficacious for prevention or treatment of pathologic thrombosis. PMID:27173725

  7. A comparison of the effects of factor XII deficiency and prekallikrein deficiency on thrombus formation.

    PubMed

    Kokoye, Yasin; Ivanov, Ivan; Cheng, Qiufang; Matafonov, Anton; Dickeson, S Kent; Mason, Shauna; Sexton, Daniel J; Renné, Thomas; McCrae, Keith; Feener, Edward P; Gailani, David

    2016-04-01

    Studies with animal models implicate the plasma proteases factor XIIa (FXIIa) and α-kallikrein in arterial and venous thrombosis. As congenital deficiencies of factor XII (FXII) or prekallikrein (PK), the zymogens of FXIIa and α-kallikrein respectively, do not cause bleeding disorders, inhibition of these enzymes may have therapeutic benefit without compromising hemostasis. The relative contributions of FXIIa and α-kallikrein to thrombosis in animal models are not clear. We compared mice lacking FXII or PK to wild type mice in established models of arterial thrombosis. Wild type mice developed carotid artery occlusion when the vessel was exposed to a 3.5% solution of ferric chloride (FeCl3). FXII-deficient mice were resistant to occlusion at 5% FeCl3 and partially resistant at 10% FeCl3. PK-deficient mice were resistant at 3.5% FeCl3 and partially resistant at 5% FeCl3. Mice lacking high molecular weight kininogen, a cofactor for PK activation and activity, were also partially resistant to thrombosis at 5% FeCl3. Induction of carotid artery thrombosis with Rose Bengal was delayed in FXII-deficient mice compared to wild type or PK-deficient animals. In human plasma supplemented with silica, DNA or collagen to induce contact activation, an antibody to the FXIIa active site was more effective at preventing thrombin generation than an antibody to the α-kallikrein active site. Similarly, the FXIIa antibody was more effective at reducing fibrin formation in human blood flowing through collagen coated-tubes. The findings suggest that inhibitors of FXIIa will have more potent anti-thrombotic effects than inhibitors of α-kallikrein. PMID:26950760

  8. [A novel molecular marker for thrombus formation and life prognosis--clinical usefulness of measurement of soluble fibrin monomer-fibrinogen complex (SF)].

    PubMed

    Koga, Shin

    2004-04-01

    For a long time fibrinopeptide A(FPA), fibrinopeptide B(FPB), D-dimer, FM test, serum FDP, and thrombin anti-thrombin complex(TAT) are being used as molecular markers to for sure diagnose hypercoagulable state and thrombus formation. Indeed these molecular markers are very useful for diagnosing thrombus formation, disseminated intravascular coagulation(DIC), and the indicator of treatment of DIC. But these molecular parameters are not enough and difficult for prognosis of the disease or predicting the complication of patients as the most important subject for clinicians. The soluble fibrin monomer-fibrinogen complex (SF) is a complex coupling fibrin monomer and fibrinogen molecules to be formed in the early-activated state of blood coagulation. Thus such a molecular complex is expected to serve as a parameter for the diagnosis of thrombus formation and DIC, in particular its early stage. The aim of the present study is to evaluate a potential usefulness of a newly developed SF test utilizing an SF specific monoclonal antibody (IF-43). We measured SF together with established other parameters in 195 patients with DIC, subclinical DIC/hypercoagulable state, and non-DIC. The diagnosis of DIC was made based on a modified version of the criteria established by the Ministry of Health, Labor and Welfare of Japan. Underlying disease includes leukemia, malignant lymphoma, myelodysplastic syndrome (MDS), multiple injury, giant ovarian tumor, prostatic cancer with multiple bone metastasis, lung cancer, breast cancer with multiple lung and bone metastasis, severe pneumoniae, sepsis, hemophagocytic syndrome (HPS), and rheumatoid arthritis. The SF levels in DIC patients were significantly higher than those in the subclinical DIC/hypercoagulable state, and the non-DIC patients. Receiver operating characteristic (ROC) analysis shows that the specificity and sensitivity of the SF assay appears to be satisfactory. As the level of SF reflects the thrombin generation activity in

  9. Apigenin inhibits platelet adhesion and thrombus formation and synergizes with aspirin in the suppression of the arachidonic acid pathway.

    PubMed

    Navarro-Núñez, L; Lozano, M L; Palomo, M; Martínez, C; Vicente, V; Castillo, J; Benavente-García, O; Diaz-Ricart, M; Escolar, G; Rivera, J

    2008-05-14

    Previous studies using washed platelets demonstrated that certain flavonoids inhibit platelet function through several mechanisms including blockade of TxA(2) receptors (TPs). We aimed to analyze the binding capacity of flavonoids to TPs in platelet rich plasma (PRP), investigated their effect in flowing blood, and evaluated the ability of apigenin to improve the efficacy of aspirin in the inhibition of platelet aggregation. The binding of flavonoids to TPs in PRP was explored using binding assays and the TP antagonist [ (3)H]SQ29548. Effects of flavonoids on platelet adhesion were assessed using arterial subendothelium with annular plate perfusion chambers, and global evaluation of apigenin on high-shear-dependent platelet function was determined by the PFA-100. To evaluate the ability of apigenin to potentiate the effect of aspirin, arachidonic acid-induced platelet aggregation was measured prior to and after consumption of subaggregatory doses of aspirin in the presence or absence of apigenin. Binding assays revealed that apigenin was an efficient competitor of [ (3)H]SQ29548 binding to PRP ( K i = 155.3 +/- 65.4 microM), and perfusion studies showed that apigenin, genistein, and catechin significantly diminished thrombus formation when compared to control (26.2 +/- 3.8, 33.1 +/- 5.2, and 26.2 +/- 5.2 vs 76.6 +/- 2.6%, respectively; p < 0.05). Apigenin, similarly to the TP antagonist SQ29548, significantly prolonged collagen epinephrine-induced PFA-100 closure time in comparison to the control and, when added to platelets that had been exposed in vivo to aspirin, potentiated its inhibitory effect on platelet aggregation. The inhibitory effect of some flavonoids in the presence of plasma, particularly apigenin, might in part rely on TxA(2) receptor antagonism. There is a clear increase in the ex vivo antiplatelet effect of aspirin in the presence of apigenin, which encourages the idea of the combined use of aspirin and certain flavonoids in patients in which

  10. Defective angiogenesis delays thrombus resolution: a potential pathogenetic mechanism underlying chronic thromboembolic pulmonary hypertension

    PubMed Central

    Panzenboeck, Adelheid; Winter, Max P; Schubert, Uwe; Voswinckel, Robert; Frey, Maria K; Jakowitsch, Johannes; Alimohammadi, Arman; Hobohm, Lukas; Mangold, Andreas; Bergmeister, Helga; Sibilia, Maria; Wagner, Erwin F; Mayer, Eckhard; Klepetko, Walter; Hoelzenbein, Thomas J; Preissner, Klaus T; Lang, Irene M

    2015-01-01

    Objective Restoration of patency is a natural target of vascular remodeling following venous thrombosis that involves vascular endothelial cells and smooth muscle cells as well as leukocytes. Acute pulmonary emboli usually resolve within six months. However, in some instances, thrombi transform into fibrous vascular obstructions, resulting in occlusion of the deep veins, or in chronic thromboembolic pulmonary hypertension (CTEPH). We proposed that dysregulated thrombus angiogenesis may contribute to thrombus persistence. Approach and Results Mice with an endothelial-cell-specific conditional deletion of vascular endothelial growth factor receptor 2/kinase insert domain protein receptor (VEGF-R2/Kdr) were utilized in a model of stagnant flow venous thrombosis closely resembling human deep vein thrombosis. Biochemical and functional analyses were performed on pulmonary endarterectomy specimens from patients with CTEPH, a human model of non-resolving venous thromboembolism. Endothelial cell-specific deletion of Kdr and subsequent ablation of thrombus vascularization delayed thrombus resolution. In accordance with these findings, organized human CTEPH thrombi were largely devoid of vascular structures. Several vessel-specific genes such as KDR, vascular endothelial cadherin and podoplanin were expressed at lower levels in white CTEPH thrombi than in organizing deep vein thrombi and organizing thrombi from aortic aneurysms. In addition, red CTEPH thrombi attenuated the angiogenic response induced by VEGF. Conclusions In the present work, we propose a mechanism of thrombus non-resolution demonstrating that endothelial cell-specific deletion of Kdr abates thrombus vessel formation, misguiding thrombus resolution. Medical conditions associated with the development of CTEPH may be compromising early thrombus angiogenesis. PMID:24526692

  11. Rheological and hemostasiological aspects of thrombus formation in the left atrial appendage in atrial fibrillation? A new strategy for prevention of cardioembolic stroke.

    PubMed

    Leithäuser, Boris; Jung, Friedrich; Park, Jai-Wun

    2010-01-01

    Atrial fibrillation (AF), as the most common cardiac rhythm disturbance, gains in importance not only for the persons affected, but also for health care and social economy due to thromboembolic events, of which stroke is the most serious, disabling, and life threatening one. Cardiac embolism is due to thrombus formation mainly in the left atrial appendage (LAA). The pathophysiology leading to increased thrombogenicity is complex and requires a remodelling of the LAA structure, decreased LAA blood flow, activation of inflammatory processes, deviations of the hemostatic/fibrinolytic system, and activation/dysfunction of endothelial/endocardial cells. Altogether, a prothrombotic state proposed by Virchow more than 150 years ago. The presence of a LAA thrombus, therefore, is a result of a dynamic process of clot formation and lysis. A comprehensive understanding of this pathophysiology is helpful to optimize the management of patients at high risk of cardioembolic stroke. Especially those with contraindications for oral anticoagulation are in a need of an alternative approach that is not associated with a long-term risk of hemorrhage and other attendant circumstances. The reasonable alternative may be the exclusion of the LAA cavity from circulation by either surgical or percutaneous catheter-based procedures. PMID:20675914

  12. Facilitating roles of murine platelet glycoprotein Ib and αIIbβ3 in phosphatidylserine exposure during vWF–collagen-induced thrombus formation

    PubMed Central

    Kuijpers, Marijke J E; Schulte, Valerie; Oury, Cécile; Lindhout, Theo; Broers, Jos; Hoylaerts, Marc F; Nieswandt, Bernhard; Heemskerk, Johan W M

    2004-01-01

    Vessel wall damage exposes collagen fibres, to which platelets adhere directly via the collagen receptors glycoprotein (GP) VI and integrin α2β1 and indirectly by collagen-bound von Willebrand factor (vWF) via the GPIb-V-IX and integrin αIIbβ3 receptor complexes. Platelet–collagen interaction under shear stimulates thrombus formation in two ways, by integrin-dependent formation of platelet aggregates and by surface exposure of procoagulant phosphatidylserine (PS). GPVI is involved in both processes, complemented by α2β1. In mouse blood flowing over collagen, we investigated the additional role of platelet–vWF binding via GPIb and αIIbβ3. Inhibition of GPIb as well as blocking of vWF binding to collagen reduced stable platelet adhesion at high shear rate. This was accompanied by delayed platelet Ca2+ responses and reduced PS exposure, while microaggregates were still formed. Inhibition of integrin αIIbβ3 with JON/A antibody, which blocks αIIbβ3 binding to both vWF and fibrinogen, reduced PS exposure and aggregate formation. The JON/A effects were not enhanced by combined blocking of GPIb–vWF binding, suggesting a function for αIIbβ3 downstream of GPIb. Typically, with blood from FcR γ-chain +/− mutant mice, expressing 50% of normal platelet GPVI levels, GPIb blockage almost completely abolished platelet adhesion and PS exposure. Together, these data indicate that, under physiological conditions of flow, both adhesive receptors GPIb and αIIbβ3 facilitate GPVI-mediated PS exposure by stabilizing platelet binding to collagen. Hence, these glycoproteins have an assistant procoagulant role in collagen-dependent thrombus formation, which is most prominent at reduced GPVI activity and is independent of the presence of thrombin. PMID:15155790

  13. “Soluble Tissue Factor” in the 21st Century: Definitions, Biochemistry, and Pathophysiological Role in Thrombus Formation

    PubMed Central

    Bogdanov, Vladimir Y.; Versteeg, Henri H.

    2016-01-01

    Tissue factor (TF), the main trigger of blood coagulation, is essential for normal hemostasis. Over the past 20 years, heightened intravascular levels and activity of TF have been increasingly perceived as an entity that significantly contributes to venous as well as arterial thrombosis. Various forms of the TF protein in the circulation have been described and proposed to be thrombogenic. Aside from cell and vessel wall-associated TF, several forms of non–cell-associated TF circulate in plasma and may serve as a causative factor in thrombosis. At the present time, no firm consensus exists regarding the extent, the vascular setting(s), and/or the mechanisms by which such TF forms contribute to thrombus initiation and propagation. Here, we summarize the existing paradigms and recent, sometimes paradigm-shifting findings elucidating the structural, mechanistic, and pathophysiological characteristics of plasma-borne TF. PMID:26408917

  14. Antithrombotic effect of argatroban on the pial vessels of the rat: a study with He-Ne laser-induced thrombus formation.

    PubMed

    Sasaki, Y; Morii, S; Yamashita, T; Yamamoto, J

    1993-01-01

    The antithrombotic effect of the synthetic thrombin inhibitor (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfon yl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate (argatroban) was investigated in cerebral vessels of the rat. An occlusive thrombus was formed in pial vessels using a He-Ne laser in a closed cranial window technique. Argatroban retarded the formation of thrombi in a dose-dependent manner. The antithrombotic effect of a single intravenous dose of argatroban at 0.5 mg/kg was diminished after 30 min in arterioles and after 50 min in venules, respectively. The antithrombotic activity was maintained, however, by continuous intravenous infusion (2 mg/kg/h). PMID:8365687

  15. Optical coherence tomography assessment of efficacy of thrombus aspiration in patients undergoing a primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

    PubMed Central

    Yamaguchi, Tomoyuki; Ino, Yasushi; Matsuo, Yoshiki; Shiono, Yasutsugu; Yamano, Takashi; Taruya, Akira; Nishiguchi, Tsuyoshi; Shimokado, Aiko; Orii, Makoto; Tanaka, Atsushi; Hozumi, Takeshi; Akasaka, Takashi

    2015-01-01

    Objective We used optical coherence tomography (OCT) to assess the impact of thrombus aspiration before angioplasty on poststenting tissue protrusions in patients undergoing a primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Methods and results A total of 188 patients with STEMI who underwent thrombus-aspiration PCI (n=113) or standard PCI (n=75) were examined in this study. OCT was performed immediately after primary PCI to assess lesion morphology in the stented segment. The minimum stent area was similar between the thrombus-aspiration PCI group and the standard PCI group [7.4 interquartile range (IQR): 5.8–9.4 vs. 7.4 IQR: 5.8–8.9 mm2, P=0.788]. The maximum tissue protrusion area [0.6 (IQR: 0.3–1.1) vs. 1.2 (IQR: 0.8–1.9) mm2, P<0.001], the mean tissue protrusion area [0.1 (IQR: 0.1–0.2) vs. 0.5 (IQR: 0.3–0.8) mm2, P<0.001], and tissue protrusion volume [2.3 (IQR: 1.3–4.3) vs. 8.3 (IQR: 5.4–14.6) mm3, P<0.001] were significantly smaller in the thrombus-aspiration PCI group compared with the standard PCI group. Minimum lumen area was significantly greater in the thrombus-aspiration PCI group compared with the standard PCI group [6.9 (IQR: 5.4–8.8) vs. 6.3 (IQR: 4.6–7.8) mm2, P=0.033]. Conclusion Thrombus aspiration before angioplasty in patients with STEMI was associated with significantly smaller tissue protrusion and larger lumen poststenting compared with standard PCI. Thrombus aspiration in primary PCI favorably influenced lesion morphologies in the stented segment. PMID:26230885

  16. Fibrinolytic treatment of thrombus on prosthetic heart valves.

    PubMed Central

    Witchitz, S; Veyrat, C; Moisson, P; Scheinman, N; Rozenstajn, L

    1980-01-01

    Fibrinolytic agents were administered for 13 episodes of thrombus formation on mitral or aortic valvar prostheses in 12 patients. The most common presenting features were pulmonary oedema (six cases) or arterial emboli (six cases). The diagnosis of thrombus formation was made by phonocardiography on the following criteria: (a) modifications of the prosthetic sounds (12 cases), (b) appearance of a valvar obstructive syndrome (10 cases). The treatment consisted of streptokinase (100 000 units/h after a loading dose, seven cases) or urokinase using either low doses (75 000 or 112 500 units/h, three cases) or moderate doses (150 000 units/h, three cases) for one to four days. Immediate complete regression of clinical and phonocardiographic anomalies was seen in eight cases. Incomplete improvement was seen in two patients, leading to operation: this was unsuccessful in one patient who had surgery on the third day, and was successful in the other on the 75th day. There were three failures leading to successful reoperative procedures in two patients and to an early death in the third patient suffering from acute myocardial infarction. One non-fatal haemopericardium was observed in a patient treated with streptokinase. No important side effect was noted during delivery in a pregnant woman. During subsequent follow-up, a recurrent episode of thrombus formation was observed in one patient, treated by fibrinolytic therapy with success. One patient had an operation for a valve replacement six months after fibrinolytic treatment because of non-thrombotic valvar dysfunction; the outcome was fatal. Six patients are alive and in good condition, with a follow-up of six months to five years. Images PMID:7437196

  17. Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intra-luminal thrombus formation

    PubMed Central

    Biasetti, Jacopo; Hussain, Fazle; Gasser, T. Christian

    2011-01-01

    Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear–stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the λ2-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau–Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth. PMID:21471188

  18. A selective, slow binding inhibitor of factor VIIa binds to a nonstandard active site conformation and attenuates thrombus formation in vivo.

    PubMed

    Olivero, Alan G; Eigenbrot, Charles; Goldsmith, Richard; Robarge, Kirk; Artis, Dean R; Flygare, John; Rawson, Thomas; Sutherlin, Daniel P; Kadkhodayan, Saloumeh; Beresini, Maureen; Elliott, Linda O; DeGuzman, Geralyn G; Banner, David W; Ultsch, Mark; Marzec, Ulla; Hanson, Stephen R; Refino, Canio; Bunting, Stuart; Kirchhofer, Daniel

    2005-03-11

    The serine protease factor VIIa (FVIIa) in complex with its cellular cofactor tissue factor (TF) initiates the blood coagulation reactions. TF.FVIIa is also implicated in thrombosis-related disorders and constitutes an appealing therapeutic target for treatment of cardiovascular diseases. To this end, we generated the FVIIa active site inhibitor G17905, which displayed great potency toward TF.FVIIa (Ki = 0.35 +/- 0.11 nM). G17905 did not appreciably inhibit 12 of the 14 examined trypsin-like serine proteases, consistent with its TF.FVIIa-specific activity in clotting assays. The crystal structure of the FVIIa.G17905 complex provides insight into the molecular basis of the high selectivity. It shows that, compared with other serine proteases, FVIIa is uniquely equipped to accommodate conformational disturbances in the Gln217-Gly219 region caused by the ortho-hydroxy group of the inhibitor's aminobenzamidine moiety located in the S1 recognition pocket. Moreover, the structure revealed a novel, nonstandard conformation of FVIIa active site in the region of the oxyanion hole, a "flipped" Lys192-Gly193 peptide bond. Macromolecular substrate activation assays demonstrated that G17905 is a noncompetitive, slow-binding inhibitor. Nevertheless, G17905 effectively inhibited thrombus formation in a baboon arterio-venous shunt model, reducing platelet and fibrin deposition by approximately 70% at 0.4 mg/kg + 0.1 mg/kg/min infusion. Therefore, the in vitro potency of G17905, characterized by slow binding kinetics, correlated with efficacious antithrombotic activity in vivo. PMID:15632123

  19. A non-discrete method for residence time calculation as an indicator of thrombus formation in cardiovascular applications

    NASA Astrophysics Data System (ADS)

    Esmaily Moghadam, Mahdi; Marsden, Alison

    2012-11-01

    Cardiovascular simulations provide a promising means to predict risk of thrombosis in grafts, devices, and surgical anatomies in adult and pediatric patients. Although the pathways for platelet activation and clot formation are not fully understood, recent findings suggest that thrombosis risk correlates with the presence of recirculation regions with high residence time (RT). Current approaches for calculating RT are often based on releasing a finite number of Lagrangian particles in the flow and calculating RT by tracking their pathways. However, this method requires several simulations for a single case study, each of which requires releasing a significant number of particles, to obtain temporal and spatial convergence. In this work, we introduce a new non-discrete method, in which RT is calculated in an Eulerian non-discrete framework, using the advection-diffusion equation. Starting with an existing and a newly developed intuitive definition for the RT, the formulation for calculating RT in a region of interest is presented. The physical significance and sensitivity of each measure of RT is discussed and an extension of these definitions to a point-wise value is presented. Application to simulations of shunt insertion for single ventricle heart patients is demonstrated.

  20. Systems Analysis of Thrombus Formation.

    PubMed

    Diamond, Scott L

    2016-04-29

    The systems analysis of thrombosis seeks to quantitatively predict blood function in a given vascular wall and hemodynamic context. Relevant to both venous and arterial thrombosis, a Blood Systems Biology approach should provide metrics for rate and molecular mechanisms of clot growth, thrombotic risk, pharmacological response, and utility of new therapeutic targets. As a rapidly created multicellular aggregate with a polymerized fibrin matrix, blood clots result from hundreds of unique reactions within and around platelets propagating in space and time under hemodynamic conditions. Coronary artery thrombosis is dominated by atherosclerotic plaque rupture, complex pulsatile flows through stenotic regions producing high wall shear stresses, and plaque-derived tissue factor driving thrombin production. In contrast, venous thrombosis is dominated by stasis or depressed flows, endothelial inflammation, white blood cell-derived tissue factor, and ample red blood cell incorporation. By imaging vessels, patient-specific assessment using computational fluid dynamics provides an estimate of local hemodynamics and fractional flow reserve. High-dimensional ex vivo phenotyping of platelet and coagulation can now power multiscale computer simulations at the subcellular to cellular to whole vessel scale of heart attacks or strokes. In addition, an integrated systems biology approach can rank safety and efficacy metrics of various pharmacological interventions or clinical trial designs. PMID:27126646

  1. Transcatheter Therapy for a Large Mobile Right Atrial Thrombus and Massive Pulmonary Embolism.

    PubMed

    Narang, Akhil; Mediratta, Anuj; Estrada, Jeremy R; Rosenberg, Jonathan; DeCara, Jeanne M; Howell, Michael D; Lang, Roberto M; Paul, Jonathan D; Nathan, Sandeep; Shah, Atman P; Blair, John E

    2016-05-01

    A variety of interventional management approaches exist for the treatment of acute pulmonary embolism (PE). However, when PE is accompanied by residual right heart thrombus, the best therapeutic options are less clear. We describe a novel combined technique of percutaneous aspiration of unstable right atrial thrombus followed by ultrasound-directed thrombolysis of massive PE. PMID:27145056

  2. Diverse Findings in Calcified Thrombus Between Histopathology and In Vivo Imaging Including Intravascular Ultrasound, Optical Coherence Tomography, and Angioscopy.

    PubMed

    Koga, Seiji; Ikeda, Satoshi; Nakata, Tomoo; Kawano, Hiroaki; Abe, Kuniko; Maemura, Koji

    2015-01-01

    A 46-year-old woman on hemodialysis due to end-stage renal disease was admitted for repeated thrombus formation in previously implanted drug-eluting stents in the right coronary artery. We could successfully aspirate this thrombus, and histopathology revealed a calcified thrombus comprising multiple microcalcifications and fibrinous materials. This is the first report showing how a calcified thrombus is visualized in vivo by intracoronary imaging modalities including intravascular ultrasound, optical coherence tomography, and angioscopy. PMID:26549397

  3. Asymptomatic large left-atrial ball thrombus. Secondary to mitral stenosis.

    PubMed Central

    Vitale, M; Agnino, A; Serena, D; Schena, S; Piscitelli, D; Fiore, T; de Luca Tupputi Schinosa, L

    1997-01-01

    We describe the very unusual case of a patient with a large, free-floating left-atrial thrombus secondary to severe mitral stenosis, in whom the peculiar symptoms and complications of a ball thrombus were absent. The patient's only symptom before the episode reported here was mild dyspnea, which was attributed to mitral stenosis. She experienced neither embolism nor syncope. While even her clinical signs did not indicate a left-atrial ball thrombus, both echocardiography and angiography showed a free-floating thrombus. Because of the risk of stroke and acute obstruction of the mitral valve, emergency surgery was performed upon diagnosis of the ball thrombus. The surgery, which consisted of removing the thrombus and replacing the mitral valve with a mechanical prosthesis, was uneventful. A computed tomographic brain scan prior to discharge did not detect any cerebral infarction. Images PMID:9456496

  4. Surgical management of left ventricular thrombus following severe dehydration.

    PubMed

    Tanaka, Yuki; Nie, Masaki; Yamamoto, Nobuyuki; Ohara, Kuniyoshi; Miyaji, Kagami

    2016-08-01

    We experienced a case involving a left ventricular ball-like thrombus caused by severe following a 150 mile cycling road race. The patient had lower-limb arterial obstruction due to systemic thromboembolism on admission with no significant embolism, including the cerebral arteries, were detected. Left ventricular wall motion was good with no evidence of left and right coronary artery occlusion; therefore, we performed emergency left ventricular thrombectomy. Although there are many reports of left ventricular thrombus following acute myocardial infarction, dehydration is a very rare cause. Herein, we describe the surgical and management approaches to the treatment of left ventricular thrombectomy in this case. PMID:26266631

  5. Coronary thrombus detected by cardiac CT angiography before cardiac catheterization.

    PubMed

    Slim, Ahmad M; Slim, Jennifer N; Haney, Brian R; Shry, Eric A

    2010-11-01

    A patient presented with a complaint of pleuritic chest discomfort with elevated cardiac biomarkers. After a cardiac magnetic resonance imaging scan for the suspicion of myopericarditis showed a potential myocardial infarct, a coronary CT scan was performed. This revealed a thrombus of the left anterior descending artery. Cardiac catheterization confirmed the findings, and a small clot was removed. To our knowledge, this is the first reported case of coronary thrombus being detected by CT angiography with cardiac catheterization correlation. Coronary CT angiography has been increasingly used to evaluate acute chest pain with a negative predictive value close to 100%. In a young patient with suspicion of myopericarditis, CT angiography proved to be useful in diagnosing thrombus in the coronary tree. PMID:20463613

  6. Spontaneous retraction of an intramyocardial dissecting hemorrhage and multiple left ventricular thrombus formations in subacute myocardial infarction and antiphospholipid syndrome: a case report with long-term follow-up.

    PubMed

    Bahlmann, Edda; Schneider, Carsten; Vitali Serdoz, Laura; Hoffmann-Riem, Martin; Broemel, Thomas; Kuck, Karl-Heinz

    2006-05-01

    This report describes a 68-year-old patient with a subacute myocardial infarction and antiphosholipid syndrome. He developed an intramyocardial dissecting hemorrhage involving the left ventricular apex and multiple left ventricular thrombus formations, documented by contrast echocardiography and magnetic resonance imaging. By use of transthoracic echocardiography, spontaneous retraction of the dissecting hemorrhage could be detected. Severe coronary 3-vessel disease was successfully treated by coronary artery bypass grafting. During follow-up of 16 months, the dissecting hematoma could not been detected. Under initiation of anticoagulant treatment with Coumadin, the patient was in stable clinical condition and improved in New York Heart Association class from III to II. The pathophysiology, diagnosis, and management of this potentially highly lethal complication is reviewed. PMID:16644445

  7. A Novel Mechanical Thrombectomy Device for Retrieval of Intravascular Thrombus

    SciTech Connect

    Monsky, Wayne L.; Finitsis, Stephanos; Cicco, Dino De; Brock, John M.; Kucharczyk, John; Latchaw, Richard E.

    2011-04-15

    Purpose: Thrombotic and embolic vascular occlusion represents a leading cause of morbidity and mortality. Currently available thrombectomy devices have limitations, including difficulty removing organized thrombus and clot fragmentation with distal embolization. A novel mechanical thrombectomy device (MTD), designed to remove both hard and soft thrombus without trauma to the blood vessel, was tested in preclinical porcine models evaluating efficacy, safety, and ease of use. Materials and Methods: A total of 26 vessels in 14 pigs underwent mechanical thrombectomy with MTD. Thrombectomy was performed in nine superficial femoral arteries, eight subclavian arteries, five primary branches of the subclavian artery, lateral thoracic artery or the thyrocervical trunk, and four external carotids. Subacute organized fibrin-laden thrombus was injected into the arteries producing vascular occlusion. The MTD was then used for thrombectomy to restore patency and blood flow. Results: Intact thrombus was retrieved from 24 of 26 of the vessels with a single pass of the MTD, resulting in complete restoration of patency in 21 vessels and partial patency in 4 vessels. In 8 cases that used an early design, the embolic material fragmented during withdrawal from the access sheath. In 4 procedures that used an early design, the MTD failed to deploy fully and the embolus was not completely captured. No intraprocedural complications or vascular damage occurred. Conclusions: The present pilot studies demonstrate basic safety and efficacy of a novel MTD with design attributes suitable for retrieval of intact acute and organized chronic thrombus. The device has potential intracranial and peripheral utility.

  8. Radiopharmaceuticals for thrombus detection

    SciTech Connect

    Knight, L.C. )

    1990-01-01

    Most of the components of the thrombotic and fibrinolytic systems have at some time been evaluated as a means of carrying a radiolabel specifically to thrombi, although very few have been promising enough to emerge from investigational status to routine clinical use. New approaches are being explored, including improved methods of labeling platelets, chemically modified forms of previously tested plasma proteins, and new biomolecules, including monoclonal antibodies specific for fibrin and platelets. The current goal is to find one or more radiotracers that bind specifically and rapidly to thrombi, and that also have a rapid blood disappearance rate, permitting a clear diagnosis within a few hours after injection. Because this test may be needed to assess the course of therapy in an anticoagulated patient, the ideal radiopharmaceutical should be able to locate thrombi without interference by anticoagulants. Until a suitable thrombus-specific radiopharmaceutical becomes generally available, many hospitals will continue to attempt to make a diagnosis with nonspecific radiopharmaceuticals that can at best provide blood pool images to indicate filling defects. Several of the new approaches seem likely to provide the radiopharmaceutical sought, although clinical trials are at an early stage.137 references.

  9. Thrombus aspiration catheter is a Dottering balloon.

    PubMed

    Sheshagiri Rao, D; Barik, Ramachandra; Prasad, Akula Siva

    2016-01-01

    Coronary angiogram in a young man with history of STEMI with delayed presentation revealed subtotal occlusion of left anterior descending artery (LAD) with large thrombotic filling defect distal to the critical lesion. PCI was preferred without delay because of ongoing chest pain. Several runs of thrombus aspiration failed to detect any visible thrombus. However, the immediate angiogram after thrombus aspiration showed complete distal embolization of the thrombus which could have been achieved by Dottering or balloon dilatation. In contrary to the general perception, does thrombus aspiration push more thrombus than it can aspirate? PMID:27543477

  10. Thrombus aspiration in ST-segment elevation myocardial infarction.

    PubMed

    Meneguz-Moreno, R A; Costa, R A; A, A; Ribamar Costa, J; Abizaid, A

    2015-12-01

    Primary percutaneous coronary intervention (PCI) has become the treatment of choice in patients with ST-segment elevation myocardial infarction (STEMI) throughout the last years. A significant number of studies have demonstrated a morbidity and mortality benefit over thrombolysis, which has been attributed to better coronary perfusion in patients undergoing primary PCI. Even though it usually achieves normal flow in the affected epicardial vessel, myocardial reperfusion is not fully restored in a significant percentage of patients. This is commonly the result of distal thrombus embolization with subsequent impairment of myocardial microcirculation. Recognition of this has led to the development of a number of devices with different mechanisms, including thrombus aspiration catheters, in order to reduce distal embolization and therefore improve myocardial perfusion. Recent studies indeed demonstrate that the use of such devices offer additional clinical advantage in patients undergoing primary PCI in comparison to the standard PCI, whether in other trials it could not be proved. This paper focuses on general mechanisms of thrombus formation and discusses favorable and unfavorable studies towards thrombus aspiration in STEMI and its main aspects and it comes up with specific subjects that could benefit or not from the procedure of thrombus aspiration. PMID:26603617

  11. Dabigatran for left ventricular thrombus.

    PubMed

    Kolekar, Satishkumar; Munjewar, Chandrashekhar; Sharma, Satyavan

    2015-01-01

    Male patient in dilated phase of hypertrophic cardiomyopathy had multiple hospitalizations during the past 2 years either due to congestive heart failure, stroke, scar epilepsy, or atrial fibrillation and ventricular tachycardia. Medication included evidence based therapy for heart failure, cordarone and warfarin. Anticoagulation had to be discontinued due to marked fluctuations in INR. Transthoracic Echocardiography (TTE) revealed a mobile mass in the left ventricle. He was treated with Dabigatran 110mg twice a day for 4 months without any bleeding or embolic episode and complete resolution of thrombus. Dabigatran is a reversible direct thrombin inhibitor and currently approved for the prevention of thromboembolic episodes in non-valvar atrial fibrillation. This case demonstrates possible thrombolytic properties of dabigatran in resolution of left ventricular thrombus. PMID:26432747

  12. Use of apixaban for an elderly patient with left atrial thrombus

    PubMed Central

    Dobashi, Shintaro; Fujino, Tadashi; Ikeda, Takanori

    2014-01-01

    An 86-year-old man had long-standing persistent atrial fibrillation, but had not received any anticoagulants. Transthoracic echocardiography revealed a large thrombus formation in the left atrium. We hesitated to use the conventional anticoagulant, warfarin, because he was very old and had dementia. We decided to resolve the thrombus at our outpatient clinic. He was started on the novel oral anticoagulant, apixaban, 2.5 mg twice daily, which is a direct factor Xa (FXa) inhibitor. After 11 weeks on that therapy, the thrombus formation had almost resolved. During oral anticoagulant therapy, no serious bleeding complications, systemic embolisms or strokes were noted. To the best of our knowledge, we are the first to report that apixaban (5 mg/day) can possibly resolve a thrombus formation in the left atrium. PMID:24962484

  13. Platelet Transport Rates and Binding Kinetics at High Shear over a Thrombus

    PubMed Central

    Bark, David L.; Ku, David N.

    2013-01-01

    Thrombus formation over a ruptured atherosclerotic plaque cap can occlude an artery with fatal consequences. We describe a computational model of platelet transport and binding to interpret rate-limiting steps seen in experimental thrombus formation over a collagen-coated stenosis. The model is used to compute shear rates in stenoses with growing boundaries. In the model, moving erythrocytes influence platelet transport based on shear-dependent enhanced diffusivity and a nonuniform platelet distribution. Adhesion is modeled as platelet-platelet binding kinetics. The results indicate that observed thrombus growth rates are limited by platelet transport to the wall for shear rates up to 6000 s−1. Above 7000 s−1, the thrombus growth rate is likely limited by binding kinetics (10−4 m/s). Thrombus growth computed from these rate-limiting steps match the thrombus location and occlusion times for experimental conditions if a lag time for platelet activation is included. Using fitted parameters, the model is then used to predict thrombus size and shape at a higher Reynolds number flow consistent with coronary artery disease. PMID:23870271

  14. Measurement of Thrombus Flux Using Transesophageal Echocardiography

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Tadashi; Hirai, Kazuki; Aoki, Masami; Miyagi, Jin; Suzuki, Masahiko; Moriya, Hideshige; Hachiya, Hiroyuki

    2006-05-01

    Deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) are serious problem of total knee replacement (TKR). These diseases may be caused by a thrombus formed during the TKR operation. Therefore, understanding the flow volume of thrombus is important for curing and preventing PTE. In this paper, we tried to understanding the situation of the flow of thrombus by using transesophageal echocardiography movies. We applied the signal processing technique the FSET to extract the anomalous information from ultrasonic echo image. As a result of processing, the time change of the flow volume of thrombus was confirmed.

  15. Novel use of the AngioVac® system to remove thrombus during simultaneous extracorporeal membrane oxygenation life support.

    PubMed

    Griffith, Kevin E; Jenkins, Eric; Copenhaver, William; Williams, David M

    2016-03-01

    Extracorporeal membrane oxygenation (ECMO) was introduced to clinical medicine over 40 years ago. While initially used as a treatment for acute respiratory failure in infants, the use of ECMO has grown to include respiratory and circulatory failure in both children and adults, cardiogenic shock, pulmonary embolism, sepsis, trauma, malignancy, pulmonary hemorrhage and as a treatment for hypothermic drowning.(1) Recent technological improvements in ECMO circuitry make it possible to minimize anticoagulation of the ECMO patient, decreasing the incidence of bleeding. Thrombus deposition within the ECMO circuit can be a life-threating complication. ECMO circuit thrombus can be contained in the circuit, adherent to cannula and deposited within the patient. The ability to remove thrombus while the patient remains on ECMO support could be a life-saving measure for some patients. The present case report outlines use of the AngioVac(®) thrombus removal system in concert with ECMO to remove a large thrombus adherent to an ECMO cannula. PMID:26034197

  16. Platelet PI3Kβ and GSK3 regulate thrombus stability at a high shear rate.

    PubMed

    Laurent, Pierre-Alexandre; Séverin, Sonia; Hechler, Béatrice; Vanhaesebroeck, Bart; Payrastre, Bernard; Gratacap, Marie-Pierre

    2015-01-29

    Class IA phosphoinositide 3-kinase β (PI3Kβ) is considered a potential drug target in arterial thrombosis, which is a major cause of death worldwide. Here we show that a striking phenotype of mice with selective p110β deletion in the megakaryocyte lineage is thrombus instability at a high shear rate, which is an effect that is not detected in the absence of p110α in platelets. The high shear rate-dependent thrombus instability in the absence of p110β is observed both ex vivo and in vivo with the formation of platelet emboli. Moreover, PI3Kβ is required for the recruitment of new platelets to a growing thrombus when a pathological high shear is applied. Treatment of human blood with AZD6482, a selective PI3Kβ inhibitor, phenocopies p110β deletion in mouse platelets, which highlights the role of the kinase activity of p110β. Within the growing platelet thrombus, p110β inactivation impairs the activating phosphorylations of Akt and the inhibitory phosphorylation of GSK3. In accord with these data, pharmacologic inhibition of GSK3 restores thrombus stability. Thus, platelet PI3Kβ is not essential for thrombus growth and stability at normal arterial shear but has a specific and critical role in maintaining the integrity of the formed thrombus on elevation of shear rate, suggesting a potential risk of embolization on treatment with PI3Kβ inhibitors. PMID:25398937

  17. Bilirubin Levels and Thrombus Burden in Patients With ST-Segment Elevation Myocardial Infarction.

    PubMed

    Hamur, Hikmet; Duman, Hakan; Bakirci, Eftal Murat; Kucuksu, Zafer; Demirelli, Selami; Kalkan, Kamuran; Degirmenci, Husnu

    2016-07-01

    We investigated whether serum bilirubin level (a marker of heme oxygenase activity) is a predictor of thrombus burden in patients with acute myocardial infarction. Patients (n = 229; male 72.9%; mean age 63 ± 13.4 years) who were admitted with ST-segment elevation myocardial infarction (STEMI) were enrolled. Patients were divided into 2 groups. Group 1 was defined as low thrombus burden and group 2 was defined as high thrombus burden. Patients with high thrombus burden had higher total bilirubin levels (14.4 [4.3-22.9] vs 7.7 [2.4-20.3] µmol/L, P ≤ .001), (0.84 [0.25-1.34] vs 0.45 [0.14-1.19] mg/dL P ≤ .001) and direct bilirubin levels (3.1 [2.1-8.4] vs 1.7 [0.5-6.5] µmol/L, P ≤ .001), (0.18 [0.03-0.49] vs 0.10 [0.03-0.38] mg/dL, P ≤ .001). At multivariate analysis, total bilirubin (odds ratio: 1.05, 95% confidence interval: 1.03-1.08, P ≤ .001) was the independent predictor of high thrombus burden. In conclusion, total bilirubin level is independently associated with high thrombus burden in patients with STEMI. PMID:26339042

  18. Plasma fibronectin promotes thrombus growth and stability in injured arterioles

    PubMed Central

    Ni, Heyu; Yuen, Peter S. T.; Papalia, Jessie M.; Trevithick, Jane E.; Sakai, Takao; Fässler, Reinhard; Hynes, Richard O.; Wagner, Denisa D.

    2003-01-01

    Mice lacking both of the best-known platelet ligands, von Willebrand factor and fibrinogen, can still form occlusive thrombi in injured arterioles. The platelets of these animals accumulate excessive amounts of fibronectin (FN). These observations led us to examine the contribution of plasma FN (pFN) to thrombus formation. Inactivation of the FN gene in FN conditional knockout mice reduced pFN levels to <2% and platelet FN to ≈20% of the levels in similarly treated control mice. The mice were then observed in a model of arterial injury to evaluate their capacity to form thrombi. The deficiency of pFN did not affect the initial platelet adhesion, but a delay of several minutes in thrombus formation was observed in the arterioles of pFN-deficient mice as compared with control mice. The thrombi that formed in the absence of pFN were stably anchored to the vessel wall but continuously shed platelets or small platelet clumps, thus slowing their growth significantly; the platelet/platelet cohesion was apparently diminished. Consequently the occlusion of pFN-deficient vessels was delayed, with the majority of vessels remaining patent at the end of the 40-min observation period. We conclude that, in addition to von Willebrand factor and fibrinogen, FN plays a significant role in thrombus initiation, growth, and stability at arterial shear rates and that deficiency in each of the three platelet ligands has its own specific impact on platelet plug formation. PMID:12606706

  19. Defective Association of the Platelet Glycoprotein Ib-IX Complex with the Glycosphingolipid-Enriched Membrane Domain Inhibits Murine Thrombus and Atheroma Formation.

    PubMed

    Zhou, Hao; Ran, Yali; Da, Qi; Shaw, Tanner S; Shang, Dan; Reddy, Anilkumar K; López, José A; Ballantyne, Christie M; Ware, Jerry; Wu, Huaizhu; Peng, Yuandong

    2016-07-01

    Localization of the platelet glycoprotein Ib-IX complex to the membrane lipid domain is essential for platelet adhesion to von Willebrand factor and subsequent platelet activation in vitro. Yet, the in vivo importance of this localization has never been addressed. We recently found that the disulfide linkage between Ibα and Ibβ is critical for the association of Ibα with the glycosphingolipid-enriched membrane domain; in this study, we established a transgenic mouse model expressing this mutant human Ibα that is also devoid of endogenous Ibα (HαSSMα(-/-)). Characterization of this model demonstrated a similar dissociation of Ibα from murine platelet glycosphingolipid-enriched membrane to that expressed in Chinese hamster ovary cells, which correlates well with the impaired adhesion of the transgenic platelets to von Willebrand factor ex vivo and in vivo. Furthermore, we bred our transgenic mice into an atherosclerosis-prone background (HαSSMα(-/-)ApoE(-/-) and HαWTMα(-/-)ApoE(-/-)). We observed that atheroma formation was significantly inhibited in mutant mice where fewer platelet-bound CD11c(+) leukocytes were circulating (CD45(+)/CD11c(+)/CD41(+)) and residing in atherosclerotic lesions (CD45(+)/CD11c(+)), suggesting that platelet-mediated adhesion and infiltration of CD11c(+) leukocytes may be one of the mechanisms. To our knowledge, these observations provide the first in vivo evidence showing that the membrane GEM is physiologically and pathophysiologically critical in the function of the glycoprotein Ib-IX complex. PMID:27206768

  20. Analysis of the role of von Willebrand factor, platelet glycoprotein VI-, and α2β1-mediated collagen binding in thrombus formation

    PubMed Central

    Shida, Yasuaki; Rydz, Natalia; Stegner, David; Brown, Christine; Mewburn, Jeffrey; Sponagle, Kate; Danisment, Ozge; Crawford, Bredon; Vidal, Barbara; Hegadorn, Carol A.; Pruss, Cynthia M.; Nieswandt, Bernhard

    2014-01-01

    Rare missense mutations in the von Willebrand factor (VWF) A3 domain that disrupt collagen binding have been found in patients with a mild bleeding phenotype. However, the analysis of these aberrant VWF-collagen interactions has been limited. Here, we have developed mouse models of collagen-binding mutants and analyzed the function of the A3 domain using comprehensive in vitro and in vivo approaches. Five loss-of-function (p.S1731T, p.W1745C, p.S1783A, p.H1786D, A3 deletion) and 1 gain-of-function (p.L1757A) variants were generated in the mouse VWF complementary DNA. The results of these various assays were consistent, although the magnitude of the effects were different: the gain-of-function (p.L1757A) variant showed consistent enhanced collagen binding whereas the loss-of-function mutants showed variable degrees of functional deficit. We further analyzed the impact of direct platelet-collagen binding by blocking glycoprotein VI (GPVI) and integrin α2β1 in our ferric chloride murine thrombosis model. The inhibition of GPVI demonstrated a comparable functional defect in thrombosis formation to the VWF−/− mice whereas α2β1 inhibition demonstrated a milder bleeding phenotype. Furthermore, a delayed and markedly reduced thrombogenic response was still evident in VWF−/−, GPVI, and α2β1 blocked animals, suggesting that alternative primary hemostatic mechanisms can partially rescue the bleeding phenotype associated with these defects. PMID:25051961

  1. Mechano-rheological properties of the murine thrombus determined via nanoindentation and finite element modeling.

    PubMed

    Slaboch, Constance L; Alber, Mark S; Rosen, Elliot D; Ovaert, Timothy C

    2012-06-01

    Deep vein thrombosis, pulmonary embolism, and abdominal aortic aneurysms are blood-related diseases that represent a major public health problem. These diseases are characterized by the formation of a thrombus (i.e., blood clot) that either blocks a major artery or causes an aortic rupture. Identifying the mechanical properties of thrombi can help determine when these incidents will occur. In this investigation, a murine thrombus, formed from platelet-rich plasma, calcium, and thrombin, was nanoindented and the elastic modulus was estimated via elastic contact theory. This information was used as input to an inverse finite element simulation, which determined optimal values for the elastic modulus and viscosity of the thrombus using a viscoelastic material model. A sensitivity analysis was also performed to determine which material parameters have the greatest affect on the simulation. Results from this investigation demonstrate the feasibility of the mechanical characterization of a murine thrombus using nanoindentation. PMID:22520420

  2. [Successful direct thrombin inhibitor treatment of a left atrial appendage thrombus developed under rivaroxaban therapy].

    PubMed

    Szegedi, Nándor; Gellér, László; Tahin, Tamás; Merkely, Béla; Széplaki, Gábor

    2016-01-24

    The authors present the history of a 62-year-old man on continuous rivaroxaban therapy who was scheduled for pulmonary vein isolation due to persistent atrial fibrillation. Preoperative transesophageal echocardiography detected the presence of left atrial appendage thrombus. Thrombophilia tests showed that the patient was heterozygous carrier of the methylene-tetrahydrofolate reductase gene mutation. The authors hypothesized that a direct thrombin inhibitor might exert a more appropriate effect against thrombosis in this case and, therefore, a switch to dabigatran was performed. After two months of anticoagulation with the direct thrombin inhibitor and folic acid supplementation the thrombus resolved. The authors underline that thrombus formation may develop in atrial fibrillation even if the patient is adequately treated with rivaroxaban. This case suggests, that methylene-tetrahydrofolate reductase gene mutation may modulate the efficacy of direct Xa factor inhibitors. According to this case history, dabigatran may be an effective therapeutic option in resolving established thrombus. PMID:26772828

  3. Acute formation of lumbar discal cyst: what is the mechanism?

    PubMed

    Aydin, S; Kucukyuruk, B; Yildirim, H; Abuzayed, B; Bozkus, H; Vural, M

    2010-12-01

    Lumbar discal cysts are extremely rare pathologies, with only few reports describing these lesions in the literature. Moreover, their definite pathogenesis is still unknown, with proposed theories based on radialogic and histologic findings. In this report, the authors present an acute formation of a discal cyst, which is reported for the first time. Also, we center our case on the discussion of the possible pathogenesis. Also, this is the first case of discal cyst reported in Turkey. A 67-year-old woman, whose complaints, and clinical and radiological findings demonstrated lumbar disc herniation with acute Modic 1 degererative changes of the adjacent end plates of L3-4 level. After medical and physical therapies, follow-up lumbar MRI has been taken to demonstrate a discal cyst formation on the adjacent intervertebral disc, showed cranially migrated cyst superior posterior on herniated disc, in 2 weeks period. The patient was treated by microsurgical resection of the cyst, and her complaints resolved completely. PMID:21423085

  4. Methods to Determine the Lagrangian Shear Experienced by Platelets during Thrombus Growth

    PubMed Central

    Pinar, Isaac P.; Arthur, Jane F.; Andrews, Robert K.; Gardiner, Elizabeth E.; Ryan, Kris; Carberry, Josie

    2015-01-01

    Platelets can become activated in response to changes in flow-induced shear; however, the underlying molecular mechanisms are not clearly understood. Here we present new techniques for experimentally measuring the flow-induced shear rate experienced by platelets prior to adhering to a thrombus. We examined the dynamics of blood flow around experimentally grown thrombus geometries using a novel combination of experimental (ex vivo) and numerical (in silico) methodologies. Using a microcapillary system, platelet aggregate formation was analysed at elevated shear rates in the presence of coagulation inhibitors, where thrombus formation is predominantly platelet-dependent. These approaches permit the resolution and quantification of thrombus parameters at the scale of individual platelets (2 μm) in order to quantify real time thrombus development. Using our new techniques we can correlate the shear rate experienced by platelets with the extent of platelet adhesion and aggregation. The techniques presented offer the unique capacity to determine the flow properties for a temporally evolving thrombus field in real time. PMID:26660525

  5. CD28 superagonist-mediated boost of regulatory T cells increases thrombo-inflammation and ischemic neurodegeneration during the acute phase of experimental stroke.

    PubMed

    Schuhmann, Michael K; Kraft, Peter; Stoll, Guido; Lorenz, Kristina; Meuth, Sven G; Wiendl, Heinz; Nieswandt, Bernhard; Sparwasser, Tim; Beyersdorf, Niklas; Kerkau, Thomas; Kleinschnitz, Christoph

    2015-01-01

    While the detrimental role of non-regulatory T cells in ischemic stroke is meanwhile unequivocally recognized, there are controversies about the properties of regulatory T cells (Treg). The aim of this study was to elucidate the role of Treg by applying superagonistic anti-CD28 antibody expansion of Treg. Stroke outcome, thrombus formation, and brain-infiltrating cells were determined on day 1 after transient middle cerebral artery occlusion. Antibody-mediated expansion of Treg enhanced stroke size and worsened functional outcome. Mechanistically, Treg increased thrombus formation in the cerebral microvasculature. These findings confirm that Treg promote thrombo-inflammatory lesion growth during the acute stage of ischemic stroke. PMID:25315859

  6. A thrombus susceptibility comparison of two pulsatile Penn State 50 cc left ventricular assist device designs.

    PubMed

    Navitsky, Michael A; Deutsch, Steven; Manning, Keefe B

    2013-01-01

    Left ventricular assist devices (LVADs) have proven successful as bridge to transplant devices for patients awaiting donor organs. While survival rates continue to increase, destination therapy remains hindered by thrombus formation within the device. Research has shown that thrombosis is correlated to the fluid dynamics within the device and may be a result of sustained shear rates below 500 s(-1) on the polyurethane blood sac used in the Penn State pulsatile LVAD. Particle image velocimetry is used to compare flow within two 50 cc LVAD designs to assess fluid patterns and quantify wall shear rates in regions known from in vivo studies to be susceptible to thrombus formation. The two designs differ in their front face geometry. The V-1 model has an outward-facing "dome" whereas the face of the V-2 model is flat. A thrombus susceptibility metric, which uses measured wall shear rates and exposure times, was applied to objectively compare pump designs over the entire cardiac cycle. For each design, there are regions where wall shear rates remained below 500 s(-1) for the entire cardiac cycle resulting in high thrombus susceptibility potential. Results of this study indicate that the V-2 device had an overall lower propensity for thrombus formation in the current region of interest. PMID:22825798

  7. A Thrombus Susceptibility Comparison of Two Pulsatile Penn State 50cc Left Ventricular Assist Device Designs

    PubMed Central

    Navitsky, Michael A.; Deutsch, Steven; Manning, Keefe B.

    2012-01-01

    Left ventricular assist devices (LVADs) have proven successful as bridge to transplant devices for patients awaiting donor organs. While survival rates continue to increase, destination therapy remains hindered by thrombus formation within the device. Research has shown that thrombosis is correlated to the fluid dynamics within the device and may be a result of sustained shear rates below 500 s−1 on the polyurethane blood sac used in the Penn State pulsatile LVAD. Particle image velocimetry is used to compare flow within two 50 cc LVAD designs to assess fluid patterns and quantify wall shear rates in regions known from in vivo studies to be susceptible to thrombus formation. The two designs differ in their front face geometry. The V-1 model has an outward facing “dome” whereas the face of the V-2 model is flat. A thrombus susceptibility metric, which uses measured wall shear rates and exposure times, was applied to objectively compare pump designs over the entire cardiac cycle. For each design, there are regions where wall shear rates remained below 500 s−1 for the entire cardiac cycle resulting in high thrombus susceptibility potential. Results of this study indicate that the V-2 device had an overall lower propensity for thrombus formation in the current region of interest. PMID:22825798

  8. Left ventricular thrombus associated with arteriovenous extra corporeal membrane oxygenation

    PubMed Central

    Makdisi, George; Hashmi, Zubair A.; Wozniak, Thomas C.

    2015-01-01

    Extra corporeal membrane oxygenation (ECMO) has remarkably progressed over the recent years. It has become an invaluable tool in the care of adults and pediatric patients with severe cardiogenic shock. At the initiation of ECMO support, the left ventricular contractility is profoundly impaired. Inadequate right ventricular drainage and bronchial circulation can lead to left ventricular distension, with potential deleterious consequences, ranging from inadequate myocardial rest, pulmonary edema, or intracardiac clot formation. Therefore, it is of extreme importance to ensure an adequate left ventricular drainage. Here we present a case of LV thrombus developed while the patient is on central venoarterial (VA) ECMO. PMID:26716054

  9. Left ventricular thrombus associated with arteriovenous extra corporeal membrane oxygenation.

    PubMed

    Makdisi, George; Hashmi, Zubair A; Wozniak, Thomas C; Wang, I-Wen

    2015-11-01

    Extra corporeal membrane oxygenation (ECMO) has remarkably progressed over the recent years. It has become an invaluable tool in the care of adults and pediatric patients with severe cardiogenic shock. At the initiation of ECMO support, the left ventricular contractility is profoundly impaired. Inadequate right ventricular drainage and bronchial circulation can lead to left ventricular distension, with potential deleterious consequences, ranging from inadequate myocardial rest, pulmonary edema, or intracardiac clot formation. Therefore, it is of extreme importance to ensure an adequate left ventricular drainage. Here we present a case of LV thrombus developed while the patient is on central venoarterial (VA) ECMO. PMID:26716054

  10. Flow residence time and regions of intraluminal thrombus deposition in intracranial aneurysms.

    PubMed

    Rayz, V L; Boussel, L; Ge, L; Leach, J R; Martin, A J; Lawton, M T; McCulloch, C; Saloner, D

    2010-10-01

    Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as "virtual ink" and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone. PMID:20499185

  11. Thrombus on Indwelling Central Venous Catheters: The Histopathology of 'Fibrin Sheaths'

    SciTech Connect

    Suojanen, James Norman; Brophy, David Paul; Nasser, Imad

    2000-03-15

    Purpose: Central venous catheters (CVC) may fail for many reasons, though 'fibrin sheaths' blocking catheter ports are usually implicated. We examined the sheaths removed from dialysis catheters to determine their histopathology.Methods: Ten catheter strippings were performed and the removed material was studied grossly and microscopically.Results: The histologic specimens showed thrombus both with and without a proteinaceous sheath.Conclusion: Dialysis catheters fail because of thrombus formation. This can occur in either the absence or presence of a protein coating on the catheter, the so-called 'fibrin sheath.'.

  12. Clinical Sequelae of Thrombus in an Inferior Vena Cava Filter

    SciTech Connect

    Ahmad, Iftikhar; Yeddula, Kalpana; Wicky, Stephan; Kalva, Sanjeeva P.

    2010-04-15

    The purpose of this study was to assess the long-term clinical sequelae of inferior vena cava (IVC) filter thrombus and the effect of anticoagulation on filter thrombus. Of 1,718 patients who had IVC filters placed during 2001-2008, 598 (34.8%) had follow-up abdominal CT. Filter thrombus was seen in 111 of the 598 (18.6%). There were 44 men (39.6%). The mean age at filter placement was 64 years. The medical diseases included cancer in 64, trauma in 15, stroke in 12, and others in 20. The frequency of filter thrombus on CT and asymptomatic filter thrombus on CT was calculated. The frequency of pulmonary embolism (PE) in patients with filter thrombus was calculated. The frequency of thrombus progression or regression (on CT, available in 56) was calculated. The effect of anticoagulation on filter thrombus regression/progression was evaluated using the Fisher exact test by comparing the group of patients who received anticoagulants versus those who did not. A P-value of <0.05 was considered significant. The overall frequency of filter thrombus was 18.6%. Total occlusion of the IVC filter was seen in 12 of 598 (2%). The filter thrombus was asymptomatic in 110 (18.3%). Filter thrombus was detected after a median of 35 days (range, 0-2082) following filter placement. Thrombus extended above the filter in 4 (3.6%); IVC thrombus below the filter was seen in 35(31.5%). Thrombus in the filter occluded <25% of the filter volume in 58 (52.3%), 25-50% in 21 (18.9%), and 50-75% in 20 (18%). Total IVC occlusion was seen in 12 (10.8%). Eighty-three patients received anticoagulation. Sixteen patients developed symptoms of PE. PE was confirmed on CT in 3 of 15 (2.7%). On follow-up, filter thrombus regressed completely in 19 (33.9%) after a median of 6 months. Filter thrombus decreased in size in 13 (23.2%) and it progressed without IVC occlusion in 7 (12.6%). In one (1.7%), filter thrombus progressed to IVC occlusion. Filter thrombus remained stable in 16 (28.6%). There was no

  13. Left ventricular mass: Myxoma or thrombus?

    PubMed Central

    Raut, Monish S.; Maheshwari, Arun; Dubey, Sumir; Joshi, Sandip

    2015-01-01

    Patient with embolic episode should always be evaluated for cardiac mass. Mass in left ventricular can be a myxoma or thrombus even in a normal functioning heart. In either case, mobile mass with embolic potential should be surgically resected. PMID:25566719

  14. A Treatment Case of Endoscopic Removal of Left Ventricular Thrombus, During Coronary Artery Bypass Graft

    PubMed Central

    Park, Hyun-Seok; Ryu, Se-Min; Cho, Seong-Joon; Park, Sung-Min; Lim, Sun-Hye

    2014-01-01

    Left ventricular thrombus is a common complication related to acute myocardial infarction. Removing this with an incision of the free wall of the left ventricle may cause fatal cardiac dysfunction or arrhythmias. Furthermore, performing incision and suture on the fragile myocardium of an acute myocardial infarction patient may cause serious bleeding complications. If there is a patient with left ventricular thrombus who needs thoracotomy for another reason, the case is attempted with the thought that if effective intraventricular visualization and manipulation can be done, fatalities caused by incision and suture may be reduced. For patients undergoing cardiopulmonary bypass, if intracardiac manipulation is required, an endoscope can be used, and given the potential complications after the incision and suturing of the infarcted tissue, the benefits are deemed sufficient. PMID:25207261

  15. A Thrombus Generation Model Applied to Aneurysms Treated with Shape Memory Polymer Foam and Metal Coils

    NASA Astrophysics Data System (ADS)

    Horn, John; Ortega, Jason; Hartman, Jonathan; Maitland, Duncan

    2015-11-01

    To prevent their rupture, intracranial aneurysms are often treated with endovascular metal coils which fill the aneurysm sac and isolate it from the arterial flow. Despite its widespread use, this method can result in suboptimal outcomes leading to aneurysm recurrence. Recently, shape memory polymer foam has been proposed as an alternative aneurysm filler. In this work, a computational model has been developed to predict thrombus formation in blood in response to such cardiovascular implantable devices. The model couples biofluid and biochemical phenomena present as the blood interacts with a device and stimulates thrombus formation. This model is applied to simulations of both metal coil and shape memory polymer foam treatments within an idealized 2D aneurysm geometry. Using the predicted thrombus responses, the performance of these treatments is evaluated and compared. The results suggest that foam-treated aneurysms may fill more quickly and more completely with thrombus than coil-filled aneurysms, potentially leading to improved long-term aneurysm healing. This work was performed in part under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  16. Thrombus in Transit through Patent Foramen Ovale.

    PubMed

    Baydoun, Hassan; Barakat, Iskander; Hatem, Elie; Chalhoub, Michel; Mroueh, Ali

    2013-01-01

    A thrombus in transit through a patent foramen ovale (PFO) with impending paradoxical embolism is an extremely rare event. Due to its transient nature, it is unable to identify the thrombus, and most of the cases have been reported at autopsy. We are reporting a case of thrombus straddling the foramen ovale which was diagnosed by echocardiography and treated surgically. Through this personal case, an exhaustive review of the literature was performed. There were 88 cases reported. We concluded that there is no medical consensus about the best option for treatment. Nevertheless, surgery, which is associated with fewer complications of recurrent embolic events than those of thrombolysis and anticoagulation, appeared to be the best approach in patients who are not at a high surgical risk. Anticoagulant treatment appears to be an acceptable therapeutic alternative to surgery, particularly in patients with comorbidities who are at high surgical risk and for patients with small PFO. Thrombolysis is linked to the highest mortality, which could be explained by the severity of the patient's initial presentation. In conclusion, and after the cumulative effects of these case reports, we propose a diagram consisting of the use of the three therapeutic options in the different clinical scenarios. PMID:24826281

  17. Thrombus in Transit through Patent Foramen Ovale

    PubMed Central

    Barakat, Iskander; Chalhoub, Michel

    2013-01-01

    A thrombus in transit through a patent foramen ovale (PFO) with impending paradoxical embolism is an extremely rare event. Due to its transient nature, it is unable to identify the thrombus, and most of the cases have been reported at autopsy. We are reporting a case of thrombus straddling the foramen ovale which was diagnosed by echocardiography and treated surgically. Through this personal case, an exhaustive review of the literature was performed. There were 88 cases reported. We concluded that there is no medical consensus about the best option for treatment. Nevertheless, surgery, which is associated with fewer complications of recurrent embolic events than those of thrombolysis and anticoagulation, appeared to be the best approach in patients who are not at a high surgical risk. Anticoagulant treatment appears to be an acceptable therapeutic alternative to surgery, particularly in patients with comorbidities who are at high surgical risk and for patients with small PFO. Thrombolysis is linked to the highest mortality, which could be explained by the severity of the patient's initial presentation. In conclusion, and after the cumulative effects of these case reports, we propose a diagram consisting of the use of the three therapeutic options in the different clinical scenarios. PMID:24826281

  18. Thrombus entrapped by patent foramen ovale in a patient with pulmonary embolism: a case report

    PubMed Central

    Nam, Sang Beom; Kim, Chan Mi; Cho, Sung-Ah; Chung, Sungchan

    2015-01-01

    Thrombus-in-transit appears to increase the risk of mortality compared to pulmonary embolism alone and can require alteration in therapeutic plan. We present the case of a biatrial thromboembolus caught in transit across a patent foramen ovale diagnosed by intraoperative transesophageal echocardiogram in a 69-year-old female with acute pulmonary embolism and subsequent acute cerebral infarction. We suggest that echocardiography should be performed in a patient with suspected pulmonary thromboembolism to evaluate right heart function and diagnose emboli in transit. PMID:25664158

  19. Thrombus entrapped in patent foramen ovale: a rare form of thrombus in transit

    PubMed Central

    Bakhshi, Hooman; Meyghani, Zahra; Shakir, Zaid; Chen, Alexander; Kershner, Dawn

    2015-01-01

    In rare cases, thrombus in transit can be entrapped in a patent foramen ovale (PFO). A patient with this condition is at high risk of embolic stroke and death. Early diagnosis and treatment is essential to help prevent stroke and death in these cases. There is no universal management guideline for this rare condition. The decision between medical versus surgical treatment should be made individually for each patient. We present a case of thrombus in transit entrapped in a PFO that was treated medically by lifelong anticoagulation. PMID:26333859

  20. [A Case of Carotid Free-Floating Thrombus Treated by Carotid Ultrasonography-Guided Endovascular Approach].

    PubMed

    Otawa, Masato; Kinkori, Takeshi; Watanabe, Kenichi; Ando, Ryo; Tambara, Masao; Arima, Toru

    2016-06-01

    We experienced a case of carotid free-floating thrombus treated by carotid ultrasonography-guided endovascular approach. A 63-year-old man was brought to our hospital with the chief complaint of sudden onset left hemiplegia. MRI revealed acute infarction of the right MCA territory due to the right M1 occlusion. Carotid ultrasonography showed a pedunculated, polypoid mobile plaque floating with the cardiac beat. We attempted ultrasonography-guided endovascular treatment. Under proximal balloon protection, the floating plaque was successfully aspirated into the Penumbra aspiration catheter. Carotid stent was also placed to stabilize the residual pedicle of the plaque. Aspirated plaque was identified as fresh thrombus by pathological examination. Carotid ultrasonography-guided endovascular approach was effective for getting the picture of real-time dynamics of the carotid FFT. PMID:27270147

  1. A woman with cystic fibrosis, severe hypoxaemia, an atrial thrombus and a patent foramen ovale: a case report

    PubMed Central

    2009-01-01

    Introduction Cystic fibrosis is usually associated with chronic pulmonary sepsis and frequent infective exacerbations. We report a very unusual cause of severe hypoxaemia in a woman with cystic fibrosis caused by thrombus formation in the right atrium. Case presentation A 21-year-old Caucasian woman with cystic fibrosis and a totally implantable venous access device presented with severe hypoxaemia. This was initially treated with antibiotics but her oxygen levels did not improve significantly. Subsequently, a transient ischaemic attack occurred. Further investigations, including a contrast echocardiogram and a cardiac magnetic resonance scan, revealed the presence of a large right atrial thrombus and right-to-left intracardiac shunt through a patent foramen ovale. Conclusion This case highlights the need to consider a right-to-left shunt in chronic respiratory diseases when hypoxaemia is out of proportion to the degree of lung function impairment. Totally implantable venous access devices should always be considered as a source of thrombus formation. PMID:19830232

  2. Ultrasound Detection of Superior Vena Cava Thrombus

    PubMed Central

    Birch, Aaron; Um, David; Laselle, Brooks

    2014-01-01

    Superior vena cava (SVC) syndrome is most commonly the insidious result of decreased vascular flow through the SVC due to malignancy, spontaneous thrombus, infections, and iatrogenic etiologies. Clinical suspicion usually leads to computed tomography to confirm the diagnosis. However, when a patient in respiratory distress requires emergent airway management, travel outside the emergency department is not ideal. With the growing implementation of point-of-care ultrasound (POCUS), clinicians may make critical diagnoses rapidly and safely. We present a case of SVC syndrome due to extensive thrombosis of the deep venous system cephalad to the SVC diagnosed by POCUS. PMID:25247051

  3. The role of neovascularisation in the resolution of venous thrombus.

    PubMed

    Modarai, Bijan; Burnand, Kevin Guiver; Humphries, Julia; Waltham, Matthew; Smith, Alberto

    2005-05-01

    Deep vein thrombosis (DVT) can give rise to chronic debilitating complications, which are expensive to treat. Anticoagulation, the standard therapy for DVT, prevents propagation, but does not remove the existing thrombus, which undergoes slow natural resolution. Alternative forms of treatment that accelerate resolution may arise from a better understanding of the cellular and molecular pathways that regulate the natural resolution of thrombi. This review will outline our current understanding of the mechanisms of thrombus resolution and the role of neovascularisation in this process. Novel experimental treatments that may one day find clinical use are also discussed. The process of thrombus resolution resembles wound healing. The mainly monocytic inflammatory infiltrate, which develops, is associated with the appearance of vascular channels. These cells may drive resolution by encouraging angiogenesis, which contributes to restoration of the vein lumen. Significant numbers of bone marrow-derived progenitor cells have also been found in naturally resolving thrombi, but their precise phenotype and their role in thrombus recanalisation is unclear. Enhanced thrombus neovascularisation and rapid vein recanalisation have been achieved in experimental models with proangiogenic agents. Recent reports of the role of bone marrow-derived progenitor cells in the revascularisation of ischaemic tissues suggest that it may be possible to obtain the same effect by delivering pluripotent or lineage specific stem cells into thrombus. These cells could contribute to thrombus recanalisation by expressing a variety of proangiogenic cytokines or by lining the new vessels that appear within the thrombus. PMID:15886791

  4. Lymphoedema caused by idiopathic lymphatic thrombus.

    PubMed

    Hara, Hisako; Mihara, Makoto; Seki, Yukio; Koshima, Isao

    2013-12-01

    Primary lymphoedema includes some diseases whose genetic anomaly is detected and others whose pathology is unknown. In this article, we report a lymphatic thrombus found in a limb with lymphoedema during lymphatico-venous anastomosis (LVA). A 32-year-old man was aware of oedema in his left calcar pedis 3 years previously, which appeared without any trigger. Indocyanine green lymphography indicated lymphatic stasis in the left calf and thigh region, and we performed LVA for the patient. During the operation, we found yellow vessels, which were thought to be lymphatic vessels filled with a yellow solid substance, just beneath the superficial fascia at the left ankle. Pathological examination of the thrombi revealed hyaline material mixed with cell components. The cells were categorised as lymphatic endothelial cells, as they were positive for podoplanin. There was no evidence of malignancy. Causes of idiopathic lymphatic thrombus such as this may be one of the causes of so-called primary lymphoedema, and evaluation of such cases may be the first step towards elucidating the mechanisms involved in the development of primary lymphoedema. PMID:23643778

  5. Acute Cytomegalovirus Infection as a Cause of Venous Thromboembolism

    PubMed Central

    Rinaldi, Francesca; Lissandrin, Raffaella; Mojoli, Francesco; Baldanti, Fausto; Brunetti, Enrico; Pascarella, Michela; Giordani, Maria Teresa

    2014-01-01

    Acute Human Cytomegalovirus (HCMV) infection is an unusual cause of venous thromboembolism, a potentially life-threatening condition. Thrombus formation can occur at the onset of the disease or later during the recovery and may also occur in the absence of acute HCMV hepatitis. It is likely due to both vascular endothelium damage caused by HCMV and impairment of the clotting balance caused by the virus itself. Here we report on two immunocompetent women with splanchnic thrombosis that occurred during the course of acute HCMV infection. Although the prevalence of venous thrombosis in patients with acute HCMV infection is unknown, physicians should be aware of its occurrence, particularly in immunocompetent patients presenting with fever and unexplained abdominal pain. PMID:24959338

  6. Magnetic resonance venography to assess thrombus resolution with edoxaban monotherapy versus parenteral anticoagulation/warfarin for symptomatic deep vein thrombosis: A multicenter feasibility study

    PubMed Central

    Piazza, Gregory; Mani, Venkatesh; Goldhaber, Samuel Z; Grosso, Michael A; Mercuri, Michele; Lanz, Hans J; Schussler, Steven; Hsu, Ching; Chinigo, Amy; Ritchie, Bruce; Nadar, Venkatesh; Cannon, Kevin; Pullman, John; Concha, Mauricio; Schul, Marlin; Fayad, Zahi A

    2016-01-01

    The feasibility of magnetic resonance venography (MRV) for measuring change in thrombus volume with a novel anticoagulation regimen versus standard anticoagulation in patients with symptomatic deep vein thrombosis (DVT) has not been assessed. Our aim was to study the feasibility of MRV to measure change in thrombus volume in patients with acute symptomatic objectively confirmed proximal DVT in an open-label multicenter trial (edoxaban Thrombus Reduction Imaging Study, eTRIS). We randomized patients in a 2:1 allocation ratio to edoxaban 90 mg/day for 10 days followed by 60 mg/day versus parenteral anticoagulation bridging to warfarin for 3 months. The primary efficacy outcome was a surrogate end point of the relative change in MRV-quantified thrombus volume from baseline to Day 14–21. A total of 85 eligible patients from 26 study sites were randomized to edoxaban monotherapy (n=56) versus parenteral anticoagulation as a ‘bridge’ to warfarin (n=29). The mean relative change in MRV-quantified thrombus volume from baseline to Day 14–21 was similar in patients treated with edoxaban and parenteral anticoagulation as a ‘bridge’ to warfarin (−50.1% vs −58.9%; 95% confidence interval of treatment difference, −12.7%, 30.2%). However, thrombus extension was observed in eight patients in the edoxaban monotherapy group and in none in the warfarin group. Rates of recurrent venous thromboembolism (3.6% vs 3.6%, p=0.45) and clinically relevant non-major bleeding (5.4% vs 7.1%, p=0.34) were also similar. No major bleeds occurred in either on-treatment group during the study period. In conclusion, MRV can assess change in thrombus volume in patients with acute DVT randomized to two different anticoagulant regimens. ClinicalTrials.gov Identifier: NCT01662908 Investigational New Drug (IND) Application: Edoxaban IND # 63266 PMID:27165711

  7. Magnetic resonance venography to assess thrombus resolution with edoxaban monotherapy versus parenteral anticoagulation/warfarin for symptomatic deep vein thrombosis: A multicenter feasibility study.

    PubMed

    Piazza, Gregory; Mani, Venkatesh; Goldhaber, Samuel Z; Grosso, Michael A; Mercuri, Michele; Lanz, Hans J; Schussler, Steven; Hsu, Ching; Chinigo, Amy; Ritchie, Bruce; Nadar, Venkatesh; Cannon, Kevin; Pullman, John; Concha, Mauricio; Schul, Marlin; Fayad, Zahi A

    2016-08-01

    The feasibility of magnetic resonance venography (MRV) for measuring change in thrombus volume with a novel anticoagulation regimen versus standard anticoagulation in patients with symptomatic deep vein thrombosis (DVT) has not been assessed. Our aim was to study the feasibility of MRV to measure change in thrombus volume in patients with acute symptomatic objectively confirmed proximal DVT in an open-label multicenter trial (edoxaban Thrombus Reduction Imaging Study, eTRIS). We randomized patients in a 2:1 allocation ratio to edoxaban 90 mg/day for 10 days followed by 60 mg/day versus parenteral anticoagulation bridging to warfarin for 3 months. The primary efficacy outcome was a surrogate end point of the relative change in MRV-quantified thrombus volume from baseline to Day 14-21. A total of 85 eligible patients from 26 study sites were randomized to edoxaban monotherapy (n=56) versus parenteral anticoagulation as a 'bridge' to warfarin (n=29). The mean relative change in MRV-quantified thrombus volume from baseline to Day 14-21 was similar in patients treated with edoxaban and parenteral anticoagulation as a 'bridge' to warfarin (-50.1% vs -58.9%; 95% confidence interval of treatment difference, -12.7%, 30.2%). However, thrombus extension was observed in eight patients in the edoxaban monotherapy group and in none in the warfarin group. Rates of recurrent venous thromboembolism (3.6% vs 3.6%, p=0.45) and clinically relevant non-major bleeding (5.4% vs 7.1%, p=0.34) were also similar. No major bleeds occurred in either on-treatment group during the study period. In conclusion, MRV can assess change in thrombus volume in patients with acute DVT randomized to two different anticoagulant regimens.ClinicalTrials.gov IDENTIFIER NCT01662908: INVESTIGATIONAL NEW DRUG IND APPLICATION EDOXABAN IND # 63266. PMID:27165711

  8. Increased Epicardial Adipose Tissue Thickness is Associated With Angiographic Thrombus Burden in the Patients With Non-ST-Segment Elevation Myocardial Infarction.

    PubMed

    Bakirci, Eftal Murat; Degirmenci, Husnu; Duman, Hakan; Inci, Sinan; Hamur, Hikmet; Buyuklu, Mutlu; Ceyhun, Gokhan; Topal, Ergun

    2015-10-01

    We aimed to evaluate the relation among epicardial adipose tissue (EAT) thickness, angiographic presence of thrombus, and the no-reflow in the patients with non-ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. The study population consisted of 229 patients. The EAT thickness and neutrophil to lymphocyte ratio (NLR) were significantly higher in the patients with coronary thrombus than in those without coronary thrombus (6.1 ± 1.1 vs 5.1 ± 1.3 mm, P < .001 and 3.4 ± 0.9 vs 2.5 ± 0.7, P < .001, respectively) and in the patients with no-reflow compared to patients with reflow. The EAT thickness was found to be correlated positively with the degree of the thrombus burden, NLR, and waist circumference and negatively with high-density lipoprotein cholesterol. Multivariate logistic regression analysis demonstrated that EAT thickness and NLR independently predicted coronary thrombus formation and no-reflow. We have suggested that EAT can play an important role in the pathophysiology of coronary thrombus formation and the no-reflow. PMID:25381157

  9. [A specific rosette formation method in assessing the immunological status of acute leukemia patients].

    PubMed

    Moroz, I A

    1985-01-01

    The paper deals with the evaluation of immunologic vigor in 88 patients suffering acute lymphoblastic leukemia. It involved a modified test of specific rosette formation of blood-circulating lymphocytes and those of the bone marrow with erythrocytes bearing leukemia cell extracts. The highest levels of rosette-forming lymphocytes were registered in the acute period prior to treatment and in recurrence. The said levels decreased gradually following chemoimmunotherapy, falling to nil in complete remission. Patients in whom the treatment had failed revealed no changes in lymphocyte response. The control group (healthy subjects and cases of nonmalignant hematologic pathology) showed levels of rosette-forming lymphocytes similar to those in acute lymphoblastic leukemia patients in remission. PMID:3861026

  10. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case.

    PubMed

    Ray, Sukanta; Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-08-01

    Valproic acid is the most widely used anti-epilep-tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up. PMID:26366333

  11. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case

    PubMed Central

    Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-01-01

    Valproic acid is the most widely used anti-epilep­tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up. PMID:26366333

  12. Talking therapy groups on acute psychiatric wards: patients' experience of two structured group formats

    PubMed Central

    Radcliffe, Jonathan; Bird, Laura

    2016-01-01

    Aims and method We report the results of a clinical audit of patients' reactions to two types of talking therapy groups facilitated by assistant psychologists and psychology graduates on three acute wards. Patients' experiences of problem-solving and interpersonal group formats were explored via focus groups and structured interviews with 29 group participants. Results Both group formats generated high satisfaction ratings, with benefits related mostly to generic factors. Clinical implications Adequately trained and supported assistant psychologists and psychology graduates can provide supportive talking groups that patients find helpful. PMID:27512586

  13. Talking therapy groups on acute psychiatric wards: patients' experience of two structured group formats.

    PubMed

    Radcliffe, Jonathan; Bird, Laura

    2016-08-01

    Aims and method We report the results of a clinical audit of patients' reactions to two types of talking therapy groups facilitated by assistant psychologists and psychology graduates on three acute wards. Patients' experiences of problem-solving and interpersonal group formats were explored via focus groups and structured interviews with 29 group participants. Results Both group formats generated high satisfaction ratings, with benefits related mostly to generic factors. Clinical implications Adequately trained and supported assistant psychologists and psychology graduates can provide supportive talking groups that patients find helpful. PMID:27512586

  14. Retrievable Vena Cava Filters in Major Trauma Patients: Prevalence of Thrombus Within the Filter

    SciTech Connect

    Mahrer, Arie; Zippel, Douglas; Garniek, Alexander; Golan, Gil; Bensaid, Paul; Simon, Daniel; Rimon, Uri

    2008-07-15

    The purpose of this study was to report the prevalence of thrombus within a retrievable vena cava filter inserted prophylactically in major trauma patients referred for filter extraction. Between November 2002 and August 2005, 80 retrievable inferior vena cava filters (68 Optease and 12 Gunther-Tulip) were inserted into critically injured trauma patients (mean injury severity score 33.5). The filters were inserted within 1 to 6 (mean 2) days of injury. Thirty-seven patients were referred for filter removal (32 with Optease and 5 with Gunther-Tulip). The indwelling time was 7 to 22 (mean 13) days. All patients underwent inferior vena cavography prior to filter removal. There were no insertion-related complications and all filters were successfully deployed. Forty-three (54%) of the 80 patients were not referred for filter removal, as these patients continued to have contraindications to anticoagulation. Thirty-seven patients (46%) were referred for filter removal. In eight of them (22%) a large thrombus was seen within the filters and they were left in place, all with the Optease device. The other 29 filters (36%) were removed uneventfully.We conclude that the relatively high prevalence of intrafilter thrombi with the Optease filter may be explained by either spontaneous thrombus formation or captured emboli.

  15. Acute effects of Solanum malacoxylon on bone formation rates in growing rats.

    PubMed

    Norrdin, R W; de Barros, C S; Queille, M L; Carré, M; Miravet, L

    1979-11-01

    The plant Solanum malacoxylon is responsible for a syndrome of hypercalcemia, soft tissue mineralization, and progressive wasting in South American cattle known as enteque seco or espichamento. There is evidence that a glycoside of 1,25-dihydroxycholecalciferol is the active principle in the plant. The basis for the hyperostosis seen in the disease is unclear. To study the acute effects on bone formation rates, 8-week-old rats were given an aqueous extract equivalent to 250 or 1000 mg of Solanum daily per os for 7 days. Bones were labeled by injection of fluochrome 2 days before the start of treatment and 2 days prior to sacrifice. Morphometric evaluation of undecalcified sections of caudal vertebrae revealed an increased amount of trabecular bone in both Solanum treated groups with no difference due to dose level. This was associated with an increase in the bone apposition rate on trabecular surfaces. No differences were found in the amount of osteoid seam width. Periosteal apposition rate and endochondral bone formation were also measured and no significant differences found. The findings indicate that acute stimulation of cell level bone formation on trabecular surfaces may play a role in the hyperostosis seen in the naturally occurring condition. PMID:116737

  16. Declotting a Thrombosed Brescia-Cimino Fistula by Manual Catheter-Directed Aspiration of the Thrombus

    SciTech Connect

    Turmel-Rodrigues, Luc A E-mail: cim.stgatien@wanadoo.fr

    2005-01-15

    Acute thrombosis of native fistulae for hemodialysis occurs more rarely than for prosthetic grafts. The vascular access should be reopened as soon as possible in order to resume regular dialysis and to avoid resorting to a temporary central line. Manual aspiration is one of the numerous methods described in this setting. Clinical examination is essential to rule out local infection, which is the only serious contraindication to percutaneous maneuvers. Two introducer-sheaths are placed in a criss-cross fashion in order to gain access to the venous outflow and to the anastomosis. Access to the venous outflow is performed first in order to check the proximal extent of the thrombosis. Heparin and antibiotics are injected systemically. A similar maneuver is then performed in the direction of the anastomosis. The aspiration phase is then initiated. A 7-9 Fr aspiration catheter is pushed through the 'venous' introducer. Manual aspiration is created through a 50 ml syringe while the catheter is progressively removed with back and forth movements. The catheter and the contents of the syringe are flushed through a gauze on the working table to evaluate the amount of thrombus which has been removed and the maneuver is repeated as often as necessary to remove all the thrombus. Once all the clots located downstream from the venous introducer have been removed, any unmasked underlying stenosis is NOT dilated at this stage since it provides protection against major embolism coming from the inflow. The aspiration catheter is then pushed through the 'arterial' introducer down to the anastomosis in order to aspirate the thrombus located between the tip of the introducer and the anastomosis. Dilatation of unmasked stenoses is finally performed using high-pressure balloons. The holes made by the two introducers are closed using a U-shaped suture with interposition of a short piece of plastic and the patient is sent back to the nephrologists for dialysis.

  17. A microstructurally inspired damage model for early venous thrombus.

    PubMed

    Rausch, Manuel K; Humphrey, Jay D

    2015-03-01

    Accumulative damage may be an important contributor to many cases of thrombotic disease progression. Thus, a complete understanding of the pathological role of thrombus requires an understanding of its mechanics and in particular mechanical consequences of damage. In the current study, we introduce a novel microstructurally inspired constitutive model for thrombus that considers a non-uniform distribution of microstructural fibers at various crimp levels and employs one of the distribution parameters to incorporate stretch-driven damage on the microscopic level. To demonstrate its ability to represent the mechanical behavior of thrombus, including a recently reported Mullins type damage phenomenon, we fit our model to uniaxial tensile test data of early venous thrombus. Our model shows an agreement with these data comparable to previous models for damage in elastomers with the added advantages of a microstructural basis and fewer model parameters. We submit that our novel approach marks another important step toward modeling the evolving mechanics of intraluminal thrombus, specifically its damage, and hope it will aid in the study of physiological and pathological thrombotic events. PMID:26523784

  18. Atrial Thrombus in a Neonate: A Diagnostic Challenge.

    PubMed

    Sheen, Alicia; De Oliveira, Elizabeth R; Kim, Richard W; Parham, David; Lakshmanan, Ashwini

    2015-04-01

    Introduction Left atrial thrombus is a rare finding in a neonate. In the previous literature, atrial thrombi have been associated with catheter placement or congenital heart disease in a preterm infant. Case We report the case of a full-term neonate with no known risk factors found to have a left atrial thrombus. The neonate was born at 38 weeks' gestation to a 31-year-old female via cesarean section who was sent to the normal nursery. On postnatal day 5, the infant was noted to have low-to-medium level of oxygen saturations (∼90%) and was transferred to the neonatal intensive care unit with an echocardiogram completed on postnatal day 6 demonstrating a mobile, pedunculated mass attached to the left atrial septum with an appearance concerning for atrial myxoma. The infant underwent surgical resection on postnatal day 8 and pathology revealed the mass to be a left atrial thrombus. Discussion The rare finding of an atrial thrombus in a neonate has previously been associated with central venous catheter placement or congenital heart disease. This case is unusual in that the patient had neither condition. Although echocardiogram findings appeared more consistent with atrial myxoma, final pathology revealed a left atrial thrombus. Additionally, hypercoagulability work-up for this neonate was largely negative. This report underscores the importance of identification, search for etiology, and prompt therapy to prevent potential catastrophic outcomes. PMID:26199791

  19. A persistent sciatic artery aneurysm containing a free-floating thrombus: report of a case.

    PubMed

    Unosawa, Satoshi; Ishii, Yusuke; Niino, Tetsuya

    2015-08-01

    A persistent sciatic artery is a rare vascular anomaly in which the sciatic artery, which involutes in the embryonic stage, persists as the blood supply to the lower limb. This vascular anomaly is often associated with aneurysm formation. A persistent sciatic artery aneurysm is a rare cause of peripheral arterial embolic disease. We herein describe the case of a 72-year-old female with a free-floating thrombus in a persistent sciatic artery aneurysm. She underwent iliac-popliteal artery bypass and exclusion of the aneurysm to prevent an embolic event. PMID:25016369

  20. Thrombus Aspirated from Patients with ST-Elevation Myocardial Infarction: Association between 3-Nitrotyrosine and Inflammatory Markers - Insights from ARTERIA Study

    PubMed Central

    Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Consuegra-Sanchez, Luciano; Avanzas, Pablo; Sanchez-Grande, Alejandro; Conesa-Zamora, Pablo

    2016-01-01

    Recent studies have demonstrated that inflammatory cells are a component that plays a role in thrombus formation in ST-elevation myocardial infarction (STEMI). 3-nitrotyrosine (3-NO2-Tyr), a specific marker for protein modification by nitric oxide-derived oxidants, is increased in human atherosclerotic lesions. The purpose of this study was to determine the possible association of inflammatory markers of coronary thrombi with nitroxidative stress. Intracoronary thrombus (n=51) and blood from the systemic circulation were obtained by thromboaspiration in 138 consecutive STEMI patients presenting for primary percutaneous coronary intervention (PCI). Each blood and intracoronary thrombus were measured simultaneously the following biomarkers: C-reactive protein (CRP), 3-NO2-Tyr, soluble CD 40 ligand (sCD40L), vascular cellular adhesion molecule-1 (VCAM-1) and haemoglobin content (only in coronary thrombus). Time delay in minutes from symptom onset to PCI was 244 ± 324. Serum CRP was positively correlated to CRP content in the thrombus (r= 0.395; p = 0.02) and serum sCD40L was negatively correlated to sCD40L in the thrombus (r= -0.394; p = 0.02). Patients were divided into tertiles according to thrombi 3-NO2-Tyr concentration: 1sttertile (<0.146ng/mg), 2ndtertile (0.146-0.485ng/mg) and 3rdtertile (>0.485ng/mg). Thus, thrombus in the highest tertile had significantly higher levels of CRP (p=0.002), VCAM-1 (p=0.003) and haemoglobin (p=0.002). In conclusion, the present study demonstrated that coronary thrombi with higher levels of 3-NO2-Tyr content often contain more inflammatory markers which could have a direct impact on the efficacy of drugs or devices used for coronary reperfusion. PMID:27429583

  1. Thrombus Aspirated from Patients with ST-Elevation Myocardial Infarction: Association between 3-Nitrotyrosine and Inflammatory Markers - Insights from ARTERIA Study.

    PubMed

    Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Consuegra-Sanchez, Luciano; Avanzas, Pablo; Sanchez-Grande, Alejandro; Conesa-Zamora, Pablo

    2016-01-01

    Recent studies have demonstrated that inflammatory cells are a component that plays a role in thrombus formation in ST-elevation myocardial infarction (STEMI). 3-nitrotyrosine (3-NO2-Tyr), a specific marker for protein modification by nitric oxide-derived oxidants, is increased in human atherosclerotic lesions. The purpose of this study was to determine the possible association of inflammatory markers of coronary thrombi with nitroxidative stress. Intracoronary thrombus (n=51) and blood from the systemic circulation were obtained by thromboaspiration in 138 consecutive STEMI patients presenting for primary percutaneous coronary intervention (PCI). Each blood and intracoronary thrombus were measured simultaneously the following biomarkers: C-reactive protein (CRP), 3-NO2-Tyr, soluble CD 40 ligand (sCD40L), vascular cellular adhesion molecule-1 (VCAM-1) and haemoglobin content (only in coronary thrombus). Time delay in minutes from symptom onset to PCI was 244 ± 324. Serum CRP was positively correlated to CRP content in the thrombus (r= 0.395; p = 0.02) and serum sCD40L was negatively correlated to sCD40L in the thrombus (r= -0.394; p = 0.02). Patients were divided into tertiles according to thrombi 3-NO2-Tyr concentration: 1(st)tertile (<0.146ng/mg), 2(nd)tertile (0.146-0.485ng/mg) and 3(rd)tertile (>0.485ng/mg). Thus, thrombus in the highest tertile had significantly higher levels of CRP (p=0.002), VCAM-1 (p=0.003) and haemoglobin (p=0.002). In conclusion, the present study demonstrated that coronary thrombi with higher levels of 3-NO2-Tyr content often contain more inflammatory markers which could have a direct impact on the efficacy of drugs or devices used for coronary reperfusion. PMID:27429583

  2. Par4 is required for platelet thrombus propagation but not fibrin generation in a mouse model of thrombosis

    PubMed Central

    Vandendries, Erik R.; Hamilton, Justin R.; Coughlin, Shaun R.; Furie, Bruce; Furie, Barbara C.

    2007-01-01

    Thrombin, a central mediator of hemostasis and thrombosis, converts fibrinogen to fibrin and is a potent platelet activator. Activated platelets provide a surface for assembly of the tenase and prothrombinase complexes required for thrombin generation. The role of thrombin-induced platelet activation in platelet accumulation and its interplay with fibrin deposition during thrombus assembly has not been fully defined. We studied these processes during laser-induced thrombus formation by using real-time digital fluorescence microscopy in mice lacking protease-activated receptor-4 (Par4), which is necessary for thrombin responsiveness in mouse platelets. Juxtamural platelet accumulation immediately after laser injury was not different in wild-type and Par4−/− mice. However, subsequent growth of platelet thrombi was markedly diminished in Par4−/− mice. At the time of maximal thrombus size in wild type, platelet accumulation was more than 10-fold higher in wild type than in Par4−/− mice. P-selectin expression, a marker of platelet activation, was reduced and delayed in Par4−/− thrombi. In contrast to platelet activation and accumulation, the rate and amount of fibrin deposition, predominantly intramural and juxtamural in this model, were indistinguishable in Par4−/− and wild-type mice. These results suggest that platelet activation by thrombin is necessary for normal propagation of a platelet thrombus at a distance from the injured vessel wall and hence for normal thrombus growth. However, platelet activation by thrombin is unnecessary for initial and limited accumulation of platelets at or near the vessel wall, and this limited accumulation of platelets and/or platelet-independent mechanism(s) of thrombin generation are sufficient for normal fibrin deposition in this model. PMID:17190826

  3. Synthetic thrombus model for in vitro studies of laser thrombolysis

    SciTech Connect

    Hermes, R.E.; Trajkovska, K.

    1998-07-01

    Laser thrombolysis is the controlled ablation of a thrombus (blood clot) blockage in a living arterial system. Theoretical modeling of the interaction of laser light with thrombi relies on the ability to perform in vitro experiments with well characterized surrogate materials. A synthetic thrombus formulation may offer more accurate results when compared to in vivo clinical experiments. The authors describe the development of new surrogate materials based on formulations incorporating chick egg, guar gum, modified food starch, and a laser light absorbing dye. The sound speed and physical consistency of the materials were very close to porcine (arterial) and human (venous) thrombi. Photographic and videotape recordings of pulsed dye laser ablation experiments under various experimental conditions were used to evaluate the new material as compared to in vitro tests with human (venous) thrombus. The characteristics of ablation and mass removal were similar to that of real thrombi, and therefore provide a more realistic model for in vitro laser thrombolysis when compared to gelatin.

  4. Advances in our understanding of mechanisms of venous thrombus resolution.

    PubMed

    Altmann, Johanna; Sharma, Smriti; Lang, Irene M

    2016-01-01

    Traditionally, venous thrombosis has been seen as the consequence of a regulated cascade of proteolytic steps leading to the polymerization of fibrinogen and fibrin crosslinking that is facilitated by platelets. A new view of thrombosis is providing a more integrated concept, with components of the vascular wall contributing to the vascular remodeling of thrombosis. Angiogenesis and inflammation are two key mechanisms that safeguard venous thrombus resolution and restitution of vascular patency after thrombosis. Disturbance of these processes leads to thrombus persistence and has potentially severe consequences for affected patients. Examples for clinical conditions associated with recurrent or persisting venous thrombosis are post-thrombotic syndrome or chronic thromboembolic pulmonary hypertension. Recently, studies using animal models of venous thrombosis have contributed to a better understanding of thrombus non-resolution that will eventually lead to modification of current treatment concepts. For example, recent data suggest that innate immunity is involved in the modification of thrombosis. PMID:26629617

  5. Traversing boundaries: thrombus in transit with paradoxical embolism.

    PubMed

    Miriyala, Varun; Awan, Muhammad Umer; Faraj, Kirmanj; Nagra, Bipinpreet

    2016-01-01

    A 72-year-old male is diagnosed with paradoxical embolus after he presented with concurrent deep vein thrombosis, stroke, and multiple arterial emboli in the presence of a patent foramen ovale (PFO). Paradoxical embolus requires the passage of a thrombus from the venous into the arterial circulation through a right-to-left shunt leading to systemic embolism. But, despite the high incidence of PFO (27.3% across all age groups by autopsy), paradoxical embolism (PDE) is uncommon, representing <2% of all arterial emboli. We present a case report where a thrombus has been directly observed passing through the PFO during an echocardiogram study; thus, clearly delineating the true cause of multiple thromboemboli and stoke in our patient. Subsequent Transesophageal Echocardiography (TEE) also interestingly showed the thrombus in transit in the aorta and pulmonary artery. PMID:27609716

  6. Right Ventricular Thrombus and Cerebral Artery Aneurysm in a Patient with Behçet's Disease.

    PubMed

    Sabzi, Feridoun; Mirzaei, Samaneh; Faraji, Reza

    2016-05-01

    We report a 35-year-old woman referred to the Imam Ali Hospital, Kermanshah, Iran, in July 2014 for evaluation of postoperative dyspnoea after neurosurgery performed seven days previously for a ruptured cerebral artery aneurysm. She was known to have Behçet's disease with a history of recurrent oral and genital aphthous ulcers and uveitis. At referral, her symptoms included vertigo, dysarthria, palpitations and chest pain. Transthoracic echocardiography (TTE) revealed a large thrombus in her right ventricle outflow tract and open-heart surgery was performed eight days after the previous surgery to remove the clot. The postoperative period was complicated by transient acute renal failure, which resolved spontaneously. The patient was discharged 13 days after the cardiac surgery on warfarin, prednisolone, azathioprine and cyclophosphamide. Cyclophosphamide and azathioprine were discontinued after three months as the symptoms had completely resolved; however, prednisolone was continued due to recurrent uveitis. A 10-month follow-up TTE scan revealed no thrombus recurrence and treatment with warfarin and prednisolone was continued. PMID:27226921

  7. Engineering of plasminogen activators for targeting to thrombus and heightening thrombolytic efficacy.

    PubMed

    Absar, S; Gupta, N; Nahar, K; Ahsan, F

    2015-09-01

    Thrombotic occlusion of the coronary artery, which triggers acute myocardial infarction, is one of the major causes of death in the USA. Currently, arterial occlusions are treated with intravenous plasminogen activators (PAs), which dissolve the clot by activating plasminogen. However, PAs indiscriminately generate plasmin, which depletes critical clotting factors (fibrinogen, factor V, and factor VIII), precipitates a lytic state in the blood, and produces bleeding complications in a large patient population. PAs have been extensively investigated to achieve thrombus specificity, to attenuate the bleeding risk, and to widen their clinical applications. In this review, we discuss various strategies that have been pursued since the beginning of thrombolytic therapy. We review the biotechnological approaches that have been used to develop mutant and chimeric PAs for thrombus selectivity, including the use of specific antibodies for targeting thrombi. We discuss particulate carrier-based systems and triggered-release concepts. We propose new hypotheses and strategies to spur future studies in this research arena. Overall, we describe the approaches and accomplishments in the development of patient-friendly and workable delivery systems for thrombolytic drugs. PMID:26074048

  8. Hypothyroid cardiomyopathy complicated by a left ventricular laminar thrombus.

    PubMed

    Van Treeck, Benjamin J; Masoud, Amgad G

    2014-01-01

    Clinical hypothyroidism is the most common hormone deficiency in the United States and is found in 0.3% of the U.S. population. It is associated with characteristic symptoms that can be readily identified by a careful history and physical examination. Hypothyroidism affects many bodily systems; in particular the cardiovascular system is impacted via multiple mechanisms.3 Occasionally hypothyroidism leads to transient left ventricular systolic dysfunction, termed hypothyroid cardiomyopathy. A rare sequela of this condition is a left ventricular thrombus, which has been described in two case reports thus far. Here we report a third case of reversible hypothyroid cardiomyopathy complicated by a left ventricular laminar thrombus. PMID:25438369

  9. Histopathological evaluation of thrombus in patients presenting with stent thrombosis. A multicenter European study: a report of the prevention of late stent thrombosis by an interdisciplinary global European effort consortium†

    PubMed Central

    Riegger, Julia; Byrne, Robert A.; Joner, Michael; Chandraratne, Sue; Gershlick, Anthony H.; ten Berg, Jurrien M.; Adriaenssens, Tom; Guagliumi, Giulio; Godschalk, Thea C.; Neumann, Franz-Josef; Trenk, Dietmar; Feldman, Laurent J.; Steg, Philippe Gabriel; Desmet, Walter; Alfonso, Fernando; Goodall, Alison H.; Wojdyla, Roman; Dudek, Dariusz; Philippi, Vanessa; Opinaldo, Sheryl; Titova, Anna; Malik, Nikesh; Cotton, James; Jhagroe, Darshni A.; Heestermans, Antonius A.C.M.; Sinnaeve, Peter; Vermeersch, Paul; Valina, Christian; Schulz, Christian; Kastrati, Adnan; Massberg, Steffen

    2016-01-01

    Background Stent thrombosis (ST) is a rare but serious complication following percutaneous coronary intervention. Analysis of thrombus composition from patients undergoing catheter thrombectomy may provide important insights into the pathological processes leading to thrombus formation. We performed a large-scale multicentre study to evaluate thrombus specimens in patients with ST across Europe. Methods Patients presenting with ST and undergoing thrombus aspiration were eligible for inclusion. Thrombus collection was performed according to a standardized protocol and specimens were analysed histologically at a core laboratory. Serial tissue cross sections were stained with haematoxylin–eosin (H&E), Carstairs and Luna. Immunohistochemistry was performed to identify leukocyte subsets, prothrombotic neutrophil extracellular traps (NETs), erythrocytes, platelets, and fibrinogen. Results Overall 253 thrombus specimens were analysed; 79 (31.2%) from patients presenting with early ST, 174 (68.8%) from late ST; 79 (31.2%) were from bare metal stents, 166 (65.6%) from drug-eluting stents, 8 (3.2%) were from stents of unknown type. Thrombus specimens displayed heterogeneous morphology with platelet-rich thrombus and fibrin/fibrinogen fragments most abundant; mean platelet coverage was 57% of thrombus area. Leukocyte infiltrations were hallmarks of both early and late ST (early: 2260 ± 1550 per mm2 vs. late: 2485 ± 1778 per mm2; P = 0.44); neutrophils represented the most prominent subset (early: 1364 ± 923 per mm2 vs. late: 1428 ± 1023 per mm2; P = 0.81). Leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction. Neutrophil extracellular traps were observed in 23% of samples. Eosinophils were present in all stent types, with higher numbers in patients with late ST in sirolimus-and everolimus-eluting stents. Conclusion In a large-scale study of histological thrombus analysis from

  10. Artificial aortic valve dysfunction due to pannus and thrombus – different methods of cardiac surgical management

    PubMed Central

    Marcinkiewicz, Anna; Kośmider, Anna; Walczak, Andrzej; Zwoliński, Radosław; Jaszewski, Ryszard

    2015-01-01

    Introduction Approximately 60 000 prosthetic valves are implanted annually in the USA. The risk of prosthesis dysfunction ranges from 0.1% to 4% per year. Prosthesis valve dysfunction is usually caused by a thrombus obstructing the prosthetic discs. However, 10% of prosthetic valves are dysfunctional due to pannus formation, and 12% of prostheses are damaged by both fibrinous and thrombotic components. The authors present two patients with dysfunctional aortic prostheses who were referred for cardiac surgery. Different surgical solutions were used in the treatment of each case. Case study 1 The first patient was a 71-year-old woman whose medical history included arterial hypertension, stable coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and hypercholesterolemia; she had previously undergone left-sided mastectomy and radiotherapy. The patient was admitted to the Cardiac Surgery Department due to aortic prosthesis dysfunction. Transthoracic echocardiography revealed complete obstruction of one disc and a severe reduction in the mobility of the second. The mean transvalvular gradient was very high. During the operation, pannus covering the discs’ surface was found. A biological aortic prosthesis was reimplanted without complications. Case study 2 The second patient was an 87-year-old woman with arterial hypertension, persistent atrial fibrillation, and COPD, whose past medical history included gastric ulcer disease and ischemic stroke. As in the case of the first patient, she was admitted due to valvular prosthesis dysfunction. Preoperative transthoracic echocardiography revealed an obstruction of the posterior prosthetic disc and significant aortic regurgitation. Transesophageal echocardiography and fluoroscopy confirmed the prosthetic dysfunction. During the operation, a thrombus growing around a minor pannus was found. The thrombus and pannus were removed, and normal functionality of the prosthetic valve was restored

  11. Variable Effect of P2Y12 Inhibition on Platelet Thrombus Volume in Flowing Blood

    PubMed Central

    Mendolicchio, G. L.; Zavalloni, D.; Bacci, M.; Corrada, E.; Marconi, M.; Lodigiani, C.; Presbitero, P.; Rota, L.; Ruggeri, Z. M.

    2010-01-01

    Background and objectives Patients treated by percutaneous coronary intervention (PCI) receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo. Methods and Results We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at the wall shear rate of 1,500 s−1. The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein (VASP) phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group and only 22.6% of individual values were above the lower normal limit. We found no correlation between thrombus volume formed onto collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function. Conclusions Measuring platelet thrombus formation in flowing blood reflects the consequences of anti-platelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk. PMID:21083646

  12. A Predictive Model of High Shear Thrombus Growth.

    PubMed

    Mehrabadi, Marmar; Casa, Lauren D C; Aidun, Cyrus K; Ku, David N

    2016-08-01

    The ability to predict the timescale of thrombotic occlusion in stenotic vessels may improve patient risk assessment for thrombotic events. In blood contacting devices, thrombosis predictions can lead to improved designs to minimize thrombotic risks. We have developed and validated a model of high shear thrombosis based on empirical correlations between thrombus growth and shear rate. A mathematical model was developed to predict the growth of thrombus based on the hemodynamic shear rate. The model predicts thrombus deposition based on initial geometric and fluid mechanic conditions, which are updated throughout the simulation to reflect the changing lumen dimensions. The model was validated by comparing predictions against actual thrombus growth in six separate in vitro experiments: stenotic glass capillary tubes (diameter = 345 µm) at three shear rates, the PFA-100(®) system, two microfluidic channel dimensions (heights = 300 and 82 µm), and a stenotic aortic graft (diameter = 5.5 mm). Comparison of the predicted occlusion times to experimental results shows excellent agreement. The model is also applied to a clinical angiography image to illustrate the time course of thrombosis in a stenotic carotid artery after plaque cap rupture. Our model can accurately predict thrombotic occlusion time over a wide range of hemodynamic conditions. PMID:26795978

  13. Flow impeding fungal thrombus in the ascending aorta.

    PubMed

    Huang, Jiapeng; Bouvette, Michael J; Hagi, Yousef; Subramanian, Sujata; Zhou, Jing; Austin, Erle H

    2008-10-01

    Mycotic endoaortitis is a rarely occurring infectious entity with an extremely high mortality rate. We report an uncommon case of Phialemonium endoaortits with its management. This large fungal thrombus in the ascending aorta caused significant impediment to the blood flow. PMID:18805204

  14. Prediction of thrombus-related mechanical prosthetic valve dysfunction using transesophageal echocardiography

    NASA Technical Reports Server (NTRS)

    Lin, S. S.; Tiong, I. Y.; Asher, C. R.; Murphy, M. T.; Thomas, J. D.; Griffin, B. P.

    2000-01-01

    Identification of thrombus-related mechanical prosthetic valve dysfunction (MPVD) has important therapeutic implications. We sought to develop an algorithm, combining clinical and echocardiographic parameters, for prediction of thrombus-related MPVD in a series of 53 patients (24 men, age 52 +/- 16 years) who had intraoperative diagnosis of thrombus or pannus from 1992 to 1997. Clinical and echocardiographic parameters were analyzed to identify predictors of thrombus and pannus. Prevalence of thrombus and diagnostic yields relative to the number of predictors were determined. There were 22 patients with thrombus, 19 patients with pannus, and 12 patients with both. Forty-two of 53 masses were visualized using transesophageal echocardiography (TEE), including 29 of 34 thrombi or both thrombi and panni and 13 of 19 isolated panni. Predictors of thrombus or mixed presentation include mobile mass (p = 0.009), attachment to occluder (p = 0.02), elevated gradients (p = 0.04), and an international normalized ratio of < or = 2.5 (p = 0.03). All 34 patients with thrombus or mixed presentation had > or = 1 predictor. The prevalence of thrombus in the presence of < or = 1, 2, and > or = 3 predictors is 14%, 69%, and 91%, respectively. Thus, TEE is sensitive in the identification of abnormal mass in the setting of MPVD. An algorithm based on clinical and transesophageal echocardiographic predictors may be useful to estimate the likelihood of thrombus in the setting of MPVD. In the presence of > or = 3 predictors, the probability of thrombus is high.

  15. Real-Time Observation of Thrombus Growth Process in an Impeller of a Hydrodynamically Levitated Centrifugal Blood Pump by Near-Infrared Hyperspectral Imaging.

    PubMed

    Sakota, Daisuke; Murashige, Tomotaka; Kosaka, Ryo; Fujiwara, Tatsuki; Nishida, Masahiro; Maruyama, Osamu

    2015-08-01

    Understanding the thrombus formation in cardiovascular devices such as rotary blood pumps is the most important issue in developing more hemocompatible devices. The objective of this study was to develop a hyperspectral imaging (HSI) method to visualize the thrombus growth process within a rotary blood pump and investigate the optical properties of the thrombus. An in vitro thrombogenic test was conducted using fresh porcine blood and a specially designed hydrodynamically levitated centrifugal blood pump with a transparent bottom. The pump rotating at 3000 rpm circulated the blood at 1.0 L/min. The bottom surface of the pump was illuminated with white light pulsed at the same frequency as the pump rotation, and the backward-scattered light was imaged using the HSI system. Using stroboscopic HSI and an image construction algorithm, dynamic spectral imaging at wavelengths ranging from 608 to 752 nm within the rotating pump was achieved. After completing the experiment, we collected the red thrombus formed in the pump impeller and quantified the thrombus hemoglobin concentration (Hbthrombus ). The spectrum changed around the center of the impeller, and the area of change expanded toward the impeller flow path. The shape corresponded approximately to the shape of the thrombus. The spectrum change indicated that the light scattering derived from red blood cells decreased. The Hbthrombus was 4.7 ± 1.3 g/dL versus a total hemoglobin of 13 ± 0.87 g/dL. The study revealed that Hbthrombus was reduced by the surrounding blood flow. PMID:26234451

  16. Comparison of C-reactive protein and fibrinogen levels in patients having anterior wall ST-Segment elevation myocardial infarction with versus without left ventricular thrombus (from a primary percutaneous coronary intervention cohort).

    PubMed

    Shacham, Yacov; Leshem-Rubinow, Eran; Ben Assa, Eyal; Rogowski, Ori; Topilsky, Yan; Roth, Arie; Steinvil, Arie

    2013-07-01

    We tested the hypothesis that admission serum inflammatory biomarkers may predict risk of early left ventricular (LV) thrombus formation in patients with first-ever anterior wall ST-segment elevation myocardial infarction (STEMI). Medical records of 207 patients admitted to our department between January 2006 and April 2012 for first-ever diagnosed anterior wall STEMI and treated with primary percutaneous coronary intervention (PPCI) were reviewed. Serum C-reactive protein (CRP) and fibrinogen levels were determined from blood samples taken before PPCI. Patients underwent an initial cardiac echocardiography on days 1 or 2 of admission and a second echocardiography on days 5 to 7 of hospitalization. An early LV thrombus was detected on the second echocardiogram in 11 patients (11 of 207, 5%), 6 of whom had also displayed an LV thrombus already during their first echocardiogram. Patients with an LV thrombus had significantly higher mean serum CRP levels than those without an LV thrombus (48 mg/L vs 8.4 mg/L, p = 0.001), and a trend for higher fibrinogen levels was also observed (398 ± 135 mg/dl vs 312 ± 82 mg/dl, p = 0.063). Following adjustment to other variables and the performance of multiple logistic regression, the CRP (relative risk 4.63, p = 0.004) and fibrinogen (relative risk 1.006, p = 0.033) levels were independent predictors of LV thrombus formation. We conclude that admission serum CRP and fibrinogen levels are independent predictors for early LV thrombus formation complicating a first-ever anterior wall STEMI. PMID:23562384

  17. Thrombus Volume Change Visualization after Endovascular Abdominal Aortic Aneurysm Repair

    NASA Astrophysics Data System (ADS)

    Maiora, Josu; García, Guillermo; Macía, Iván; Legarreta, Jon Haitz; Boto, Fernando; Paloc, Céline; Graña, Manuel; Abuín, Javier Sanchez

    A surgical technique currently used in the treatment of Abdominal Aortic Aneurysms (AAA) is the Endovascular Aneurysm Repair (EVAR). This minimally invasive procedure involves inserting a prosthesis in the aortic vessel that excludes the aneurysm from the bloodstream. The stent, once in place acts as a false lumen for the blood current to travel down, and not into the surrounding aneurysm sac. This procedure, therefore, immediately takes the pressure off the aneurysm, which thromboses itself after some time. Nevertheless, in a long term perspective, different complications such as prosthesis displacement or bloodstream leaks into or from the aneurysmatic bulge (endoleaks) could appear causing a pressure elevation and, as a result, increasing the danger of rupture. The purpose of this work is to explore the application of image registration techniques to the visual detection of changes in the thrombus in order to assess the evolution of the aneurysm. Prior to registration, both the lumen and the thrombus are segmented

  18. Cardiac Fibroelastoma versus Thrombus: Echocardiographic Evidence Can Be Misleading

    PubMed Central

    2016-01-01

    We present a case of a young female with stroke symptoms who underwent valve sparing resection of a presumed fibroelastoma based on echocardiographic findings. After confirming embolic stroke, she underwent excision of the lesion, which on pathology revealed a nonbacterial thrombus. Ultimately, this led to a more extensive work-up leading to the discovery of a papillary serous ovarian carcinoma, the underlying cause of her hypercoagulable state. The initial echocardiographic findings painted the clear picture of a papillary tumor on the aortic valve which was likely the source of the emboli resulting in ischemic stroke. This unique case presentation illustrates that imaging, including echocardiography, may not always coincide with the clinical diagnosis. Thus, understanding the differential diagnoses of cardiac masses is of vital clinical significance. The distinction of fibroelastoma versus the much less common finding of aortic thrombus may lead to early diagnosis of malignancy and prevention of life threatening events due to stroke or undiagnosed disease. PMID:27547468

  19. Thromboxane A2 exacerbates acute lung injury via promoting edema formation.

    PubMed

    Kobayashi, Koji; Horikami, Daiki; Omori, Keisuke; Nakamura, Tatsuro; Yamazaki, Arisa; Maeda, Shingo; Murata, Takahisa

    2016-01-01

    Thromboxane A2 (TXA2) is produced in the lungs of patients suffering from acute lung injury (ALI). We assessed its contribution in disease progression using three different ALI mouse models. The administration of hydrochloric acid (HCl) or oleic acid (OA)+ lipopolysaccharide (LPS) caused tissue edema and neutrophil infiltration with TXA2 production in the lungs of the experimental mice. The administration of LPS induced only neutrophil accumulation without TXA2 production. Pretreatment with T prostanoid receptor (TP) antagonist attenuated the tissue edema but not neutrophil infiltration in these models. Intravital imaging and immunostaining demonstrated that administration of TP agonist caused vascular hyper-permeability by disrupting the endothelial barrier formation in the mouse ear. In vitro experiments showed that TP-stimulation disrupted the endothelial adherens junction, and it was inhibited by Ca(2+) channel blockade or Rho kinase inhibition. Thus endogenous TXA2 exacerbates ALI, and its blockade attenuates it by modulating the extent of lung edema. This can be explained by the endothelial hyper-permeability caused by the activation of TXA2-TP axis, via Ca(2+)- and Rho kinase-dependent signaling. PMID:27562142

  20. Thromboxane A2 exacerbates acute lung injury via promoting edema formation

    PubMed Central

    Kobayashi, Koji; Horikami, Daiki; Omori, Keisuke; Nakamura, Tatsuro; Yamazaki, Arisa; Maeda, Shingo; Murata, Takahisa

    2016-01-01

    Thromboxane A2 (TXA2) is produced in the lungs of patients suffering from acute lung injury (ALI). We assessed its contribution in disease progression using three different ALI mouse models. The administration of hydrochloric acid (HCl) or oleic acid (OA)+ lipopolysaccharide (LPS) caused tissue edema and neutrophil infiltration with TXA2 production in the lungs of the experimental mice. The administration of LPS induced only neutrophil accumulation without TXA2 production. Pretreatment with T prostanoid receptor (TP) antagonist attenuated the tissue edema but not neutrophil infiltration in these models. Intravital imaging and immunostaining demonstrated that administration of TP agonist caused vascular hyper-permeability by disrupting the endothelial barrier formation in the mouse ear. In vitro experiments showed that TP-stimulation disrupted the endothelial adherens junction, and it was inhibited by Ca2+ channel blockade or Rho kinase inhibition. Thus endogenous TXA2 exacerbates ALI, and its blockade attenuates it by modulating the extent of lung edema. This can be explained by the endothelial hyper-permeability caused by the activation of TXA2-TP axis, via Ca2+- and Rho kinase-dependent signaling. PMID:27562142

  1. Defining and Regulating Acute Inflammatory Lesion Formation during the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.

    PubMed

    Bolton, Christopher; Smith, Paul

    2015-01-01

    The primary pathology of the human central nervous system disease multiple sclerosis (MS) and the animal counterpart experimental autoimmune encephalomyelitis (EAE) includes immunological and inflammatory events. Immune system involvement in MS has been widely debated but the role of inflammation has received less attention. Classic acute inflammation features vasculitis, resident tissue macrophage and mast cell participation plus the involvement of circulatory-derived neutrophils and platelets. Pre-lesion development in MS incorporates cerebral vasculitis, activated resident microglia in normal appearing white matter together with infiltrating cell types and factors indicative of an acute inflammatory reaction. Similarly, the formation of perivascular lesions during early EAE includes characteristic neurovasculitis, the participation of central nervous system microglial phenotypes plus haemopoietic cells and mediators, signifying an ongoing acute inflammatory response. EAE has been extensively used as a screen to select drugs for MS treatment but has been criticised as unrepresentative of the human condition due to fundamental differences in disease induction and pathogenesis. The review provides compelling evidence for a distinct acute inflammatory phase in MS lesion formation that is convincingly reproduced in early EAE pathology. Moreover, consideration of drug efficacy studies undertaken during initial EAE validates the occurrence of an acute inflammatory phase in disease pathogenesis. Critical appraisal, recognition and acceptance of the mutual acute inflammatory components inherent in the primary pathology of MS and EAE reveals new targets and encourages confident and reliable employment of the animal model in the assessment of novel compounds for the control of key primary pathological events in human demyelinating disease. PMID:26177741

  2. A high throughput passive dosing format for the Fish Embryo Acute Toxicity test.

    PubMed

    Vergauwen, Lucia; Schmidt, Stine N; Stinckens, Evelyn; Maho, Walid; Blust, Ronny; Mayer, Philipp; Covaci, Adrian; Knapen, Dries

    2015-11-01

    High throughput testing according to the Fish Embryo Acute Toxicity (FET) test (OECD Testing Guideline 236) is usually conducted in well plates. In the case of hydrophobic test substances, sorptive and evaporative losses often result in declining and poorly controlled exposure conditions. Therefore, our objective was to improve exposure conditions in FET tests by evaluating a passive dosing format using silicone O-rings in standard 24-well polystyrene plates. We exposed zebrafish embryos to a series of phenanthrene concentrations until 120h post fertilization (hpf), and obtained a linear dilution series. We report effect values for both mortality and sublethal morphological effects based on (1) measured exposure concentrations, (2) (lipid normalized) body residues and (3) chemical activity. The LC50 for 120hpf was 310μg/L, CBR50 (critical body residue) was 2.72mmol/kg fresh wt and La50 (lethal chemical activity) was 0.047. All values were within ranges expected for baseline toxicity. Impaired swim bladder inflation was the most pronounced morphological effect and swimming activity was reduced in all exposure concentrations. Further analysis showed that the effect on swimming activity was not attributed to impaired swim bladder inflation, but rather to baseline toxicity. We conclude that silicone O-rings (1) produce a linear dilution series of phenanthrene in the 120hpf FET test, (2) generate and maintain aqueous concentrations for reliable determination of effect concentrations, and allow for obtaining mechanistic toxicity information, and (3) cause no toxicity, demonstrating its potential as an extension of the FET test when testing hydrophobic chemicals. PMID:26026258

  3. Matrix Metalloproteinase 9 (MMP-9) Regulates Vein Wall Biomechanics in Murine Thrombus Resolution

    PubMed Central

    Nguyen, Khanh P.; McGilvray, Kirk C.; Puttlitz, Christian M.; Mukhopadhyay, Subhradip; Chabasse, Christine; Sarkar, Rajabrata

    2015-01-01

    Objective Deep venous thrombosis is a common vascular problem with long-term complications including post-thrombotic syndrome. Post-thrombotic syndrome consists of leg pain, swelling and ulceration that is related to incomplete or maladaptive resolution of the venous thrombus as well as loss of compliance of the vein wall. We examine the role of metalloproteinase-9 (MMP-9), a gene important in extracellular remodeling in other vascular diseases, in mediating thrombus resolution and biomechanical changes of the vein wall. Methods and Results The effects of targeted deletion of MMP-9 were studied in an in vivo murine model of thrombus resolution using the FVB strain of mice. MMP-9 expression and activity significantly increased on day 3 after DVT. The lack of MMP-9 impaired thrombus resolution by 27% and this phenotype was rescued by the transplantation of wildtype bone marrow cells. Using novel biomechanical techniques, we demonstrated that the lack of MMP-9 significantly decreased thrombus-induced loss of vein wall compliance. Biomechanical analysis of the contribution of individual structural components showed that MMP-9 affected the elasticity of the extracellular matrix and collagen-elastin fibers. Biochemical and histological analyses correlated with these biomechanical effects as thrombi of mice lacking MMP-9 had significantly fewer macrophages and collagen as compared to those of wildtype mice. Conclusions MMP-9 mediates thrombus-induced loss of vein wall compliance by increasing stiffness of the extracellular matrix and collagen-elastin fibers during thrombus resolution. MMP-9 also mediates macrophage and collagen content of the resolving thrombus and bone-marrow derived MMP-9 plays a role in resolution of thrombus mass. These disparate effects of MMP-9 on various aspects of thrombus illustrate the complexity of individual protease function on biomechanical and morphometric aspects of thrombus resolution. PMID:26406902

  4. Thrombus burden and myocardial damage during primary percutaneous coronary intervention.

    PubMed

    Napodano, Massimo; Dariol, Gilberto; Al Mamary, Ahmed H; Marra, Martina Perazzolo; Tarantini, Giuseppe; D'Amico, Gianpiero; Frigo, Anna Chiara; Buja, Paolo; Razzolini, Renato; Iliceto, Sabino

    2014-05-01

    Large thrombus burden (LTB) lesions in the context of primary percutaneous coronary intervention (p-PCI) have been related to unsuccessful angiographic reperfusion and unfavorable clinical outcomes. However, the hazard of LTB treatment on myocardial damage has not been evaluated. We investigated the impact of LTB on myocardial damage using contrast-enhanced cardiac magnetic resonance (CE-CMR) in the setting of p-PCI. In 327 patients, who underwent p-PCI without thrombus aspiration within 12 hours from symptom onset, we prospectively assessed the impact of LTB on infarct size and microvascular damage using CE-CMR. LTB was defined by the presence of Thrombolysis In Myocardial Infarction thrombus score ≥3 in patent infarct-related artery (IRA); or by "cut-off" occlusion pattern and/or large reference vessel diameter (≥3.5 mm) in occluded IRA. One hundred ninety-seven patients (60.2%) showed LTB and 130 (39.8%) did not. Distal embolization occurred in 18.8% patients with versus 6.9% without LTB (p = 0.003). At CE-CMR, patients with LTB had larger infarct size index (27.5 ± 11.1 vs 22.1 ± 17.5, p = 0.009) and more often transmural necrosis (70.5% vs 55.4%, p = 0.008) compared with patients without LTB. Excluding patients with distal embolization, patients with LTB still had larger necrosis. At multivariate analysis, occluded (IRA) at baseline, anterior infarction, and presence of LTB predicted transmural necrosis. In conclusion, LTB in the setting of p-PCI is related to larger myocardial damage as detected by CE-CMR, regardless of angiographic detectable distal embolization. PMID:24630783

  5. Human resistin promotes neutrophil proinflammatory activation and neutrophil extracellular trap formation and increases severity of acute lung injury.

    PubMed

    Jiang, Shaoning; Park, Dae Won; Tadie, Jean-Marc; Gregoire, Murielle; Deshane, Jessy; Pittet, Jean Francois; Abraham, Edward; Zmijewski, Jaroslaw W

    2014-05-15

    Although resistin was recently found to modulate insulin resistance in preclinical models of type II diabetes and obesity, recent studies also suggested that resistin has proinflammatory properties. We examined whether the human-specific variant of resistin affects neutrophil activation and the severity of LPS-induced acute lung injury. Because human and mouse resistin have distinct patterns of tissue distribution, experiments were performed using humanized resistin mice that exclusively express human resistin (hRTN(+/-)(/-)) but are deficient in mouse resistin. Enhanced production of TNF-α or MIP-2 was found in LPS-treated hRtn(+/-/-) neutrophils compared with control Rtn(-/-/-) neutrophils. Expression of human resistin inhibited the activation of AMP-activated protein kinase, a major sensor and regulator of cellular bioenergetics that also is implicated in inhibiting inflammatory activity of neutrophils and macrophages. In addition to the ability of resistin to sensitize neutrophils to LPS stimulation, human resistin enhanced neutrophil extracellular trap formation. In LPS-induced acute lung injury, humanized resistin mice demonstrated enhanced production of proinflammatory cytokines, more severe pulmonary edema, increased neutrophil extracellular trap formation, and elevated concentration of the alarmins HMGB1 and histone 3 in the lungs. Our results suggest that human resistin may play an important contributory role in enhancing TLR4-induced inflammatory responses, and it may be a target for future therapies aimed at reducing the severity of acute lung injury and other inflammatory situations in which neutrophils play a major role. PMID:24719460

  6. Non typable-Haemophilus influenzae biofilm formation and acute otitis media

    PubMed Central

    2014-01-01

    Background Non-typable Haemophilus influenzae (NT-Hi) infection is frequently associated with acute otitis media (AOM) treatment failure, recurrence or chronic otitis media. Persistence of otopathogens in a biofilm-structured community was implicated in these situations. Here, we compared biofilm production by H. influenzae strains obtained by culture of middle ear fluid (MEF) from children with AOM treatment failure and by strains isolated from nasopharyngeal (NP) samples from healthy children or those with AOM (first episode or recurrence). We aimed to evaluate an association of clinical signs and in vitro biofilm formation and establish risk factors of carrying a biofilm-producing strain. Methods We used a modification of the microtiter plate assay with crystal violet staining to compare biofilm production by 216 H. influenzae strains: 41 in MEF from children with AOM treatment failure (group MEF), 43 in NP samples from healthy children (NP group 1), 88 in NP samples from children with a first AOM episode (NP group 2, n = 43) or recurrent (NP group 3, n = 45) and 44 in NP samples from children with AOM associated with conjunctivitis (NP group 4). Results At all, 106/216 (49%) H. influenzae strains produced biofilm as did 26/43 (60.5%) in NP samples from healthy children. Biofilm production in MEF samples and NP samples did not significantly differ (40.5% vs 60.5%, 55.8%, 56.8% and 31.1% for NP groups 1, 2, 3 and 4, respectively). On multivariate analysis, only presence of conjunctivitis was significantly associated with low biofilm production (OR = 0.3, CI [0.16-0.60], p = 0.001). The ampicillin resistance of H. influenzae produced by penicillin-binding protein modification was significantly associated with low biofilm production (p = 0.029). Conclusion We found no association of biofilm production and AOM treatment failure or recurrence. Biofilm production was low from H. influenzae strains associated with conjunctivitis-otitis syndrome

  7. Performance of a thrombectomy device for aspiration of thrombus with various sizes based on a computational fluid dynamic modeling.

    PubMed

    Soleimani, Sajjad; Dubini, Gabriele; Pennati, Giancarlo

    2016-06-01

    It is important to thoroughly remove the thrombus within the course of aspiration thrombectomy; otherwise, it may lead to further embolization. The performance of the aspiration thrombectomy device with a generic geometry is studied through the computational approach. In order to model the thrombus aspiration, a real left coronary artery is chosen while thrombi with various sizes are located at the bifurcation area of the coronary artery and, depending on the size of the thrombus, it is stretched toward the side branches. The thrombus occupies the artery resembling the blood current obstruction in the coronary vessel similar to the situation that leads to heart attack. It is concluded that the aspiration ability of the thrombectomy device is not linked to the thrombus size; it is rather linked to the aspiration pressure and thrombus age (organized versus fresh thrombus). However, the aspiration time period correlates to the thrombus size. The minimum applicable aspiration pressure is also investigated in this study. PMID:26351782

  8. Right Ventricular Thrombus and Cerebral Artery Aneurysm in a Patient with Behçet’s Disease

    PubMed Central

    Sabzi, Feridoun; Mirzaei, Samaneh; Faraji, Reza

    2016-01-01

    We report a 35-year-old woman referred to the Imam Ali Hospital, Kermanshah, Iran, in July 2014 for evaluation of postoperative dyspnoea after neurosurgery performed seven days previously for a ruptured cerebral artery aneurysm. She was known to have Behçet’s disease with a history of recurrent oral and genital aphthous ulcers and uveitis. At referral, her symptoms included vertigo, dysarthria, palpitations and chest pain. Transthoracic echocardiography (TTE) revealed a large thrombus in her right ventricle outflow tract and open-heart surgery was performed eight days after the previous surgery to remove the clot. The postoperative period was complicated by transient acute renal failure, which resolved spontaneously. The patient was discharged 13 days after the cardiac surgery on warfarin, prednisolone, azathioprine and cyclophosphamide. Cyclophosphamide and azathioprine were discontinued after three months as the symptoms had completely resolved; however, prednisolone was continued due to recurrent uveitis. A 10-month follow-up TTE scan revealed no thrombus recurrence and treatment with warfarin and prednisolone was continued. PMID:27226921

  9. AngioVac extraction of intra-atrial hepatoma masquerading as PICC-associated thrombus

    PubMed Central

    Abboud, Samir; Raparia, Kirtee; Ubago, Julianne M.; Resnick, Scott

    2016-01-01

    Thrombus associated with peripherally inserted central catheterization is not uncommon. Treatment is typically conservative; however, more aggressive therapies can be considered in patients with tenuous medical condition. The authors present a patient with metastatic hepatocellular carcinoma masquerading as peripherally inserted central catheter-associated intra-atrial thrombus, subsequently removed via vacuum-assisted mechanical thrombectomy. PMID:26509915

  10. AngioVac extraction of intra-atrial hepatoma masquerading as PICC-associated thrombus.

    PubMed

    Abboud, Samir; Raparia, Kirtee; Ubago, Julianne M; Resnick, Scott

    2016-01-01

    Thrombus associated with peripherally inserted central catheterization is not uncommon. Treatment is typically conservative; however, more aggressive therapies can be considered in patients with tenuous medical condition. The authors present a patient with metastatic hepatocellular carcinoma masquerading as peripherally inserted central catheter-associated intra-atrial thrombus, subsequently removed via vacuum-assisted mechanical thrombectomy. PMID:26509915

  11. Dual antiplatelet agents and Rivaroxaban for massive intracoronary thrombus in STEMI.

    PubMed

    Jamal, Nasiruddin; Bapumia, Mustaafa

    2015-11-01

    Management of intracoronary thrombus in patients presenting more than 12 hours after the onset of ST elevation myocardial infarction is challenging. We present such a case which had massive thrombus in left anterior descending artery. It was managed successfully with dual antiplatelet agents and factor Xa inhibitor rivaroxaban administered orally. PMID:26576274

  12. Dual antiplatelet agents and Rivaroxaban for massive intracoronary thrombus in STEMI

    PubMed Central

    Jamal, Nasiruddin; Bapumia, Mustaafa

    2015-01-01

    Key Clinical Message Management of intracoronary thrombus in patients presenting more than 12 hours after the onset of ST elevation myocardial infarction is challenging. We present such a case which had massive thrombus in left anterior descending artery. It was managed successfully with dual antiplatelet agents and factor Xa inhibitor rivaroxaban administered orally. PMID:26576274

  13. Tumour thrombus consistency has no impact on survival in patients with renal cell carcinoma.

    PubMed

    Gołąbek, T; Przydacz, M; Okoń, K; Kopczyński, J; Bukowczan, J; Sobczyński, R; Curyło, Ł; Gołąbek, K; Curyło, Ł; Chłosta, P

    2016-06-01

    The prognosis of renal cell carcinoma (RCC) with venous tumour thrombus (VTT) is variable and not always possible to predict. The prognostic impact and independence of tumour thrombus-related factors including the recently introduced tumour thrombus consistency (TTC) on overall survival remain controversial. The aim of this study was to investigate the prognostic role of TTC in patients' survival. We determined the tumour thrombus consistency (solid vs. friable) in a cohort of 84 patients with RCC and VTT who underwent nephrectomy with thrombectomy, and performed a retrospective evaluation of the patients' data from the prospectively maintained database. A total of 45% of patients had solid thrombus (sTT) and 55% had friable thrombus (fTT). The venous tumour thrombus consistency was not predictive of overall survival. Further studies, preferably prospective and with a larger number of patients, are needed to validate the obtained results, as well as to evaluate the usefulness of tumour thrombus consistency in clinical practice for stratifying the risk of recurrence and planning further follow-up. PMID:27543869

  14. Platelet-Derived CCL5 Regulates CXC Chemokine Formation and Neutrophil Recruitment in Acute Experimental Colitis.

    PubMed

    Yu, Changhui; Zhang, Songen; Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Thorlacius, Henrik

    2016-02-01

    Accumulating data suggest that platelets not only regulate thrombosis and haemostasis but also inflammatory processes. Platelets contain numerous potent pro-inflammatory compounds, including the chemokines CCL5 and CXCL4, although their role in acute colitis remains elusive. The aim of this study is to examine the role of platelets and platelet-derived chemokines in acute colitis. Acute colitis is induced in female Balb/c mice by administration of 5% dextran sodium sulfate (DSS) for 5 days. Animals receive a platelet-depleting, anti-CCL5, anti-CXCL4, or a control antibody prior to DSS challenge. Colonic tissue is collected for quantification of myeloperoxidase (MPO) activity, CXCL5, CXCL2, interleukin-6 (IL-6), and CCL5 levels as well as morphological analyses. Platelet depletion reduce tissue damage and clinical disease activity index in DSS-exposed animals. Platelet depletion not only reduces levels of CXCL2 and CXCL5 but also levels of CCL5 in the inflamed colon. Immunoneutralization of CCL5 but not CXCL4 reduces tissue damage, CXC chemokine expression, and neutrophil recruitment in DSS-treated animals. These findings show that platelets play a key role in acute colitis by regulating CXC chemokine generation, neutrophil infiltration, and tissue damage in the colon. Moreover, our results suggest that platelet-derived CCL5 is an important link between platelet activation and neutrophil recruitment in acute colitis. PMID:26089223

  15. Increased platelet count and leucocyte–platelet complex formation in acute symptomatic compared with asymptomatic severe carotid stenosis

    PubMed Central

    McCabe, D; Harrison, P; Mackie, I; Sidhu, P; Purdy, G; Lawrie, A; Watt, H; Machin, S; Brown, M

    2005-01-01

    Objective: The risk of stroke in patients with recently symptomatic carotid stenosis is considerably higher than in patients with asymptomatic stenosis. In the present study it was hypothesised that excessive platelet activation might partly contribute to this difference. Methods: A full blood count was done and whole blood flow cytometry used to measure platelet surface expression of CD62P, CD63, and PAC1 binding and the percentage of leucocyte–platelet complexes in patients with acute (0–21 days, n = 19) and convalescent (79–365 days) symptomatic (n = 16) and asymptomatic (n = 16) severe (⩾70%) carotid stenosis. Most patients were treated with aspirin (37.5–300 mg daily) although alternative antithrombotic regimens were more commonly used in the symptomatic group. Results: The mean platelet count was higher in patients with acute and convalescent symptomatic compared with asymptomatic carotid stenosis. There were no significant differences in the median percentage expression of CD62P and CD63, or PAC1 binding between the acute or convalescent symptomatic and asymptomatic patients. The median percentages of neutrophil–platelet (p = 0.004), monocyte–platelet (p = 0.046), and lymphocyte–platelet complexes (p = 0.02) were higher in acute symptomatic than in asymptomatic patients. In patients on aspirin monotherapy, the percentages of neutrophil–platelet and monocyte–platelet complexes (p = 0.03) were higher in acute symptomatic (n = 11) than asymptomatic patients (n = 14). In the convalescent phase, the median percentages of all leucocyte–platelet complexes in the symptomatic group dropped to levels similar to those found in the asymptomatic group. Conclusion: Increased platelet count and leucocyte–platelet complex formation may contribute to the early excess risk of stroke in patients with recently symptomatic carotid stenosis. PMID:16107361

  16. Antiadhesive effect of fibrinogen: a safeguard for thrombus stability

    PubMed Central

    Lishko, Valeryi K.; Burke, Timothy; Ugarova, Tatiana

    2007-01-01

    The recruitment of phagocytic leukocytes to sites of vessel wall injury plays an important role in thrombus dissolution by proteases elaborated on their adhesion. However, leukocyte adhesion to the fibrin clot can be detrimental at the early stages of wound healing when hemostatic plug integrity is critical for preventing blood loss. Adhesion of circulating leukocytes to the insoluble fibrin(ogen) matrix is mediated by integrins and occurs in the presence of a high concentration of plasma fibrinogen. In this study, the possibility that soluble fibrinogen could protect fibrin from excessive adhesion of leukocytes was examined. Fibrinogen was a potent inhibitor of adhesion of U937 monocytoid cells and neutrophils to fibrin gel and immobilized fibrin(ogen). An investigation of the mechanism by which soluble fibrinogen exerts its influence on leukocyte adhesion indicated that it did not block integrins but rather associated with the fibrin(ogen) substrate. Consequently, leukocytes that engage fibrinogen molecules loosely bound to the surface of fibrin(ogen) matrix are not able to consolidate their grip on the substrate; subsequently, cells detach. This conclusion is based on the evidence obtained in adhesion studies using various cells and performed under static and flow conditions. These findings reveal a new role of fibrinogen in integrin-mediated leukocyte adhesion and suggest that this mechanism may protect the thrombus from premature dissolution. PMID:16849640

  17. Novel risk predictor for thrombus deposition in abdominal aortic aneurysms

    NASA Astrophysics Data System (ADS)

    Nestola, M. G. C.; Gizzi, A.; Cherubini, C.; Filippi, S.; Succi, S.

    2015-10-01

    The identification of the basic mechanisms responsible for cardiovascular diseases stands as one of the most challenging problems in modern medical research including various mechanisms which encompass a broad spectrum of space and time scales. Major implications for clinical practice and pre-emptive medicine rely on the onset and development of intraluminal thrombus in which effective clinical therapies require synthetic risk predictors/indicators capable of informing real-time decision-making protocols. In the present contribution, two novel hemodynamics synthetic indicators, based on a three-band decomposition (TBD) of the shear stress signal, are introduced. Extensive fluid-structure computer simulations of patient-specific scenarios confirm the enhanced risk-prediction capabilities of the TBD indicators. In particular, they permit a quantitative and accurate localization of the most likely thrombus deposition in realistic aortic geometries, where previous indicators would predict healthy operation. The proposed methodology is also shown to provide additional information and discrimination criteria on other factors of major clinical relevance, such as the size of the aneurysm.

  18. Left atrial giant thrombus infected by Escherichia Coli. Case report

    PubMed Central

    Dedeilias, Panagiotis; Roussakis, Antonios; Koletsis, Efstratios N; Zervakis, Dimitrios; Hountis, Panagiotis; Prokakis, Christos; Balaka, Christina; Bolos, Konstantinos

    2008-01-01

    Background Left atrial thrombi are mostly related to mitral valve disease. The differential diagnosis of clots and myxomas in the left atrium is mostly based on echocardiography. Infection of intracardiac thrombi is extremely rare and mostly reported in ventricular clots or aneurysms following myocardial infarction. Case presentation We present the case of a 65 year old female with a history of mitral valve disease and chronic atrial fibrillation who suffered repeated embolic strokes and a giant infected clot in the left atrium. Although the patient underwent prompt surgery with removal of the clot and valve replacement the complication of septic emboli to the CNS led her to death. To the best of our knowledge this is the second report of an infected left atrial thrombus. Conclusion The case is a representative example of a neglected and undertreated patient with catastrophic consequences. Anticoagulant therapy in patients with mitral valve disease and atrial fibrillation should be applied according the currently available guidelines and standards in order to avoid analogous paradigms in the future. Mitral valve substitution should be considered in patients with mitral valve disease presenting thromboembolic complications. Surgery should be considered as the treatment of choice in cases of organized left atrial thrombus and suspected tumor or infected mass. PMID:18433486

  19. Intra-aneurysmal thrombus modification after flow-diversion.

    PubMed

    Zanaty, Mario; Jabbour, Pascal M; Bou Sader, Roula; Chalouhi, Nohra; Tjoumakaris, Stavropoula; Rosenwasser, Robert H; Fernando Gonzalez, L

    2015-01-01

    Flow diversion has been successfully used to treat large and giant intracranial aneurysms that present with mass effect. We conducted a retrospective review, evaluating the modification of thrombi in this aneurysm type after treatment with the Pipeline Embolization Device (ev3 Endovascular, Plymouth, MN, USA) and the effects of these modifications on symptoms. Eight patients, seven of whom were female, harbored eight partially thrombosed large or giant aneurysms. Five of the eight aneurysms presented with symptomatic mass effect. At 1 year follow-up, complete occlusion occurred in 75% (6/8) of patients. On average, the longest thrombus diameter measured 22.31 mm before treatment and 14.05 mm 1 year afterwards. Seven of the eight thrombi regressed, as did their aneurysms. All six patients with shrunken thrombi had tremendous symptom improvement and became asymptomatic in the following year. The current findings seem to reflect the size variation of the intra-aneurysmal thrombus rather than the size of the aneurysm itself. PMID:25192591

  20. Lnk regulates integrin αIIbβ3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo

    PubMed Central

    Takizawa, Hitoshi; Nishimura, Satoshi; Takayama, Naoya; Oda, Atsushi; Nishikii, Hidekazu; Morita, Yohei; Kakinuma, Sei; Yamazaki, Satoshi; Okamura, Satoshi; Tamura, Noriko; Goto, Shinya; Sawaguchi, Akira; Manabe, Ichiro; Takatsu, Kiyoshi; Nakauchi, Hiromitsu; Takaki, Satoshi; Eto, Koji

    2009-01-01

    The nature of the in vivo cellular events underlying thrombus formation mediated by platelet activation remains unclear because of the absence of a modality for analysis. Lymphocyte adaptor protein (Lnk; also known as Sh2b3) is an adaptor protein that inhibits thrombopoietin-mediated signaling, and as a result, megakaryocyte and platelet counts are elevated in Lnk–/– mice. Here we describe an unanticipated role for Lnk in stabilizing thrombus formation and clarify the activities of Lnk in platelets transduced through integrin αIIbβ3–mediated outside-in signaling. We equalized platelet counts in wild-type and Lnk–/– mice by using genetic depletion of Lnk and BM transplantation. Using FeCl3- or laser-induced injury and in vivo imaging that enabled observation of single platelet behavior and the multiple steps in thrombus formation, we determined that Lnk is an essential contributor to the stabilization of developing thrombi within vessels. Lnk–/– platelets exhibited a reduced ability to fully spread on fibrinogen and mediate clot retraction, reduced tyrosine phosphorylation of the β3 integrin subunit, and reduced binding of Fyn to integrin αIIbβ3. These results provide new insight into the mechanism of αIIbβ3-based outside-in signaling, which appears to be coordinated in platelets by Lnk, Fyn, and integrins. Outside-in signaling modulators could represent new therapeutic targets for the prevention of cardiovascular events. PMID:20038804

  1. Successful Percutaneous Coronary Intervention through a Severely Bent Artificial Ascending Aorta Using the DIO Thrombus Aspiration Catheter.

    PubMed

    Fujikake, Akinori; Komatsu, Takaaki; Taguchi, Isao

    2016-01-01

    A 66-year-old man was admitted to our institute because of chest pain. He had undergone replacement of the ascending aorta due to aortic dissection 9 years previously. We made a diagnosis of acute coronary syndrome, and coronary artery angiography was performed. Although the right coronary artery was successfully cannulated, a severe bend of the artificial aorta made it very difficult to advance the catheter into the left coronary artery. Ultimately, a DIO thrombus aspiration catheter was used to enter the left coronary artery, and a stent was implanted successfully. The DIO catheter is very useful when the selection of a guiding catheter is complicated, such as in the case of severe vessel tortuosity or a bend of the ascending aorta. PMID:27516912

  2. Successful Percutaneous Coronary Intervention through a Severely Bent Artificial Ascending Aorta Using the DIO Thrombus Aspiration Catheter

    PubMed Central

    Fujikake, Akinori

    2016-01-01

    A 66-year-old man was admitted to our institute because of chest pain. He had undergone replacement of the ascending aorta due to aortic dissection 9 years previously. We made a diagnosis of acute coronary syndrome, and coronary artery angiography was performed. Although the right coronary artery was successfully cannulated, a severe bend of the artificial aorta made it very difficult to advance the catheter into the left coronary artery. Ultimately, a DIO thrombus aspiration catheter was used to enter the left coronary artery, and a stent was implanted successfully. The DIO catheter is very useful when the selection of a guiding catheter is complicated, such as in the case of severe vessel tortuosity or a bend of the ascending aorta. PMID:27516912

  3. Phosphatidylserine index as a marker of the procoagulant phenotype of acute myelogenous leukemia cells

    NASA Astrophysics Data System (ADS)

    Tormoen, Garth W.; Recht, Olivia; Gruber, András; Levine, Ross L.; McCarty, Owen J. T.

    2013-10-01

    Patients with acute myelogenous leukemia (AML) are at risk for thrombotic complications. Risk to develop thrombosis is closely tied to leukemia subtype, and studies have shown an association between leukocytosis and thrombosis in AML M3. We evaluated the relative roles of cell count and the surface expression of tissue factor (TF) and phosphatidylserine (PS) in the procoagulant phenotype of AML cell lines. The TF-positive AML M3 cell lines, NB4 and HL60, and AML M2 cell line, AML14, exhibited both extrinsic tenase and prothrombinase activity in a purified system and promoted experimental thrombus formation. In contrast, the TF-negative AML cell line, HEL, exhibited only prothrombinase activity and did not affect the rate of occlusive thrombus formation. In plasma, NB4, HL60 and AML14 shortened clotting times in a cell-count, PS- and TF-dependent manner. Exposure of cultured NB4, HL60, and AML14 cells to the chemotherapeutic agent daunorubicin increased their extrinsic tenase activity and PS expression. Clot initiation time inversely correlated with logarithm of PS index, defined as the product of multiplying leukocyte count with cell surface PS exposure. We propose that leukemia cell PS index may serve as a biomarker for procoagulant activity.

  4. Pathogenesis and early management of non-ST-segment elevation acute coronary syndromes.

    PubMed

    Ayala, Tomas H; Schulman, Steven P

    2006-02-01

    NSTE ACS is a clinically significant problem. Endothelial dysfunction triggered by traditional cardiovascular risk factors (and perhaps by other as yet unidentified risks) in the susceptible host leads to the formation and development of atherosclerotic plaque. Inflammatory mediators and mechanical stresses contribute to plaque rupture by disrupting the protective fibrous cap. In about 25% of patients who have ACS, typically those who are younger, female, or smokers, plaque erosion seems to be the main underlying pathologic mechanism. Endothelial alteration, inflammation,or exposure of the lipid core results in the release of TF, vWF, and PAF. The release of these factors leads to platelet activation and aggregation as well as to the formation of a fibrin clot, resulting in arterial thrombosis that occludes the vessel. A variety of factors, including circulating catecholamines, LDL levels, blood glucose levels, and systemic thrombogenic factors, can affect the extent and stability of the thrombus, thereby determining whether the occlusion is complete and fixed, labile and nonocclusive (NSTE ACS),or clinically silent resulting in a mural thrombus and plaque growth. The acute treatment of NSTEACS is directed at interrupting the prothrombotic environment surrounding the ruptured plaque; thus, antiplatelet agents such as aspirin, clopidogrel, and glycoprotein IIb/IIla receptor antagonists,as well as anticoagulants such as heparin, are the mainstays of early therapy. PMID:16326254

  5. Disseminated Intravascular Coagulation with Congestive Heart Failure and Left Ventricular Thrombus: A Case Report with Literature Review of 7 Cases

    PubMed Central

    Belov, Dmitri; Lyubarova, Radmila; Fein, Steven; Torosoff, Mikhail

    2015-01-01

    Patient: Male, 55 Final Diagnosis: Disseminated intravascular coagulation Symptoms: Leg pain • short of breath • swelling legs Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual clinical course Background: Coagulation abnormalities can accompany acute congestive heart failure (CHF). However, disseminated intravascular coagulation (DIC) is rarely documented in such patients. DIC is characterized by generalized excessive activation of coagulation pathways followed by their depletion with secondary activation of anticoagulation and fibrinolysis. Treatment of the cause is an integral part of management of DIC; thus, recognition of the cause is critical. Case Report: A 55-year-old previously healthy man presented with breathlessness, swelling of both legs, and left leg pain. His physical exam result was consistent with decompensated heart failure. Further testing revealed multiple deep venous thrombi in the upper and lower extremities, arterial occlusion in the left popliteal artery, and an unusual cyst-like left ventricular thrombus. His laboratory evaluation was consistent with severe acute DIC. The patient was managed aggressively with diuretics, transfusions of platelets, and cryoprecipitate and was subsequently anticoagulated. His platelet count and coagulation parameters normalized and coronary angiography did not reveal any obstructive lesions. On day 22, an echocardiogram revealed and MRI confirmed that the intracardiac thrombus had disappeared. He underwent revascularization of the left leg and was successfully discharged from the hospital. Conclusions: Severe biventricular non-ischemic cardiac dysfunction with intra-cardiac thrombi should be considered in patients presenting with DIC. In addition to anticoagulation, treatment of underlying heart failure is critical in such cases. PMID:25637329

  6. Quantification of experimental venous thrombus resolution by longitudinal nanogold-enhanced micro-computed tomography

    PubMed Central

    Grover, Steven P.; Saha, Prakash; Jenkins, Julia; Mukkavilli, Arun; Lyons, Oliver T.; Patel, Ashish S.; Sunassee, Kavitha; Modarai, Bijan; Smith, Alberto

    2015-01-01

    Introduction The assessment of thrombus size following treatments directed at preventing thrombosis or enhancing its resolution has generally relied on physical or histological methods. This cross-sectional design imposes the need for increased numbers of animals for experiments. Micro-computed tomography (microCT) has been used to detect the presence of venous thrombus in experimental models but has yet to be used in a quantitative manner. In this study, we investigate the use of contrast-enhanced microCT for the longitudinal assessment of experimental venous thrombus resolution. Materials and methods Thrombi induced by stenosis of the inferior vena cava in mice were imaged by contrast-enhanced microCT at 1, 7 and 14 days post-induction (n = 18). Thrombus volumes were determined longitudinally by segmentation and 3D volume reconstruction of microCT scans and by standard end-point histological analysis at day 14. An additional group of thrombi were analysed solely by histology at 1, 7 and 14 days post-induction (n = 15). Results IVC resident thrombus was readily detectable by contrast-enhanced microCT. MicroCT-derived measurements of thrombus volume correlated well with time-matched histological analyses (ICC = 0.75, P < 0.01). Thrombus volumes measured by microCT were significantly greater than those derived from histological analysis (P < 0.001). Intra- and inter-observer analyses were highly correlated (ICC = 0.99 and 0.91 respectively, P < 0.0001). Further histological analysis revealed noticeable levels of contrast agent extravasation into the thrombus that was associated with the presence of neovascular channels, macrophages and intracellular iron deposits. Conclusion Contrast-enhanced microCT represents a reliable and reproducible method for the longitudinal assessment of venous thrombus resolution providing powerful paired data. PMID:26489729

  7. Free floating left atrial ball thrombus: a rare cause of stroke.

    PubMed

    Rider, Oliver J; Malhotra, Aneil; Newton, James D

    2013-10-01

    In the setting of mitral valve stenosis and atrial fibrillation, left atrial ball thrombus is a rare but recognized cause of stroke and can occur even in the presence of therapeutic anticoagulation. This case report highlights the need for echocardiography to rule out treatable cardioembolic substrates for stroke. We report a case of cardioembolic stroke as a result of free floating left atrial ball thrombus presenting as a complication of rheumatic mitral valve disease. This case highlights that, in all patients with a history of structural heart disease, atrial fibrillation, or rheumatic fever, prompt cardiac ultrasound to exclude free floating atrial thrombus is essential. PMID:22959106

  8. Deficiency of Src homology 2 domain–containing inositol 5-phosphatase 1 affects platelet responses and thrombus growth

    PubMed Central

    Séverin, Sonia; Gratacap, Marie-Pierre; Lenain, Nadège; Alvarez, Laetitia; Hollande, Etienne; Penninger, Josef M.; Gachet, Christian; Plantavid, Monique; Payrastre, Bernard

    2007-01-01

    Platelets are critical for normal hemostasis. Their deregulation can lead to bleeding or to arterial thrombosis, a primary cause of heart attack and ischemic stroke. Src homology 2 domain–containing inositol 5-phosphatase 1 (SHIP1) is a 5-phosphatase capable of dephosphorylating the phosphatidylinositol 3,4,5-trisphosphate second messenger into phosphatidylinositol 3,4-bisphosphate. SHIP1 plays a critical role in regulating the level of these 2 lipids in platelets. Using SHIP1-deficient mice, we found that its loss affects platelet aggregation in response to several agonists with minor effects on fibrinogen binding and β3 integrin tyrosine phosphorylation. Accordingly, SHIP1-null mice showed defects in arterial thrombus formation in response to a localized laser-induced injury. Moreover, these mice had a prolonged tail bleeding time. Upon stimulation, SHIP1-deficient platelets showed large membrane extensions, abnormalities in the open canalicular system, and a dramatic decrease in close cell-cell contacts. Interestingly, SHIP1 appeared to be required for platelet contractility, thrombus organization, and fibrin clot retraction. These data indicate that SHIP1 is an important element of the platelet signaling machinery to support normal hemostasis. To our knowledge, this is the first report unraveling an important function of SHIP1 in the activation of hematopoietic cells, in contrast to its well-documented role in the negative regulation of lymphocytes. PMID:17347685

  9. Resolution of Internal Carotid Arterial Thrombus by the Thrombolytic Action of Dabigatran: A first case report.

    PubMed

    Akiyama, Hisanao; Hoshino, Masashi; Shimizu, Takahiro; Hasegawa, Yasuhiro

    2016-04-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) have been reported to cause resolution of intracardiac thrombus, but there have been no reported cases of internal carotid arterial thrombus resolution.We report a case of a 76-year-old man in whom an internal carotid arterial thrombus resolved after administration of the NOAC dabigatran at a dose of 110 mg twice daily.This is the first reported case of carotid arterial thrombus resolution after oral intake of NOAC (direct thrombin and factor Xa inhibitors), to the best of our knowledge.We conclude that this case had major clinical significance because it might represent one of the multiple effects of NOACs. PMID:27057852

  10. Novel Percutaneous Radiofrequency Ablation of Portal Vein Tumor Thrombus: Safety and Feasibility

    SciTech Connect

    Mizandari, Malkhaz; Ao, Guokun; Zhang Yaojun; Feng Xi; Shen Qiang; Chen Minshan; Lau, Wan Yee; Nicholls, Joanna; Jiao Long; Habib, Nagy

    2013-02-15

    We report our experience of the safety of partial recanalization of the portal vein using a novel endovascular radiofrequency (RF) catheter for portal vein tumor thrombosis. Six patients with liver cancer and tumor thrombus in the portal vein underwent percutaneous intravascular radiofrequency ablation (RFA) using an endovascular bipolar RF device. A 0.035-inch guidewire was introduced into a tributary of the portal vein and through which a 5G guide catheter was introduced into the main portal vein. After manipulation of the guide catheter over the thrombus under digital subtraction angiography, the endovascular RF device was inserted and activated around the thrombus. There were no observed technique specific complications, such as hemorrhage, vessel perforation, or infection. Post-RFA portography showed partial recanalization of portal vein. RFA of portal vein tumor thrombus in patients with hepatocellular carcinoma is technically feasible and warrants further investigation to assess efficacy compared with current recanalization techniques.

  11. Une angiocholite secondaire à un thrombus tumoral d'une tumeur neuroendocrine primitive du foie

    PubMed Central

    Baba, Hicham; Allaoui, Mohamed; Elfahssi, Mohammed; Bounaim, Ahmed; Ali, Abdelmounaim Ait; Oukabli, Mohamed; Sair, Khalid; Zentar, Aziz

    2015-01-01

    Nous rapportons le cas exceptionnel d'une patiente de 54 ans prise en charge pour une angiocholite due à un thrombus tumoral, d'une tumeur neuroendocrine primitive (TNE Ive) du foie, dans la voie biliaire principale. PMID:26966504

  12. INTERCONNECTION BETWEEN NITRIC OXIDE FORMATION AND HYPERSENSITIVITY PARAMETERS UNDER GUINEA PIG MODEL OF ACUTE ASTHMA WITH MULTIPLE CHALLENGES.

    PubMed

    Parilova, O O; Shandrenko, S G

    2015-01-01

    An immunoregulatory role of nitric oxide (NO) in the development of adaptive immune responses associated with allergic diseases is very important. The present study extended these observations by the examination of the reciprocal changes in characteristic immunologic parameters of the disease and NO level of bronchoalveolar lavage (BAL) cells under guinea pig model of acute asthma with multiple challenges. Development of guinea pig Th2 mediated asthma was accompanied by increasing the level of allergic markers: ovalbumin (OVA) specific IgG and IL-4. We demonstrated that the infiltrate of airway cells contributes to NO synthesis in the respiratory tract during allergic inflammation. The level of intracellular NO formation significantly correlated with plasma allergen specific IgG value in OVA-induced asthma. The presented data evidence that the elevated intracellular NO level in BAL fluid may reflect a nitrosative stress in respiratory tract in general, when allergic asthma exacerbation is present. PMID:26717602

  13. Glutathione transferase activity and formation of macromolecular adducts in two cases of acute methyl bromide poisoning.

    PubMed Central

    Garnier, R; Rambourg-Schepens, M O; Müller, A; Hallier, E

    1996-01-01

    OBJECTIVES: To determine the activity of glutathione transferase and to measure the S-methylcysteine adducts in blood proteins, after acute inhalation exposure to methyl bromide. To examine the influence of the polymorphism of glutathione-S-transferase theta (GSTT1) on the neurotoxicity of methyl bromide. METHODS: Two workers acutely exposed to methyl bromide with inadequate respiratory protective devices were poisoned. Seven weeks after the accident, blood samples were drawn from both patients, for measurement of glutathione transferase activity in erythrocytes (conjugator status--that is, GSTT1 phenotype) and measurement of binding products of methyl bromide with blood proteins. Conjugator status was determined by a standard procedure. The binding product of methyl bromide, S-methylcysteine, was measured in globin and albumin. RESULTS: Duration and intensity of exposure were identical for both patients as they worked together with the same protective devices and with similar physical effort. However, one patient had very severe poisoning, whereas the other only developed mild neurotoxic symptoms. The first patient was a "conjugator" with normal glutathone transferase activity, whereas this activity was undetectable in the erythrocytes of the second patient, who consequently had higher concentrations of S-methylcysteine adduct in albumin (149 v 91 nmol/g protein) and in globin (77 v 30 nmol/g protein). CONCLUSIONS: Methyl bromide is genotoxic and neurotoxic. Its genotoxicity seems to be the consequence of the alkylating activity of the parent compound, and conjugation to glutathione has a protective effect. The data presented here suggest a different mechanism for methyl bromide neurotoxicity which could be related to the transformation of methylglutathione into toxic metabolites such as methanethiol and formaldehyde. If such metabolites are the ultimate toxic species, N-acetylcysteine treatment could have a toxifying rather than a detoxifying effect. PMID:8704864

  14. Nitric oxide formation in acutely rejecting cardiac allografts correlates with GTP cyclohydrolase I activity

    PubMed Central

    2005-01-01

    Inducible nitric oxide synthase (iNOS) is a prominent component of the complex array of mediators in acute graft rejection. While NO production is determined by iNOS expression, BH4 (tetrahydrobiopterin), a cofactor of iNOS synthesized by GTP cyclohydrolase I, has been considered critical in sustaining NO production. In the present study, we examined time-dependent changes in iNOS and GTP cyclohydrolase I in rat cardiac allografts. The increase in iNOS protein and mRNA in allografts was similar at POD4 (post-operative day 4) and POD6. However, the peak increase in intragraft NO level at POD4 was not sustained at POD6. This disparity could not be explained by any decrease in iNOS enzyme activity measured ex vivo with optimal amounts of substrate and cofactors. Lower iNOS activity could be explained by changes in total biopterin levels in allografts at POD4 that was decreased to baseline at POD6. Changes in biopterin production correlated with lower GTP cyclohydrolase I protein levels but not by any change in GTP cyclohydrolase I mRNA. Functionally, allografts displayed bradycardia and distended diastolic and systolic dimensions at POD6 but not at POD4. Likewise, histological rejection scores were increased at POD4 but with a secondary increased stage at POD6. It is hypothesized that the dissimilar amounts of NO at early and later stages of rejection is due to uncoupling of iNOS arising from disproportionate synthesis of BH4. These findings provide insight into a potential pathway regulating NO bioactivity in graft rejection. Such knowledge may potentially assist in the design of newer strategies to prevent acute graft rejection. PMID:16000090

  15. Less invasive treatment option for renal carcinoma with venous tumor thrombus

    PubMed Central

    Nagy, Zoltán; Pánovics, József; Szendrői, Attila; Szász, Attila Marcell; Harsányi, László; Romics, Imre

    2014-01-01

    Aim To retrospectively analyze patients treated by renal tumor and venous tumor thrombus (VTT) removal and to introduce a less stressful and safer surgical method without thoracotomy in Neves level 3 cases. Methods From 2002 to 2011, 33 patients underwent surgery for renal cell cancer combined with tumor thrombus of the inferior vena cava. Preoperative symptoms, tumor-node-metastasis classification of tumors, thrombus extension classified by Neves and Zincke system, types of surgical interventions, complications, postoperative management, and survival results were analyzed. Results Ten patients had level 1, 17 had level 2, and 6 had level 3 thrombi according to Neves and Zincke. In 5 patients with level 3 thrombi, the liver was mobilized without thoracotomy and in 1 patient endoluminal occlusion was utilized. There was no intraoperative mortality. The median survival time of 10 patients who died during follow-up period was 36.6 months (range, 1-116 months). Conclusion Renal cell cancer complicated with tumor thrombus without metastasis can be curable by performing a complete resection. The thrombus level determines the surgical approach and method. Our results confirm that level 3 caval vein tumor thrombus can be safely surgically treated by laparotomy with liver mobilization. Thoracotomy, use of cardiopulmonary bypass, and hypothermic circulatory arrest can be avoided with adequate liver- and vascular surgery methods. PMID:24891285

  16. Histological and Biomechanical Changes in a Mouse Model of Venous Thrombus Remodeling

    PubMed Central

    Lee, Y.-U.; Lee, A.Y.; Humphrey, J.D.; Rausch, M.K.

    2016-01-01

    BACKGROUND Deep vein thrombosis and the risk of pulmonary embolism are significant causes of morbidity and mortality. Much remains unclear, however, about the mechanisms by which a venous thrombus initiates, progresses, or resolves. In particular, there is a pressing need to characterize the evolving mechanical properties of a venous thrombus for its mechanical integrity is fundamental to many disease sequelae. OBJECTIVE The primary goal of the present study was to initiate a correlation between evolving histological changes and biomechanical properties of venous thrombus. METHODS We employed an inferior vena cava ligation model in mice to obtain cylindrical samples of thrombus that were well suited for mechanical testing and that could be explanted at multiple times following surgery. Using uniaxial micro-mechanical testing, we collected stress-stretch data that were then fit with a microstructurally-inspired material model before submitting the samples to immunohistological examination. RESULTS We found that venous thrombus underwent a radially inward directed replacement of fibrin with collagen between 2 weeks and 4 weeks of development, which was accompanied by the infiltration of inflammatory and mesenchymal cells. These histological changes correlated with a marked increase in material stiffness. CONCLUSIONS We demonstrated that 2 to 4 week old venous thrombus undergoes drastic remodeling from a fibrin-dominated mesh to a collagen-dominated microstructure and that these changes are accompanied by dramatic changes in biomechanical behavior. PMID:26444224

  17. Management of Primitive Neuroectodermal Tumor of the Kidney with Inferior Vena Cava Thrombus

    PubMed Central

    Gupta, Sahil; Majumder, Kaustav; Chahal, Anurag; Saini, Ashish K.; Gupta, Arjun

    2016-01-01

    Primitive neuroectodermal tumors (PNET) are an aggressive group of small round cell tumors usually arising in the nervous system and affecting children. They have a tendency for local invasion, distant spread and formation of tumor thrombi. The kidney is a rare primary location for these tumors. Outcomes are frequently poor due to late diagnosis (Wilms tumor is a more common tumor in this population) and early spread. Immunohistochemistry is invaluable in making the diagnosis of PNET. We report a case of a primary renal PNET with extensive tumor thrombus into the inferior vena cava, and lung metastasis in a pediatric patient, and its successful management. Our 14-year-old patient with renal PNET was managed with radical nephrectomy, thrombectomy and chemotherapy and remains disease free to date. The diagnosis of renal PNETs should be considered in young adult patients who present with aggressive renal masses at initial presentations. Despite its aggressive nature, good outcomes can be achieved by a multimodality therapeutic strategy. PMID:26989372

  18. Renal Dysfunction on Admission Predicts No-Reflow Phenomenon in Patients Undergoing Manual Thrombus Aspiration during Primary Percutaneous Coronary Intervention

    PubMed Central

    Sensoy, Baris; Uzunget, Sezen Baglan; Acikgoz, SadikKadri; Sensoy, Nur; Sen, Fatih; Acar, Burak; Canpolat, Uğur; Ozeke, Ozcan; Cay, Serkan; Maden, Orhan

    2016-01-01

    Background No-reflow is a frequent complication during percutaneous coronary intervention (PCI) for acute ST segment elevation myocardial infarction (STEMI). Available data is limited regarding its impact on short-term outcomes in patients undergoing manual thrombus aspiration. Renal impairment is also associated with higher complication rates in STEMI. Herein, we aimed to evaluate the impact of baseline renal dysfunction on the no- reflow phenomenon and the association of no-reflow phenomenon with early clinical outcomes. Methods A total of 94 consecutive STEMI patients who underwent primary stent-based PCI and thrombus aspiration were enrolled. No-reflow was established by the use of angiographic and electrocardiographic reperfusion criteria, respectively. Additionally angiographic and clinical follow-up data were also recorded. Results In our study, the no-reflow phenomenon was observed in 10 patients (11%) angiographically and in 23 patients (24%) electrocardiographically. Whereas, the the estimated glomerular filtration rate (eGFR) [odds ratio (OR) 10.4], hypertension (OR 6.2), previous MI (OR 6.5), previous PCI history, (OR 4.2), predilatation (OR 7.2), final balloon pressure (OR 0.9) were found to be the significant predictors of angiographic no-reflow, only reperfusion time was the predictor of electrocardiographic no-reflow (OR 1.12) at univariate analysis. After adjustment, lower eGFR (OR 14.8) was found to be the independent predictor for angiographic no-reflow. In-hospital mortality was more common in patients with either no-reflow condition separately. Conclusions Longer ischemic time and lower initial eGFR values were associated with no-reflow phenomenon. Irrespective of poor reperfusion criteria, no-reflow phenomenon is associated with in-hospital outcome. Future efforts should be made to reduce the incidence of no-reflow especially in patients with lower initial eGFR values. PMID:27122949

  19. Effects of acute methamphetamine on emotional memory formation in humans: encoding vs consolidation.

    PubMed

    Ballard, Michael E; Weafer, Jessica; Gallo, David A; de Wit, Harriet

    2015-01-01

    Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH), administered either before (encoding phase) or immediately after (consolidation phase) study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60) were randomly assigned to either an encoding group (N = 29) or a consolidation group (N = 31). Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg) either 45 min before (encoding) or immediately after (consolidation) viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29) or adequate sleepers (6 or more hours; n = 31) prior to analyses. For adequate sleepers, METH (20 mg) administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative), compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies. PMID:25679982

  20. Effects of Acute Methamphetamine on Emotional Memory Formation in Humans: Encoding vs Consolidation

    PubMed Central

    Ballard, Michael E.; Weafer, Jessica; Gallo, David A.; de Wit, Harriet

    2015-01-01

    Understanding how stimulant drugs affect memory is important for understanding their addictive potential. Here we examined the effects of acute d-methamphetamine (METH), administered either before (encoding phase) or immediately after (consolidation phase) study on memory for emotional and neutral images in healthy humans. Young adult volunteers (N = 60) were randomly assigned to either an encoding group (N = 29) or a consolidation group (N = 31). Across three experimental sessions, they received placebo and two doses of METH (10, 20 mg) either 45 min before (encoding) or immediately after (consolidation) viewing pictures of emotionally positive, neutral, and negative scenes. Memory for the pictures was tested two days later, under drug-free conditions. Half of the sample reported sleep disturbances following the high dose of METH, which affected their memory performance. Therefore, participants were classified as poor sleepers (less than 6 hours; n = 29) or adequate sleepers (6 or more hours; n = 31) prior to analyses. For adequate sleepers, METH (20 mg) administered before encoding significantly improved memory accuracy relative to placebo, especially for emotional (positive and negative), compared to neutral, stimuli. For poor sleepers in the encoding group, METH impaired memory. METH did not affect memory in the consolidation group regardless of sleep quality. These results extend previous findings showing that METH can enhance memory for salient emotional stimuli but only if it is present at the time of study, where it can affect both encoding and consolidation. METH does not appear to facilitate consolidation if administered after encoding. The study also demonstrates the important role of sleep in memory studies. PMID:25679982

  1. Extensive tumor thrombus in a case of carcinoma lung detected by F18-FDG-PET/CT.

    PubMed

    Mudalsha, Ravina; Jacob, Mj; Pandit, Ag; Jora, Charu

    2011-04-01

    Tumor thrombus is a rare complication of solid cancers, mainly seen in cases of renal cell carcinoma, wilm's tumor, testicular carcinoma, adrenal cortical carcinoma and hepatocellular carcinoma.[1] Tumor thrombus in inferior vena cava is a rare complication of primary carcinoma lung. It should be identified so as to rule out venous thromboembolism and avoiding unnecessary anticoagulant therapy. We describe a case where F18-Fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET/CT) helped to identify extensive tumor thrombus. PMID:22174524

  2. Extensive tumor thrombus in a case of carcinoma lung detected by F18-FDG-PET/CT

    PubMed Central

    Mudalsha, Ravina; Jacob, MJ; Pandit, AG; Jora, Charu

    2011-01-01

    Tumor thrombus is a rare complication of solid cancers, mainly seen in cases of renal cell carcinoma, wilm's tumor, testicular carcinoma, adrenal cortical carcinoma and hepatocellular carcinoma.[1] Tumor thrombus in inferior vena cava is a rare complication of primary carcinoma lung. It should be identified so as to rule out venous thromboembolism and avoiding unnecessary anticoagulant therapy. We describe a case where F18-Fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET/CT) helped to identify extensive tumor thrombus. PMID:22174524

  3. Molecular MRI of intracranial thrombus in a rat ischemic stroke model

    PubMed Central

    Uppal, Ritika; Ay, Ilknur; Dai, Guangping; Kim, Young Ro; Sorensen, A. Gregory; Caravan, Peter

    2010-01-01

    Background and Purpose Intracranial thrombus is a principal feature in most ischemic stroke, and thrombus location and size may correlate with outcome and response to thrombolytic therapy. EP-2104R, a fibrin-specific molecular MR agent, was previously shown to enhance extracranial thrombi in animal models and recently, in clinical trials. The purpose of this work was to determine if a fibrin-specific molecular MR probe could noninvasively characterize intracranial thrombi. Methods Embolic stroke was induced in adult rats by occlusion of the right internal carotid artery with an aged thrombus. Diffusion weighted imaging, time of flight angiography, and high resolution three dimensional T1-weighted MRI were performed at 4.7T prior to and following contrast agents EP-2104R (10 µmol/kg, n=6) or Gd-DTPA (200 µmol/kg, control, n=5). Gd levels in thrombus, brain, and blood were determined by ex vivo elemental analysis. Results In all animals, MR angiography revealed a flow deficit and diffusion-weighted imaging showed a hyperintensity consistent with ischemia. EP-2104R-enhanced MRI resulted in visualization of all occlusive thrombi (6/6) as well as vessel wall enhancement in all 6 animals with high contrast to noise relative to blood (10.7 post EP-2104R vs. 0.54 pre, p<0.0001). Gd-DTPA injected animals showed no occlusive thrombus or vessel wall enhancement (0/5). The concentration of Gd in the thrombus post-EP2104 was 18 times that in the blood pool. Conclusions EP-2104R enhanced MRI successfully identifies intracranial thrombus in a rat embolic stroke model. PMID:20395615

  4. Disseminated tuberculosis with acute respiratory distress syndrome lacking granuloma formation in the lung.

    PubMed

    Nakao, Akira; Ishii, Hiroshi; Igata, Fumiyasu; Kushima, Hisako; Fujita, Masaki; Hisano, Satoshi; Watanabe, Kentaro

    2016-09-01

    A 66-year-old woman, who had been treated with systemic corticosteroids for four months for vasculitis of unknown etiology, was referred to our department due to a fever, dyspnea and patchy ground-glass opacities on chest computed tomography. As transbronchial biopsy specimens were suggestive of interstitial pneumonia, the prescribed dose of corticosteroids was increased. However, the patient developed pyrexia and presented diffuse ground-glass attenuation in the lungs bilaterally. Antituberculous drugs were administered because a previous blood interferon-gamma release assay was positive, however, the patient died of severe respiratory failure within several days, and cultures of her blood, urine and bone marrow posthumously revealed Mycobacterium tuberculosis. An autopsy revealed multiple foci of air-space pneumonia containing numerous acid-fast bacilli without granuloma formation, accompanied by diffuse alveolar damage. An immunosuppressive condition might inhibit air-space pneumonia to become granulomatous inflammation as an initial stage of pulmonary tuberculosis. PMID:26972247

  5. Acute Myocardial Infarction in Nephrotic Syndrome.

    PubMed

    Krishna, Kavita; Hiremath, Shirish; Lakade, Sachin; Davakhar, Sudarshan

    2015-11-01

    A 28 year old male, known case of nephrotic syndrome since 12 years, hypertensive presented with acute myocardial infarction (AMI) and accelerated hypertension. Coronary angiography revealed 100% thrombotic occlusion of mid left anterior descending artery, treated with thrombus aspiration and intracoronary tirofiban and nitroglycerine. He was stabilized within 24 hours. The pathogenesis of AMI in nephrotic syndrome has been discussed with this case report. PMID:27608787

  6. Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages

    PubMed Central

    Ran, Lin; Yu, Qilin; Zhang, Shu; Xiong, Fei; Cheng, Jia; Yang, Ping; Xu, Jun-Fa; Nie, Hao; Zhong, Qin; Yang, Xueli; Yang, Fei; Gong, Quan; Kuczma, Michal; Kraj, Piotr; Gu, Weikuan; Ren, Bo-Xu; Wang, Cong-Yi

    2015-01-01

    ABSTRACT Acute schistosomiasis is characterized by pro-inflammatory responses against tissue- or organ-trapped parasite eggs along with granuloma formation. Here, we describe studies in Cx3cr1−/− mice and demonstrate the role of Cx3cr1 in the pathoetiology of granuloma formation during acute schistosomiasis. Mice deficient in Cx3cr1 were protected from granuloma formation and hepatic injury induced by Schistosoma japonicum eggs, as manifested by reduced body weight loss and attenuated hepatomegaly along with preserved liver function. Notably, S. japonicum infection induced high levels of hepatic Cx3cr1 expression, which was predominantly expressed by infiltrating macrophages. Loss of Cx3cr1 rendered macrophages preferentially towards M2 polarization, which then led to a characteristic switch of the host immune defense from a conventional Th1 to a typical Th2 response during acute schistosomiasis. This immune switch caused by Cx3cr1 deficiency was probably associated with enhanced STAT6/PPAR-γ signaling and increased expression of indoleamine 2,3-dioxygenase (IDO), an enzyme that promotes M2 polarization of macrophages. Taken together, our data provide evidence suggesting that CX3CR1 could be a viable therapeutic target for treatment of acute schistosomiasis. PMID:26035381

  7. Segmentation of the thrombus of giant intracranial aneurysms from CT angiography scans with lattice Boltzmann method.

    PubMed

    Chen, Yu; Navarro, Laurent; Wang, Yan; Courbebaisse, Guy

    2014-01-01

    Computed Tomography Angiography (CTA) plays an essential role in the diagnosis, treatment evaluation, and monitoring of cerebral aneurysms. Segmentation of CTA medical images of giant intracranial aneurysms (GIA) provides quantitative measurements of thrombus and aneurysms geometrical characteristics allowing 3D reconstruction. In fact, GIA demonstrated neuroradiological features and propensity of partial or total spontaneous intra-aneurysmal thrombosis generating a thrombus. Despite intensive researches on medical image segmentation, aneurysm (Lumen, Thrombus, and Parent Blood Vessels) segmentation remains as a difficult problem that has not been yet resolved. In this paper, we proposed a Lattice Boltzmann Geodesic Active Contour Method (LBGM) for aneurysm segmentation in CTA images in order to estimate both the volumes of the thrombus and the aneurysm. Although the noise in the CTA images is very strong and the edges of the thrombus are not so different than the surrounding tissues, the aneurysms are segmented effectively. Based on these results, a method using a dome-neck aspect ratio (AR) parameter for the evaluation of the Spontaneous Thrombosis (ST) phenomena demonstrates the promising potentiality of this LBGM for clinical applications. PMID:24077409

  8. Registration, segmentation, and visualization of confocal microscopy images of arterial thrombus

    NASA Astrophysics Data System (ADS)

    Garg, Ishita; Camp, Jon J.; McBane, Robert; Wysokinski, Waldemar; Robb, Richard A.

    2004-05-01

    Arterial thrombosis causes death or paralysis of an organ, as it migrates to and localizes in different parts of the body. Massive pulmonary emboli cause 50,000 deaths per year. The cause and origin of arterial thrombosis is not well understood nor objectively characterized. The object of this study was to investigate the microscopic structure of arterial thrombus to better understand this pathology. Confocal microscopy cross-sectional images of an embolized thrombus in the coronary artery were obtained. Adjacent pairs of sections were stained with two different stains, fibrin and CD61, to reveal mutually complementary information. The very thin adjacent slices were treated as one slice. Adjacent slices were registered by a combination of manual and automatic techniques using Analyze software developed in the Biomedical Imaging Resource at Mayo. After smoothing the images with a median filter, the CD61 and fibrin stained section images were used together to segment the tissues by multispectral classification. The image volume was classified into background, platelets and surrounding tissue, and thrombus. The segmented volume was then rendered for visualization and analysis of structure of the thrombus in three dimensions. Preliminary results are promising. Such correlation of structural and histological information may be helpful in determining the origin of the thrombus.

  9. Synthetic thrombus model for in-vitro studies of laser thrombolysis

    NASA Astrophysics Data System (ADS)

    Hermes, Robert E.; Trajkovska, Keti

    1998-05-01

    Laser thrombolysis is the controlled ablation of a thrombus (blood clot) blockage in a living arterial system. Theoretical modeling of the interaction of laser light with thrombi relies on the ability to perform in vitro experiments with well characterized surrogate materials. A synthetic thrombus formulation may offer more accurate results when compared to in vivo clinical experiments. We describe here the development of new surrogate materials based on formulations incorporating chicken egg, guar gum, modified food starch, and a laser light absorbing dye. The sound speed and physical consistency of the materials were very close to porcine (arterial) and human (venous) thrombi. Photographic and videotape recordings of pulsed dye laser ablation experiments under various experimental conditions were used to evaluate the new material as compared to in vitro tests with human (venous) thrombus. The characteristics of ablation and mass removal were similar to that of real thrombi, and therefore provide a more realistic model for in vitro laser thrombolysis when compared to gelatin.

  10. Thrombus imaging in a primate model with antibodies specific for an external membrane protein of activated platelets

    SciTech Connect

    Palabrica, T.M.; Furie, B.C.; Konstam, M.A.; Aronovitz, M.J.; Connolly, R.; Brockway, B.A.; Ramberg, K.L.; Furie, B.

    1989-02-01

    The activated platelet is a potential target for the localization of thrombi in vivo since, after stimulation and secretion of granule contents, activated platelets are concentrated at sites of blood clot formation. In this study, we used antibodies specific for a membrane protein of activated platelets to detect experimental thrombi in an animal model. PADGEM (platelet activation-dependent granule-external membrane protein), a platelet alpha-granule membrane protein, is translocated to the plasma membrane during platelet activation and granule secretion. Since PADGEM is internal in unstimulated platelets, polyclonal anti-PADGEM and monoclonal KC4 antibodies do not bind to circulating resting platelets but do interact with activated platelets. Dacron graft material incubated with radiolabeled KC4 or anti-PADGEM antibodies in the presence of thrombin-activated platelet-rich plasma bound most of the antibody. Imaging experiments with 123I-labeled anti-PADGEM in baboons with an external arterial-venous Dacron shunt revealed rapid uptake in the thrombus induced by the Dacron graft; control experiments with 123I-labeled nonimmune IgG exhibited minimal uptake. Deep venous thrombi, formed by using percutaneous balloon catheters to stop blood flow in the femoral vein of baboons, were visualized with 123I-labeled anti-PADGEM. Thrombi were discernible against blood pool background activity without subtraction techniques within 1 hr. No target enhancement was seen with 123I-labeled nonimmune IgG. 123I-labeled anti-PADGEM cleared the blood pool with an initial half-disappearance time of 6 min and did not interfere with hemostasis. These results indicate that radioimmunoscintigraphy with anti-PADGEM antibodies can visualize thrombi in baboon models and is a promising technique for clinical thrombus detection in humans.

  11. Application of cystoscope in surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus.

    PubMed

    Li, Nan; Wei, Xu-Biao; Cheng, Shu-Qun

    2016-06-14

    Development of portal vein tumor thrombus deteriorates the prognosis of hepatocellular carcinoma, while surgical treatment can offer a promising prognosis for selected patients. However, the possibility of residual lesions in portal vein after conventional thrombectomy is a main risk factor leading to postoperative recurrence. Therefore, ensuring the complete removal of tumor thrombus during operation is critical to improve prognosis. For the first time, we report here one case of hepatocellular carcinoma with portal vein tumor thrombus in which cystoscope was successfully applied as a substitute of intravascular endoscope to visualize the cavity of the portal vein. The patient was a 61-year-old man with a 7-cm tumor in the right lobe of the liver, with tumor thrombus invading the right branch and adjacent to the conjunction of the portal vein. After removal of the tumor, the Olympus CYF-VA2 cystoscope was used to check the portal vein from the opening stump of the right branch of the portal vein. In this case, residual thrombus tissue was found near the opening stump and the conjunction of the portal vein. The residual lesion was carefully retrieved from the stump after retraction of the cystoscope. The procedure was repeated until no residual lesion was found. The whole duration time of thrombectomy was 22.5 (15 + 7.5) min. The patient was free from recurrence at 8 months after the procedure. Our work indicated that the cystoscope is a suitable substitute, with a proper size and function to check the portal vein system and ensure the curability of thrombectomy. Although well-designed clinic trails are still needed, this procedure may further improve the postoperative prognosis of hepatocellular carcinoma with portal vein tumor thrombus. PMID:27298574

  12. Application of cystoscope in surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus

    PubMed Central

    Li, Nan; Wei, Xu-Biao; Cheng, Shu-Qun

    2016-01-01

    Development of portal vein tumor thrombus deteriorates the prognosis of hepatocellular carcinoma, while surgical treatment can offer a promising prognosis for selected patients. However, the possibility of residual lesions in portal vein after conventional thrombectomy is a main risk factor leading to postoperative recurrence. Therefore, ensuring the complete removal of tumor thrombus during operation is critical to improve prognosis. For the first time, we report here one case of hepatocellular carcinoma with portal vein tumor thrombus in which cystoscope was successfully applied as a substitute of intravascular endoscope to visualize the cavity of the portal vein. The patient was a 61-year-old man with a 7-cm tumor in the right lobe of the liver, with tumor thrombus invading the right branch and adjacent to the conjunction of the portal vein. After removal of the tumor, the Olympus CYF-VA2 cystoscope was used to check the portal vein from the opening stump of the right branch of the portal vein. In this case, residual thrombus tissue was found near the opening stump and the conjunction of the portal vein. The residual lesion was carefully retrieved from the stump after retraction of the cystoscope. The procedure was repeated until no residual lesion was found. The whole duration time of thrombectomy was 22.5 (15 + 7.5) min. The patient was free from recurrence at 8 months after the procedure. Our work indicated that the cystoscope is a suitable substitute, with a proper size and function to check the portal vein system and ensure the curability of thrombectomy. Although well-designed clinic trails are still needed, this procedure may further improve the postoperative prognosis of hepatocellular carcinoma with portal vein tumor thrombus. PMID:27298574

  13. Multimodality Treatment for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

    PubMed Central

    Wang, Kang; Guo, Wei Xing; Chen, Min Shan; Mao, Yi Lei; Sun, Bei Cheng; Shi, Jie; Zhang, Yao Jun; Meng, Yan; Yang, Ye Fa; Cong, Wen Ming; Wu, Meng Chao; Lau, Wan Yee; Cheng, Shu Qun

    2016-01-01

    Abstract The optimal treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains controversial. We aimed to investigate the best treatment for patients with HCC with PVTT. From January 2002 to January 2014, the data from all consecutive patients with HCC with PVTT who underwent surgical treatment (ST),TACE,TACE combined with sorafenib (TACE-Sor), or TACE combined with radiotherapy (TACE-RT) in the 4 largest tertiary hospitals in China were analyzed retrospectively. The patients were divided into 3 subtypes according to the extent of PVTT in the portal vein (type I-III). The primary endpoint was overall survival (OS). A total of 1580 patients with HCC with PVTT were included in the study. The median survival times (MST) for ST (n = 745) for type I, II, and III patients (95% CI) were 15.9 (13.3–18.5), 12.5 (10.7–14.3), and 6.0 (4.3–7.7) months, respectively. The corresponding figures for patients after TACE (n = 604) were 9.3 (5.6–12.9), 4.9 (4.1–5.7), and 4.0 (3.1–4.9), respectively; for patients after TACE-Sor (n = 113) 12.0 (6.6–17.4), 8.9 (6.7–11.1), and 7.0 (3.0–10.9), respectively; and for patients after TACE-RT (n = 118) 12.2 (0–24.7), 10.6 (6.8–14.5), and 8.9 (5.2–12.6), respectively. Comparison among the different treatments for the 3 subtypes of PVTT patients after propensity score (PS) matching showed the effectiveness of ST to be the best for type I and type II PVTT patients, and TACE-RT was most beneficial for type III patients. Treatment was an independent risk factor of OS. ST was the best treatment for type I and II PVTT patients with Child-Pugh A and selected B liver function. TACE-RT should be given to type III PVTT patients. PMID:26986115

  14. Floating, non-occlusive, mobile aortic thrombus and splenic infarction associated with protein C deficiency.

    PubMed

    Sanon, Saurabh; Phung, Man Kien; Lentz, Rob; Buja, L Maximilian; Tung, Poyee Pansy; McPherson, David D; Fuentes, Francisco

    2009-12-01

    The authors report the case of a patient with isolated protein C deficiency detected later in life, presenting with a mobile aortic thrombus and splenic infarction. Only one such case has been previously described. This case emphasizes the importance of including the aorta in the search for a cause of systemic embolization and highlights the diagnostic options and management dilemmas. Although anticoagulation with subsequent reassessment of thrombus size can be considered for layered thrombi, mobile thrombi warrant early surgical intervention to minimize the risk for systemic embolization. This patient was treated surgically with encouraging results. PMID:19647398

  15. The prevention of circulatory collapse in left atrial myxoma or left atrail thrombus patients.

    PubMed

    Sun, Jie; Ding, Zhengnian

    2016-05-01

    Some patients with myxoma or thrombus may develop to severe hypotension or sudden death. In this article, we hypothesize a clinical scenario that when the myxoma or thrombus blocks in the mitral valve and causes significant hypotension during anesthesia or surgery. Increasing cardiac preload will be an effective preventive method to increasing the mitral valve annulus and decreasing the severity of stenosis, as a result it will prevent circulatory collapse. Our hypothesis will decrease the possibility of lethal mitral valve stenosis induced by left atrial mass blocking the mitral valve area. In addition, we should also maintain a relative slow heart rate and a relative high systemic vascular resistance. PMID:27063074

  16. Intracardiac thrombus in Behçet's disease: four new cases and a comprehensive literature review.

    PubMed

    Aksu, Tolga; Tufekcioglu, Omac

    2015-07-01

    Behçet's disease (BD) is a multisystem inflammatory disorder. Intracardiac thrombus formation (ICTF) is an uncommon but important complication of BD. To highlight recent insights into this disease, we aimed to review ICTF and other systemic involvements associated with ICTF in BD. We conducted a comprehensive review of the relevant literature in MEDLINE and EMBASE from 1966 to 2014 to analyze cumulated data about ICTF in BD. We aimed to evaluate 93 cases of BD with ICT (group 1), four of which have been recently identified and have not been discussed in the relevant literature yet, and to compare the frequency of pulmonary, venous and arterial involvements in group 1 and general Behçet population (group 2). The right heart was the most common site of ICTF in group 1. Pulmonary involvement, venous involvement (especially venous thrombosis) and arterial involvement were more frequent in group 1 than in group 2 (56 vs. 0.7 %, 42 vs. 10 % and 38 vs. 0.8 %, respectively, p < 0.0001). The diagnosis of BD should be considered if a patient presents with a mass in the right-sided cardiac chambers, even in the absence of the characteristic clinical manifestations of the illness. This approach is particularly applicable if the patient is a young man from the Mediterranean basin or the Middle East. All Behçet patients with ICTF must be investigated with thoracic computed tomography for pulmonary and arterial involvements and lower extremity venous Doppler ultrasonography for venous thrombosis, regardless of whether they are symptomatic for these systems. PMID:25381640

  17. Spontaneous echo contrast masking thrombus in giant left atrium of mitral stenosis-a dilemma in clinical diagnosis.

    PubMed

    Islam, Akm Monwarul; Salam, Md Abdus; Sayeed, Md Zahidus; Kibria, Md Golam

    2015-01-01

    Spontaneous echo contrast (SEC) and thrombus in enlarged left atrium (LA) are common in mitral valvular disease (MVD) and SEC is considered to be a prethrombotic condition. Reliable exclusion of LA thrombus is important before any definitive curative attempts like percutaneous transluminal mitral commissurotomy (PTMC), closed mitral commissurotomy (CMC) or innovative therapies like pulmonary vein isolation and percutaneous closure of the LA appendage. Echocardiography, particularly the transesophageal echocardiography (TEE) is considered to be the gold standard for the diagnosis and to exclude LA thrombus. However, LA thrombus may remain rarely undetected even by TEE potentially making the interventions a risky job. We present a case of mitral stenosis (MS) with giant LA where profuse, dense SEC masked the underlying thrombus in the LA cavity. PMID:26649032

  18. Spontaneous echo contrast masking thrombus in giant left atrium of mitral stenosis-a dilemma in clinical diagnosis

    PubMed Central

    Islam, AKM Monwarul; Salam, Md. Abdus; Sayeed, Md. Zahidus; Kibria, Md. Golam

    2015-01-01

    Spontaneous echo contrast (SEC) and thrombus in enlarged left atrium (LA) are common in mitral valvular disease (MVD) and SEC is considered to be a prethrombotic condition. Reliable exclusion of LA thrombus is important before any definitive curative attempts like percutaneous transluminal mitral commissurotomy (PTMC), closed mitral commissurotomy (CMC) or innovative therapies like pulmonary vein isolation and percutaneous closure of the LA appendage. Echocardiography, particularly the transesophageal echocardiography (TEE) is considered to be the gold standard for the diagnosis and to exclude LA thrombus. However, LA thrombus may remain rarely undetected even by TEE potentially making the interventions a risky job. We present a case of mitral stenosis (MS) with giant LA where profuse, dense SEC masked the underlying thrombus in the LA cavity. PMID:26649032

  19. Clinical update on the therapeutic use of clopidogrel: treatment of acute ST-segment elevation myocardial infarction (STEMI)

    PubMed Central

    Tran, Huyen; Mehta, Shamir R; Eikelboom, John W

    2006-01-01

    The pathogenesis of ST-elevation myocardial infarction (STEMI) involves plaque disruption, platelet aggregation and intracoronary artery thrombus formation. Aspirin is the cornerstone of antiplatelet therapy in patients with STEMI, reducing the risk of recurrent myocardial infarction or death during the acute phase and long term by about one-quarter. Recent large randomized trials have demonstrated that the addition of clopidogrel to aspirin reduces the risk of major ischemic events by up to a further one-third in patients with STEMI treated with fibrinolytic therapy and undergoing percutaneous coronary intervention, with no significant increase in bleeding. Thus, dual antiplatelet therapy with the combination of clopidogrel and aspirin is becoming the new standard of care for the management of patients with STEMI. PMID:17323592

  20. The Acute Coagulopathy of Trauma is due to Impaired Initial Thrombin Generation but not Clot Formation or Clot Strength

    PubMed Central

    Harr, Jeffrey N.; Moore, Ernest E.; Wohlauer, Max V.; Droz, Nathan; Fragoso, Miguel; Banerjee, Anirban; Silliman, Christopher C.

    2011-01-01

    The Acute Coagulopathy of Trauma (ACOT) has been described as a very early hypocoagulable state, but the mechanism remains controversial. One proposed mechanism is tissue hypoperfusion leading to protein C activation, with subsequent inhibition of Factors V and VIII. Variability in trauma has impeded the use of clinical data towards the elucidation of the mechanisms of ACOT, but thrombelastography (TEG) may provide insight by assessing hemostatic function from initial thrombin activation to fibrinolysis. We hypothesized that, in a controlled animal model of trauma/hemorrhagic shock, clotting factor dysfunction is the predominant mechanism in early ACOT. Methods Rats anesthetized by inhaled isoflurane (n=6) underwent laparotomy, and hemorrhage was induced to maintain a MAP of 35 mmHg for 30 minutes. Rats were then resuscitated with twice their shed blood volume in normal saline. TEG was performed at baseline, shock, and post-resuscitation periods. No heparin was given. Statistical analysis was performed by ANOVA with post-hoc Fisher’s test. Results Coagulation factor function was significantly impaired in the early stages of trauma/hemorrhagic shock. TEG R and SP-values were significantly increased from baseline to shock (p<0.001) and from shock to post-resuscitation periods (p<0.05). Delta (R-SP), a measure of thrombin generation, showed a significant increase (p<0.05) from baseline to shock. No significant changes were found in K, Angle, MA, and LY30 values. Conclusion Clotting factor derangement leading to impaired thrombin generation is the principle etiology of ACOT in this model and not the dynamics of clot formation, fibrin cross-linking, clot strength/platelet function, or fibrinolysis. PMID:21550061

  1. Direct observation of von Willebrand factor elongation and fiber formation on collagen during acute whole blood exposure to pathological flow

    PubMed Central

    Colace, T. V.; Diamond, S. L.

    2013-01-01

    Objective In severe stenosis, von Willebrand Factor (vWF) experiences millisecond exposures to pathological wall shear rates (γw). We sought to evaluate the deposition of vWF onto collagen surfaces under flow in these environments. Methods and Results Distinct from shear experiments that last many seconds, we deployed microfluidic devices for single-pass perfusion of whole blood or platelet free plasma (PFP) over fibrillar type 1 collagen (< 50 msec transit time) at pathological γw or spatial wall shear rate gradient (grad γw). Using fluorescent anti-vWF, long thick vWF fibers (>20 μm) bound to collagen were visualized at constant γw > 30,000 s−1 during perfusion of PFP, a process enhanced by EDTA. Rapid acceleration or deceleration of EDTA-PFP at grad γw = ± 5.5 × 105 to 4.3 × 107 s−1/cm did not promote vWF deposition. At 19,400 s−1, EDTA-blood perfusion resulted in rolling vWF-platelet nets, while blood perfusion (normal Ca2+) generated large vWF/platelet deposits that repeatedly embolized and were blocked by anti-GPIb or the α IIbβ3 inhibitor GR144053 and did not require grad γw. Blood perfusion at venous shear rate (200 s−1) produced a stable platelet deposit that was a substrate for massive but unstable vWF-platelet aggregates when flow was increased to 7800 s−1. Conclusion Triggered by collagen and enhanced by platelet GPIb and α IIbβ3, vWF fiber formation occurred during acute exposures to pathological γw and did not require gradients in wall shear rate. PMID:23104847

  2. Intramyocardial injections of human mesenchymal stem cells following acute myocardial infarction modulate scar formation and improve left ventricular function.

    PubMed

    Otto Beitnes, Jan; Oie, Erik; Shahdadfar, Aboulghassem; Karlsen, Tommy; Müller, Regine M B; Aakhus, Svend; Reinholt, Finn P; Brinchmann, Jan E

    2012-01-01

    Cell therapy is a promising treatment modality to improve heart function in acute myocardial infarction. However, the mechanisms of action and the most suitable cell type have not been finally determined. We performed a study to compare the effects of mesenchymal stem cells (MSCs) harvested from different tissues on LV function and explore their effects on tissue structure by morphometry and histological staining for species and lineage relationship. MSCs from skeletal muscle (SM-MSCs) and adipose tissue (ADSCs) were injected in the myocardium of nude rats 1 week after myocardial infarction. After 4 weeks of observation, LVEF was significantly improved in the SM-MSCs group (39.1%) and in the ADSC group (39.6%), compared to the placebo group (31.0%, p < 0.001 for difference in change between groups). Infarct size was smaller after cell therapy (16.3% for SM-MSCs, 15.8% for ADSCs vs. 26.0% for placebo, p < 0.001), and the amount of highly vascularized granulation tissue in the border zone was significantly increased in both groups receiving MSCs (18.3% for SM-MSCs, 22.6% for ADSCs vs. 13.1% for placebo, p = 0.001). By in situ hybridization, moderate engraftment of transplanted cells was found, but no transdifferentiation to cardiomyocytes, endothelial cells, or smooth muscle cells was observed. We conclude that MSC injections lead to improved LVEF after AMI in rats predominantly by reduction of infarct size. After 4 weeks, we observed modulation of scar formation with significant increase in granulation tissue. Transdifferentiation of MSCs to cardiomyocytes or vascular cells did not contribute significantly in this process. MSCs from skeletal muscle and adipose tissue had similar effects. PMID:22410280

  3. Catheter fragmentation of acute massive pulmonary thromboembolism: distal embolisation and pulmonary arterial pressure elevation.

    PubMed

    Nakazawa, K; Tajima, H; Murata, S; Kumita, S-I; Yamamoto, T; Tanaka, K

    2008-11-01

    The aim of this study was to evaluate the relationship between pulmonary arterial pressure and distal embolisation during catheter fragmentation for the treatment of acute massive pulmonary thromboembolism with haemodynamic impairment. 25 patients with haemodynamic impairment (8 men and 17 women; aged 27-82 years) were treated by mechanical thrombus fragmentation with a modified rotating pigtail catheter. After thrombus fragmentation, all patients received local fibrinolytic therapy, followed by manual clot aspiration using a percutaneous transluminal coronary angioplasty (PTCA) guide catheter. Pulmonary arterial pressure was continuously recorded during the procedure. The Friedman test and Wilcoxon test were applied for statistical analysis. Distal embolisation was confirmed by digital subtraction angiography in 7 of the 25 patients. A significant rise in mean pulmonary arterial pressure occurred after thrombus fragmentation (before: 34.1 mmHg; after: 37.9 mmHg; p<0.05), and this group showed a significant decrease in mean pulmonary arterial pressure after thrombus aspiration (25.7 mmHg; p<0.05). No distal embolisation was seen in 18 of the 25 patients, and a significant decrease in mean pulmonary arterial pressure was confirmed after thrombus fragmentation (before: 34.2 mmHg; after: 28.1 mmHg: p<0.01), and after thrombus aspiration (23.3 mmHg; p<0.01). In conclusion, distal embolisation and a rise in pulmonary arterial pressure can occur during mechanical fragmentation using a rotating pigtail catheter for the treatment of life-threatening acute massive pulmonary thromboembolism; thrombolysis and thrombus aspiration can provide partial recanalization and haemodynamic stabilization. Continuous monitoring of pulmonary arterial pressure may contribute to the safety of these interventional procedures. PMID:18941044

  4. Using Daily Plasma-Free Hemoglobin Levels for Diagnosis of Critical Pump Thrombus in Patients Undergoing ECMO or VAD Support.

    PubMed

    Neal, James R; Quintana, Eduard; Pike, Roxann B; Hoyer, James D; Joyce, Lyle D; Schears, Gregory

    2015-06-01

    Patients supported with extracorporeal membrane oxygenation (ECMO) or short-term centrifugal ventricular assist devices (VADs) are at risk for potential elevation of plasma-free hemoglobin (pfHb) during treatment. The use of pfHb testing allows detection of subclinical events with avoidance of propagating injury. Among 146 patients undergoing ECMO and VAD from 2009 to 2014, five patients experienced rapid increases in pfHb levels over 100 mg/dL. These patients were supported with CardioHelp, Centrimag, or Pedimag centrifugal pumps. Revolutions per minute of the pump head and flow in the circuit in three of the patients did not change, to maintain patient flow during the period that pfHb level spiked. Two patients had unusual vibrations originating from the pump head during the pfHb spike. Four patients had pump head replacement. Following intervention, trending pfHb levels demonstrated a rapid decline over the next 12 hours, returning to baseline within 48 hours. Two of the three patients who survived to discharge also experienced acute kidney injury, which was attributed to pfHb elevations. The kidney injury resolved over time. The architecture of centrifugal pumps may have indirectly contributed to red blood cell damage due to thrombus, originally from the venous line or venous cannula, being snared in the pump fins or pump head. PMID:26405358

  5. Influence of Thrombus Age on the Mechanical Thrombectomy Efficacy of the Amplatz Thrombectomy Device In Vitro

    SciTech Connect

    Grimm, Jan Jahnke, Thomas; Muhle, Claus; Heller, Martin; Mueller-Huelsbeck, Stefan

    2003-06-15

    Purpose: To determine the efficacy of thrombectomy for the Amplatz Thrombectomy Device (ATD) according to the age of the thrombus. Methods: Thrombectomy was performed with the 7 Fr or 8 Fr ATD. Five-day-old or 8-day-old thrombi were made from porcine blood by clotting within silicone tubes to be used in a flow model. Emboli sizes, weight, remaining thrombus and activation time were evaluated. Results: The age of the thrombus had no influence on the activation time necessary for complete thrombolysis. A significant difference was found in the overall amount of embolization only with the 7 Fr device although a similar trend was shown with the 8 Fr device. The amount of embolized thrombotic material was higher for both devices if older thrombi (i.e., 8 days old) we reprocessed. The overall impression was that the 8 Fr device showed slightly better results (less remaining thrombus and embolization). Conclusion: A tendency toward higher amounts of embolization was observed if older thrombi were used in the model. Therefore the interventional radiologist should be aware of the potentially higher risk of peripheral embolization when performing mechanical thrombectomy(with the ATD) in older thrombotic occlusions, especially since the higher rate of embolization was mainly due to an increased proportion of larger embolic particles (1 mm), which are clinically more significant.

  6. A systems approach to hemostasis: 2. Computational analysis of molecular transport in the thrombus microenvironment

    PubMed Central

    Tomaiuolo, Maurizio; Stalker, Timothy J.; Welsh, John D.; Diamond, Scott L.; Sinno, Talid

    2014-01-01

    Hemostatic thrombi formed after a penetrating injury have a heterogeneous architecture in which a core of highly activated, densely packed platelets is covered by a shell of less-activated, loosely packed platelets. In the first manuscript in this series, we show that regional differences in intrathrombus protein transport rates emerge early in the hemostatic response and are preserved as the thrombus develops. Here, we use a theoretical approach to investigate this process and its impact on agonist distribution. The results suggest that hindered diffusion, rather than convection, is the dominant mechanism responsible for molecular movement within the thrombus. The analysis also suggests that the thrombus core, as compared with the shell, provides an environment for retaining soluble agonists such as thrombin, affecting the extent of platelet activation by establishing agonist-specific concentration gradients radiating from the site of injury. This analysis accounts for the observed weaker activation and relative instability of platelets in the shell and predicts that a failure to form a tightly packed thrombus core will limit thrombin accumulation, a prediction tested by analysis of data from mice with a defect in clot retraction. PMID:24951425

  7. A Computational Model of Biochemomechanical Effects of Intraluminal Thrombus on the Enlargement of Abdominal Aortic Aneurysms.

    PubMed

    Virag, Lana; Wilson, John S; Humphrey, Jay D; Karšaj, Igor

    2015-12-01

    Abdominal aortic aneurysms (AAAs) typically develop an intraluminal thrombus (ILT), yet most computational models of AAAs have focused on either the mechanics of the wall or the hemodynamics within the lesion, both in the absence of ILT. In the few cases wherein ILT has been modeled directly, as, for example, in static models that focus on the state of stress in the aortic wall and the associated rupture risk, thrombus has been modeled as an inert, homogeneous, load-bearing material. Given the biochemomechanical complexity of an ILT, there is a pressing need to consider its diverse effects on the evolving aneurysmal wall. Herein, we present the first growth and remodeling model that addresses together the biomechanics, mechanobiology, and biochemistry of thrombus-laden AAAs. Whereas it has been shown that aneurysmal enlargement in the absence of ILT depends primarily on the stiffness and turnover of fibrillar collagen, we show that the presence of a thrombus within lesions having otherwise the same initial wall composition and properties can lead to either arrest or rupture depending on the biochemical effects (e.g., release of proteases) and biomechanical properties (e.g., stiffness of fibrin) of the ILT. These computational results suggest that ILT should be accounted for when predicting the potential enlargement or rupture risk of AAAs and highlight specific needs for further experimental and computational research. PMID:26070724

  8. New method for treatment of inferior vena cava tumor thrombus – case study

    PubMed Central

    Nagy, Zoltán; Gyurkovics, Endre; Pajor, Péter; Tarjányi, Mária; Szijártó, Attila; Vari, Sandor G.

    2015-01-01

    Conventional surgical therapy for advanced renal venous tumor thrombi results in high morbidity, so there is a need for less invasive techniques. This report presents the first case of a successful inferior vena cava (IVC) tumor thrombus removal without complications with balloon catheter (BC) via internal jugular vein (IJV), called the venous tumor thrombus pushing with balloon catheter (VTTP BC). Under the control of transesophageal echocardiogram and fluoroscope, a balloon catheter was sleeved on the guide wire, which was already inserted into the right internal jugular vein (IJV) and was driven distally above the IVC tumor thrombus. The balloon was inflated to occlude the IVC for prevention of pulmonary embolization. After the occlusion, the guide wire was driven to the cavotomy and was opened at the ostium of the right renal vein. It was pulled at both ends and stretched to serve as a rail. The balloon was gently pushed toward the cavotomy and the thrombectomy was completed. This is a less invasive method for treatment of venous tumor thrombus level 3 that can reduce surgical time, blood loss, and complication rates compared to the existing surgical methods. Also, it can be performed without thoracotomy, cardiopulmonary bypass, hypothermic circulatory arrest, and liver mobilization. PMID:25891873

  9. Closure of Left Atrial Appendage With Persistent Distal Thrombus Using an Amplatzer Amulet Occluder.

    PubMed

    Lange, Mathias; Bültel, Helmut; Weglage, Heinrich; Löffeld, Patrick; Wichter, Thomas

    2016-09-01

    A 73-year-old patient with permanent atrial fibrillation presented for left atrial appendage (LAA) occlusion. Transesophageal echocardiography demonstrated a thrombus in the distal LAA. This image series illustrates a "no touch" technique that was used to ensure successful implantation of an Amplatzer Amulet LAA occlusion device without the use of an embolization protection system. PMID:27591691

  10. Endobronchial ultrasound for the detection of chronic pulmonary artery thrombus.

    PubMed

    Dhillon, Samjot Singh; Harris, Kassem

    2016-01-01

    Endobronchial ultrasound (EBUS) has been shown to be able to successfully identify acute/subacute pulmonary thromboembolism (PE). Most reported cases have required confirmation by computerized tomography (CT) angiography. This report demonstrates a case where CT angiography was not conclusive and the EBUS was useful in clarifying the chronic process inside the pulmonary artery compatible with clinical diagnosis of chronic pulmonary artery thrombosis. PMID:27503162

  11. Echocardiographic detection of free-floating thrombus in left ventricle during coronary artery bypass grafting

    PubMed Central

    Vaggar, Jagadeesh N.; Gadhinglajkar, Shrinivas; Pillai, Vivek; Sreedhar, Rupa; Cahndran, Roshith; Roy, Suddhadeb

    2015-01-01

    We report an incident of detection of a free-floating thrombus in the left ventricle (LV) using intraoperative two-dimensional (2D) and three-dimensional (3D) transesophageal echocardiography (TEE) during proximal coronary artery bypass graft anastomosis. A 58-year-old man presented to us with a 6-month history of chest pain without any history suggestive of myocardial infarction or transient ischemic attacks. His preoperative echocardiography revealed the systolic dysfunction of LV, mild hypokinesia of basal and mid-anterior wall, and the absence of an aneurysm. He was scheduled for on-pump coronary artery bypass surgery. On intraoperative TEE before establishing cardiopulmonary bypass (CPB), a small immobile mass was found attached to LV apical area. After completion of distal coronary artery grafting, when the aortic cross-clamp was removed, the heart was filled partially and beating spontaneously. TEE examination using 2D mode revealed a free-floating mass in the LV, which was suspected to be a thrombus. Additional navigation using biplane and 3D modes confirmed the presence of the thrombus and distinguished it from papillary muscles and artifact. The surgeon opened the left atrium after re-establishing electromechanical quiescence and removed a thrombus measuring 1.5 cm × 1 cm from the LV. The LV mass in the apical region was no longer seen after discontinuation of CPB. Accurate TEE-detection and timely removal of the thrombus averted disastrous embolic complications. Intraoperative 2D and recent biplane and 3D echocardiography modes are useful monitoring tools during the conduct of CPB. PMID:26440248

  12. Novel treatment of coronary artery fistulae concealing severe coronary artery lesion: using thrombus aspiration catheter as a delivery guide.

    PubMed

    Korkmaz, Levent; Acar, Zeydin; Dursun, Ihsan; Akyüz, Ali Rıza; Korkmaz, Ayca Ata

    2014-03-01

    In this case report, we present the occlusion of multiple coronary artery fistulae originating from proximal left anterior descending (LAD) and right sinus valsavla and empting to the pulmonary artery at the same place. We occluded LAD fistulae by using thrombus aspiration catheter as a delivery guide. To the best of our knowlege, this is the first case of occlusion of coronary fistulae with the help of thrombus aspiration catheter. Our experience may suggest that thrombus aspiration catheters can be used in treating coronary artery fistulae with difficult anotomy. PMID:24748888

  13. Novel treatment of coronary artery fistulae concealing severe coronary artery lesion: using thrombus aspiration catheter as a delivery guide

    PubMed Central

    Korkmaz, Levent; Acar, Zeydin; Dursun, İhsan; Akyüz, Ali Rıza; Korkmaz, Ayca Ata

    2014-01-01

    In this case report, we present the occlusion of multiple coronary artery fistulae originating from proximal left anterior descending (LAD) and right sinus valsavla and empting to the pulmonary artery at the same place. We occluded LAD fistulae by using thrombus aspiration catheter as a delivery guide. To the best of our knowlege, this is the first case of occlusion of coronary fistulae with the help of thrombus aspiration catheter. Our experience may suggest that thrombus aspiration catheters can be used in treating coronary artery fistulae with difficult anotomy. PMID:24748888

  14. Reduced Formation of Oxidative Stress Biomarkers and Migration of Mononuclear Phagocytes in the Cochleae of Chinchilla after Antioxidant Treatment in Acute Acoustic Trauma

    PubMed Central

    Du, Xiaoping; Choi, Chul-Hee; Chen, Kejian; Cheng, Weihua; Floyd, Robert A.; Kopke, Richard D.

    2011-01-01

    Objective. Inhibition of inflammation and free radical formation in the cochlea may be involved in antioxidant treatment in acute acoustic trauma. Procedure. Chinchilla were exposed to 105 dB sound pressure level octave band noise for 6 hours. One group of chinchilla was treated with antioxidants after noise exposure. Auditory brainstem responses, outer hair cell counts, and immunohistochemical analyses of biomarkers in the cochlea were conducted. Results. The antioxidant treatment significantly reduced hearing threshold shifts, outer hair cell loss, numbers of CD45+ cells, as well as 4-hydroxy-2-nonenal and nitrotyrosine formation in the cochlea. Conclusion. Antioxidant treatment may provide protection to sensory cells by inhibiting formation of reactive oxygen and nitrogen products and migration of mononuclear phagocytes in the cochlea. The present study provides further evidence of effectiveness of antioxidant treatment in reducing permanent hearing loss. PMID:21961007

  15. Transcatheter closure of atrial septal defect and patent foramen ovale in adult patients using the Amplatzer occlusion device: no evidence for thrombus deposition with antiplatelet agents.

    PubMed

    Brandt, Roland R; Neumann, Thomas; Neuzner, Jörg; Rau, Matthias; Faude, Ingrid; Hamm, Christian W

    2002-10-01

    Transcatheter closure of atrial septal defect (ASD) and patent foramen ovale (PFO) using the Amplatzer septal occluder (AGA Medical, Minneapolis, Minn) is an alternative to surgical closure. There are only limited data on the thrombogenic potential of the device. Thirty-seven patients (14 men, 23 women) underwent device closure of their ASD (n = 21) or PFO (n = 16) at a mean age of 47 +/- 14 years (range, 18-72). The device was successfully deployed in all patients. Thirty-three of 37 patients received antiplatelet therapy with clopidogrel bisulfate and aspirin for a total of 6 months. Four patients in atrial fibrillation were also anticoagulated (international normalized ratio 2.0 to 3.0). No thrombus was detected in any patient on either side of the device by transthoracic and transesophageal echocardiography and there were no cases of symptomatic thromboembolism. Right-to-left interatrial shunting was diagnosed by contrast transesophageal echocardiography with the Valsalva's maneuver. At 1-month follow-up, minimal right-to-left shunting was detected in 6 patients (2 PFO, 4 ASD). Two patients (PFO) had minimal shunting at 1 month but not at 6 months. In 3 patients (ASD), inducible right-to-left shunting persisted at 6 months. In conclusion, our results obtained from a modest number of patients indicate that antiplatelet therapy is safe and effective in preventing thrombus formation on the septal occluder surface. PMID:12373252

  16. Effects of material properties on laser-induced bubble formation in absorbing liquids and on submerged targets

    NASA Astrophysics Data System (ADS)

    Shangguan, HanQun; Casperson, Lee W.; Shearin, Alan; Paisley, Dennis L.; Prahl, Scott A.

    1997-05-01

    Pulsed laser ablation of blood clots in a fluid-filled blood vessel is accomplished by an explosive evaporation process. The resulting vapor bubble rapidly expands and collapses to disrupt the thrombus (blood clot). The hydrodynamic pressures following the bubble expansion and collapse can also be used as a driving force to deliver clot-dissolving agents into thrombus for enhancement of laser thrombolysis. Thus, the laser-induced bubble formation plays an important role in the thrombus removal process. In this study the effects of material properties on laser-induced cavitation bubbles formed in liquids and on submerged targets have been visualized with a microsecond strobe or high speed framing camera.

  17. Acute effects of ethanol or d-amphetamine on the locomotor activity of larval zebrafish in a microtiter plate format.

    EPA Science Inventory

    As part of an effort to develop a rapid in vivo screen for EPA’s prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae. We are assessing the acute effects of prototypic drugs that are known to act on the central ...

  18. Adrenal cortical carcinoma with tumor thrombus extension into the right atrium: A case report

    PubMed Central

    WANG, YIMIN; ZHOU, FENG; PAN, HAO; JIN, BAIYE

    2016-01-01

    Adrenal cortical carcinoma (ACC) is a rare aggressive malignant tumor associated with a poor prognosis. Patients with ACC usually present with abnormal hormone secretion, tumor growth or encroachment on the surrounding viscera. An early diagnosis of ACC is considered challenging. The present study reports a case of ACC with tumor thrombus extension into the inferior vena cava and right atrium. A 33-year-old male patient exhibited symptoms of gynecomastia and abdominal distention, which were due to the abnormal hormone secretion levels and to the presence of a large mass in the right adrenal gland. An en bloc resection of the tumor was the selected treatment option. Extirpation of the tumor thrombus was performed by means of extracorporeal circulation. No signs of metastasis or recurrence were identified at the 1-month follow-up. PMID:27313728

  19. A floating right heart thrombus in transit across tricuspid valve causing an endocardial friction rub

    PubMed Central

    Kanjirakadavath, Babu; Krishnan, M.N.; Vinayakumar, D.; Raju, Deepak; Nithin, P.G.; Rajesh, K.F.; Sreekumar, Pradeep

    2013-01-01

    We report a 42-year-old lady on combined oral contraceptive pills with deep venous thrombosis and mild pulmonary embolism, who developed shock, while being treated with heparin. On auscultation, there was an unexpected loud, superficial, squeaky, triphasic friction rub over the left lower parasternal area. Simultaneous echocardiogram revealed a large serpiginous, freely floating mass in right atrium, prolapsing freely to right ventricular inlet across the tricuspid valve. The endocardial friction rub persisted for about 24 h as long as the thrombus was intracardiac and disappeared when the thrombus disappeared from right heart, occluding the proximal left pulmonary artery. She died due to shock awaiting surgery. We highlight that such a rub in a patient with deep venous thrombosis, though rare, may be an important clue to impending pulmonary embolism. PMID:23993010

  20. A case of carbon monoxide poisoning with thrombus in the heart: a case report.

    PubMed

    Yildirim, Cuma; Günay, Nurullah; Büyükaslan, Hasan; Küçükdurmaz, Zekeriya; Bozkurt, Selim

    2005-12-15

    Carbon monoxide is a nonirritant, odorless, colorless gas, and is lighter than air. It is an end product of the incomplete combustion of hydrocarbons. Its effects are most prominent in organs sensitive to oxygen deprivation, such as the heart, brain, and kidney. Carbon monoxide poisoning becomes more abundant in winter and at cold places. In Turkey, every year we see several deaths due to poisonous gas leaks from coal or wood stoves. Deaths particularly due to hypoxia-related central nervous system damage and ventricular dysrhythmias are observed. On the other hand, an association between thromboembolic accidents and carbon monoxide poisoning has been shown in literature. Thromboembolic accidents in the mesenteric, central nervous system, and extremities are reported. However, no atrial thrombus has been mentioned. In this study, a case of an atrial thrombus associated with carbon monoxide poisoning following a diagnosis of carbon monoxide poisoning and treatment in the emergency room is reported and the literature is revisited. PMID:16282157

  1. No clinical benefit from manual thrombus aspiration in patients with non-ST-elevation myocardial infarction

    PubMed Central

    Dziewierz, Artur; Rakowski, Tomasz; Tokarek, Tomasz; Mielecki, Waldemar; Żabówka, Anna; Plens, Krzysztof; Dudek, Dariusz

    2016-01-01

    Introduction There are scarce data on the usefulness of manual thrombectomy among patients with non-ST-elevation myocardial infarction (NSTEMI). Early positive reports were not supported by the clinical outcome in the recent TATORT-NSTEMI (Thrombus Aspiration in Thrombus Containing Culprit Lesions in Non-ST-Elevation Myocardial Infarction) study. Aim To analyze the long-term outcome of NSTEMI patients treated with manual thrombectomy during percutaneous coronary intervention (PCI) in the Polish multicenter National Registry of Drug Eluting Stents (NRDES) study. Material and methods There were 13 catheterization laboratories in Poland that enrolled patients in NRDES Registry in 2010–2011. Patients with a diagnosis of NSTEMI were divided into two groups: those that were treated with manual thrombectomy for their primary PCI (T) and those who were not (NT). Results There were 923 patients diagnosed with NSTEMI in NRDES. Aspiration thrombectomy was used in 71 (7.7%) patients and the remaining 852 (92.3%) NSTEMI cases were treated without thrombectomy during the index PCI. Thrombectomy was more often used in patients with TIMI less than 1, thrombus grades 4 and 5 and older male patients. Percutaneous coronary interventions complications such as distal embolization and slow flow were more often observed in the thrombectomy subgroup. Overall mortality at 1 year was 1.69% in the T and 5.92% in the NT group (p = 0.24 and p = 0.32 after propensity score matching adjustment with p = 0.11 in the multivariate logistic regression model). Conclusions There was no mortality benefit from thrombus aspiration in NSTEMI patients at 1-year follow-up. PMID:26966447

  2. Percutaneous balloon mitral valvuloplasty with bilateral carotid protection in 2 cases of left atrial thrombus.

    PubMed

    Bansal, N O; Duggal, Bhanu; Omnath, R

    2010-01-01

    We present 2 cases of mitral stenosis with left atrial thrombus who underwent Balloon Mitral Valvotomy with bilateral carotid protection using SpiderFX, distal protection devices to minimize the risk of neuroembolic stroke. One patient was critical MS in congestive heart failure with a highly mobile left atrial appendage clot (LAA) and the second patient was a young female who declined surgery and had an LAA clot which did not respond to warfarin therapy. PMID:21180315

  3. Intraoperative bronchoscopic visualization of left ventricular assist device thrombus.

    PubMed

    Yost, Gardner; Bhat, Geetha; Modi, Sejal; Pappas, Pat; Tatooles, Antone

    2016-07-01

    Despite advancements in left ventricular assist device (LVAD) design and clinical management, device thrombosis remains a pertinent complication. Limited imaging makes precise visualization of clot location and shape very challenging. We report the usage of videobronchoscopic exploration of explanted LVADs for direct visualization of clot in two patients. This technique is a rapid and inexpensive means of improving our understanding of LVAD clot formation and may be useful in surgical exploration of inflow and outflow tracts during LVAD exchange. PMID:26452760

  4. Spinal Cord Infarction Caused by Non-dissected and Unruptured Thoracoabdominal Aortic Aneurysm with Intraluminal Thrombus.

    PubMed

    Ki, Young Jin; Jeon, Byoung Hyun; Bang, Heui Je

    2012-04-01

    Spinal cord infarction, especially anterior spinal artery syndrome, is a relatively rare disease. We report a case of spinal cord infarction caused by thoracoabdominal aortic aneurysm with intraluminal thrombus. A 52-year-old man presented with sudden onset paraplegia. At first, he was diagnosed with cervical myelopathy due to a C6-7 herniated intervertebral disc, and had an operation for C6-7 discetomy and anterior interbody fusion. Approximately 1 month after the operation, he was transferred to the department of rehabilitation in our hospital. Thoracoabdominal aortic aneurysm with intraluminal thrombus was found incidentally on an enhanced computed tomography scan, and high signal intensities were detected at the anterior horns of gray matter from the T8 to cauda equina level on T2-weighted magnetic resonance imaging. There was no evidence of aortic rupture, dissection, or complete occlusion of the aorta. We diagnosed his case as a spinal cord infarction caused by thoracoabdominal aortic aneurysm with intraluminal thrombus. PMID:22639759

  5. Automated Delineation of Vessel Wall and Thrombus Boundaries of Abdominal Aortic Aneurysms Using Multispectral MR Images

    PubMed Central

    Rodriguez-Vila, B.; Tarjuelo-Gutierrez, J.; Sánchez-González, P.; Verbrugghe, P.; Fourneau, I.; Maleux, G.; Herijgers, P.; Gomez, E. J.

    2015-01-01

    A correct patient-specific identification of the abdominal aortic aneurysm is useful for both diagnosis and treatment stages, as it locates the disease and represents its geometry. The actual thickness and shape of the arterial wall and the intraluminal thrombus are of great importance when predicting the rupture of the abdominal aortic aneurysms. The authors describe a novel method for delineating both the internal and external contours of the aortic wall, which allows distinguishing between vessel wall and intraluminal thrombus. The method is based on active shape model and texture statistical information. The method was validated with eight MR patient studies. There was high correspondence between automatic and manual measurements for the vessel wall area. Resulting segmented images presented a mean Dice coefficient with respect to manual segmentations of 0.88 and a mean modified Hausdorff distance of 1.14 mm for the internal face and 0.86 and 1.33 mm for the external face of the arterial wall. Preliminary results of the segmentation show high correspondence between automatic and manual measurements for the vessel wall and thrombus areas. However, since the dataset is small the conclusions cannot be generalized. PMID:26236390

  6. Association of Intraluminal Thrombus, Hemodynamic Forces, and Abdominal Aortic Aneurysm Expansion Using Longitudinal CT Images.

    PubMed

    Zambrano, Byron A; Gharahi, Hamidreza; Lim, ChaeYoung; Jaberi, Farhad A; Choi, Jongeun; Lee, Whal; Baek, Seungik

    2016-05-01

    While hemodynamic forces and intraluminal thrombus (ILT) are believed to play important roles on abdominal aortic aneurysm (AAA), it has been suggested that hemodynamic forces and ILT also interact with each other, making it a complex problem. There is, however, a pressing need to understand relationships among three factors: hemodynamics, ILT accumulation, and AAA expansion for AAA prognosis. Hence this study used longitudinal computer tomography scans from 14 patients and analyzed the relationship between them. Hemodynamic forces, represented by wall shear stress (WSS), were obtained from computational fluid dynamics; ILT accumulation was described by ILT thickness distribution changes between consecutives scans, and ILT accumulation and AAA expansion rates were estimated from changes in ILT and AAA volume. Results showed that, while low WSS was observed at regions where ILT accumulated, the rate at which ILT accumulated occurred at the same rate as the aneurysm expansion. Comparison between AAAs with and without thrombus showed that aneurysm with ILT recorded lower values of WSS and higher values of AAA expansion than those without thrombus. Findings suggest that low WSS may promote ILT accumulation and submit the idea that by increasing WSS levels ILT accumulation may be prevented. PMID:26429788

  7. Deficiency of endogenous acute phase serum amyloid A protects apoE−/− mice from angiotensin II-induced abdominal aortic aneurysm formation

    PubMed Central

    Webb, NR; De Beer, MC; Wroblewski, JM; Ji, A; Bailey, W; Shridas, P; Charnigo, RJ; Noffsinger, VP; Witta, J; Howatt, DA; Balakrishnan, A; Rateri, DL; Daugherty, A; De Beer, FC

    2016-01-01

    Objective Rupture of abdominal aortic aneurysm (AAA), a major cause of death in the aged population, is characterized by vascular inflammation and matrix degradation. Serum amyloid A (SAA), an acute phase reactant linked to inflammation and matrix metalloproteinase induction, correlates with aortic dimensions before aneurysm formation in humans. We investigated whether SAA deficiency in mice impacts AAA formation during angiotensin II (AngII) infusion. Approach and Results Plasma SAA increased ~60-fold in apoE−/− mice 24 hours after i.p. AngII injection (100 μg/kg; n = 4) and ~15-fold after chronic 28-day AngII infusion (1,000 ng/kg/min; n = 9). AAA incidence and severity after 28-day AngII infusion was significantly reduced in apoE−/− mice lacking both acute phase SAA isoforms (SAAKO; n = 20) compared to apoE−/− mice (SAAWT; n = 20) as assessed by in vivo ultrasound and ex vivo morphometric analyses, despite a significant increase in systolic blood pressure in SAAKO mice compared to SAAWT mice after AngII infusion. Atherosclerotic lesion area of the aortic arch was similar in SAAKO and SAAWT mice after 28-day AngII infusion. Immunostaining detected SAA in AAA tissues of AngII-infused SAAWT mice that co-localized with macrophages, elastin breaks, and enhanced matrix metalloproteinase (MMP) activity. MMP-2 activity was significantly lower in aortas of SAAKO mice compared to SAAWT mice after 10-day AngII infusion. Conclusion Lack of endogenous acute phase SAA protects against experimental AAA through a mechanism that may involve reduced MMP-2 activity. PMID:25745063

  8. Acute and chronic complications of laser angioplasty: vascular wall damage and formation of aneurysms in the atherosclerotic rabbit.

    PubMed

    Lee, G; Ikeda, R M; Theis, J H; Chan, M C; Stobbe, D; Ogata, C; Kumagai, A; Mason, D T

    1984-01-15

    Acute and chronic vascular responses to laser exposure in atherosclerotic rabbits were studied. In 7 rabbits fed an atherogenic diet for 3 to 5 months before the study to induce aortic atherosclerosis, a flexible quartz fiber, 400 micron core diameter, attached to an argon ion laser was passed anterogradely or retrogradely to the atherosclerotic ascending aorta. The laser was turned on using power intensities of 1 to 2 W for 3 seconds. After laser treatment, the aortas were studied acutely in 3 rabbits and chronically in 4 rabbits after recovery for 1 to 14 days. In 2 rabbits studied acutely, the argon laser produced a vaporized crater within the atherosclerotic plaque at the endothelial surface; however, in 1 there was also vascular damage extending deep into the medial layer. In addition, aortic aneurysm with muscular wall damage occurred in 2 of the 4 animals studied chronically. Thus, vascular complications may arise when catheter laser angioplasty is randomly applied without visualizing specific plaque targets or without using safe dose increments of power intensities and durations of exposure. This study suggests caution in the clinical use of intensive phototherapy to cardiovascular lesions and stresses the need for further understanding of laser vascular consequences before application of laser angioplasty in patients. PMID:6695725

  9. Epiplakin Deficiency Aggravates Murine Caerulein-Induced Acute Pancreatitis and Favors the Formation of Acinar Keratin Granules

    PubMed Central

    Wögenstein, Karl L.; Szabo, Sandra; Lunova, Mariia; Wiche, Gerhard; Haybaeck, Johannes; Strnad, Pavel; Boor, Peter; Wagner, Martin; Fuchs, Peter

    2014-01-01

    Epiplakin, a member of the plakin protein family, is exclusively expressed in epithelial tissues and was shown to bind to keratins. Epiplakin-deficient (EPPK−/−) mice showed no obvious spontaneous phenotype, however, EPPK−/− keratinocytes displayed faster keratin network breakdown in response to stress. The role of epiplakin in pancreas, a tissue with abundant keratin expression, was not yet known. We analyzed epiplakin’s expression in healthy and inflamed pancreatic tissue and compared wild-type and EPPK−/− mice during caerulein-induced acute pancreatitis. We found that epiplakin was expressed primarily in ductal cells of the pancreas and colocalized with apicolateral keratin bundles in murine pancreatic acinar cells. Epiplakin’s diffuse subcellular localization in keratin filament-free acini of K8-deficient mice indicated that its filament-associated localization in acinar cells completely depends on its binding partner keratin. During acute pancreatitis, epiplakin was upregulated in acinar cells and its redistribution closely paralleled keratin reorganization. EPPK−/− mice suffered from aggravated pancreatitis but showed no obvious regeneration phenotype. At the most severe stage of the disease, EPPK−/− acinar cells displayed more keratin aggregates than those of wild-type mice. Our data propose epiplakin to be a protective protein during acute pancreatitis, and that its loss causes impaired disease-associated keratin reorganization. PMID:25232867

  10. Incremental Value of Three-Dimensional Transesophageal Echocardiography over the Two-Dimensional Technique in the Assessment of a Thrombus in Transit through a Patent Foramen Ovale.

    PubMed

    Thind, Munveer; Ahmed, Mustafa I; Gok, Gulay; Joson, Marisa; Elsayed, Mahmoud; Tuck, Benjamin C; Townsley, Matthew M; Klas, Berthold; McGiffin, David C; Nanda, Navin C

    2015-05-01

    We report a case of a right atrial thrombus traversing a patent foramen ovale into the left atrium, where three-dimensional transesophageal echocardiography provided considerable incremental value over two-dimensional transesophageal echocardiography in its assessment. As well as allowing us to better spatially characterize the thrombus, three-dimensional transesophageal echocardiography provided a more quantitative assessment through estimation of total thrombus burden. PMID:25827179

  11. Long term follow up of patients with anterior myocardial infarction complicated by left ventricular thrombus in the thrombolytic era.

    PubMed Central

    Mooe, T.; Teien, D.; Karp, K.; Eriksson, P.

    1996-01-01

    OBJECTIVES: To examine the appearance and resolution of left ventricular thrombi and to study the relation between thrombus and mortality during long term follow up after anterior myocardial infarction. DESIGN: Ninety nine consecutive patients were prospectively studied until the last included patient had been followed for one year. Streptokinase and aspirin were used routinely, anticoagulants only after a decision by the attending physician. Echocardiography was performed within 3 d of admission, before discharge, and after one, three, and 12 months. SETTING: Umeå University Hospital, a teaching hospital in Northern Sweden. MAIN OUTCOME MEASURES: Left ventricular thrombus, segmental myocardial function, and mortality during follow up. RESULTS: Thirty patients (30%) had a thrombus on discharge. One month, three months, and 12 months after hospital discharge, the thrombus had resolved in 81%, 84%, and 90% of the patients, respectively. The proportion of resolved thrombi at one month was high irrespective of whether anticoagulants were given (10/11, 91%) or not (12/16, 75%), P = 0.4. New thrombi appeared in 12 patients after discharge and resolution and reapperance of thrombi continued during the follow up period. Patients who developed a thrombus during the hospital stay (n = 44, 44%) had more extensive myocardial dysfunction on discharge (P < 0.001) and significantly higher mortality during the follow up period than those without a thrombus (23% v 7%, P < 0.01). CONCLUSIONS: With routine thrombolytic and aspirin treatment of anterior myocardial infarction, left ventricular thrombi usually resolve during the first month after hospital discharge. Appearance and resolution of thrombi continue, however, in a significant proportion of the patients during long term follow up. A left ventricular thrombus during the initial hospital stay is associated with high long term mortality. PMID:8800987

  12. Targeting thrombin long-term after an acute coronary syndrome: Opportunities and challenges.

    PubMed

    De Caterina, Raffaele; Goto, Shinya

    2016-06-01

    Patients after an acute coronary syndrome (ACS) are at increased risk of recurrent thrombotic events, justifying the search for additional antithrombotic treatments. The pathophysiology of ACS involves arterial thrombus formation, in turn occurring because of a combination of platelet activation and fibrin formation, with thrombin playing a key role in both. Antiplatelet therapy, targeting the thromboxane pathway and the ADP P2Y12 receptor has been widely accepted for secondary prevention after an ACS. Now, data from recent clinical trials in such patients also encourage the pursuit of inhibiting thrombin formation or thrombin-mediated platelet activation in addition to antiplatelet therapy. This "triple pathway inhibition", including inhibition of thrombin activity or thrombin receptor(s), is currently an option in pure ACS, but already a must in the setting of ACS accompanied by atrial fibrillation (AF), where anticoagulants have been shown to be much more effective than antiplatelet agents in preventing stroke. We here discuss the challenges of managing combined thrombin activity or receptor inhibition and antiplatelet therapy in all such patients. Translating this into practice still requires further studies and patient tailoring to fully exploit its potential. PMID:26994821

  13. Acute Myocardial Infarction Following Blunt Chest Trauma and Coronary Artery Dissection.

    PubMed

    Abdolrahimi, Safar Ali; Sanati, Hamid Reza; Ansari-Ramandi, Mohammad Mostafa; Heris, Saeed Oni; Maadani, Mohsen

    2016-06-01

    Blunt chest traumatic coronary artery dissection is an uncommon cause of atherosclerotic and non-atherosclerotic Acute Myocardial Infarction (AMI). Injuries of the coronary artery after blunt chest trauma are caused by different mechanisms such as vascular spasm, dissection and intimal tear or rupture of an existing thrombus formation. Chest pain might be masked by other injuries in patients with multiple traumas in car accident. Present case report is on a 37-year-old male without any specific past medical history who reported to the emergency department of a hospital with chest discomfort and was discharged with the impression of chest wall pain. After three days he experienced severe chest pain and he was admitted with the impression of acute coronary syndrome and underwent coronary angiography which showed Left Anterior Descending (LAD) artery dissection. The possibility of injury of the coronary artery should be kept in mind after blunt trauma to the chest. This condition is sometimes underdiagnosed. Its diagnosis may be difficult because chest pain can be interpreted as being secondary to chest wall contusion or it may be overshadowed by other injuries. Coronary dissection diagnosis after chest trauma requires clinical suspicion and systematic evaluation. Electrocardiography (ECG) should be done for every patient with thoracic trauma as the clinical findings may be misleading. PMID:27504338

  14. Acute Myocardial Infarction Following Blunt Chest Trauma and Coronary Artery Dissection

    PubMed Central

    Abdolrahimi, Safar Ali; Sanati, Hamid Reza; Ansari-Ramandi, Mohammad Mostafa; Heris, Saeed Oni

    2016-01-01

    Blunt chest traumatic coronary artery dissection is an uncommon cause of atherosclerotic and non-atherosclerotic Acute Myocardial Infarction (AMI). Injuries of the coronary artery after blunt chest trauma are caused by different mechanisms such as vascular spasm, dissection and intimal tear or rupture of an existing thrombus formation. Chest pain might be masked by other injuries in patients with multiple traumas in car accident. Present case report is on a 37-year-old male without any specific past medical history who reported to the emergency department of a hospital with chest discomfort and was discharged with the impression of chest wall pain. After three days he experienced severe chest pain and he was admitted with the impression of acute coronary syndrome and underwent coronary angiography which showed Left Anterior Descending (LAD) artery dissection. The possibility of injury of the coronary artery should be kept in mind after blunt trauma to the chest. This condition is sometimes underdiagnosed. Its diagnosis may be difficult because chest pain can be interpreted as being secondary to chest wall contusion or it may be overshadowed by other injuries. Coronary dissection diagnosis after chest trauma requires clinical suspicion and systematic evaluation. Electrocardiography (ECG) should be done for every patient with thoracic trauma as the clinical findings may be misleading. PMID:27504338

  15. Comparison of the Effectiveness of Three Methods of Recanalization in a Model of the Middle Cerebral Artery: Thrombus Aspiration via a 4F Catheter, Thrombus Aspiration via the GP Thromboaspiration Device, and Mechanical Thrombectomy Using the Solitaire Thrombectomy Device.

    PubMed

    Tennuci, Christopher; Pearce, Gillian; Wong, Julian; Nayak, Sanjeev; Jones, Tom; Lally, Frank; Roffe, Christine

    2011-01-01

    Introduction. This paper compares different approaches to recanalization in a model of the middle cerebral artery (MCA). Methods. An occlusive thrombus (lamb's blood) was introduced into the MCA of a model of the cerebral circulation perfused with Hartmann's solution (80 pulsations/min, mean pressure 90 mm Hg). Three methods of clot retrieval were tested: thrombus aspiration via a 4F catheter (n = 26), thrombus aspiration via the GP thrombus aspiration device (GPTAD) (n = 30), and mechanical thrombectomy via the Solitaire Device (n = 30). Results. Recanalization rate was similar for all 3 approaches (62%, 77%, and 85%). Time to recanalization was faster with aspiration devices (41 SD 42 s for 4F and 61 SD 21 s for GPTAD) than with the Solitaire (197 SD 64 s P < .05 Kruksal-Wallis). Clot fragmentation was the same in the Solitaire (23%) and the GPTAD (23%), but higher with the 4F (53%, P < .05). Conclusion. In this model, thrombus aspiration was faster than mechanical thrombectomy, and similarly effective at recanalization. These results should be confirmed in vivo. PMID:21603169

  16. Comparison of the Effectiveness of Three Methods of Recanalization in a Model of the Middle Cerebral Artery: Thrombus Aspiration via a 4F Catheter, Thrombus Aspiration via the GP Thromboaspiration Device, and Mechanical Thrombectomy Using the Solitaire Thrombectomy Device

    PubMed Central

    Tennuci, Christopher; Pearce, Gillian; Wong, Julian; Nayak, Sanjeev; Jones, Tom; Lally, Frank; Roffe, Christine

    2011-01-01

    Introduction. This paper compares different approaches to recanalization in a model of the middle cerebral artery (MCA). Methods. An occlusive thrombus (lamb's blood) was introduced into the MCA of a model of the cerebral circulation perfused with Hartmann's solution (80 pulsations/min, mean pressure 90 mm Hg). Three methods of clot retrieval were tested: thrombus aspiration via a 4F catheter (n = 26), thrombus aspiration via the GP thrombus aspiration device (GPTAD) (n = 30), and mechanical thrombectomy via the Solitaire Device (n = 30). Results. Recanalization rate was similar for all 3 approaches (62%, 77%, and 85%). Time to recanalization was faster with aspiration devices (41 SD 42 s for 4F and 61 SD 21 s for GPTAD) than with the Solitaire (197 SD 64 s P < .05 Kruksal-Wallis). Clot fragmentation was the same in the Solitaire (23%) and the GPTAD (23%), but higher with the 4F (53%, P < .05). Conclusion. In this model, thrombus aspiration was faster than mechanical thrombectomy, and similarly effective at recanalization. These results should be confirmed in vivo. PMID:21603169

  17. Inferior vena cava tumor thrombus that directly infiltrated from paracaval lymph node metastases in a patient with recurrent hepatocellular carcinoma

    PubMed Central

    2013-01-01

    Herein, we present the case of a patient with recurrent hepatocellular carcinoma (HCC) who had paracaval lymph node (LN) metastases with an inferior vena cava (IVC) tumor thrombus after a hepatectomy. A 65-year-old man with chronic hepatitis B virus infection received an extended anterior segmentectomy because of two hepatic tumors, located in segments 7 and 8. Histological examination of both resected specimens showed mostly moderately differentiated HCC with some poorly differentiated areas, and liver cirrhosis (A2/F4). Because the patient had an elevated α-fetoprotein serum level, abdominal computed tomography (CT) was performed. Abdominal CT revealed a 9-mm-diameter recurrent tumor in hepatic segment 3 and paracaval LN metastases with an IVC tumor thrombus at 8 months after the first operation. The patient received transcatheter arterial chemoembolization as treatment for the intrahepatic recurrence, following resection of the paracaval LN metastases and removal of the IVC tumor thrombus. In this case, the paracaval LN metastases had directly infiltrated the IVC via the lumbar veins, resulting in an IVC tumor thrombus, which usually develops from an intrahepatic tumor via the hepatic vein. The development of an IVC tumor thrombus with HCC recurrence, as in this case, is very rare, and based on a PubMed search, we believe this report may be the first to describe this condition. PMID:23915104

  18. Hepatocellular Carcinoma With Tumor Thrombus Occupying the Right Atrium and Portal Vein: A Case Report and Literature Review.

    PubMed

    Luo, Xin; Zhang, Binhao; Dong, Shuilin; Zhang, Bixiang; Chen, Xiaoping

    2015-08-01

    Hepatocellular carcinoma (HCC) patients with tumor thrombus extended through the major hepatic veins and inferior vena cava into the right atrium (RA) are rare, and most cases are considered as the advanced stage with a poor prognosis.We report a case of HCC with a tumor thrombus extending into the RA and a tumor thrombus in the portal vein. A literature search for case reports was performed on PubMed.Compared with the published literature, our case is one of the youngest patients, but with the most advanced HCC that invades both the hepatic inflow and outflow vasculature. For this patient, we resected the tumor thrombus in the RA with the use of cardiopulmonary bypass, and then removed the tumor thrombus in the portal vein and ligated the left branch of portal vein. Because of insufficient remnant liver volume, microwave ablation and transcatheter arterial chemoembolization were performed to control the growth of HCC. The patient survived 6 months after surgery.This case suggests that for patients with extension of HCC into the RA and portal vein, surgery is a useful therapeutic modality, even in case that liver tumor cannot be resected. PMID:26313767

  19. Management dilemmas in acute pulmonary embolism

    PubMed Central

    Condliffe, Robin; Elliot, Charlie A; Hughes, Rodney J; Hurdman, Judith; Maclean, Rhona M; Sabroe, Ian; van Veen, Joost J; Kiely, David G

    2014-01-01

    Background Physicians treating acute pulmonary embolism (PE) are faced with difficult management decisions while specific guidance from recent guidelines may be absent. Methods Fourteen clinical dilemmas were identified by physicians and haematologists with specific interests in acute and chronic PE. Current evidence was reviewed and a practical approach suggested. Results Management dilemmas discussed include: sub-massive PE, PE following recent stroke or surgery, thrombolysis dosing and use in cardiac arrest, surgical or catheter-based therapy, failure to respond to initial thrombolysis, PE in pregnancy, right atrial thrombus, role of caval filter insertion, incidental and sub-segmental PE, differentiating acute from chronic PE, early discharge and novel oral anticoagulants. Conclusion The suggested approaches are based on a review of the available evidence and guidelines and on our clinical experience. Management in an individual patient requires clinical assessment of risks and benefits and also depends on local availability of therapeutic interventions. PMID:24343784

  20. Acute suppression of TGF-ß with local, sustained release of tranilast against the formation of fibrous capsules around silicone implants.

    PubMed

    Park, Subin; Park, Min; Kim, Byung Hwi; Lee, Ji Eun; Park, Hyo Jin; Lee, Seung Ho; Park, Chun Gwon; Kim, Myung Hun; Kim, Ryul; Kim, Eun Hee; Heo, Chan Yeong; Choy, Young Bin

    2015-02-28

    We propose the acute, local suppression of transforming growth factor beta (TGF-ß), a major profibrotic cytokine, to reduce fibrosis around silicone implants. To this end, we prepared silicone implants that were able to release tranilast, a TGF-ß inhibitor, in a sustained manner for 5 days or 15 days. We performed histologic and immunohistochemical analyses for 12 weeks after the implantation of the implants in living rats. The capsule thicknesses and collagen densities significantly decreased compared with those around the non-treated silicone implants. Notably, early suppression of TGF-ß affected the fibrogenesis that actually occurs at the late stage of wound healing. This change may be ascribed to the decrease in monocyte recruitment mediated by early TGF-ß during the acute inflammatory reaction. Thus, a significant decrease in differentiated macrophages was observed along with a decrease in the quantity of TGF-ß and fibroblasts during the subsequent inflammation stage; these changes led to a diminished fibrotic capsule formation. PMID:25528612

  1. Formation of aversive memories associated with conditioned drug withdrawal requires BDNF expression in the amygdala in acute morphine-dependent rats

    PubMed Central

    Ju, Yun-yue; Long, Jian-dong; Liu, Yao; Liu, Jing-gen

    2015-01-01

    Aim: Brain-derived neurotrophic factor (BDNF) plays an important role in learning and memory in multiple brain areas. In the present study, we investigated the roles of BDNF in aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats. Methods: Conditioned place aversion (CPA) was induced in male SD rats exposed to a single dose of morphine (10 mg/kg, sc) followed by naloxone (0.3 mg/kg, sc). In some rats, BDNF receptor antagonist K252a (8.5 ng per side) or BDNF scavenger TrkB-FC (0.65 μg per side) was bilaterally microinjected into amygdala before naloxone injection. BDNF mRNA and protein expression levels in amygdala were detected after the behavior testing. Results: CPA behavior was induced in rats by the naloxone-precipitated morphine withdrawal, which was accompanied by significantly increased levels of BDNF mRNA and protein in the amygdala. Bilateral microinjection of TrkB-FC or K252a into the amygdala completely blocked CPA behavior in the rats. Conclusion: Formation of aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats requires BDNF expression in the amygdala. PMID:26567727

  2. Acute leukemia after radiotherapy in a patient with Turcot's syndrome. Impaired colony formation in skin fibroblast cultures after irradiation

    SciTech Connect

    Li, F.P.; Little, J.B.; Bech-Hansen, N.T.; Paterson, M.C.; Arlett, C.; Garnick, M.B.; Mayer, R.J.

    1983-02-01

    Colonic polyposis and carcinoma developed in a woman with Turcot's syndrome at the age of 31 years; astrocytoma developed when she was 37. Her brother and sister had died of astrocytoma at the ages of 18 and 33 years, respectively. Progressive neutropenia developed in the patient three months after radiotherapy for her brain tumor and acute myelomonocytic leukemia 19 months after treatment. Three laboratories independently evaluated cultures of her skin fibroblasts for in vitro sensitivity to cell killing (loss of colony-forming ability) by x-rays. Survival assays consistently revealed slight but significant radiosensitivity in an early-passage (six to 10 doublings) fibroblast subculture. A later subculture (21 to 29 doublings) showed no abnormality, a possible effect of selective in vitro loss of radiosensitive cells.

  3. Role of Leukocyte Elastase in Preventing Cellular Re-Colonization of the Mural Thrombus

    PubMed Central

    Fontaine, Vincent; Touat, Ziad; Mtairag, El Mostafa; Vranckx, Roger; Louedec, Liliane; Houard, Xavier; Andreassian, Bernard; Sebbag, Uriel; Palombi, Tonino; Jacob, Marie-Paule; Meilhac, Olivier; Michel, Jean-Baptiste

    2004-01-01

    To explore possible mechanisms responsible for the absence of cell re-colonization of mural thrombi in aneurysms, we analyzed the release and storage of leukocyte proteases in the most luminal layer versus intermediate and abluminal layers of 10 mural thrombi of human abdominal aortic aneurysms. The luminal layer contained many polymorphonuclear leukocytes (PMNs), which released pro-matrix metalloproteinase (MMP)-9 and MMP-8. Leukocyte elastase was also stored and released by the luminal layer (immunohistochemistry, activity on synthetic substrates, and casein zymography). Acid buffer allowed extraction of leukocyte elastase from the luminal layer, which was inhibited by elastase inhibitors. Casein zymography of luminal extracts and conditioned medium from formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMNs exhibited a similar lysis pattern, corresponding to elastase activity. Smooth muscle cell (SMC) seeding resulted in colonization of the intermediate thrombus layer ex vivo but not of the luminal layer. Extracts of the luminal layer induced loss of anchorage of both cultured human smooth muscle cells and stromal cells of bone marrow origin (anoikis). This anoikis was prevented by preincubation of the extracts with serine protease inhibitors. Moreover, adhesion of human SMCs and stromal bone marrow cells on fibrin gels was strongly inhibited when the gel was preincubated with pure elastase, medium of fMLP-stimulated PMNs, or extracts of luminal layers of mural thrombi. This loss of cell anchorage was prevented by the preincubation of the medium or extracts with α1-antitrypsin, but not when α1-antitrypsin was added after binding of elastase to the fibrin gel. In conclusion, elastase released by PMNs trapped within the mural thrombus impairs the spontaneous anchorage of mesenchymal cells to a fibrin matrix. This phenomenon could be one mechanism by which cellular healing of the mural thrombus in aneurysms is prevented. PMID:15161642

  4. Acute tissue injury activates satellite cells and promotes sarcoma formation via the HGF/c-MET signaling pathway

    PubMed Central

    Van Mater, David; Añó, Leonor; Blum, Jordan M.; Webster, Micah T.; Huang, WeiQiao; Williams, Nerissa; Ma, Yan; Cardona, Diana M.; Fan, Chen-Min; Kirsch, David G.

    2015-01-01

    Some patients with soft tissue sarcoma (STS) report a history of injury at the site of their tumor. While this phenomenon is widely reported, there are relatively few experimental systems that have directly assessed the role of injury in sarcoma formation. We recently described a mouse model of STS whereby p53 is deleted and oncogenic Kras is activated in muscle satellite cells via a Pax7CreER driver following intraperitoneal injection with tamoxifen. Here, we report that after systemic injection of tamoxifen, the vast majority of Pax7-expressing cells remain quiescent despite mutation of p53 and Kras. The fate of these muscle progenitors is dramatically altered by tissue injury, which leads to faster kinetics of sarcoma formation. In adult muscle, quiescent satellite cells will transition into an active state in response to hepatocyte growth factor (HGF). We show that modulating satellite cell quiescence via intramuscular (IM) injection of HGF increases the penetrance of sarcoma formation at the site of injection, which is dependent on its cognate receptor c-MET. Unexpectedly, the tumor promoting effect of tissue injury also requires c-Met. These results reveal a mechanism by which HGF/c-MET signaling promotes tumor formation after tissue injury in a mouse model of primary STS, and they may explain why some patients develop a STS at the site of injury. PMID:25503558

  5. Right atrial thrombus associated with subclavian catheter developed due to total parenteral nutrition application

    PubMed Central

    Sahin, Nursel; Basarici, Ibrahim; Erbasan, Ozan

    2016-01-01

    Central venous catheterization as a frequent routine clinical procedure may have significant complications. Mechanical complications may occur during catheter placement, whereas thromboembolic and infectious complications can be seen during follow-up. Total parenteral nutrition (TPN) associated central venous catheterizations may result in early mechanical complications and thrombotic and infectious complications in the long term. This paper describes a patient diagnosed as mitochondrial neurogastrointestinal encephalomyopathy requiring long-term central venous catheterization for TPN implementation, who had an infected thrombus on the catheter tip resected by cardiac surgery. PMID:27212985

  6. Residual Inferior Vena Cava Thrombus Detected by Transesophageal Echocardiography After Resection of a Malignant Adrenal Mass.

    PubMed

    Burbano, Nelson H; Vlah, Claudene; Argalious, Maged

    2015-10-15

    A 43-year-old woman with a history of the Cushing syndrome secondary to adrenocortical carcinoma presented to the operating room for right adrenalectomy, hepatectomy, nephrectomy, and inferior vena cava (IVC) thrombectomy. Initial intraoperative transesophageal echocardiogram (TEE) confirmed the presence of an IVC tumor below the hepatic veins. Total vascular exclusion of the liver was necessary to perform the operation. A repeat TEE showed a residual thrombus within the IVC prompting an additional cavotomy to successfully remove the entire mass. The remainder of the procedure finalized uneventfully. The case highlights the importance of TEE monitoring for noncardiac surgery with thrombotic involvement of the IVC. PMID:26466307

  7. Resolution of a warfarin and dabigatran-resistant left atrial appendage thrombus with apixaban.

    PubMed

    Miwa, Yosuke; Minamishima, Toshinori; Sato, Toshiaki; Sakata, Konomi; Yoshino, Hideaki; Soejima, Kyoko

    2016-06-01

    The majority of embolisms associated with atrial fibrillation (AF) are from the left atrial appendage (LAA). To treat the existing thrombus, warfarin and novel anticoagulants have been used. However, there has been no clinical information regarding the difference of the effects of congealing the fibrinogenolysis system among these oral anticoagulants. Here, we report a case of persistent AF, in whom apixaban, factor Xa inhibitor resolved an LAA clot refractory to warfarin and direct thrombin inhibition. Factor Xa inhibitor, apixaban, could resolve the left appendage thrombosis refractory to warfarin and dabigatran. PMID:27354873

  8. A multimodality vascular imaging phantom of an abdominal aortic aneurysm with a visible thrombus

    SciTech Connect

    Allard, Louise; Chayer, Boris; Qin Zhao; Soulez, Gilles; Roy, David; Cloutier, Guy

    2013-06-15

    Purpose: With the continuous development of new stent grafts and implantation techniques, it has now become technically feasible to treat abdominal aortic aneurysms (AAA) with challenging anatomy using endovascular repair with standard, fenestrated, or branched stent-grafts. In vitro experimentations are very useful to improve stent-graft design and conformability or imaging guidance for stent-graft delivery or follow-up. Vascular replicas also help to better understand the limitation of endovascular approaches in challenging anatomy and possibly improve surgical planning or training by practicing high risk clinical procedures in the laboratory to improve outcomes in the operating room. Most AAA phantoms available have a very basic anatomy, which is not representative of the clinical reality. This paper presents a method of fabrication of a realistic AAA phantom with a visible thrombus, as well as some mechanical properties characterizing such phantom. Methods: A realistic AAA geometry replica of a real patient anatomy taken from a multidetector computed tomography (CT) scan was manufactured. To demonstrate the multimodality imaging capability of this new phantom with a thrombus visible in magnetic resonance (MR) angiography, CT angiography (CTA), digital subtraction angiography (DSA), and ultrasound, image acquisitions with all these modalities were performed by using standard clinical protocols. Potential use of this phantom for stent deployment was also tested. A rheometer allowed defining hyperelastic and viscoelastic properties of phantom materials. Results: MR imaging measurements of SNR and CNR values on T1 and T2-weighted sequences and MR angiography indicated reasonable agreement with published values of AAA thrombus and abdominal components in vivo. X-ray absorption also lay within normal ranges of AAA patients and was representative of findings observed on CTA, fluoroscopy, and DSA. Ultrasound propagation speeds for developed materials were also in

  9. Is Dabigatran As Effective As Warfarin on Cardiac Thrombus in a Patient With Atrial Fibrillation? A Challenging Question.

    PubMed

    Sunbul, Murat; Cincin, Altug; Mammadov, Ceyhun; Mutlu, Bulent

    2016-01-01

    Atrial fibrillation (AF) is an important risk factor for cardioembolic stroke. Warfarin is an effective treatment in reducing the risk of cardioembolic stroke in patients with AF. New anticoagulants have been widely using for stroke prophylaxis in patients with nonvalvular AF. Previous studies have suggested that thrombolytic therapy is effective treatment choice in patients with pulmonary embolisms. Warfarin therapy is also effective on prevention or treatment of cardiac thrombus in patients with AF. However, there are no evidence-based data on treatment of cardiac thrombus with new oral anticoagulants in patients with AF. In our case report, we reported an AF patient with cardiac thrombus and pulmonary embolism under dabigatran therapy. PMID:25415546

  10. Unusual Finding of a Tumor Thrombus Arising From Osteosarcoma Detected on 18F-NaF PET/CT.

    PubMed

    Verma, Priyanka; Purandare, Nilendu; Agrawal, Archi; Shah, Sneha; Rangarajan, Venkatesh

    2016-06-01

    Osteosarcoma is the most common bone sarcoma in adolescents and children. Tumor thrombus arising from osteosarcoma is rare. We describe the case of a 13-year-old girl with osteosarcoma of the right femur, in whom the F-NaF PET/CT was done for initial staging to look for skeletal metastases. The scan showed abnormal increased tracer uptake in the primary tumor and the right common femoral and external iliac vein representing a tumor thrombus. Our case emphasizes the importance of extraosseous findings on F-NaF PET/CT, which may result in important management changes. PMID:26909709

  11. Left Ventricular Thrombus as a Complication of Clozapine-Induced Cardiomyopathy: A Case Report and Brief Literature Review

    PubMed Central

    Malik, Shahbaz A.; Malik, Sarah; Dowsley, Taylor F.; Singh, Balwinder

    2015-01-01

    A 48-year-old male with history of schizoaffective disorder on clozapine presented with chest pain, dyspnea, and new left bundle branch block. He underwent coronary angiography, which revealed no atherosclerosis. The patient's workup was unrevealing for a cause for the cardiomyopathy and thus it was thought that clozapine was the offending agent. The patient was taken off clozapine and started on guideline directed heart failure therapy. During the course of hospitalization, he was also discovered to have a left ventricular (LV) thrombus for which he received anticoagulation. To our knowledge, this is the first case report of clozapine-induced cardiomyopathy complicated by a LV thrombus. PMID:26664756

  12. Clinical predictors and outcomes of patients with left ventricular thrombus following ST-segment elevation myocardial infarction.

    PubMed

    Garber, Adam M; Mentz, Robert J; Al-Khalidi, Hussein R; Shaw, Linda K; Fiuzat, Mona; O'Connor, Christopher M; Velazquez, Eric J

    2016-04-01

    We aimed to characterize the independent predictors of LVT following STEMI and the association with outcomes. The clinical predictors of left ventricular thrombus (LVT) formation after ST-segment elevation myocardial infarction (STEMI) are not well-defined in the contemporary era. We performed a retrospective analysis of STEMI patients at Duke from 2000 to 2011 who had a transthoracic echocardiogram within 90 days post-STEMI and compared patients with and without LVT (LVT+ vs. LVT-). Univariate Cox proportional hazards regression models of baseline characteristics were examined and significant variables were used in a multivariable model to assess adjusted relationships with LVT. A multivariable Cox PH survival model with covariate adjustments was used for assessment of LVT and long-term mortality. Of all eligible patients, 1734 patients met inclusion criteria and 4.3 % (N = 74) had a LVT. LVT+ patients tended to have a history of heart failure (HF) and higher initial troponin compared to LVT- patients. After adjustment, higher heart rate, non-white race, HF severity, and presence of left anterior descending artery (LAD) disease were independent predictors of LVT. There was a trend toward an association between LVT and increased all-cause mortality (HR 1.36; 95 % CI 0.84-2.21, P = 0.22), however this was not statistically significant. LVT was seen in over 4 % of this contemporary post-STEMI population. Several baseline characteristics were independently associated with LVT: Heart rate, HF severity, LAD disease, and non-white race. Prospective studies are warranted to determine whether anticoagulation in patients at increased risk for LVT improves outcomes. PMID:26202909

  13. Left ventricular assist device inflow cannula thrombus: characterization with two-dimensional transthoracic echocardiography.

    PubMed

    Missov, Emil

    2013-01-01

    Thrombotic complications are inherent to current generation nonpulsatile left ventricular assist devices. The clinical expression of device thrombosis ranges from catastrophic failure to protracted and indolent. We report the case of a 79-year-old patient who received a left ventricular assist device as destination therapy and presented only with vague clinical symptoms. He was found to have a large thrombus in close proximity with the inflow cannula at the left ventricular apex, raising the question of mechanical obstruction. We describe the step-by-step contrast-enhanced two-dimensional transthoracic echocardiographic examination which allowed to obtain diagnostic acoustic tomograms of the inflow cannula and obviated the need for any additional imaging modalities. Transthoracic echocardiography (TTE) is the most common imaging modality used in the clinical follow-up of left ventricular assist device recipients. A frequent clinical indication for TTE is to exclude left ventricular apical thrombus near the inflow cannula. Imaging of the inflow cannula at the left ventricular apex in the traditional apical 4 chamber, apical 2 chamber, and parasternal long axis views is challenging by TTE mainly because of poor acoustic windows, image artifacts, large body habitus, and operator experience. PMID:24172272

  14. Development of Ga-67 labeled DFO-DAS-fibrinogen conjugate as a thrombus imaging agent.

    PubMed

    Yamaoka, S

    1987-01-01

    A cluster method developed for labeling large molecular proteins with radioactive metal was applied for 67Ga-labeled fibrinogen. A large number of deferoxamine (DFO) was introduced to human fibrinogen using dialdehyde strarch (DAS) as a spacer-functional polymer. The synthesized DFO-DAS-fibrinogen mentioned above was easily labeled with GaCl3 (67Ga) solution (2 mCi/5 mg). The basic investigations found that 67Ga-DFO-DAS-fibrinogen was applicable to the diagnosis of thrombus, and clinical trials were carried out under the physician-sponsored IND. In our further investigation, improvement of the 67Ga-DFO-DAS-fibrinogen reagent was attempted to obtain high specific radioactivity. This was accomplished with the more familiar 67Ga citrate. From the results of a series of experiments, 67Ga-DFO-DAS-fibrinogen of a new composition labeled using 67Ga citrate with high specific radioactivity (2 mCi/3 mg) was prepared, and both reagents were evaluated as thrombus imaging agents from the chemical and biological aspects. The labeling efficiency and clottability of both 67Ga-DFO-DAS-fibrinogen conjugates were satisfactorily high, more than 95% and 80%, respectively. The biodistribution in rats showed that both 67Ga-DFO-DAS-fibrinogen conjugates were essentially the same. These results suggest that there are no significant differences between reagents. At present, the improved reagents are being supplied for the second clinical trials under physician-sponsored IND. PMID:3438481

  15. Management of inferior vena cava tumor thrombus in locally advanced renal cell carcinoma

    PubMed Central

    Psutka, Sarah P.

    2015-01-01

    The diagnosis of renal cell carcinoma is accompanied by intravascular tumor thrombus in up to 10% of cases, of which nearly one-third of patients also have concurrent metastatic disease. Surgical resection in the form of radical nephrectomy and caval thrombectomy represents the only option to obtain local control of the disease and is associated with durable oncologic control in approximately half of these patients. The objective of this clinical review is to outline the preoperative evaluation for, and operative management of patients with locally advanced renal cell carcinoma with venous tumor thrombi involving the inferior vena cava. Cornerstones of the management of these complex patients include obtaining high-quality imaging to characterize the renal mass and tumor thrombus preoperatively, with further intraoperative real-time evaluation using transesophageal echocardiography, careful surgical planning, and a multidisciplinary approach. Operative management of patients with high-level caval thrombi should be undertaken in high-volume centers by surgical teams with capacity for bypass and invasive intraoperative monitoring. In patients with metastatic disease at presentation, cytoreductive nephrectomy and tumor thrombectomy may be safely performed with simultaneous metastasectomy if possible. In the absence of level one evidence, neoadjuvant targeted therapy should continue to be viewed as experimental and should be employed under the auspices of a clinical trial. However, in patients with significant risk factors for postoperative complications and mortality, and especially in those with metastatic disease, consultation with medical oncology and frontline targeted therapy may be considered. PMID:26445601

  16. A Novel Technique for Endovascular Removal of Large Volume Right Atrial Tumor Thrombus

    SciTech Connect

    Nickel, Barbara; McClure, Timothy Moriarty, John

    2015-08-15

    Venous thromboembolic disease is a significant cause of morbidity and mortality, particularly in the setting of large volume pulmonary embolism. Thrombolytic therapy has been shown to be a successful treatment modality; however, its use somewhat limited due to the risk of hemorrhage and potential for distal embolization in the setting of large mobile thrombi. In patients where either thrombolysis is contraindicated or unsuccessful, and conventional therapies prove inadequate, surgical thrombectomy may be considered. We present a case of percutaneous endovascular extraction of a large mobile mass extending from the inferior vena cava into the right atrium using the Angiovac device, a venovenous bypass system designed for high-volume aspiration of undesired endovascular material. Standard endovascular methods for removal of cancer-associated thrombus, such as catheter-directed lysis, maceration, and exclusion, may prove inadequate in the setting of underlying tumor thrombus. Where conventional endovascular methods either fail or are unsuitable, endovascular thrombectomy with the Angiovac device may be a useful and safe minimally invasive alternative to open resection.

  17. [Successful endovascular repair of a ruptured thoracoabdominal aortic aneurysm with severe mural thrombus].

    PubMed

    Nakao, Yoshihisa; Akagi, Haruhiko; Irie, Hiroshi; Sakaguchi, Shoji; Sakai, Kei

    2014-11-01

    A 51-year-old man was transferred to our hospital on an emergency basis complaining of a sudden onset of severe left lumbar back pain. An emergency contrasted computed tomography showed a ruptured thoracoabdominal aortic aneurysm( rTAAA:Crawford classification type III). The ruptured site was near the aortic bifurcation, and the aneurysm had a relatively narrow segment with an extensive mural thrombus just below the renal arteries. Considering the high mortality of open surgery for the rTAAA and the poor general condition of the patient, we decided to perform endovascular aneurysm repair (EVAR) as a rescue procedure using the narrowed segment by the thrombus for a proximal landing zone. The abdominal part of the thoracoabdominal aortic aneurysm (TAAA) was successfully excluded with a stent graft to obtain complete hemostasis. The postoperative course was uneventful except for the need for hemodialysis. Even though there is a risk of developing late type 1 endoleak, this procedure can be a feasible option as a rescue procedure or a bridge to radical open surgery for ruptured TAAA in a specially anatomical setting like this case. PMID:25391465

  18. Early embolic events complicating intravenous thrombolysis for acute ischemic stroke.

    PubMed

    Chou, Ping Song; Lin, Chien Hung; Chao, Hai Lun; Chao, A Ching

    2012-11-01

    Intravenous recombinant tissue plasminogen activator (IV rt-PA) is the only established thrombolytic therapy for acute ischemic stroke. However, secondary embolism after IV rt-PA for acute ischemic stroke is recognized as an uncommon complication, and the pathophysiology is unclear. We describe a 72-year-old man with acute infarction in the territory of left anterior cerebral artery who developed new infarction in the territory of right middle cerebral artery and acute peripheral arterial occlusion after IV rt-PA therapy. It suggested a central embolic source. Because the patient has paroxysmal atrial fibrillation (Af), the possible embolic sources may come from fragmentation of pre-existing intra-atrial clot. Although Af and the presence of cardiac thrombus are not contraindication for IV rt-PA in acute ischemic stroke, our case and review suggested that the administration of IV rt-PA to patients with known Af and intracardiac thrombus could represent a particular risk situation and should be carefully evaluated. PMID:22205004

  19. Adhesion- and Degranulation-Promoting Adapter Protein Promotes CD8 T Cell Differentiation and Resident Memory Formation and Function during an Acute Infection.

    PubMed

    Fiege, Jessica K; Beura, Lalit K; Burbach, Brandon J; Shimizu, Yoji

    2016-09-15

    During acute infections, naive Ag-specific CD8 T cells are activated and differentiate into effector T cells, most of which undergo contraction after pathogen clearance. A small population of CD8 T cells persists as memory to protect against future infections. We investigated the role of adhesion- and degranulation-promoting adapter protein (ADAP) in promoting CD8 T cell responses to a systemic infection. Naive Ag-specific CD8 T cells lacking ADAP exhibited a modest expansion defect early after Listeria monocytogenes or vesicular stomatitis virus infection but comparable cytolytic function at the peak of response. However, reduced numbers of ADAP-deficient CD8 T cells were present in the spleen after the peak of the response. ADAP deficiency resulted in a greater frequency of CD127(+) CD8 memory precursors in secondary lymphoid organs during the contraction phase. Reduced numbers of ADAP-deficient killer cell lectin-like receptor G1(-) CD8 resident memory T (TRM) cell precursors were present in a variety of nonlymphoid tissues at the peak of the immune response, and consequently the total numbers of ADAP-deficient TRM cells were reduced at memory time points. TRM cells that did form in the absence of ADAP were defective in effector molecule expression. ADAP-deficient TRM cells exhibited impaired effector function after Ag rechallenge, correlating with defects in their ability to form T cell-APC conjugates. However, ADAP-deficient TRM cells responded to TGF-β signals and recruited circulating memory CD8 T cells. Thus, ADAP regulates CD8 T cell differentiation events following acute pathogen challenge that are critical for the formation and selected functions of TRM cells in nonlymphoid tissues. PMID:27521337

  20. Hybrid procedures for acute limb ischemia.

    PubMed

    de Donato, G; Setacci, F; Sirignano, P; Galzerano, G; Raucci, A; Palasciano, G; Setacci, C

    2010-12-01

    The most efficient treatment for acute arterial embolism is operative embolectomy using Fogarty's balloon catheter, especially if a single large artery is involved. Unfortunately, although the early surgical success of arterial thromboembolectomy often seems acceptable, the early clinical outcome still remains unsatisfactory. This may be related to the incomplete restoration of perfusion (i.e., residual thrombus in distal vessels not reached by the balloon catheter thromboembolectomy), propagation of residual thrombi or presence of underlying steno-occlusive lesions. In such a situation a meticulous intraoperative assessment of the adequacy of clot removal is decisive. Residual thrombus, chronic atherosclerotic disease and even vessel injuries secondary to balloon catheter passage can be corrected by endovascular techniques (hybrid procedures). The combination of surgical and endovascular options may overcome the limitations that characterize the traditional approach, and it is likely that in the future many treatments will be a mix of techniques that can be performed by vascular surgeons in the operating room or in a dedicated endovascular suite. This review article summarizes the hybrid treatment options for acute arterial occlusion caused by either embolism or local thrombosis. PMID:21124280

  1. Hybrid procedures for acute limb ischemia.

    PubMed

    Setacci, C; De Donato, G; Setacci, F; Sirignano, P; Galzerano, G

    2012-02-01

    The most efficient treatment for acute arterial embolism is operative embolectomy using Fogarty's balloon catheter, especially if a single large artery is involved. Unfortunately, although the early surgical success of arterial thromboembolectomy often seems acceptable, the early clinical outcome still remains unsatisfactory. This may be related to the incomplete restoration of perfusion (i.e. residual thrombus in distal vessels not reached by the balloon catheter thromboembolectomy), propagation of residual thrombi or presence of underlying steno-occlusive lesions. In such a situation a meticulous intraoperative assessment of the adequacy of clot removal is decisive. Residual thrombus, chronic atherosclerotic disease and even vessel injuries secondary to balloon catheter passage can be corrected by endovascular techniques (hybrid procedures). The combination of surgical and endovascular options may overcome the limitations that characterize the traditional approach, and it is likely that in the future many treatments will be a mix of techniques that can be performed by vascular surgeons in the operating room or in a dedicated endovascular suite. This review article summarizes the hybrid treatment options for acute arterial occlusion caused by either embolism or local thrombosis. PMID:22433732

  2. Thrombus Degradation by Fibrinolytic Enzyme of Stenotrophomonas sp. Originated from Indonesian Soybean-Based Fermented Food on Wistar Rats

    PubMed Central

    Tjandrawinata, Raymond R.

    2016-01-01

    Objective. To evaluate thrombus degrading effect of a fibrinolytic enzyme from food origin Stenotrophomonas sp. of Indonesia. Methods. Prior to animal study, the enzyme safety was tested using cell culture. The effect on expression of tissue plasminogen activator was also analysed in the cell culture. For in vivo studies, 25 Wistar rats were used: normal control, negative control, treatment groups with crude and semipurified enzyme given orally at 25 mg/kg, and positive control group which received Lumbrokinase at 25 mg/kg. Blood clot in the tail was induced by kappa carrageenan injection at 1 mg/kg BW. Results. Experiment with cell culture confirmed the enzyme safety at the concentration used and increased expression of tPA. Decreasing of thrombus was observed in the positive group down to 70.35 ± 23.11% of the negative control animals (100%). The thrombus observed in the crude enzyme treatment was down to 56.99 ± 15.95% and 71.5 ± 15.7% for semipurified enzyme. Scanning electron microscopy showed clearly that bood clots were found in the animals injected with kappa carrageenan; however, in the treatment and positive groups, the clot was much reduced. Conclusions. Oral treatment of enzyme from Stenotrophomonas sp. of Indonesian fermented food was capable of degrading thrombus induced in Wistar rats.

  3. Local Quantification of Wall Thickness and Intraluminal Thrombus Offer Insight into the Mechanical Properties of the Aneurysmal Aorta.

    PubMed

    Martufi, Giampaolo; Satriano, Alessandro; Moore, Randy D; Vorp, David A; Di Martino, Elena S

    2015-08-01

    Wall stress is a powerful tool to assist clinical decisions in rupture risk assessment of abdominal aortic aneurysms. Key modeling assumptions that influence wall stress magnitude and distribution are the inclusion or exclusion of the intraluminal thrombus in the model and the assumption of a uniform wall thickness. We employed a combined numerical-experimental approach to test the hypothesis that abdominal aortic aneurysm (AAA) wall tissues with different thickness as well as wall tissues covered by different thrombus thickness, exhibit differences in the mechanical behavior. Ultimate tissue strength was measured from in vitro tensile testing of AAA specimens and material properties of the wall were estimated by fitting the results of the tensile tests to a histo-mechanical constitutive model. Results showed a decrease in tissue strength and collagen stiffness with increasing wall thickness, supporting the hypothesis of wall thickening being mediated by accumulation of non load-bearing components. Additionally, an increase in thrombus deposition resulted in a reduction of elastin content, collagen stiffness and tissue strength. Local wall thickness and thrombus coverage may be used as surrogate measures of local mechanical properties of the tissue, and therefore, are possible candidates to improve the specificity of AAA wall stress and rupture risk evaluations. PMID:25631202

  4. Swine Model of Thrombotic Caval Occlusion Created by Autologous Thrombus Injection with Assistance of Intra-caval Net Knitting

    PubMed Central

    Shi, Wan-Yin; Wu, Shuang; Hu, Lan-Yue; Liu, Chang-Jian; Gu, Jian-Ping

    2015-01-01

    To evaluate the feasibility of a swine model of thrombotic inferior vena cava (IVC) occlusion (IVCO) created by autologous thrombus injection with assistance of intra-caval net knitting. Sixteen pigs were included and divided into two groups: Group A (n = 10), IVCO model created by knitting a caval net followed by autologous thrombus injection; Group B (n = 6), control model created by knitting a net and normal saline injection. Venography was performed to assess each model and the associated thrombotic occlusion. The vessels were examined histologically to analyse the pathological changes postoperatively. IVCO model was successfully created in 10 animals in Group A (100%). Immediate venography showed extensive clot burden in the IVC. Postoperative venography revealed partial caval occlusion at 7 days, and complete occlusion coupled with collateral vessels at 14 days. Histologically, Group A animals had significantly greater venous wall thickening, with CD163-positive and CD3-positive cell infiltration. Recanalization channels were observed at the margins of the thrombus. By contrast, no thrombotic occlusion of the IVC was observed in Group B. The thrombotic IVCO model can be reliably established in swine. The inflammatory reaction may contribute to the caval thrombus propagation following occlusion. PMID:26680253

  5. Precise control of caval and hepatic vessels: Surgical technique to treat level III caval thrombus concomitant to renal cell carcinoma

    PubMed Central

    Chen, Ming; Xu, Bin; Liu, Ning; Jiang, Hua; Wang, Yiduo; Yang, Yu; Zhang, Xiaowen; Sun, Chao; Liu, Jing; Zhu, Weidong; Chen, Shuqiu

    2015-01-01

    Introduction: We investigated the surgical techniques, safety, and prevention of complications of nephrectomy and removal of tumour thrombus for treating level III inferior vena cava (IVC) concomitant to renal cell carcinoma (RCC). We did this by precise controlling IVC and hepatic vessels without a vascular bypass. Methods: In this series, we included 5 patients with level III IVC tumour thrombus below the hepatic vein concomitant to RCC. After precisely controlling the IVC and hepatic vessels, we then removed the thrombus en bloc with the renal vein. Blood loss volume, IVC clamping time, hypotension time, resuscitation, cardiocerebrovascular complications, and postoperative organ dysfunction were observed. Results: Surgery was successfully performed without perioperative death. Blood loss volume was 900 to 1500 mL, operation time was 165 to 250 minutes, vascular clamping time was 8 to 12 minutes, and intraoperative hypotension time was 9 to 12 minutes. Serious perioperative complications were not observed. Local recurrence was not observed during the 9 to 24 months of follow-up. One patient exhibited disease-free survival, 3 developed lung or liver metastasis, and 1 died 11 months after surgery. Conclusion: Precise control of IVC and hepatic pedicle vessels, without vascular bypass, is a safe and effective surgical treatment for level III tumor thrombus below the hepatic vein concomitant to RCC. The procedure was conducted without increased risks of intraoperative hypotensive shock, difficult resuscitation, pulmonary embolism, and multiple organ dysfunctions. PMID:26600890

  6. Carotid artery free-floating thrombus caused by paradoxical embolization from greater saphenous vein ascending thrombophlebitis.

    PubMed

    Irace, Luigi; Gabrielli, Roberto; Rosati, Maria Sofia; Giannoni, Maria Fabrizia; Castiglione, Anna; Laurito, Antonella; Gossetti, Bruno

    2013-05-01

    Stroke of unknown origin in young patients is seen to be closely correlated with patent foramen ovale (PFO) than stroke in patients with established stroke mechanisms. We report a case of a young woman without cardiovascular risk factors who was admitted to our emergency department with listlessness and altered mental status. The clinical examination revealed right lower limb swelling. Magnetic resonance imaging and contrast-enhanced computed tomographic scans revealed a free floating thrombus of the left internal carotid artery (ICA) with a large bilateral frontal ischemic lesion. The diagnosis of a medium-sized PFO with moderate right-to-left contrast shunting was made after transesophageal echocardiography. No other cardiac sources for embolization were detected, while an ascending thrombophlebitis of the right greater saphenous vein was detected by venous Doppler ultrasonography. These findings support the diagnosis of ICA free-floating thrombus caused by paradoxical embolization (via the PFO) of clot from the greater saphenous vein. The patient underwent emergency saphenofemoral disconnection with femoral vein thrombectomy and subsequently carotid artery thrombectomy under general anesthesia. No carotid atheromatous wall lesions were detected at surgical exploration; no immunologic pathology, hypercoagulable status, or malignancy were recorded. No hemorrhagic cerebral complications were observed in the postoperative period, and the patient had an improvement of her neurologic status (a reduction of the National Institutes of Health Stroke Scale score from 7 to 3). Her recovery was uneventful. The patient was transferred for rehabilitation on postoperative day 5 with oral anticoagulation. Six-month ultrasound follow-up revealed deep and superficial venous system and carotid artery patency. The patient was asymptomatic and anticoagulation was discontinued. Paradoxical cerebral embolization through a PFO is a rare phenomenon that, in our patient, appeared to have

  7. Comprehensive treatments for hepatocellular carcinoma with tumor thrombus in major portal vein

    PubMed Central

    Ye, Hai-Hong; Ye, Jia-Zhou; Xie, Zhi-Bo; Peng, Yu-Chong; Chen, Jie; Ma, Liang; Bai, Tao; Chen, Jun-Ze; Lu, Zhan; Qin, Hong-Gui; Xiang, Bang-De; Li, Le-Qun

    2016-01-01

    AIM: To evaluate the efficacy of transcatheter arterial chemoembolisation (TACE) compared with surgical intervention and sorafenib for treatment of hepatocellular carcinoma (HCC) in patients with tumor thrombus extending to the main portal vein. METHODS: From 2009 to 2013, a total of 418 HCC patients with tumor thrombus extending to the main portal vein were enrolled in this study and divided into four groups. These groups underwent different treatments as follows: TACE (n = 307), surgical intervention (n = 54), sorafenib (n = 15) and palliative treatment (n = 42). Overall survival rates were determined by Kaplan-Meier method, and differences between the groups were identified through log-rank analysis. Cox’s proportional hazard model was used to identify the risk factors for survival. RESULTS: The mean survival periods for patients in the TACE, surgical intervention, sorafenib and palliative treatment groups were 10.39, 4.13, 5.54 and 2.82 mo, respectively. For the TACE group, the 3-, 6-, 12- and 24-mo survival rates were 94.1%, 85.9%, 51.5% and 0.0%, respectively. The corresponding rates were 60.3%, 22.2%, 0.0% and 0.0% for the surgical intervention group and 50.9%, 29.5%, 0.0% and 0.0% for the sorafenib group. Evidently, the results in the TACE group were significantly higher than those in the other groups (P < 0.0001). Furthermore, no significant difference among survival rates was observed between TACE with/without sorafenib (10.22 mo vs 10.52 mo, P = 0.615). No significant difference in survival rates was also found among the surgical intervention, sorafenib and palliative treatment groups (P > 0.05). These values significantly increased after TACE with/without sorafenib compared with other treatments (P < 0.05). CONCLUSION: For HCC patients with tumor thrombus extending to the main portal vein, TACE can yield a higher survival rate than surgical intervention or sorafenib treatment. PMID:27053855

  8. Interobserver Variability in Target Definition for Hepatocellular Carcinoma With and Without Portal Vein Thrombus: Radiation Therapy Oncology Group Consensus Guidelines

    PubMed Central

    Hong, Theodore S.; Bosch, Walter R.; Krishnan, Sunil; Kim, Tae K.; Mamon, Harvey J.; Shyn, Paul; Ben-Josef, Edgar; Seong, Jinsil; Haddock, Michael G.; Cheng, Jason C.; Feng, Mary U.; Stephans, Kevin L.; Roberge, David; Crane, Christopher; Dawson, Laura A.

    2014-01-01

    Purpose Defining hepatocellular carcinoma (HCC) gross tumor volume (GTV) requires multimodal imaging, acquired in different perfusion phases. The purposes of this study were to evaluate the variability in contouring and to establish guidelines and educational recommendations for reproducible HCC contouring for treatment planning. Methods and Materials Anonymous, multiphasic planning computed tomography scans obtained from 3 patients with HCC were identified and distributed to a panel of 11 gastrointestinal radiation oncologists. Panelists were asked the number of HCC cases they treated in the past year. Case 1 had no vascular involvement, case 2 had extensive portal vein involvement, and case 3 had minor branched portal vein involvement. The agreement between the contoured total GTVs (primary + vascular GTV) was assessed using the generalized kappa statistic. Agreement interpretation was evaluated using Landis and Koch’s interpretation of strength of agreement. The S95 contour, defined using the simultaneous truth and performance level estimation (STAPLE) algorithm consensus at the 95% confidence level, was created for each case. Results Of the 11 panelists, 3 had treated >25 cases in the past year, 2 had treated 10 to 25 cases, 2 had treated 5 to 10 cases, 2 had treated 1 to 5 cases, 1 had treated 0 cases, and 1 did not respond. Near perfect agreement was seen for case 1, and substantial agreement was seen for cases 2 and 3. For case 2, there was significant heterogeneity in the volume identified as tumor thrombus (range 0.58–40.45 cc). For case 3, 2 panelists did not include the branched portal vein thrombus, and 7 panelists contoured thrombus separately from the primary tumor, also showing significant heterogeneity in volume of tumor thrombus (range 4.52–34.27 cc). Conclusions In a group of experts, excellent agreement was seen in contouring total GTV. Heterogeneity exists in the definition of portal vein thrombus that may impact treatment planning

  9. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy

    PubMed Central

    Angelillo-Scherrer, Anne; Burnier, Laurent; Flores, Nathalie; Savi, Pierre; DeMol, Maria; Schaeffer, Paul; Herbert, Jean-Marc; Lemke, Greg; Goff, Stephen P.; Matsushima, Glenn K.; Earp, H. Shelton; Vesin, Christian; Hoylaerts, Marc F.; Plaisance, Stéphane; Collen, Désiré; Conway, Edward M.; Wehrle-Haller, Bernhard; Carmeliet, Peter

    2005-01-01

    Mechanisms regulating thrombus stabilization remain largely unknown. Here, we report that loss of any 1 of the Gas6 receptors (Gas6-Rs), i.e., Tyro3, Axl, or Mer, or delivery of a soluble extracellular domain of Axl that traps Gas6 protects mice against life-threatening thrombosis. Loss of a Gas6-R does not prevent initial platelet aggregation but impairs subsequent stabilization of platelet aggregates, at least in part by reducing “outside-in” signaling and platelet granule secretion. Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the β3 integrin, thereby amplifying outside-in signaling via αIIbβ3. Blocking the Gas6-R–αIIbβ3 integrin cross-talk might be a novel approach to the reduction of thrombosis. PMID:15650770

  10. Direct thrombus aspiration using the Penumbra system for the treatment of pediatric intracranial dissection.

    PubMed

    Fujimoto, Motoaki; Tateshima, Satoshi; Ali, Latisha; Raychev, Radoslav; Vinuela, Fernando

    2013-11-01

    We describe a case of a 15-year-old girl who developed a spontaneous intracranial arterial dissection with distal middle cerebral artery (MCA) occlusions. From the digital subtraction angiography provided, the dissection flap appeared to originate at the internal carotid artery terminus with extension into the right M1 segment and occluding the right anterior cerebral artery, A1 segment. CT perfusion study showed salvageable tissue in the posterior MCA territory, including the motor cortex. In order to avoid further injury to the dissection, clot retrieval systems were not a treatment option. We therefore performed selective thrombus aspiration with the Penumbra system for the occluded central and precentral arteries distal to the non-occlusive dissecting lesion. Sufficient recanalization was achieved and the patient made a marked recovery. Although mechanical thrombectomy with the use of retrieval intracranial stent systems has demonstrated satisfactory recanalization rates, the aspiration methodology remains useful for patients with an accompanying proximal vascular lesion. PMID:23188785

  11. Left atrial thrombus under dabigatran in a patient with nonvalvular atrial fibrillation.

    PubMed

    Janssen, A M; van de Kerkhof, D; Szabó, B; Durian, M F; van der Voort, P H

    2016-08-01

    Dabigatran is a new direct competitive inhibitor of thrombin and is equally effective and safe as warfarin in the prevention of thromboembolism in patients with nonvalvular atrial fibrillation. We present a case of a 60-year-old man with persistent nonvalvular atrial fibrillation who switched from acenocoumarol to dabigatran 110 mg twice daily. After five months the patient developed a large atrial thrombus, occlusion of the tibial arteries of the right foot, cerebellar infarction and multiple infarctions in kidneys and spleen. Blood test showed a dabigatran concentration of 35 ng/ml six hours after intake, correlating with a low trough concentration of 24-27 ng/mL and significantly increased thromboembolic risk. Other risk factors for thromboembolism were excluded. The present case indicates that in selected patients, there might be an indication for dose adjustments based on serum levels of dabigatran to ensure patient efficacy (thromboembolic events) and safety (bleeding). PMID:27571947

  12. Thrombus-trapping efficiency of the LGM (Vena Tech) and titanium Greenfield filters in vivo.

    PubMed

    Millward, S F; Marsh, J I; Pon, C; Moher, D

    1992-02-01

    To assess the trapping efficiency of two vena cava filters, 326 radiopaque thrombi 5 mm in diameter were injected into adult sheep: four with LG-Medical (LGM) and four with titanium Greenfield (TG) filters. Thrombi were sequentially injected and not removed. Trapping was monitored fluoroscopically, and the pressure gradient across the filter was measured. The LGM filter trapped 70% of 5 x 5-mm and 100% of 5 x 10-mm thrombi; the TG, 26% of 5 x 5-mm, 34% of 5 x 10-mm, and 37% of 5 x 30-mm thrombi. The LGM filter required an average of 2.0 mL of trapped thrombus to occlude the filter, compared with 6.4 mL for the TG. These differences were statistically significant. These data indicate that in this model, the LGM filter traps thrombi more efficiently than the TG filter but is more likely to produce caval occlusion. PMID:1540709

  13. Complex Perioperative Decision-Making: Liver Resection in a Patient with Extensive Superior Vena Cava/Right Atrial Thrombus and Superior Vena Cava Syndrome

    PubMed Central

    Lekowski, Robert W.

    2016-01-01

    The perioperative management of patients suffering from extensive superior vena cava (SVC) thrombus complicated by SVC syndrome presents unique challenges. The anesthesiologist needs to be prepared for possible thrombus dislodgement resulting in pulmonary embolism and also has to assess the need for fluid resuscitation given the dangers of massive intravenous fluid application via the upper extremities. We present our perioperative approach in management of a patient scheduled for right hepatectomy who was previously diagnosed with extensive SVC and right atrial (RA) thrombus complicated by SVC syndrome. PMID:26904303

  14. Acute glomerulonephritis.

    PubMed

    Yoshizawa, N

    2000-09-01

    Acute glomerulonephritis (AGN) is a representative disease of acute nephritic syndrome characterized by the sudden appearance of edema, hematuria, proteinuria, and hypertension. The prototype of AGN is acute poststreptococcal glomerulonephritis (APSGN). "Nephritogenic streptococci" are defined as organisms that are cultured from a patient who develops AGN. Although only a limited number of M-types of streptococci have been recognized as "nephritogenic streptococci", all M-types of streptococci may have nephritogenic potential because the genes for major putative nephritogenic antigens such as SPEB and NAPIr are found to be present in all group A streptococci thus far examined. Pathogenic mechanisms for APSGN involving both humoral and cell-mediated immunity have been recently proposed. The role of humoral immunity is presumed to be mediated by the in situ formation of nephritogenic streptococcal antigen-antibody complexes and circulating immune complexes. While in the cellular immune component a role for delayed-type hypersensitivity has been suggested to contribute to the pathogenesis of APSGN. PMID:10969898

  15. Variations in elemental compositions of rat hippocampal formation between acute and latent phases of pilocarpine-induced epilepsy: an X-ray fluorescence microscopy study.

    PubMed

    Chwiej, J; Dulinska, J; Janeczko, K; Appel, K; Setkowicz, Z

    2012-06-01

    There is growing experimental evidence that tracing the elements involved in brain hyperexcitability, excitotoxicity, and/or subsequent neurodegeneration could be a valuable source of data on the molecular mechanisms triggering or promoting further development of epilepsy. The most frequently used experimental model of the temporal lobe epilepsy observed in clinical practice is the one based on pilocarpine-induced seizures. In the frame of this study, the elemental anomalies occurring for the rat hippocampal tissue in acute and silent periods after injection of pilocarpine in rats were compared. X-ray fluorescence microscopy was applied for the topographic and quantitative elemental analysis. The differences in the levels of elements such as P, S, K, Ca, Fe, Cu, and Zn between the rats 3 days (SE72) and 6 h (SE6) after pilocarpine injection as well as naive controls were examined. Comparison of SE72 and control groups showed, for specific areas of the hippocampal formation, lower levels of P, K, Cu, and Zn, and an increase in Ca accumulation. These results as well as further analysis of the differences between the SE72 and SE6 groups confirmed that seizure-induced excitotoxicity as well as mossy fiber sprouting are the mechanisms involved in the neurodegenerative processes which may finally lead to spontaneous seizures in the chronic period of the pilocarpine model. Moreover, in the light of the results obtained, Cu seems to play a very important role in the pathogenesis of epilepsy in this animal model. For all areas analyzed, the levels of this element recorded in the latent period were not only lower than those for controls but were even lower than the levels found in the acute period. The decreased hippocampal accumulation of Cu in the phase of behavior and EEG stabilization, a possible inhibitory effect of this element on excitatory amino acid receptors, and enhanced seizure susceptibility in Menkes disease (an inherited Cu transport disorder leading to Cu

  16. Enhanced nitric oxide generation from nitric oxide synthases as the cause of increased peroxynitrite formation during acute restraint stress: Effects on carotid responsiveness to angiotensinergic stimuli in type-1 diabetic rats.

    PubMed

    Moreira, Josimar D; Pernomian, Larissa; Gomes, Mayara S; Moreira, Rafael P; do Prado, Alejandro F; da Silva, Carlos H T P; de Oliveira, Ana M

    2016-07-15

    Diabetes mellitus is associated with reactive oxygen and nitrogen species accumulation. Behavioral stress increases nitric oxide production, which may trigger a massive impact on vascular cells and accelerate cardiovascular complications under oxidative stress conditions such as Diabetes. For this study, type-1 Diabetes mellitus was induced in Wistar rats by intraperitoneal injection of streptozotocin. After 28 days, cumulative concentration-response curves for angiotensin II were obtained in endothelium-intact carotid rings from diabetic rats that underwent to acute restraint stress for 3h. The contractile response evoked by angiotensin II was increased in carotid arteries from diabetic rats. Acute restraint stress did not alter angiotensin II-induced contraction in carotid arteries from normoglycaemic rats. However acute stress combined with Diabetes increased angiotensin II-induced contraction in carotid rings. Western blot experiments and the inhibition of nitric oxide synthases in functional assays showed that neuronal, endothelial and inducible nitric oxide synthase isoforms contribute to the increased formation of peroxynitrite and contractile hyperreactivity to angiotensin II in carotid rings from stressed diabetic rats. In summary, these findings suggest that the increased superoxide anion generation in carotid arteries from diabetic rats associated to the increased local nitric oxide synthases expression and activity induced by acute restrain stress were responsible for exacerbating the local formation of peroxynitrite and the contraction induced by angiotensin II. PMID:27118175

  17. In Vivo Magnetization Transfer and Diffusion-Weighted Magnetic Resonance Imaging Detects Thrombus Composition in a Mouse Model of Deep Vein Thrombosis

    PubMed Central

    Saha, Prakash; Modarai, Bijan; Smith, Alberto; Botnar, René M.

    2014-01-01

    Background Deep vein thrombosis remains a major health problem necessitating accurate diagnosis. Thrombolysis is associated with significant morbidity and is effective only for the treatment of unorganized thrombus. We tested the feasibility of in vivo magnetization transfer (MT) and diffusion-weighted magnetic resonance imaging to detect thrombus organization in a murine model of deep vein thrombosis. Methods and Results Deep vein thrombosis was induced in the inferior vena cava of male BALB/C mice. Magnetic resonance imaging was performed at days 1, 7, 14, 21, and 28 after thrombus induction using MT, diffusion-weighted, inversion-recovery, and T1-mapping protocols. Delayed enhancement and T1 mapping were repeated 2 hours after injection of a fibrin contrast agent. Finally, excised thrombi were used for histology. We found that MT and diffusion-weighted imaging can detect histological changes associated with thrombus aging. MT rate (MTR) maps and percentage of MT rate (%MTR) allowed visualization and quantification of the thrombus protein content, respectively. The %MTR increased with thrombus organization and was significantly higher at days 14, 21, and 28 after thrombus induction (days 1, 7, 14, 21, 28: %MTR=2483±451, 2079±1210, 7029±2490, 10 295±4356, 32 994±25 449; Panova<0.05). There was a significant positive correlation between the %MTR and the histological protein content of the thrombus (r=0.70; P<0.05). The apparent diffusion coefficient was lower in erythrocyte-rich and collagen-rich thrombus (0.72±0.10 and 0.69±0.05 [×10−3 mm2/s]). Thrombus at days 7 and 14 had the highest apparent diffusion coefficient values (0.95±0.09 and 1.10±0.18 [×10−3 mm2/s]). Conclusions MT and diffusion-weighted magnetic resonance imaging sequences are promising for the staging of thrombus composition and could be useful in guiding medical intervention. PMID:23564561

  18. [Outcome of Resection of Inferior Vena Cava Superior to the Renal Vein in Renal Cell Carcinoma with Vena Caval Tumor Thrombus].

    PubMed

    Kashima, Soki; Narita, Shintaro; Saito, Mitsuru; Takahashi, Makoto; Maita, Shinya; Tsuruta, Hiroshi; Numakura, Kazuyuki; Maeno, Atsushi; Inoue, Takamitsu; Tsuchiya, Norihiko; Satoh, Shigeru; Yamamoto, Hiroshi; Yamamoto, Yuzo; Habuchi, Tomonori

    2016-06-01

    Surgical management with radical nephrectomy and thrombectomy has often been performed in renal cell carcinoma (RCC) with tumor thrombus infiltrating the inferior vena cava (IVC). We retrospectively reviewed the outcomes of IVC resection without venous reconstruction in patients with RCC and IVC thrombus at our institution. Eight patients with right RCC underwent radical nephrectomy and IVC resection superior to the level of the renal vein without venous reconstruction from August 2005 to February 2015. Thoracotomy, liver mobilization, and extracorporeal circulation were performed based on the IVC thrombus level. We assessed surgical outcomes, perioperative complications, and survival. At presentation, four patients had level IIIa IVC thrombus, three had level IIIb IVC thrombus, and one had level IV IVC thrombus. Perioperative imaging showed that three of the four patients who underwent neoadjuvant molecular targeting therapy achieved down-staging of the tumor thrombus level. The median operative time was 406 min, and the median estimated blood loss was 3,135 ml. With regard to IVC resectionassociated perioperative complications, one patient needed extracorporeal circulation with IVC ligation and Pringle maneuver owing to low blood pressure. Another patient underwent temporary hemodialysis for 8 days after surgery. There were no perioperative deaths, and none of the patients required permanent hemodialysis. Three patients survived the mean observation period of 25 months, including one patient with no recurrence. Three patients achieved long-term survival of more than 2 years. IVC resection without venous reconstruction may be a feasible option for patients with RCC and IVC tumor thrombus. Further study is needed to determine the most appropriate candidates for this procedure. PMID:27452491

  19. Prompt recognition and percutaneous coronary intervention leads to favorable myocardial recovery after ST-segment elevation myocardial infarction secondary to acute promyelocytic leukemia: pediatric case report.

    PubMed

    Thomas, Tamara O; Ramachandran, Preeti; Jefferies, John L; Beekman, Robert H; Hor, Kan; Lorts, Angela

    2013-01-01

    Acute myocardial infarction (AMI) is extremely rare in children, and unlike the adult disease, the etiology of the infarction is rarely due to atherosclerotic coronary disease. This unique reported case involved a 15-year-old boy with severe chest pain who presented with an ST-segment-elevation myocardial infarction secondary to in situ thrombus formation in the left anterior descending (LAD) coronary artery. The initial electrocardiogram (ECG) had a Q-wave pattern in V6 and ST depression in the inferior leads with ST-segment elevation in reciprocal leads. The cardiac enzymes and routine labs showed evidence of myocardial damage. The boy was urgently taken to the cardiac catheterization laboratory for percutaneous coronary intervention, where complete occlusion of the LAD was found and successfully stented. Eventually, a peripheral blood smear showed pancytopenia with 38 % hypergranular blast-like cells consistent with acute myeloid leukemia (AML), and chemotherapy with all-transretinoic acid was implemented. This first pediatric case report of an AML-associated AMI emphasizes the benefit resulting from expedient reperfusion of the ischemic myocardium by quick reestablishment of coronary perfusion. It also emphasizes the limitations of existing noninvasive technologies in detecting myocardial viability. PMID:23263162

  20. Acute Bronchitis

    MedlinePlus

    ... or though physical contact (for example, on unwashed hands). Being exposed to tobacco smoke, air pollution, dusts, vapors, and fumes can also cause acute bronchitis. Less often, bacteria can also cause acute bronchitis. To diagnose acute ...

  1. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... control. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  2. Free-floating thrombus of the carotid artery with a homozygous methylenetetrahydrofolate reductase gene mutation: a case report.

    PubMed

    Colak, Necmettin; Nazli, Yunus; Kosehan, Dilek; Alpay, Mehmet Fatih; Cakir, Omer

    2013-02-01

    Free-floating thrombus (FFT) of the carotid artery is a rare condition of currently unknown etiology. We describe a symptomatic patient with an FFT in the left common carotid artery. A duplex ultrasonography scan showed the presence of a mobile floating thrombus moving in cyclical motion with the cardiac cycles in the left common carotid artery. During emergency surgery, an FFT was seen at this location and removed. No underlying wall defect was seen at the time of surgery. In a genetic screening test, TT homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphisms was detected. The patient recovered uneventfully, with no neurogical events. Lifelong anticoagulant therapy was recommended. An aggressive surgical approach is recommended in the patient to prevent embolic episodes. PMID:22101856

  3. Massive renal urothelial carcinoma with renal vein tumor thrombus, pancreatic infiltration and adrenal metastasis: A case report

    PubMed Central

    Li, Tao; Gao, Liang; Wu, Weilu; Chen, Peng; Bu, Siyuan; Wei, Qiang; Yang, Lu

    2016-01-01

    A 49-year-old female patient presented with a massive left renal tumor, recurrent left flank pain and gross hematuria. The tumor was accompanied by a renal vein tumor thrombus, pancreatic infiltration and a solitary adrenal metastasis. Radical nephrectomy, distal pancreatectomy, ipsilateral adrenalectomy and splenectomy were performed. Histopathological examination suggested high-grade urothelial carcinoma (UC); however, tumor recurrence and multiple metastases were detected only 3 months after the surgery, and the patient succumbed during follow-up 1 month later. To the best of our knowledge, this is the first case of renal UC of such advanced stage with renal vein tumor thrombus, pancreatic infiltration and a solitary adrenal metastasis. PMID:27446406

  4. ANCA-negative eosinophilic granulomatosis with polyangitis (EGPA) manifesting as a large intracardiac thrombus and glomerulonephritis with angionecrosis.

    PubMed

    Saito, Yuichi; Okada, Sho; Funabashi, Nobusada; Kobayashi, Yoshio

    2016-01-01

    A 59-year-old woman with a history of bronchial asthma presented with a prolonged fever and eosinophilia. There was transient proteinuria and troponin level was elevated. Antineutrophil cytoplasmic antibody was negative and she did not fulfil criteria for eosinophilic granulomatosis with polyangitis (EGPA). Echocardiography showed a large apical mass in the left ventricle, but there was no systolic dysfunction, local asynergy or ventricular remodelling. On MRI, apical mass was compatible with a thrombus and endocardial region was diffusely damaged. Loeffler endocarditis-like cardiac manifestation led to meticulous examination, which found no aetiology for eosinophilia. Finally, renal biopsy revealed eosinophil infiltration and glomerular angionecrosis, confirming as EGPA. This case highlights the isolated large cardiac thrombus as a rare presenting sign for EGPA and underscores current complicated strategy to diagnose EGPA. Of note, this clinical challenge was mostly caused by inchoate comprehension of hypereosinophilia-related disorders. PMID:27591039

  5. Differentiation of cardiac thrombus from cardiac tumor combining cardiac MRI and 18F-FDG-PET/CT Imaging.

    PubMed

    Rinuncini, Massimo; Zuin, Marco; Scaranello, Fiorenzo; Fejzo, Majlinda; Rampin, Lucia; Rubello, Domenico; Faggian, Giuseppe; Roncon, Loris

    2016-06-01

    Radiological differentiation of an unknown cardiac masse is often a challenging issue. 18F-FDG-PET/CT imaging was performed to evaluate a left ventricle mass visualized on transthoracic echocardiogram (TTE) and cardiac magnetic resonance (CMR) in a patient with an history of ischemic heart disease. The metabolically inert area on the PET/CT, corresponding to the relatively homogenous hypodensity in the LV, was thought to represent an old organized LV thrombus. Histopathological examination confirmed the imaging diagnosis. PMID:27038712

  6. Thrombembolic occlusion of crural arteries following transcatheter aortic valve implantation--successful endovascular recanalization using a thrombus aspiration device.

    PubMed

    Malyar, Nasser M; Kaleschke, Gerrit; Reinecke, Holger

    2012-05-01

    Transcatheter aortic valve implantation (TAVI) has become an increasingly used alternative to conventional surgical valve replacement in patients with severe aortic valve stenosis (AS) and high operative risk. We here describe a case of a TAVI performed in local anesthesia causing intraprocedural thromboembolic occlusion of non-stenotic crural arteries and its immediate successful therapeutic management by means of endovascular recanalization using a thrombus aspiration device. PMID:22565625

  7. Holmium:YAG laser angioplasty: treatment of acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Topaz, On

    1993-06-01

    We report our clinical experience with a group of 14 patients who presented with acute myocardial infarction. A holmium:YAG laser was applied to the infarct-related artery. This laser emits 250 - 600 mJ per pulse, with a pulse length of 250 microseconds and repetition rate of 5 Hz. Potential benefits of acute thrombolysis by lasers include the absence of systemic lytic state; a shortened thrombus clearing time relative to using thrombolytics; safe removal of the intracoronary thrombus and facilitation of adjunct balloon angioplasty. Potential clinical difficulties include targeting the obstructive clot and plaque, creation of debris and distal emboli and laser-tissue damage. It is conceivable that holmium:YAG laser can be a successful thrombolytic device as its wave length (2.1 microns) coincides with strong water absorption peaks. Since it is common to find an atherosclerotic plaque located under or distal to the thrombotic occlusion, this laser can also be applied for plaque ablation, and the patient presenting with acute myocardial infarction can clearly benefit from the combined function of this laser system.

  8. A Floating Thrombus Anchored at the Proximal Anastomosis of a Woven Thoracic Graft Mimicking a Genuine Aortic Dissection.

    PubMed

    Li, Bin; Liu, Bing; Fu, Yijun; Bondarenko, Olexandr; Verdant, Alain; Rochette-Drouin, Olivier; Lin, Jing; Bourget, Jean-Michel; Guzman, Randolph; Wang, Lu; Zhang, Ze; Douville, Yvan; Germain, Lucie; Jing, Zaiping; Guidoin, Robert

    2015-01-01

    An aortoesophageal fistula following surgery for a ruptured 6.6-cm thoracic aneurysm in a 69-year-old female was repaired using a 34-mm woven prosthetic graft. A follow-up computed tomography (CT) scan at 10 days postoperatively revealed a dissection-like picture in the region of the graft, which was treated conservatively. The patient eventually died from sepsis and multiorgan failure. At autopsy, the graft was retrieved in situ and studied by detailed gross, microscopy, and scanning electron microscopy (SEM) examination. Gross observation confirmed that the dissection resulted from the rolling of the internal capsule downstream. A massive thrombus anchored at the proximal anastomosis and held by a narrow head was also noted. The thrombus demonstrated reorganization in the area of the anastomosis, with a false lumen in its distal half. The reminder of the thrombus consisted of layered fibrin. After gross examination, the fabric graft was found to be flawless. Additional detailed studies were also done using microscopy, SEM, and gross examination. PMID:26756557

  9. Massive Pulmonary Embolism: Treatment with Thrombus Fragmentation and Local Fibrinolysis with Recombinant Human-Tissue Plasminogen Activator

    SciTech Connect

    Stock, Klaus Wilhelm; Jacob, Augustinus Ludwig; Schnabel, Karl Jakob; Bongartz, Georg; Steinbrich, Wolfgang

    1997-09-15

    Purpose: To report the results of thrombus fragmentation in combination with local fibrinolysis using recombinant human-tissue plasminogen activator (rtPA) in patients with massive pulmonary embolism. Methods: Five patients with massive pulmonary embolism were treated with thrombus fragmentation followed by intrapulmonary injection of rtPA. Clot fragmentation was performed with a guidewire, angiographic catheter, and balloon catheter. Three patients had undergone recent surgery; one of them received a reduced dosage of rtPA. Results: All patients survived and showed clinical improvement with a resultant significant (p < 0.05) decrease in the pulmonary blood pressure (mean systolic pulmonary blood pressure before treatment, 49 mmHg; 4 hr after treatment, 28 mmHg). Angiographic follow-up in three patients revealed a decrease in thrombus material and an increase in pulmonary perfusion. Two patients developed retroperitoneal hematomas requiring transfusion. Conclusion: Clot fragmentation and local fibrinolysis with rtPA was an effective therapy for massive pulmonary embolism. Bleeding at the puncture site was a frequent complication.

  10. [Survival after Sorafenib Treatment for Advanced Recurrent Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava].

    PubMed

    Matoba, Hideaki; Seta, Shinsuke

    2015-11-01

    A 72-year-old man with chronic viral hepatitis type B undergoing surgery for hepatocellular carcinoma was found to have a recurrent tumor in the left liver with peritoneal dissemination near the inferior vena cava(IVC)and tumor thrombus in the IVC. For this patient diagnosed with Barcelona clinic liver cancer (BCLC) classification stage C hepatocellular carcinoma, we initiated 800 mg/body sorafenib. Two weeks after the initiation of sorafenib, the patient experienced grade 3 hand-foot syndrome, after which, the dose of sorafenib was reduced to 400 mg/body. After 1 year, CT showed an enlarged tumor in the left liver and multiple metastases to the lung. However, no remarkable difference was observed in the peritoneal dissemination and the tumor thrombus. He has been receiving sorafenib for 19 months with a good quality of life. Sorafenib can be provided on an outpatient basis and it may facilitate long-term survival for patients with advanced recurrent hepatocellular carcinoma with IVC tumor thrombus. This clinical condition is very rare, and the standard treatment for it still has not been established. PMID:26805098

  11. Imaging of occlusive thrombi in acute ischemic stroke

    PubMed Central

    Gasparian, GG; Sanossian, N; Shiroishi, MS; Liebeskind, DS

    2015-01-01

    Thrombi, or clots, often occlude proximal segments of the cerebral arterial circulation in acute ischemic stroke. Thromboembolic occlusion or thrombi superimposed on atherosclerotic plaque are the principal focus of acute stroke therapies such as thrombolysis or thrombectomy. We review the imaging characteristics of thrombi on multimodal CT and MRI, angiography and ultrasonography, summarizing recent studies that facilitate therapeutic decision-making from these noninvasive studies. Information about the location, size and imaging characteristics can be ascertained using these techniques. Imaging findings in relation to occlusive thrombus have been correlated with clot pathology, response to therapeutic interventions, and clinical outcome. Diagnostic evaluation of occlusive thrombi on noninvasive studies now constitutes an integral component of acute stroke management. PMID:25545291

  12. Symptomatic Patients with Intraluminal Carotid Thrombus: Outcome with a Strategy of Initial Anticoagulation

    PubMed Central

    Vellimana, Ananth K.; Kadkhodayan, Yasha; Rich, Keith M.; Cross, Dewitte T.; Moran, Christopher J.; Zazulia, Allyson R.; Lee, Jin-Moo; Chicoine, Michael R.; Dacey, Ralph G.; Derdeyn, Colin P.; Zipfel, Gregory J.

    2013-01-01

    Background Optimal treatment for patients with symptomatic intraluminal carotid thrombus (ICT) remains poorly defined. Methods We performed a retrospective chart review of patients presenting to our institution between 2001 and 2011 with symptomatic ICT. Results Twenty-four patients (16 males, 8 females) with ICT presented with ischemic stroke (n=18) or TIA (n=6). All were treated initially with anticoagulation ± antiplatelet drugs. Eight of these patients had no or mild carotid stenosis on initial angiography and were treated with medical management alone. The remaining 16 patients had moderate or severe carotid stenosis on initial angiography. Of these, 10 underwent delayed revascularization (endarterectomy, n=8; angioplasty and stenting, n=2), 2 refused revascularization, and 4 were treated with medical therapy alone. One patient had multiple TIAs despite medical therapy and eventually underwent CEA; the remaining 23 patients had no TIAs. No patient suffered ischemic or hemorrhagic stroke while on anticoagulation, during the perioperative period or in long-term follow up; one patient died of an unrelated condition (mean follow-up = 16.4 months). Conclusion Our results suggest that initial anticoagulation of symptomatic ICT results in a low rate of recurrent ischemic events and that carotid revascularization, if indicated, can be safely performed in a delayed manner. PMID:23061393

  13. Transarterial chemoembolization combined with sorafenib for the treatment of hepatocellular carcinoma with hepatic vein tumor thrombus

    PubMed Central

    Zhang, Yong-Fa; Wei, Wei; Wang, Jia-Hong; Xu, Li; Jian, Pei-En; Xiao, Cheng-Zuo; Zhong, Xiao-Ping; Shi, Ming; Guo, Rong-Ping

    2016-01-01

    Objective To compare the treatment outcomes of sorafenib plus transarterial chemoembolization (TACE) vs TACE alone in patients with hepatocellular carcinoma (HCC) and hepatic vein tumor thrombus (HVTT). Methods Twenty patients who were initially diagnosed with HCC and HVTT and received TACE combined with sorafenib during February 2009 to October 2013 were included in the study. To minimize selection bias, these patients were compared with 60 case-matched controls selected from a pool of 81 patients (in a 1:3 ratio) who received TACE alone during the same period. The primary end point was overall survival (OS). The secondary end points were time to progression, disease control rate, and adverse events. Results After a median follow-up period of 12.5 months (range, 1.03–44.23 months), the OS of the combined group was found to be significantly higher compared with the monotherapy group (14.9 vs 6.1 months, P=0.010). The time to progression was found to be significantly longer in the combined group (4.9 vs 2.4 months, P=0.016). Univariate and multivariate analyses revealed that the treatment allocation was an independent predictor of OS. Conclusion Sorafenib plus TACE was well tolerated and was more effective in treating patients with advanced HCC and HVTT. Future trials with prospective larger samples are required to validate these results. PMID:27471398

  14. Impact of poroelasticity of intraluminal thrombus on wall stress of abdominal aortic aneurysms

    PubMed Central

    2012-01-01

    Background The predictions of stress fields in Abdominal Aortic Aneurysm (AAA) depend on constitutive descriptions of the aneurysm wall and the Intra-luminal Thrombus (ILT). ILT is a porous diluted structure (biphasic solid–fluid material) and its impact on AAA biomechanics is controversially discussed in the literature. Specifically, pressure measurements showed that the ILT cannot protect the wall from the arterial pressure, while other (numerical and experimental) studies showed that at the same time it reduces the stress in the wall. Method To explore this phenomenon further a poroelastic description of the ILT was integrated in Finite Element (FE) Models of the AAA. The AAA model was loaded by a pressure step and a cyclic pressure wave and their transition into wall tension was investigated. To this end ILT’s permeability was varied within a microstructurally motivated range. Results The two-phase model verified that the ILT transmits the entire mean arterial pressure to the wall while, at the same time, it significantly reduces the stress in the wall. The predicted mean stress in the AAA wall was insensitive to the permeability of the ILT and coincided with the results of AAA models using a single-phase ILT description. Conclusion At steady state, the biphasic ILT behaves like a single-phase material in an AAA model. Consequently, computational efficient FE single-phase models, as they have been exclusively used in the past, accurately predict the wall stress in AAA models. PMID:22931215

  15. [A case of surgical resection for liver metastasis of gastric cancer with portal vein tumor thrombus].

    PubMed

    Hata, Tomoki; Wada, Hiroshi; Tomimaru, Yoshito; Tomokuni, Akira; Hama, Naoki; Kawamoto, Koichi; Kobayashi, Shogo; Asaoka, Tadafumi; Marubashi, Shigeru; Eguchi, Hidetoshi; Umeshita, Koji; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro; Nagano, Hiroaki

    2014-11-01

    A 58-year-old man presented with anorexia and weight loss in April 2010. Endoscopic examination revealed a type 3 tumor extending from the gastric cardia to the antrum. Preoperative imaging showed liver metastasis (S8; 2 cm) and direct invasion of the cancer into the pancreas. We administered 4 courses of chemotherapy (DCS) for the unresectable tumor; the impact of the therapy was partial response (PR). We performed total gastrectomy, D2 dissection, splenectomy, distal pancreatectomy, and partial hepatectomy (S8) in April 2011. The patient was treated with 8 courses of adjuvant chemotherapy with S-1. In April 2012, abdominal computed tomography (CT) revealed a solitary recurrent lesion in the liver (S2). After 7 courses of chemotherapy(weekly paclitaxel), abdominal CT and magnetic resonance imaging (MRI) revealed a tumor thrombus in the portal vein extending from P2 to the umbilical portion (UP). We performed left hepatectomy and cholecystectomy due to the absence of new lesions. Histopathological findings revealed that the poorly differentiated adenocarcinoma had metastasized to the liver. Abdominal CT revealed the presence of multiple recurrent metastases in the liver, 4 months after the surgery. The patient died 27 months after the initial surgery and 7 months after the last operation. PMID:25731448

  16. Interobserver Variability in Target Definition for Hepatocellular Carcinoma With and Without Portal Vein Thrombus: Radiation Therapy Oncology Group Consensus Guidelines

    SciTech Connect

    Hong, Theodore S.; Bosch, Walter R.; Krishnan, Sunil; Kim, Tae K.; Mamon, Harvey J.; Ben-Josef, Edgar; Seong, Jinsil; Haddock, Michael G.; Cheng, Jason C.; Feng, Mary U.; Stephans, Kevin L.; Roberge, David; and others

    2014-07-15

    Purpose: Defining hepatocellular carcinoma (HCC) gross tumor volume (GTV) requires multimodal imaging, acquired in different perfusion phases. The purposes of this study were to evaluate the variability in contouring and to establish guidelines and educational recommendations for reproducible HCC contouring for treatment planning. Methods and Materials: Anonymous, multiphasic planning computed tomography scans obtained from 3 patients with HCC were identified and distributed to a panel of 11 gastrointestinal radiation oncologists. Panelists were asked the number of HCC cases they treated in the past year. Case 1 had no vascular involvement, case 2 had extensive portal vein involvement, and case 3 had minor branched portal vein involvement. The agreement between the contoured total GTVs (primary + vascular GTV) was assessed using the generalized kappa statistic. Agreement interpretation was evaluated using Landis and Koch's interpretation of strength of agreement. The S95 contour, defined using the simultaneous truth and performance level estimation (STAPLE) algorithm consensus at the 95% confidence level, was created for each case. Results: Of the 11 panelists, 3 had treated >25 cases in the past year, 2 had treated 10 to 25 cases, 2 had treated 5 to 10 cases, 2 had treated 1 to 5 cases, 1 had treated 0 cases, and 1 did not respond. Near perfect agreement was seen for case 1, and substantial agreement was seen for cases 2 and 3. For case 2, there was significant heterogeneity in the volume identified as tumor thrombus (range 0.58-40.45 cc). For case 3, 2 panelists did not include the branched portal vein thrombus, and 7 panelists contoured thrombus separately from the primary tumor, also showing significant heterogeneity in volume of tumor thrombus (range 4.52-34.27 cc). Conclusions: In a group of experts, excellent agreement was seen in contouring total GTV. Heterogeneity exists in the definition of portal vein thrombus that may impact treatment planning

  17. Endovascular Treatment of Phlegmasia Cerulea Dolens with Impending Venous Gangrene: Manual Aspiration Thrombectomy as the First-Line Thrombus Removal Method

    SciTech Connect

    Oguzkurt, Levent Ozkan, Ugur; Demirturk, Orhan S.; Gur, Serkan

    2011-12-15

    Purpose: Our purpose was to report the outcome of endovascular treatment with manual aspiration thrombectomy as the first-line thromboablative method for phlegmasia cerulea dolens. Methods: Between October 2006 and May 2010, seven consecutive patients (5 women, 2 men; age range, 31-80 years) with the diagnosis of phlegmasia cerulea dolens secondary to acute iliofemoral deep venous thrombosis had endovascular treatment with manual aspiration thrombectomy. Catheter-directed thrombolysis and stent placement were used as adjunctive procedures. Phlegmasia was left-sided in five and right-sided in two patients. Results: All patients had associated great saphenous vein thrombosis in addition to iliofemoral deep vein thrombosis (DVT). Aspiration thrombectomy completely removed the thrombus from the popliteal vein to the inferior vena cava (IVC) in all cases. Three patients with May-Thurner syndrome had stent placement in the left common iliac vein. Two patients had early recurrences. Repeated aspiration thrombectomy was unsuccessful in one patient. There were no complications related to the procedure. One patient who had been successfully treated died of sepsis and another patient who had unsuccessful repeated interventions had below-the-knee amputation. Overall, the clinical success and survival rates of patients in this study were 86%. On follow-up, three patients with successful treatment were asymptomatic with no deep venous insufficiency. One of these patients died during the 4-month follow-up period. Two patients had mild ankle swelling with deep venous insufficiency. Conclusions: Manual aspiration thrombectomy with adjunctive use of catheter-directed thrombolysis and stent placement is an effective endovascular treatment method with high clinical success and survival rates for phlegmasia cerulean dolens.

  18. Is long-term anticoagulation after acute thromboembolic limb ischemia always necessary?

    PubMed Central

    Forbes, Thomas L.; DeRose, Guy; Harris, Kenneth A.

    2002-01-01

    Objective After thromboembolectomy, patients with acute limb ischemia often receive anticoagulant therapy to prevent recurrent events. Patients with atrial fibrillation or cardiac thrombus have a higher risk of recurrent emboli than those without these risk factors. This study examines the importance of long-term anticoagulation in these 2 groups. Design A review of patients presenting with acute limb ischemia over a 5-year period (1994–1999). Setting A university-affiliated medical centre. Patients Fifty patients divided into 2 groups: 19 (38%) patients with atrial fibrillation (group 1) and 31 (62%) patients with no atrial fibrillation or cardiac thrombus (group 2) as confirmed by transthoracic echocardiography. Intervention All patients underwent surgical thromboembolectomy and received postoperative anticoagulant therapy. Outcome measures Mortality, limb loss, further thromboembolic events and bleeding complications as determined by telephone survey. Results There was a significant difference in 5-year survival (group 1, 84%; group 2, 64%) and early limb loss (group 1, 0%; group 2, 13%). Further thromboembolic events and bleeding complications were rare but were more common in group 1. In group 2 there were no instances of recurrent thromboemboli and no bleeding complications although only 39% of patients in this group were taking angicoagulants at the end of the study period. Conclusions Patients with extremity thromboemboli without atrial fibrillation or cardiac thrombus may not be at the same risk for recurrent events as those with these risk factors, and long-term anticoagulant therapy may not be as necessary in this group. PMID:12387535

  19. Bimodal Thrombus Imaging: Simultaneous PET/MR Imaging with a Fibrin-targeted Dual PET/MR Probe—Feasibility Study in Rat Model

    PubMed Central

    Uppal, Ritika; Catana, Ciprian; Ay, Ilknur; Benner, Thomas; Sorensen, A. Gregory

    2011-01-01

    Purpose: To image thrombus by using magnetic resonance (MR) imaging and positron emission tomography (PET) simultaneously in a rat arterial thrombus model with a dual PET/MR probe. Materials and Methods: Animal studies were approved by the institutional animal use committee. A dual PET/MR probe was synthesized by means of partial exchange of gadolinium for copper 64 (64Cu) in the fibrin-targeted MR probe EP-2104R. A preformed 25-mm thrombus was injected into the right internal carotid artery of a rat. Imaging was performed with a clinical 3.0-T MR imager with an MR-compatible human PET imager. Rats (n = 5) were imaged prior to and after systemic administration of the dual probe by using simultaneous PET/MR. The organ distribution of 64Cu and gadolinium was determined ex vivo (n = 8), 2 hours after injection by using well counting and inductively coupled plasma mass spectrometry, respectively. Signal intensity ratios (SIRs) between the thrombus-containing and contralateral vessel were computed from PET images and MR data before and after probe administration. Results: The dual probe was synthesized with greater than 98% radiochemical purity. Thrombus enhancement was observed in all five animals at both MR (SIR[postprobe]/SIR[preprobe] = 1.71 ± 0.35, P = .0053) and PET (SIR = 1.85 ± 0.48, P = .0087) after injection of the dual PET/MR probe. Ex vivo analysis at 2 hours after injection showed the highest 64Cu and gadolinium concentrations, after the excretory organs (kidney and liver), to be in the thrombus. Conclusion: A fibrin-targeted dual PET/MR probe enables simultaneous, direct MR and PET imaging of thrombus. © RSNA, 2010 PMID:21177389

  20. Acute chylous peritonitis due to acute pancreatitis.

    PubMed

    Georgiou, Georgios K; Harissis, Haralampos; Mitsis, Michalis; Batsis, Haralampos; Fatouros, Michalis

    2012-04-28

    We report a case of acute chylous ascites formation presenting as peritonitis (acute chylous peritonitis) in a patient suffering from acute pancreatitis due to hypertriglyceridemia and alcohol abuse. The development of chylous ascites is usually a chronic process mostly involving malignancy, trauma or surgery, and symptoms arise as a result of progressive abdominal distention. However, when accumulation of "chyle" occurs rapidly, the patient may present with signs of peritonitis. Preoperative diagnosis is difficult since the clinical picture usually suggests hollow organ perforation, appendicitis or visceral ischemia. Less than 100 cases of acute chylous peritonitis have been reported. Pancreatitis is a rare cause of chyloperitoneum and in almost all of the cases chylous ascites is discovered some days (or even weeks) after the onset of symptoms of pancreatitis. This is the second case in the literature where the patient presented with acute chylous peritonitis due to acute pancreatitis, and the presence of chyle within the abdominal cavity was discovered simultaneously with the establishment of the diagnosis of pancreatitis. The patient underwent an exploratory laparotomy for suspected perforated duodenal ulcer, since, due to hypertriglyceridemia, serum amylase values appeared within the normal range. Moreover, abdominal computed tomography imaging was not diagnostic for pancreatitis. Following abdominal lavage and drainage, the patient was successfully treated with total parenteral nutrition and octreotide. PMID:22563182

  1. Antiplatelet and anticoagulation agents in acute coronary syndromes: what is the current status and what does the future hold?

    PubMed

    Huber, Kurt; Bates, Eric R; Valgimigli, Marco; Wallentin, Lars; Kristensen, Steen Dalby; Anderson, Jeffrey L; Lopez Sendon, Jose Luis; Tubaro, Marco; Granger, Christopher B; Bode, Christoph; Ohman, Erik Magnus; Steg, Philippe Gabriel

    2014-11-01

    Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio. PMID:25440788

  2. Hepatic resection or transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus.

    PubMed

    Zheng, Ninggang; Wei, Xiaodong; Zhang, Dongzhi; Chai, Wenxiao; Che, Ming; Wang, Jiangye; Du, Binbin

    2016-06-01

    The role of hepatic resection in hepatocellular carcinoma (HCC) with accompanying portal vein tumor thrombus (PVTT) remains controversial. This study aimed to evaluate the surgical outcomes of hepatic resection compared with those of transarterial chemoembolization (TACE) in HCC patients. A retrospective study was conducted using the medical records of 230 HCC patients with portal vein invasion who underwent hepatic resection (96 patients) or TACE (134 patients). The baseline characteristics, tumor characteristics, clinicopathological parameters, and overall survival rates were compared between the 2 groups. The baseline and tumor characteristics were comparable between the hepatic resection and TACE groups. The overall complication rate was 35.4% in the hepatic resection group, which was significantly lower than that in the TACE group (73.0%, P <0.001). However, the serious complication rate (grade ≥3) in the hepatic resection group was 13.5%, which was significantly higher than that in the TACE group (P = 0.003). The cumulative overall survival rates at 1, 3, and 5 years in the hepatic resection group were 86.5%, 60.4%, and 33.3%, respectively. These rates were much higher than those in the TACE group (1-year: 77.6%; 3-year: 47.8%; and 5-year: 20.9%; P = 0.021). The long-term survival was notably better in the patients with types I and II PVTT than in the patients with types III and IV PVTT (P <0.05). The univariate and multivariate analyses indicated that types III and IV PVTT and TACE may have contributed to the poor overall survival following surgery. In HCC patients with PVTT and compensated liver function, hepatic resection is a safe and effective surgical protocol, particularly for patients with type I or II PVTT. PMID:27367992

  3. Hepatic resection or transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus

    PubMed Central

    Zheng, Ninggang; Wei, Xiaodong; Zhang, Dongzhi; Chai, Wenxiao; Che, Ming; Wang, Jiangye; Du, Binbin

    2016-01-01

    Abstract The role of hepatic resection in hepatocellular carcinoma (HCC) with accompanying portal vein tumor thrombus (PVTT) remains controversial. This study aimed to evaluate the surgical outcomes of hepatic resection compared with those of transarterial chemoembolization (TACE) in HCC patients. A retrospective study was conducted using the medical records of 230 HCC patients with portal vein invasion who underwent hepatic resection (96 patients) or TACE (134 patients). The baseline characteristics, tumor characteristics, clinicopathological parameters, and overall survival rates were compared between the 2 groups. The baseline and tumor characteristics were comparable between the hepatic resection and TACE groups. The overall complication rate was 35.4% in the hepatic resection group, which was significantly lower than that in the TACE group (73.0%, P <0.001). However, the serious complication rate (grade ≥3) in the hepatic resection group was 13.5%, which was significantly higher than that in the TACE group (P = 0.003). The cumulative overall survival rates at 1, 3, and 5 years in the hepatic resection group were 86.5%, 60.4%, and 33.3%, respectively. These rates were much higher than those in the TACE group (1-year: 77.6%; 3-year: 47.8%; and 5-year: 20.9%; P = 0.021). The long-term survival was notably better in the patients with types I and II PVTT than in the patients with types III and IV PVTT (P <0.05). The univariate and multivariate analyses indicated that types III and IV PVTT and TACE may have contributed to the poor overall survival following surgery. In HCC patients with PVTT and compensated liver function, hepatic resection is a safe and effective surgical protocol, particularly for patients with type I or II PVTT. PMID:27367992

  4. Inhibition of SA Node at Supine Position in Right Atrial Thrombus Complicating Behçet’s Disease – From Cardiac Surgical Point of View

    PubMed Central

    Hijazi, Emad Mohamed; Ibdah, Rasheed Khaled; Rawashdeh, Sukina Ismael; Saadeh, Abdullah Mahmoud; Al-Balas, Hamzeh Ibrahim

    2016-01-01

    Patient: Female, 27 Final Diagnosis: Right atrial thrombus compressing the sinoatrial node Symptoms: Dyspnea • cough and hemoptysis with supine bradycardia reaching 36/min and dizziness Medication: — Clinical Procedure: Cardiac surgical intervention removing the mechanical cause if conservative management failed can be done safely Specialty: Surgery Objective: Rare disease Background: Behçet’s disease (BD) is a chronic multi-systemic disease of unknown cause. Intra-cardiac thrombus (ICT) complicating BD is extremely rare. In general, cardiac manifestations in BD are associated with poor prognosis. Chest computed tomography (CT) scan and echocardiogram are excellent modalities for diagnosis and patient assessment. Cardiac surgical intervention can be done safely using an on-pump technique when medical management has failed. Case Report: We report on a case of a 27-year-old Jordanian woman diagnosed with BD who presented with dyspnea, cough, and hemoptysis, with supine bradycardia reaching 36 beats/minute and dizziness which disappear on sitting or standing position, and with heart rate reaching 76 beats/minute. Right atrial thrombus was identified using transthoracic echocardiogram and chest CT scan. After medical management failed, cardiac surgical intervention became an option and targeted extraction of the right atrial thrombus compressing the sinoatrial node (SA node). Conclusions: In BD, right atrial thrombus compressing the SA node is rare. If conservative management has failed, cardiac surgical intervention removing the mechanical cause can be done safely, either using on-pump with cross clamp or on-pump with beating heart technique. PMID:27311379

  5. A long-surviving case of gastric cancer with main portal vein tumor thrombus after surgical resection and postoperative S-1 therapy.

    PubMed

    Sato, Shinsuke; Nagai, Erina; Taki, Yusuke; Watanabe, Masaya; Takahashi, Michiro; Kyoden, Yusuke; Ohata, Ko; Kanemoto, Hideyuki; Oba, Noriyuki; Taku, Keisei; Suzuki, Makoto; Takagi, Masakazu

    2016-08-01

    Gastric cancer patients with main portal vein tumor thrombus usually have a short survival time, owing to its aggressive behavior. Herein, we report a long-surviving case of gastric cancer with main portal vein tumor thrombus. A 78-year-old man presenting with anorexia and body weight loss was diagnosed with gastric cancer. The patient was referred to our hospital for further examination and treatment. Endoscopy revealed a type 3 tumor (8.0 cm in length) in the body of the stomach. Biopsy led to the diagnosis of moderately differentiated adenocarcinoma. Enhanced computed tomography revealed a large tumor thrombus extending from the gastric coronary vein to the portal trunk. A total gastrectomy with lymphadenectomy, splenectomy, and thrombectomy was performed. Postoperative chemotherapy with S-1 was administered for 18 months. The patient died a natural death without recurrence at 49 postoperative months. To the best of our knowledge, the patient was the oldest to be diagnosed with gastric cancer with main portal vein tumor thrombus at diagnosis, who survived >36 months. Although gastric cancer with main portal vein tumor thrombus is a rare occurrence, its prognosis is extremely poor. Intensive surgery and long-term chemotherapy may be effective at improving survival time in these patients. PMID:27318995

  6. Photographic studies of laser-induced bubble formation in absorbing liquids and on submerged targets: implications for drug delivery with microsecond laser pulses

    NASA Astrophysics Data System (ADS)

    Shangguan, HanQun; Casperson, Lee W.; Paisley, Dennis L.; Prahl, Scott A.

    1998-08-01

    Pulsed laser ablation of blood clots in a fluid-filled blood vessel is accompanied by an explosive evaporation process. The resulting vapor bubble rapidly expands and collapses to disrupt the thrombus (blood clot). The hydrodynamic pressures following the bubble expansion and collapse can also be used as a driving force to deliver clot-dissolving agents into thrombus for enhancement of laser thrombolysis. Thus, the laser-induced bubble formation plays an important role in the thrombus removal process. We investigate the effects of boundary configurations and materials on bubble formation with time-resolved flash photography and high- speed photography. Potential applications in drug delivery using microsecond laser pulses are then discussed.

  7. CT Findings of Intrarenal Yolk Sac Tumor with Tumor Thrombus Extending into the Inferior Vena Cava: A Case Report

    PubMed Central

    Lin, ShaoChun; Li, XueHua; Feng, ShiTing; Peng, ZhenPeng; Huang, SiYun; Li, ZiPing

    2014-01-01

    Yolk sac tumor (YST) is a rare germ cell neoplasm of childhood that usually arises from the testis or ovary. The rare cases of YST in various extragonadal locations have been reported, but the primary intrarenal YST is even more uncommon. Here, we report a case of a primary intrarenal YST with tumor thrombus of the inferior vena cava and left renal vein in a 2-year-old boy, with an emphasis on the CT features. To our knowledge, this is the first reported case of an intrarenal YST with intravascular involvement. PMID:25246826

  8. Acute Bronchitis

    MedlinePlus

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

  9. Scorpion envenomation-induced acute thrombotic inferior myocardial infarction.

    PubMed

    Baykan, Ahmet Oytun; Gür, Mustafa; Acele, Armağan; Şeker, Taner; Çaylı, Murat

    2016-01-01

    The occurrence of a serious cardiac emergency following scorpion envenomation has rarely been reported and, when so, mostly presented as non-ST segment elevation myocardial infarction, cardiogenic shock, or myocarditis. Possible mechanisms include imbalance in blood pressure and coronary vasospasm caused by the combination of sympathetic excitation, scorpion venom-induced release of catecholamines, and the direct effect of the toxin on the myocardium. We report a case of a 55-year-old man who presented with acute inferior wall myocardial infarction (MI) within 2 h of being stung by a scorpion. Coronary angiogram revealed total thrombotic occlusion of the left circumflex artery, which was treated successfully with glycoprotein IIb/IIIa inhibitor, thrombus aspiration, antivenom serum, and supportive therapy. Therefore, life-threatening MI can complicate the clinical course during some types of scorpion envenomation and should be managed as an acute coronary syndrome. PMID:26875137

  10. Endovascular Treatment of Acute Thrombosis of Cerebral Veins and Sinuses

    PubMed Central

    Yakovlev, Sergey Borisovich; Bocharov, Aleksei Vasilievich; Mikeladze, Ketevan; Gasparian, Sergey Surenovich; Serova, Natalia Konstantinovna; Shakhnovich, Alexander Romanovich

    2014-01-01

    Summary Acute thrombosis of cerebral veins and sinuses (ATCVS) is a multifactorial disease with grave consequences. Because of its rare occurrence there are no proven treatment guidelines. Sixteen patients with ATCVS were treated. The final diagnosis was confirmed by digital subtraction angiography. Sinus catheterization was performed via transfemoral venous access. Treatment included mechanical manipulation of thrombi and thrombolytic therapy. A regression of clinical symptoms with a concomitant decrease of intracranial hypertension was achieved in all patients. Long-term results were studied in eight patients: none presented clinical signs of intracranial hypertension. Endovascular transvenous recanalization is an effective treatment for acute thrombosis of cerebral veins and sinuses. Along with the local thrombolysis, significant potential in the treatment of this complex pathology lies in the transvenous endovascular techniques of mechanical thrombus extraction, especially in patients with intracranial hemorrhage for whom the use of thrombolytic agents is restricted. PMID:25196622

  11. Manual Thrombus Aspiration and the Improved Survival of Patients With Unstable Angina Pectoris Treated With Percutaneous Coronary Intervention (30 Months Follow-Up)

    PubMed Central

    Yildiz, Bekir S.; Bilgin, Murat; Zungur, Mustafa; Alihanoglu, Yusuf I.; Kilic, Ismail D.; Buber, Ipek; Ergin, Ahmet; Kaftan, Havane A.; Evrengul, Harun

    2016-01-01

    Abstract The clinical effect of intracoronary thrombus aspiration during percutaneous coronary intervention in patients with unstable angina pectoris is unknown. In this study, we aimed to assess how thrombus aspiration during percutaneous coronary intervention affects in-hospital and 30-month mortality and complications in patients with unstable angina pectoris. We undertook an observational cohort study of 645 consecutive unstable angina pectoris patients who had performed percutaneous coronary intervention from February 2011 to March 2013. Before intervention, 159 patients who had culprit lesion with thrombus were randomly assigned to group 1 (thrombus aspiration group) and group 2 (stand-alone percutaneous coronary intervention group). All patients were followed-up 30 months until August 2015. Thrombus aspiration was performed in 64 patients (46%) whose cardiac markers (ie, creatinine kinase [CK-MB] mass and troponin T) were significantly lower after percutaneous coronary intervention than in those of group 2 (CK-MB mass: 3.80 ± 1.11 vs 4.23 ± 0.89, P = 0.012; troponin T: 0.012 ± 0.014 vs 0.018 ± 0.008, P = 0.002). Left ventricular ejection fraction at 6, 12, and 24 months postintervention was significantly higher in the group 1. During a mean follow-up period of 28.87 ± 6.28 months, mortality rates were 6.3% in the group 1 versus 12.9% in the group 2. Thrombus aspiration was also associated with significantly less long-term mortality in unstable angina pectoris patients (adjusted HR: 4.61, 95% CI: 1.16–18.21, P = 0.029). Thrombus aspiration in the context of unstable angina pectoris is associated with a limited elevation in cardiac enzymes during intervention that minimises microembolization and significantly improves both of epicardial flow and myocardial perfusion, as shown by angiographic TIMI flow grade and frame count. Thrombus aspiration during percutaneous coronary intervention in unstable angina pectoris patients

  12. Bioresorbable vascular scaffold implantation in acute coronary syndromes: clinical evidence, tips and tricks

    PubMed Central

    Giacchi, Giuseppe; Ortega-Paz, Luis; Ishida, Kohki; Sabaté, Manel

    2015-01-01

    Percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) is routine treatment for patients with acute coronary syndromes (ACS). However, permanent metallic caging of the vessel has several shortcomings, such as side branch jailing and impossibility of late lumen enlargement. Moreover, DES PCI is affected by vasomotion impairment. In ACS a high thrombus burden and vasospasm lead to a higher risk of acute and late acquired stent malapposition than in stable patients. This increases the risk of acute, late and very late stent thrombosis. In this challenging clinical setting, the implantation of bioresorbable vascular scaffolds (BVS) could represent an appealing therapeutic option. Temporary vessel scaffolding has proved to have several advantages over metallic stent delivery, such as framework reabsorption, late lumen enlargement, side branch patency, and recovery of physiological reactivity to vasoactive stimuli. In the thrombotic environment of ACS, BVS implantation has the benefit of capping the thrombus and the vulnerable plaque. Bioresorbable vascular scaffolds also seems to reduce the incidence of angina during follow-up. Acute coronary syndromes patients may therefore benefit more from temporary polymeric caging than from permanent stent platform implantation. The aim of this review is to update the available knowledge concerning the use of BVS in ACS patients, by analyzing the potential pitfalls in this challenging clinical setting and presenting tricks to overcome these limitations. PMID:26677353

  13. Bioresorbable vascular scaffold implantation in acute coronary syndromes: clinical evidence, tips and tricks.

    PubMed

    Giacchi, Giuseppe; Ortega-Paz, Luis; Brugaletta, Salvatore; Ishida, Kohki; Sabaté, Manel

    2015-01-01

    Percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) is routine treatment for patients with acute coronary syndromes (ACS). However, permanent metallic caging of the vessel has several shortcomings, such as side branch jailing and impossibility of late lumen enlargement. Moreover, DES PCI is affected by vasomotion impairment. In ACS a high thrombus burden and vasospasm lead to a higher risk of acute and late acquired stent malapposition than in stable patients. This increases the risk of acute, late and very late stent thrombosis. In this challenging clinical setting, the implantation of bioresorbable vascular scaffolds (BVS) could represent an appealing therapeutic option. Temporary vessel scaffolding has proved to have several advantages over metallic stent delivery, such as framework reabsorption, late lumen enlargement, side branch patency, and recovery of physiological reactivity to vasoactive stimuli. In the thrombotic environment of ACS, BVS implantation has the benefit of capping the thrombus and the vulnerable plaque. Bioresorbable vascular scaffolds also seems to reduce the incidence of angina during follow-up. Acute coronary syndromes patients may therefore benefit more from temporary polymeric caging than from permanent stent platform implantation. The aim of this review is to update the available knowledge concerning the use of BVS in ACS patients, by analyzing the potential pitfalls in this challenging clinical setting and presenting tricks to overcome these limitations. PMID:26677353

  14. Development of thrombus-resistant and cell compatible crimped polyethylene terephthalate cardiovascular grafts using surface co-immobilized heparin and collagen.

    PubMed

    Al Meslmani, Bassam; Mahmoud, Gihan; Strehlow, Boris; Mohr, Eva; Leichtweiß, Thomas; Bakowsky, Udo

    2014-10-01

    Short-term patency of polyethylene terephthalate (PET) cardiovascular grafts is determined mainly by the inherent thrombogenicity and improper endothelialization following grafts implantation. The aim of the present study was to immobilize heparin to develop thrombus resistant grafts. Additionally, collagen was co-immobilized to enhance the host cell compatibility. The synthetic woven and knitted forms of crimped PET grafts were surface modified by Denier reduction to produce functional carboxyl groups. The produced groups were used as anchor sites for covalent immobilization of heparin or co-immobilization of heparin/collagen by the end-point method. The modified surface was characterized using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The biological activity of immobilized molecules was investigated in vitro using direct blood coagulation test, and "platelet deposition under flow condition. Furthermore, the biocompatibility of modified grafts with host cells was assessed using L929 cell as model. All modified grafts showed significant resistance against fibrin and clot formation. The number of deposited platelets on heparin-immobilized woven and knitted grafts obviously decreased by 3 fold and 2.8 fold per unit surface area respectively, while the heparin/collagen co-immobilized grafts showed only a decrease by 1.7 and 1.8 fold compared to unmodified PET. Heparin-immobilized grafts reported no significant effect on L929 cells adhesion and growth (P>0.05), conversely, collagen co-immobilization considerably increased cell adhesion almost ~1.3 fold and 2 fold per unit surface area for woven and knitted grafts respectively. Our results emphasize that immobilization of heparin minimized the inherent thrombogenicity of the PET grafts. The simultaneous co-immobilization of collagen supported host cell adhesion and growth required for the grafts biocompatibility. PMID:25175248

  15. Thrombus-Targeted Theranostic Microbubbles: A New Technology towards Concurrent Rapid Ultrasound Diagnosis and Bleeding-free Fibrinolytic Treatment of Thrombosis

    PubMed Central

    Wang, Xiaowei; Gkanatsas, Yannik; Palasubramaniam, Jathushan; Hohmann, Jan David; Chen, Yung Chih; Lim, Bock; Hagemeyer, Christoph E; Peter, Karlheinz

    2016-01-01

    Rationale: Myocardial infarction and stroke are leading causes of morbidity/mortality. The typical underlying pathology is the formation of thrombi/emboli and subsequent vessel occlusion. Systemically administered fibrinolytic drugs are the most effective pharmacological therapy. However, bleeding complications are relatively common and this risk as such limits their broader use. Furthermore, a rapid non-invasive imaging technology is not available. Thereby, many thrombotic events are missed or only diagnosed when ischemic damage has already occurred. Objective: Design and preclinical testing of a novel 'theranostic' technology for the rapid non-invasive diagnosis and effective, bleeding-free treatment of thrombosis. Methods and Results: A newly created, innovative theranostic microbubble combines a recombinant fibrinolytic drug, an echo-enhancing microbubble and a recombinant thrombus-targeting device in form of an activated-platelet-specific single-chain antibody. After initial in vitro proof of functionality, we tested this theranostic microbubble both in ultrasound imaging and thrombolytic therapy using a mouse model of ferric-chloride-induced thrombosis in the carotid artery. We demonstrate the reliable highly sensitive detection of in vivo thrombi and the ability to monitor their size changes in real time. Furthermore, these theranostic microbubbles proofed to be as effective in thrombolysis as commercial urokinase but without the prolongation of bleeding time as seen with urokinase. Conclusions: We describe a novel theranostic technology enabling simultaneous diagnosis and treatment of thrombosis, as well as monitoring of success or failure of thrombolysis. This technology holds promise for major progress in rapid diagnosis and bleeding-free thrombolysis thereby potentially preventing the often devastating consequences of thrombotic disease in many patients. PMID:27022419

  16. Laser-Activated Shape Memory Polymer Microactuator for Thrombus Removal Following Ischemic Stroke: Preliminary In Vitro Analysis

    SciTech Connect

    Small, W; Metzger, M F; Wilson, T S; Maitland, D J

    2004-09-23

    Due to the narrow (3-hour) treatment window for effective use of the thrombolytic drug recombinant tissue-type plasminogen activator (rt-PA), there is a need to develop alternative treatments for ischemic stroke. We are developing an intravascular device for mechanical thrombus removal using shape memory polymer (SMP). We propose to deliver the SMP microactuator in its secondary straight rod form (length = 4 cm, diameter = 350 {micro}m) through a catheter distal to the vascular occlusion. The microactuator, which is mounted on the end of an optical fiber, is then transformed into its primary corkscrew shape by laser heating (diode laser, {lambda} = 800 nm) above its soft phase glass transition temperature (T{sub gs} = 55 C). Once deployed, the microactuator is retracted and the captured thrombus is removed to restore blood flow. The SMP is doped with indocyanine green (ICG) dye to increase absorption of the laser light. Successful deployment of the microactuator depends on the optical properties of the ICG-doped SMP and the optical coupling efficiency of the interface between the optical fiber and the SMP. Spectrophotometry, thermal imaging, and computer simulation aided the initial design effort and continue to be useful tools for optimization of the dye concentration and laser power. Thermomechanical testing was performed to characterize the elastic modulus of the SMP. We have demonstrated laser-activation of the SMP microactuator in air at room temperature, suggesting this concept is a promising therapeutic alternative to rt-PA.

  17. A systems approach to hemostasis: 1. The interdependence of thrombus architecture and agonist movements in the gaps between platelets

    PubMed Central

    Welsh, John D.; Stalker, Timothy J.; Voronov, Roman; Muthard, Ryan W.; Tomaiuolo, Maurizio; Diamond, Scott L.

    2014-01-01

    Hemostatic thrombi develop a characteristic architecture in which a core of highly activated platelets is covered by a shell of less-activated platelets. Here we have used a systems biology approach to examine the interrelationship of this architecture with transport rates and agonist distribution in the gaps between platelets. Studies were performed in mice using probes for platelet accumulation, packing density, and activation plus recently developed transport and thrombin activity probes. The results show that intrathrombus transport within the core is much slower than within the shell. The region of slowest transport coincides with the region of greatest packing density and thrombin activity, and appears prior to full platelet activation. Deleting the contact-dependent signaling molecule, Sema4D, delays platelet activation, but not the emergence of the low transport region. Collectively, these results suggest a timeline in which initial platelet accumulation and the narrowing gaps between platelets create a region of reduced transport that facilitates local thrombin accumulation and greater platelet activation, whereas faster transport rates within the shell help to limit thrombin accumulation and growth of the core. Thus, from a systems perspective, platelet accumulation produces an altered microenvironment that shapes thrombus architecture, which in turn affects agonist distribution and subsequent thrombus growth. PMID:24951424

  18. Detection of lower limb deep venous thrombosis in asymptomatic high risk patients using a new radiolabelled thrombus specific agent

    SciTech Connect

    Butler, S.P.; Rahman, T.; Boyd S.J.

    1995-05-01

    Deep venous thrombosis is a serious consequence of major orthopaedic surgery and non invasive screening with either venous ultrasound or impedance plethysmography is unreliable for detecting or excluding DVT in this group. A new method of thrombus detection has been devised using Tc-99m labelled inhibited recombinant tissue plasminogen activator. The accuracy of scanning with this new radiopharmaceutical in asymptomatic high risk patients was evaluated using venography as the gold standard. 36 consecutive asymptomatic high risk patients (17 total hip, 19 total knee replacements) underwent both a contrast venogram on the operated leg and scintigraphic scan 7 days following operation. Scintigraphic imaging was performed at 4 hours post injection. For the purpose of this analysis, each venogram was divided into a proximal and a distal segment. Venograms were interpreted as being positive, negative or uninterpretable in each segment. Similar analysis of the scintigraphic scans was performed except that all segments were considered to be of diagnostic quality. 57 segments were able to be analysed. Of the 13 thrombosed segments (1 proximal, 12 calf), 12 had positive scans; in the 44 non thrombosed segments, 40 had negative scans. Thus in detecting lower limb thrombosis, scanning had a sensitivity of 92% and a specificity of 91%. Scintigraphic scanning with this new radiopharmaceutical permits accurate detection of thrombus in high risk patients.

  19. Acute Hemodynamic Efficacy of a 32-ml Subcutaneous Counterpulsation Device in a Calf Model of Diminished Cardiac Function

    PubMed Central

    Koenig, Steven C.; Litwak, Kenneth N.; Giridharan, Guruprasad A.; Pantalos, George M.; Dowling, Robert D.; Prabhu, Sumanth D.; Slaughter, Mark S.; Sobieski, Michael A.; Spence, Paul A.

    2010-01-01

    The acute hemodynamic efficacy of an implantable counter-pulsation device (CPD) was evaluated. The CPD is a valveless single port, 32-ml stroke volume blood chamber designed to be connected to the human axillary artery using a simple surface surgical procedure. Blood is drawn into the pump during systole and ejected during diastole. The acute hemodynamic effects of the 32-ml CPD were compared to a standard clinical 40-ml intra-aortic balloon pump (IABP) in calves (80 kg, n = 10). The calves were treated by a single oral dose of Monensin to produce a model of diminished cardiac function (DCF). The CPD and IABP produced similar increases in cardiac output (6% CPD vs. 5% IABP, p > 0.5) and reduction in left ventricular external work (14% CPD vs. 13% IABP, p > 0.5) compared to DCF (p < 0.05). However, the ratio of diastolic coronary artery flow to left ventricular external work increase from DCF baseline (p < 0.05) was greater with the CPD compared to the IABP (15% vs. 4%, p < 0.05). The CPD also produced a greater reduction in left ventricular myocardial oxygen consumption from DCF baseline (p < 0.05) compared to the IABP (13% vs. 9%, p < 0.05) despite each device providing similar improvements in cardiac output. There was no early indication of hemolysis, thrombus formation, or vascular injury. The CPD provides hemodynamic efficacy equivalent to an IABP and may become a therapeutic option for patients who may benefit from prolonged counterpulsation. PMID:19033769

  20. Acute hemodynamic efficacy of a 32-ml subcutaneous counterpulsation device in a calf model of diminished cardiac function.

    PubMed

    Koenig, Steven C; Litwak, Kenneth N; Giridharan, Guruprasad A; Pantalos, George M; Dowling, Robert D; Prabhu, Sumanth D; Slaughter, Mark S; Sobieski, Michael A; Spence, Paul A

    2008-01-01

    The acute hemodynamic efficacy of an implantable counterpulsation device (CPD) was evaluated. The CPD is a valveless single port, 32-ml stroke volume blood chamber designed to be connected to the human axillary artery using a simple surface surgical procedure. Blood is drawn into the pump during systole and ejected during diastole. The acute hemodynamic effects of the 32-ml CPD were compared to a standard clinical 40-ml intra-aortic balloon pump (IABP) in calves (80 kg, n = 10). The calves were treated by a single oral dose of Monensin to produce a model of diminished cardiac function (DCF). The CPD and IABP produced similar increases in cardiac output (6% CPD vs. 5% IABP, p > 0.5) and reduction in left ventricular external work (14% CPD vs. 13% IABP, p > 0.5) compared to DCF (p < 0.05). However, the ratio of diastolic coronary artery flow to left ventricular external work increase from DCF baseline (p < 0.05) was greater with the CPD compared to the IABP (15% vs. 4%, p < 0.05). The CPD also produced a greater reduction in left ventricular myocardial oxygen consumption from DCF baseline (p < 0.05) compared to the IABP (13% vs. 9%, p < 0.05) despite each device providing similar improvements in cardiac output. There was no early indication of hemolysis, thrombus formation, or vascular injury. The CPD provides hemodynamic efficacy equivalent to an IABP and may become a therapeutic option for patients who may benefit from prolonged counterpulsation. PMID:19033769

  1. In Vitro Streptococcus pneumoniae Biofilm Formation and In Vivo Middle Ear Mucosal Biofilm in a Rat Model of Acute Otitis Induced by S. pneumoniae

    PubMed Central

    Yadav, Mukesh Kumar; Chae, Sung-Won

    2012-01-01

    Objectives Streptococcus pneumoniae is one of the most common pathogens of otitis media (OM) that exists in biofilm, which enhances the resistance of bacteria against antibiotic killing and diagnosis, compared to the free-floating (planktonic) form. This study evaluated biofilm formation by S. pneumoniae on an abiotic surface and in the middle ear cavity in a rat model of OM. Methods In vitro biofilm formation was evaluated by inoculation of a 1:100 diluted S. pneumoniae cell suspension in a 96-well microplate. Adherent cells were quantified spectrophotometrically following staining with crystal violet by measurement of optical density at 570 nm. The ultrastructure of pneumococcal biofilm was assessed by scanning electron microscopy (SEM). For in vitro biofilm study, S. pneumoniae cell suspensions containing 1×107 colony forming units were injected through transtympanic membrane into the middle ear cavity of Sprague Dawley rats. The ultrastructure of middle ear mucus was observed by SEM 1 and 2 weeks post-inoculation. Results The in vitro study revealed robust biofilm formation by S. pneumoniae after 12-18 hours of incubation in high glucose medium, independent of exogenously supplied competence stimulating peptide and medium replacement. Adherent cells formed three-dimensional structures approximately 20-30 µm thick. The in vivo study revealed that ciliated epithelium was relatively resistant to biofilm formation and that biofilm formation occurred mainly on non-ciliated epithelium of the middle ear cavity. One week after inoculation, biofilm formation was high in 50% of the treated rats and low in 25% of the rats. After 2 weeks, biofilm formation was high and low in 25% and 37.5% of rats, respectively. Conclusion The results imply that glucose level is important for the S. pneumoniae biofilm formation and S. pneumoniae biofilm formation may play important role in the pathophysiology of OM. PMID:22977710

  2. Animal Model of Acute Deep Vein Thrombosis

    SciTech Connect

    Roy, Sumit; Laerum, Frode; Brosstad, Frank; Kvernebo, Knut; Sakariassen, Kjell S.

    1998-07-15

    Purpose: To develop an animal model of acute deep vein thrombosis (DVT). Methods: In part I of the study nine juvenile domestic pigs were used. Each external iliac vein was transluminally occluded with a balloon catheter. Thrombin was infused through a microcatheter in one leg according to one of the following protocols: (1) intraarterial (IA): 1250 U at 25 U/min in the common femoral artery (n= 3); (2) intravenous (IV): 5000 U in the popliteal vein at 500 U/min (n= 3), or at 100 U/min (n= 3). Saline was administered in the opposite leg. After the animals were killed, the mass of thrombus in the iliofemoral veins was measured. The pudendoepiploic (PEV), profunda femoris (PF), and popliteal veins (PV) were examined. Thrombosis in the tributaries of the superficial femoral vein (SFVt) was graded according to a three-point scale (0, +, ++). In part II of the study IV administration was further investigated in nine pigs using the following three regimens with 1000 U at 25 U/min serving as the control: (1) 1000 U at 100 U/min, (2) 250 U at 25 U/min, (3) 250 U at 6.25 U/min. Results: All animals survived. In part I median thrombus mass in the test limbs was 1.40 g as compared with 0.25 g in the controls (p= 0.01). PEV, PFV and PV were thrombosed in all limbs infused with thrombin. IV infusion was more effective in inducing thrombosis in both the parent veins (mass 1.32-1.78 g) and SVFt (++ in 4 of 6 legs), as compared with IA infusion (mass 0.0-1.16 g; SFVt ++ in 1 of 3 legs). In part II thrombus mass in axial veins ranged from 1.23 to 2.86 g, and showed no relationship with the dose of thrombin or the rate of infusion. Tributary thrombosis was less extensive with 250 U at 25 U/min than with the other regimens. Conclusion: Slow distal intravenous thrombin infusion in the hind legs of pigs combined with proximal venous occlusion induces thrombosis in the leg veins that closely resembles clinical DVT in distribution.

  3. Acute nephritic syndrome

    MedlinePlus

    Glomerulonephritis - acute; Acute glomerulonephritis; Nephritis syndrome - acute ... Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease. Common causes ...

  4. Inhibition of SA Node at Supine Position in Right Atrial Thrombus Complicating Behçet's Disease - From Cardiac Surgical Point of View.

    PubMed

    Hijazi, Emad Mohamed; Ibdah, Rasheed Khaled; Rawashdeh, Sukina Ismael; Saadeh, Abdullah Mahmoud; Al-Balas, Hamzeh Ibrahim

    2016-01-01

    BACKGROUND Behçet's disease (BD) is a chronic multi-systemic disease of unknown cause. Intra-cardiac thrombus (ICT) complicating BD is extremely rare. In general, cardiac manifestations in BD are associated with poor prognosis. Chest computed tomography (CT) scan and echocardiogram are excellent modalities for diagnosis and patient assessment. Cardiac surgical intervention can be done safely using an on-pump technique when medical management has failed. CASE REPORT We report on a case of a 27-year-old Jordanian woman diagnosed with BD who presented with dyspnea, cough, and hemoptysis, with supine bradycardia reaching 36 beats/minute and dizziness which disappear on sitting or standing position, and with heart rate reaching 76 beats/minute. Right atrial thrombus was identified using transthoracic echocardiogram and chest CT scan. After medical management failed, cardiac surgical intervention became an option and targeted extraction of the right atrial thrombus compressing the sinoatrial node (SA node). CONCLUSIONS In BD, right atrial thrombus compressing the SA node is rare. If conservative management has failed, cardiac surgical intervention removing the mechanical cause can be done safely, either using on-pump with cross clamp or on-pump with beating heart technique. PMID:27311379

  5. Predictors of thrombus burden and no-reflow of infarct-related artery in patients with ST-segment elevation myocardial infarction: importance of platelet indices.

    PubMed

    Cakici, Musa; Cetin, Mustafa; Balli, Mehmet; Akturk, Erdal; Dogan, Adnan; Oylumlu, Muhammed; Abus, Sabri; Yildiz, Emrah; Sungur, Azmi; Celiker, Meral

    2014-10-01

    Preprocedural high-thrombus burden (HTB) of infarct-related artery (IRA) is a harbinger of procedural complications following primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). The HTB of IRA can lead to poor outcomes by various mechanisms, including no-reflow phenomenon, increased myocardial necrosis and with subsequent reduced survival benefit at follow-up. In this study, we investigated the relationship between all platelet indices on admission and thrombus burden and the no-reflow phenomenon after primary PCI of IRA in patients with STEMI. We retrospectively enrolled 475 patients with STEMI undergoing primary PCI. Study population was divided into two groups according to the thrombolysis in myocardial infarction thrombus grade of IRA as low-thrombus burden or HTB. There were no statistically significant differences in platelet indices, including platelet count, platelet-large cell ratio (P-LCR), mean platelet volume (MPV) and platelet distribution with (PDW) among the groups. However, in the subgroup analysis, P-LCR, MPV and PDW were significantly higher in the no-reflow patients than reflow patients despite similar platelet count (P for all < 0.001). The cutoff value of P-LCR for predicting no-reflow was 26.5% with a sensitivity of 67.0% and a specificity of 62% (area under the curve, 0.689; 95% confidence interval, 0.614-0.765; P < 0.001). Furthermore, P-LCR, MPV and PDW had similar AUC (0.689, P < 0.001; 0.688, P < 0.001; and 0.677, P < 0.001; respectively) for predicting no-reflow phenomenon after primary PCI. As a result, all of the platelet indices have no effect on thrombus load of IRA, however, these parameters seem to impair epicardial perfusion after primary PCI. PMID:24806326

  6. A low-dose, dual-phase cardiovascular CT protocol to assess left atrial appendage anatomy and exclude thrombus prior to left atrial intervention.

    PubMed

    Lazoura, Olga; Ismail, Tevfik F; Pavitt, Christopher; Lindsay, Alistair; Sriharan, Mona; Rubens, Michael; Padley, Simon; Duncan, Alison; Wong, Tom; Nicol, Edward

    2016-02-01

    Assessment of the left atrial appendage (LAA) for thrombus and anatomy is important prior to atrial fibrillation (AF) ablation and LAA exclusion. The use of cardiovascular CT (CCT) to detect LAA thrombus has been limited by the high incidence of pseudothrombus on single-pass studies. We evaluated the diagnostic accuracy of a two-phase protocol incorporating a limited low-dose delayed contrast-enhanced examination of the LAA, compared with a single-pass study for LAA morphological assessment, and transesophageal echocardiography (TEE) for the exclusion of thrombus. Consecutive patients (n = 122) undergoing left atrial interventions for AF were assessed. All had a two-phase CCT protocol (first-past scan plus a limited, 60-s delayed scan of the LAA) and TEE. Sensitivity, specificity, diagnostic accuracy, positive (PPV) and negative predictive values (NPV) were calculated for the detection of true thrombus on first-pass and delayed scans, using TEE as the gold standard. Overall, 20/122 (16.4 %) patients had filling defects on the first-pass study. All affected the full delineation of the LAA morphology; 17/20 (85 %) were confirmed as pseudo-filling defects. Three (15 %) were seen on late-pass and confirmed as true thrombi on TEE; a significant improvement in diagnostic performance relative to a single-pass scan (McNemar Chi-square 17, p < 0.001). The sensitivity, specificity, diagnostic accuracy, PPV and NPV was 100, 85.7, 86.1, 15.0 and 100 % respectively for first-pass scans, and 100 % for all parameters for the delayed scans. The median (range) additional radiation dose for the delayed scan was 0.4 (0.2-0.6) mSv. A low-dose delayed scan significantly improves the identification of true LAA anatomy and thrombus in patients undergoing LA intervention. PMID:26420491

  7. Acute sacroiliitis.

    PubMed

    Slobodin, Gleb; Rimar, Doron; Boulman, Nina; Kaly, Lisa; Rozenbaum, Michael; Rosner, Itzhak; Odeh, Majed

    2016-04-01

    The purpose of this study was to review the data on the etiology, risk factors, clinical presentations, and diagnosis of acute sacroiliitis. A Pubmed search utilizing the indexing term "acute sacroiliitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. The diagnosis of acute sacroiliitis is often challenging because of both the relative rarity of this presentation and diverse character of acute sacroiliac pain, frequently mimicking other, more prevalent disorders. Technetium bone scintigraphy can localize the disease process to the sacroiliac joint, while computed tomography or magnetic resonance imaging can be used for the detailed characterization and the extent of the disease as well as the diagnosis of complications. Pyogenic sacroiliitis is by far the most common cause of acute sacroiliitis. Brucellosis, acute sacroiliitis in the course of reactive arthritis, and crystalline-induced sacroiliitis frequently imitate pyogenic sacroiliitis. Acute sacroiliitis can rarely be also related to hematological malignancies or treatment with isotretinoin. Awareness to the possibility of acute sacroiliitis and a thorough physical examination are the necessary prerequisites to its timely diagnosis, while the appropriate laboratory and imaging studies should confirm the precise diagnosis and direct the appropriate treatment strategy. PMID:26847855

  8. AngioVac Aspiration for Paradoxical Emboli Protection through a Fenestrated Fontan During Central Venous Thrombus Manipulation

    SciTech Connect

    Al-Hakim, Ramsey; Patel, Komal; Moriarty, John M.

    2015-06-15

    This case reports describes a 39-year-old female with a history of surgically repaired hypoplastic left heart syndrome who presented with a left peripherally inserted central catheter (PICC) with associated large volume subclavian and brachiocephalic vein thrombus. Due to the presence of a right-to-left shunt via a fenestrated Fontan, there was clinical concern for a paradoxical embolism during removal of the PICC. The AngioVac aspiration system was successfully utilized to aspirate thromboemboli from the level of the proximal Glenn shunt during manipulation and removal of the PICC. This is the first reported case to demonstrate the safe and effective use of the AngioVac aspiration system for protection of paradoxical emboli through a cardiac right-to-left shunt during a procedure at high risk for thromboembolism.

  9. AngioVac Aspiration for Paradoxical Emboli Protection through a Fenestrated Fontan During Central Venous Thrombus Manipulation.

    PubMed

    Al-Hakim, Ramsey; Patel, Komal; Moriarty, John M

    2015-06-01

    This case reports describes a 39-year-old female with a history of surgically repaired hypoplastic left heart syndrome who presented with a left peripherally inserted central catheter (PICC) with associated large volume subclavian and brachiocephalic vein thrombus. Due to the presence of a right-to-left shunt via a fenestrated Fontan, there was clinical concern for a paradoxical embolism during removal of the PICC. The AngioVac aspiration system was successfully utilized to aspirate thromboemboli from the level of the proximal Glenn shunt during manipulation and removal of the PICC. This is the first reported case to demonstrate the safe and effective use of the AngioVac aspiration system for protection of paradoxical emboli through a cardiac right-to-left shunt during a procedure at high risk for thromboembolism. PMID:25008372

  10. Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial

    PubMed Central

    Jolly, Sanjit S; Cairns, John A; Yusuf, Salim; Rokoss, Michael J; Gao, Peggy; Meeks, Brandi; Kedev, Sasko; Stankovic, Goran; Moreno, Raul; Gershlick, Anthony; Chowdhary, Saqib; Lavi, Shahar; Niemela, Kari; Bernat, Ivo; Cantor, Warren J; Cheema, Asim N; Steg, Philippe Gabriel; Welsh, Robert C; Sheth, Tej; Bertrand, Olivier F; Avezum, Alvaro; Bhindi, Ravinay; Natarajan, Madhu K; Horak, David; Leung, Raymond C M; Kassam, Saleem; Rao, Sunil V; El-Omar, Magdi; Mehta, Shamir R; Velianou, James L; Pancholy, Samir; Džavík, Vladimír

    2016-01-01

    Summary Background Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice. Methods The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10 732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov, number NCT01149044. Findings Between Aug 5, 2010, and July 25, 2014, 10 732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not

  11. Horseshoe thrombus in a patient with mechanical prosthetic mitral valve: A case report and review of literature

    PubMed Central

    Mehra, Sanjay; Movahed, Assad; Espinoza, Carlos; Marcu, Constantin B

    2015-01-01

    Patients with prosthetic cardiac valves are at high risk for thromboembolic complications and need life long anticoagulation with warfarin, which can be associated with variable dose requirements and fluctuating level of systemic anticoagulation and may predispose to thromboembolic and or hemorrhagic complications. Prosthetic cardiac valve thrombosis is associated with high morbidity and mortality. A high index of suspicion is essential for prompt diagnosis. Transthoracic echocardiography, and if required transesophageal echocardiography are the main diagnostic imaging modalities. Medically stable patients can be managed with thrombolytic therapy and anticoagulation, while some patients may require surgical thrombectomy or valve replacement. We present a case report of a patient with prosthetic mitral valve and an unusually large left atrial thrombus with both thromboembolic and hemorrhagic complications. PMID:26380832

  12. Acute Superior Mesenteric Venous Thrombosis: Transcatheter Thrombolysis and Aspiration Thrombectomy Therapy by Combined Route of Superior Mesenteric Vein and Artery in Eight Patients

    SciTech Connect

    Yang, Shuofei Liu, Baochen Ding, Weiwei He, Changsheng Wu, Xingjiang Li, Jieshou

    2015-02-15

    PurposeTo assess the feasibility, effectiveness, and safety of catheter-directed thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery (SMV+SMA) for acute superior mesenteric venous thrombosis (ASMVT).MethodsThis retrospective study reviewed eight ASMVT patients with transcatheter direct thrombolysis and aspiration thrombectomy therapy via SMV and indirect thrombolysis via SMA during a period of 14 months. The demographics, etiology, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. Anatomic and imaging classification of location and extent of thrombus at diagnosis and degree of thrombus lysis were described.ResultsTechnical success was achieved with substantial improvement in symptoms and thrombus resolution after thrombolytic therapy in all patients. The local urokinase infusion by SMA and SMV was performed for 5–7 (6.13 ± 0.83) and 7–15 (12 ± 2.51) days. Anticoagulation was performed catheter-directed and then orally throughout hospitalization and after discharge. Four patients required delayed localized bowel resection after thrombolytic therapy with no death. Thrombolytic therapy was not interrupted despite minor bleeding at the puncture site in two patients and sepsis in another two postoperatively. Nearly complete removal of thrombus was demonstrated by contrast-enhanced CT scan and portography before discharge. Patients were discharged in 10–27 (19.25 ± 4.89) days after admission. No recurrence developed during the follow-up of 10–13 (12.13 ± 0.99) months.ConclusionsCatheter-directed thrombolytic and aspiration therapy via SMV+SMA is beneficial for ASMVT in avoiding patient death, efficient resolving thrombus, rapid improving symptoms, reversing extensive intestinal ischemia, averting bowel resection, or localizing infarcted bowel segment and preventing short bowel syndrome.

  13. [Drug-induced acute kidney injury].

    PubMed

    Derungs, Adrian

    2015-12-01

    Due to their physiological function, the kidneys are exposed to high concentrations of numerous drugs and their metabolites, making them vulnerable to drug-related injuries. This article provides an overview of the pathophysiological mechanisms involved in nephrotoxicity, the most common nephrotoxic drugs, and the risk factors for the occurrence of drug-induced acute kidney injuries. NSAIDs, diuretics, ACE inhibitors, and angiotensin II receptor blockers (ARBs} are the most frequent prerenal causes of an acute elevation in creatinine levels. Primary vascular damage arises from thrombotic microangiopathy (e. g. due to cic/osporin, tacrolimus, muromonab-CD3, mitomycin C, quinine, ticlopidine, clopidogrel}. Anticoagulants and thrombolytic medications lead to secondary blood vessel damage by cholesterol emboli, embolism of thrombus material into the periphery or bleeding. Tubulopathies can be observed on treatment with ifosfamide and cisplatin (rarely with cyclophosphamide or carboplatin), aminoglycosides, vancomycin, and radiocontrast agents. Immunological mechanisms underlie interstitial nephritides, which are induced by drugs in about 85% of cases. In drug-induced glomerulopathies;- renal biopsy allows closer identification of the triggering medication. Drug-induced systemic lupus erythematosus (SLE} represents a special form of immune complex glomerulonephritis and can be triggered by procainamide, hydralazine, isoniazid, methyldopa, quinidine, chlorpromazine, and propylthiouracil. Crystal-induced kidney injury is caused by precipitation of drugs (e. g. aciclovir, sulfonamide antibiotics, methotrexate, indinavir) in the renal tubules and the urine-conducting organs with consecutive obstruction thereof. PMID:26654816

  14. Endovascular Interventions for Acute and Chronic Lower Extremity Deep Venous Disease: State of the Art

    PubMed Central

    Sista, Akhilesh K.; Vedantham, Suresh; Kaufman, John A.

    2015-01-01

    The societal and individual burden caused by acute and chronic lower extremity venous disease is considerable. In the past several decades, minimally invasive endovascular interventions have been developed to reduce thrombus burden in the setting of acute deep venous thrombosis to prevent both short- and long-term morbidity and to recanalize chronically occluded or stenosed postthrombotic or nonthrombotic veins in symptomatic patients. This state-of-the-art review provides an overview of the techniques and challenges, rationale, patient selection criteria, complications, postinterventional care, and outcomes data for endovascular intervention in the setting of acute and chronic lower extremity deep venous disease. Online supplemental material is available for this article. © RSNA, 2015 PMID:26101920

  15. The mtDNA nt7778 G/T Polymorphism Augments Formation of Lymphocytic Foci but Does Not Aggravate Cerulein-Induced Acute Pancreatitis in Mice

    PubMed Central

    Müller, Sarah; Krüger, Burkhard; Lange, Falko; Bock, Cristin N.; Nizze, Horst; Glass, Änne; Ibrahim, Saleh M.; Jaster, Robert

    2014-01-01

    A polymorphism in the ATP synthase 8 (ATP8) gene of the murine mitochondrial genome, G-to-T transversion at position 7778, has been suggested to increase susceptibility to multiple autoimmune diseases, including autoimmune pancreatitis (AIP). The polymorphism also induces mitochondrial reactive oxygen species generation, secretory dysfunction and β-cell mass adaptation. Here, we have used two conplastic mouse strains, C57BL/6N-mtAKR/J (B6-mtAKR; nt7778 G; control) and C57BL/6N-mtFVB/N (B6-mtFVB; nt7778 T), to address the question if the polymorphism also affects the course of cerulein-induced acute pancreatitis in mice. Therefore, two age groups of mice (3 and 12-month-old, respectively) were subjected to up to 7 injections of the secretagogue cerulein (50 µg/kg body weight) at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of α-amylase and activities of myeloperoxidase (MPO) in lung tissue. A comparison of cerulein-induced pancreatic tissue damage and increases of α-amylase and MPO activities showed no differences between the age-matched groups of both strains. Interestingly, histological evaluation of pancreatic tissue of both untreated and cerulein-treated B6-mtAKR and B6-mtFVB mice also revealed the presence of infiltrates of immune cells surrounding ducts and vessels; a finding that is compatible with an early stage of AIP. After recovery from cerulein-induced pancreatitis (day 7 after the injections), 12-month-old B6-mtFVB mice but not B6-mtAKR mice displayed aggravated lymphocytic lesions. A comparison of 12-month-old mice with other age groups of both strains revealed that lymphocytic foci were largely absent in 3-month-old mice, while 24-month-old mice were more affected. Together, our data suggest that the mtDNA nt7778 G/T polymorphism does not aggravate cerulein-induced acute pancreatitis. Autoimmune-like lesions, however, may progress faster if additional tissue

  16. Evidence for direct involvement of epirubicin in the formation of chromosomal translocations in t(15;17) therapy-related acute promyelocytic leukemia

    PubMed Central

    Mays, Ashley N.; Osheroff, Neil; Xiao, Yuanyuan; Wiemels, Joseph L.; Felix, Carolyn A.; Byl, Jo Ann W.; Saravanamuttu, Kandeepan; Peniket, Andrew; Corser, Robert; Chang, Cherry; Hoyle, Christine; Parker, Anne N.; Hasan, Syed K.; Lo-Coco, Francesco; Solomon, Ellen

    2010-01-01

    Therapy-related acute promyelocytic leukemia (t-APL) with t(15;17)(q22;q21) involving the PML and RARA genes is associated with exposure to agents targeting topoisomerase II (topoII), particularly mitoxantrone and epirubicin. We previously have shown that mitoxantrone preferentially induces topoII-mediated DNA damage in a “hotspot region” within PML intron 6. To investigate mechanisms underlying epirubicin-associated t-APL, t(15;17) genomic breakpoints were characterized in 6 cases with prior breast cancer. Significant breakpoint clustering was observed in PML and RARA loci (P = .009 and P = .017, respectively), with PML breakpoints lying outside the mitoxantrone-associated hotspot region. Recurrent breakpoints identified in the PML and RARA loci in epirubicin-related t-APL were shown to be preferential sites of topoII-induced DNA damage, enhanced by epirubicin. Although site preferences for DNA damage differed between mitoxantrone and epirubicin, the observation that particular regions of the PML and RARA loci are susceptible to these agents may underlie their respective propensities to induce t-APL. PMID:19884644

  17. Selective inhibition of thromboxane synthesis partially protected while inhibition of angiotensin II formation did not protect rats against acute renal failure induced with glycerol.

    PubMed

    Papanicolaou, N; Hatziantoniou, C; Bariety, J

    1986-01-01

    Acute renal failure (ARF) was induced in 35 week-old conscious female Wistar rats, by intramuscular (IM) injection of glycerol. Intraperitoneal (IP) injection of imidazole, an inhibitor of thromboxane (TXA2) synthesis, partially protected the animals against ARF. This protection was accompanied by a significant decrease in renal TXB2 (the stable chemical metabolite of TXA2) and a significant increase in renal 6-keto-PGF1 alpha (the stable chemical metabolite of PGI2) synthesis. Intraperitoneal injection of captopril (SQ 14225) an angiotensin-converting-enzyme inhibitor, did not protect the animals against ARF. This lack of protection was accompanied by a significant increase in renal TXB2 and a significant decrease in renal 6-keto-PGF1 alpha synthesis. The results suggest that: (a) the renin-angiotensin (R-A) system does not play a role, or has only a secondary one in the development of ARF; (b) thromboxane A2 (the most potent vasoconstrictor and platelet aggregator agent known) is the preponderant agent responsible for the development of this pathological syndrome. PMID:3513208

  18. Acute malocclusion.

    PubMed

    Dupont, John S

    2006-01-01

    Acute malocclusion can result from disturbances in the maxillary/mandibular tooth relationship. These alterations in the occlusal position can result from high fillings, sinus problems, abscesses, periodontal disease, and moving or erupting teeth. Conditions seen less frequently include acute malocclusions secondary to an event (such as trauma) that make a stable dental relationship an unstable one. Patients can demonstrate any of a number of clinical conditions that interfere with their comfort and ability to function. This article provides information on some of the less familiar causes of acute malocclusion. PMID:16689064

  19. Acute Scorpion Pancreatitis in Trinidad

    PubMed Central

    Bartholomew, Courtenay

    1970-01-01

    Over a two-month period 30 patients were admitted to hospital following stings of the scorpion of Trinidad, the Tityus trinitatis. In 24 cases acute pancreatitis developed soon after the sting, but in nine of these no abdominal pain occurred. All the patients made an uneventful recovery. Although such complications have been reported no pseudocyst formations or acute haemorrhagic pancreatitis occurred in this series. PMID:5443968

  20. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is almost always caused by viruses that attack the lining of the bronchial tree ... infection. As your body fights back against these viruses, more swelling occurs and more mucus is produced. ...

  1. Acute Pericarditis

    MedlinePlus

    ... large pericardial effusions). Acute pericarditis usually responds to colchicine or NSAIDs (such as aspirin and ibuprofen ) taken ... reduce pain but relieves it by reducing inflammation. Colchicine also decreases the chance of pericarditis returning later. ...

  2. Correlation of Recombinant Integrase Activity and Functional Preintegration Complex Formation during Acute Infection by Replication-Defective Integrase Mutant Human Immunodeficiency Virus

    PubMed Central

    Li, Xiang; Koh, Yasuhiro

    2012-01-01

    Previous studies characterized two types of replication-defective human immunodeficiency virus type 1 (HIV-1) integrase mutants: class I, which are specifically blocked at the integration step, and class II, which harbor additional virion production and/or reverse transcription defects. Class I mutant enzymes supported little if any metal ion-dependent 3′-processing and DNA strand transfer activities in vitro, whereas class II enzymes displayed partial or full catalytic function in studies with simplified assay designs, suggesting that defective interaction(s) with heterologous integrase binding proteins might underlie the class II mutant viral phenotype. To address this hypothesis, class I and II mutant enzymes were interrogated under expanded sets of in vitro conditions. The majority failed to catalyze the concerted integration of two viral DNA ends into target DNA, highlighting defective integrase function as the root cause of most class II in addition to all class I mutant virus infection defects. One mutant protein, K264E, in contrast, could support the wild-type level of concerted integration activity. After accounting for its inherent reverse transcription defect, HIV-1K264E moreover formed preintegration complexes that supported the efficient integration of endogenous viral DNA in vitro and normal levels and sequences of 2-long terminal repeat-containing circle junctions during acute infection. K264E integrase furthermore efficiently interacted in vitro with two heterologous binding partners, LEDGF/p75 and reverse transcriptase. Our results underscore the physiological relevance of concerted integration assays for tests of integrase mutant function and suggest that the K264E mutation disrupts an interaction with an intranuclear integrase binding partner that is important for HIV-1 integration. PMID:22278243

  3. [A case of an elderly patient having advanced hepatocellular carcinoma with tumor thrombus in the inferior vena cava treated with chemo-radio-therapy--intraarterial infusion of weekly high dose 5-FU (WHF)].

    PubMed

    Yabuuchi, Shinichi; Katayose, Yu; Rikiyama, Toshiki; Oikawa, Masaya; Yamamoto, Kuniharu; Onogawa, Toru; Hayashi, Hiroki; Muto, Mitsuhisa; Unno, Michiaki

    2006-11-01

    The patient was an 81-year-old man, diagnosed with advanced huge hepatocellular carcinoma (HCC) with tumor thrombus extending into the inferior vena cava (Vv3), for which resection was judged impossible. The radio therapy (51 Gy) for tumor thrombus was carried out, and he received a weekly hepatic arterial infusion therapy (weekly high-dose 5-fluorouracil (5-FU)) for these legions. After 8 cycles, the CT scan revealed a minor response of the tumor (SD), and,the tumor marker reduced. After 10 months, these legions had markedly regressed (PR), the tumor thrombus in the inferior vena cava was not detectable. There were no severe side effects. Ten months since the start of chemo-radio therapy, the positron emission tomography (PET) revealed a metastatic tumor of the femoral bone in recurrence. In conclusion, some elderly patients of advanced HCC with tumor thrombus may obtain a long term survival through this treatment. PMID:17212102

  4. γH2AX formation kinetics in PBMCs of rabbits exposed to acute and fractionated radiation and attenuation of focus frequency through preadministration of a combination of podophyllotoxin and rutin hydrate.

    PubMed

    Yashavarddhan, M H; Shukla, Sandeep K; Srivastava, Nitya N; Suar, Mrutyunjay; Dutta, Sangeeta; Kalita, Bhargab; Ranjan, Rajiv; Singh, Abhinav; Bajaj, Sania; Gupta, Manju L

    2016-07-01

    DNA damage can be assessed by the quantitation of γH2AX foci that form at DSB sites. This study examines the generation and persistence of γH2AX foci, variability in foci size after acute and fractionated radiation exposure, and the effect of pretreatment with a safe radioprotective formulation termed G-003M on foci generation and persistence. G-003M contains a combination of podophyllotoxin and rutin hydrate, and was administered intramuscularly to rabbits 1 hr prior to Co(60) gamma irradiation. Rabbits were assigned to one of the following treatment groups: untreated, G-003M alone, irradiated (single dose 8 Gy, fractionated 2 Gy/day for 4 days or single dose 2 Gy) or G-003M preadministration followed by radiation exposure. Foci continuously persisted for a week in peripheral blood mononuclear cells of rabbits exposed to a single 8 Gy dose. However, the number of foci gradually decreased after reaching a maximum at 1 h. In rabbits exposed to fractionated radiation, foci detected 1 hr after the final exposure were significantly larger (P < 0.001) than in rabbits exposed to a single 8 Gy dose, but disappeared completely after 24 h. In both groups, foci reappeared on days 11-15 in terminally ill animals. G-003M pretreatment significantly (P < 0.05) attenuated the formation of γH2AX foci in all irradiated rabbits. This study reveals that γH2AX focus assessment could be used to confirm radiation exposure, that focus size reflects the type of radiation exposure (acute or fractionated), that the re-appearance of foci is a strong indicator of imminent death in animals, and that G-003M provides protection against radiation. Environ. Mol. Mutagen. 57:455-468, 2016. © 2016 Wiley Periodicals, Inc. PMID:27338557

  5. Slow release delivery of rioprostil by an osmotic pump inhibits the formation of acute aspirin-induced gastric lesions in dogs and accelerates the healing of chronic lesions without incidence of side effects.

    PubMed

    Katz, L B; Shriver, D A

    1989-10-01

    Rioprostil, a primary alcohol prostaglandin E1 analog, inhibits gastric acid secretion and prevents gastric lesions induced by a variety of irritants in experimental animals. Because rioprostil is relatively short-acting, it would be of significant benefit clinically if its duration of action could be extended to allow once daily dosing. This investigation demonstrates that when administered via an osmotically driven pump (Osmet, Alza Corp.), rioprostil prevents the acute effects of aspirin on the gastric mucosa of dogs, accelerates the healing of aspirin-induced gastric lesions, and heals preexisting aspirin-induced gastric lesions during chronic administration of aspiring. The potency of rioprostil against acute gastric lesion formation was greatest when delivered from a 24-hr release pump (ED50 = 0.77 micrograms/kg/24 hr) and was 37 times greater than when administered as a single oral bolus. In addition, this activity occurred at doses which had little or no gastric antisecretory activity in betazole-stimulated Heidenhain pouch dogs. When delivered from a 24-hr pump, rioprostil (100 micrograms/kg/24 hr) healed preexisting aspirin-induced gastric lesions within 8 days after removal of aspirin, or after 15 days during continued daily aspirin administration. Additional studies determined that administration of rioprostil at doses of 720, 1440, or 2160 micrograms/kg/24 hr (935-2805 times the gastroprotective ED50 in 24 hr pumps) was well tolerated, with only slight, transient increases in body temperature, softening of the stools, and mild sedation at the highest dose. Administration of rioprostil daily for 5 days at 960 micrograms/kg/24 hr from 24-hr release pumps was also well tolerated by all dogs with no evidence of any accumulation of effect of rioprostil. In summary, administration of rioprostil via an osmotic pump increases its potency and duration of action against the gastric lesion-inducing effect of aspirin, and maintains a wide ratio of safety. PMID

  6. Acute Carotid Artery Stent Thrombosis Due to Dual Antiplatelet Resistance

    SciTech Connect

    Köklü, Erkan Arslan, Şakir; Yüksel, İsa Öner; Bayar, Nermin; Koç, Pınar

    2015-08-15

    Carotid artery stenting (CAS) is a revascularization modality that is an alternative to carotid endarterectomy. The efficacy of CAS in primary and secondary prevention from ischemic stroke has been demonstrated in various trials. Acute thrombosis of CAS is a rare complication that can lead to dramatic and catastrophic consequences. We discuss a case of acute CAS thrombosis in a patient who had previously undergone successful CAS. CAS was performed in a 73-year-old man who had had dysarthria lasting 2 weeks with 95 % stenosis in his left internal carotid artery. An acute cerebrovascular event resulting in right-sided hemiplegia developed 24 h after the procedure. Computed tomographic carotid angiography revealed complete occlusion of the stent with thrombus. The cause of stent thrombosis was thought to be antiaggregant resistance to both acetylsalicylic acid and clopidogrel. The most important cause of acute CAS thrombosis is inadequate or ineffective antiaggregant therapy. Evaluating patients who are candidates for CAS for acetylsalicylic acid and clopidogrel resistance may preclude this complication.

  7. Acute Anteroseptal Myocardial Infarction after a Negative Exercise Stress Test

    PubMed Central

    Al-Alawi, Abdullah M.; Janardan, Jyotsna; Peck, Kah Y.; Soward, Alan

    2016-01-01

    A myocardial infarction is a rare complication which can occur after an exercise stress test. We report a 48-year-old male who was referred to the Mildura Cardiology Practice, Victoria, Australia, in August 2014 with left-sided chest pain. He underwent an exercise stress test which was negative for myocardial ischaemia. However, the patient presented to the Emergency Department of the Mildura Base Hospital 30 minutes after the test with severe retrosternal chest pain. An acute anteroseptal ST segment elevation myocardial infarction was observed on electrocardiography. After thrombolysis, he was transferred to a tertiary hospital where coronary angiography subsequently revealed significant left anterior descending coronary artery stenosis. Thrombus aspiration and a balloon angioplasty were performed. The patient was discharged three days after the surgical procedure in good health. PMID:27226918

  8. An Atypically Large, Free-Floating Thrombus Extending From the Lung to the Left Atrium via a Pulmonary Vein: A Case Report.

    PubMed

    Wang, Wei; Li, Xuechang; Song, Weian; Zhang, Yunshan; Yue, Caiying; Shang, Liqun; Li, Jun; Wen, Feng; Liu, Junqiang; Zha, Peng

    2015-11-01

    An atypically large, free-floating thrombus extending from primary pulmonary malignancy into the left atrium (LA) is a rare phenomenon. Here, we report a 61-year-old man presenting with a large mass in the lower lobe of the left lung, extending to LA via the left inferior pulmonary vein.The thrombus remained clinically silent and was detected by computed tomography (CT) and transthoracic echocardiography. To prevent life-threatening complications including systemic embolism and sudden death, the patient underwent surgical excision of the mass under cardiopulmonary bypass. Pathology of the tumor and the embolus was confirmed as moderately differentiated squamous cell carcinoma. Furthermore, immunohistochemical studies demonstrated consistency of the tumor cells in this pathological category.The patient tolerated the surgery well and his condition began to improve gradually after the operation. PMID:26579798

  9. Acute myelogenous leukemia (AML) - children

    MedlinePlus

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  10. Additional manual thrombus aspiration for ST-segment elevation myocardial infarction during percutaneous coronary intervention: an updated meta-analysis

    PubMed Central

    Zhang, Yan; Peng, Li; Fan, Yong-Yan; Lu, Cai-Yi

    2016-01-01

    Background The clinical efficacy and safety of adjunctive thrombus aspiration (TA) in patients with ST-segment elevation myocardial infarction (STEMI) during percutaneous coronary intervention (PCI) remain controversial. Methods Twenty five eligible randomized controlled trials were included to compare the use of thrombus aspiration (TA) with PCI and PCI-only for STEMI. The primary endpoint was all-cause mortality and death. The secondary endpoints were major adverse cardiac events (MACE), recurrent infarction (RI), target vessel revascularization (TVR), stent thrombosis (ST), perfusion surrogate markers and stroke. Results TIMI flow grade 3 and MBG 2–3 were significantly increased in the TA plus PCI arm compared with the PCI-only arm [relative risk (RR): 1.05, 95% confidence intervals (CI): 1.02–1.09, P = 0.004] and (RR: 1.68, 95% CI: 1.40–2.00, P < 0.001), respectively. There were no significant differences in all-cause mortality, MACEs, TVR and ST rates between the two groups. The RI rate was lower in the TA plus PCI arm than that in the PCI-only arm with short-term follow-up duration (RR: 0.60, 95% CI: 0.38–0.96, P = 0.03), but there was no significant difference in RI incidence over the medium- or long-term follow-up periods (RR: 1.00, 95% CI: 0.77–1.29, P = 0.98), and (RR: 0.96, 95% CI: 0.81–1.15, P = 0.69), respectively. There were statistically significant differences in the rates of crude stroke and stroke over the medium- or long-term follow-up periods and the crude stroke rate in the TA plus PCI (RR: 1.60, 95% CI: 1.08–2.38, P = 0.02) and (RR: 1.43, 95% CI: 1.03–1.98, P = 0.03), respectively; this was not observed between the two arms during the short-term follow-up period (RR: 1.47, 95% CI: 0.97–2.21, P = 0.07). Conclusions Routine TA-assisted PCI in STEMI patients can improve myocardial reperfusion and get limited benefits related to the clinical endpoints, which may be associated with stroke risk. PMID:27403144

  11. Early application of negative pressure wound therapy to acute wounds contaminated with Staphylococcus aureus: An effective approach to preventing biofilm formation

    PubMed Central

    LI, TONGTONG; ZHANG, LIHAI; HAN, LI; WANG, GUOQI; YIN, PENG; LI, ZHIRUI; ZHANG, LICHENG; GUO, QI; LIU, DAOHONG; TANG, PEIFU

    2016-01-01

    Negative pressure wound therapy (NPWT) has been demonstrated to be effective at preventing biofilm-associated infections; however, its role in biofilm prevention is unknown. The present study evaluated the effect of NPWT on biofilm prevention when rapidly initiated following wound contamination. Full-thickness dermal wounds (8 mm) were created in rabbit ears and inoculated with green fluorescent protein-labeled Staphylococcus aureus (S. aureus). At 6 h following inoculation, continuous NPWT at −125 mmHg was initiated, with the wounds on the contralateral ear left untreated in order to serve as self-controls. S. aureus rapidly formed mature biofilms in the wound beds post-inoculation, with a persistent bacterial burden of ~105−107 colony-forming units (CFUs)/wound and impaired wound healing. Compared with the untreated group, NPWT resulted in a significant reduction in biofilm matrix, which was verified by scanning electron microscopy and epifluorescence. A reduction in bacterial counts followed (P<0.05) with ~103 CFUs/wound on postoperative day 13 and improvement in all healing parameters (P<0.05) relative to control wounds. The results of the present investigation suggest that NPWT is an effective strategy to impeding the formation of S. aureus wound biofilms when initiated rapidly following bacterial contamination. The early application of NPWT, aimed at biofilm prevention, may improve wound care. PMID:26997991

  12. Acute Pneumonia.

    PubMed

    Arshad, Hammad; Fasanya, Adebayo; Cheema, Tariq; Singh, Anil C

    2016-01-01

    Acute pneumonia is an active infection of the lungs that results when an individual at risk gets exposed to a particular microbiological pathogen. Acute pneumonia is the leading cause of death in the United States that is attributable to an infection. The risk factors, pathogenesis, and microbiological organisms involved differ if the pneumonia develops in the community versus health care-associated environment. The development of concise and comprehensive guidelines has led to an improvement in the management of the problem. However, the emergence of multidrug-resistant organisms and the increase in the percentage of elderly population keep mortality risk very substantial. PMID:26919676

  13. Combination of Superselective Arterial Embolization and Radiofrequency Ablation for the Treatment of a Giant Renal Angiomyolipoma Complicated with Caval Thrombus

    PubMed Central

    Stamatiou, Konstantinos N.; Moschouris, Hippocrates; Marmaridou, Kiriaki; Kiltenis, Michail; Kladis-Kalentzis, Konstantinos; Malagari, Katerina

    2016-01-01

    This is a case of a 78-year-old male patient with multiple angiomyolipomas of a solitary right kidney. The largest of these tumors (maximum diameter: 13.4 cm) caused significant extrinsic compression of the inferior vena cava complicated by thrombosis of this vessel. Treatment of thrombosis with anticoagulants had been ineffective and the patient had experienced a bleeding episode from the largest right renal angiomyolipoma, which had been treated by transarterial embolization in another institution, 4 months prior to our intervention. Our approach included superselective transarterial embolization of the dominant, right kidney angiomyolipoma with hydrogel microspheres, which was combined, 20 days later, with ultrasonographically guided radiofrequency ablation. Both interventions were uneventful. Computed tomography 2 months after ablation showed a 53% reduction in tumor volume, reduced space-occupying effect on inferior vena cava, and resolution of caval thrombus. Nine months after intervention the patient has had no recurrence of thrombosis or hemorrhage and no tumor regrowth has been observed. The combination of superselective transarterial embolization and radiofrequency ablation seems to be a feasible, safe, and efficient treatment of large renal angiomyolipomas. PMID:27293932

  14. Combination of Superselective Arterial Embolization and Radiofrequency Ablation for the Treatment of a Giant Renal Angiomyolipoma Complicated with Caval Thrombus.

    PubMed

    Stamatiou, Konstantinos N; Moschouris, Hippocrates; Marmaridou, Kiriaki; Kiltenis, Michail; Kladis-Kalentzis, Konstantinos; Malagari, Katerina

    2016-01-01

    This is a case of a 78-year-old male patient with multiple angiomyolipomas of a solitary right kidney. The largest of these tumors (maximum diameter: 13.4 cm) caused significant extrinsic compression of the inferior vena cava complicated by thrombosis of this vessel. Treatment of thrombosis with anticoagulants had been ineffective and the patient had experienced a bleeding episode from the largest right renal angiomyolipoma, which had been treated by transarterial embolization in another institution, 4 months prior to our intervention. Our approach included superselective transarterial embolization of the dominant, right kidney angiomyolipoma with hydrogel microspheres, which was combined, 20 days later, with ultrasonographically guided radiofrequency ablation. Both interventions were uneventful. Computed tomography 2 months after ablation showed a 53% reduction in tumor volume, reduced space-occupying effect on inferior vena cava, and resolution of caval thrombus. Nine months after intervention the patient has had no recurrence of thrombosis or hemorrhage and no tumor regrowth has been observed. The combination of superselective transarterial embolization and radiofrequency ablation seems to be a feasible, safe, and efficient treatment of large renal angiomyolipomas. PMID:27293932

  15. Inferior Vena Caval Tumor Thrombus in Giant Cell Tumor of Sacrum – An Unusual Complication Treated with Multimodality Management

    PubMed Central

    Gulia, Ashish; Puri, Ajay; Byregowda, Suman; Rekhi, Bharat; Laskar, Siddhartha; Shetty, Nitin

    2015-01-01

    Introduction: Giant cell tumor is the most common benign lesion encountered. It accounts for 5 % of all skeletal tumors. It mainly affects the epiphysis of long bones and rarely axial bones. In axial bones, sacrum is the most common site to be affected. Case report: A 23 year old female with giant cell tumor of sacrum was treated initially with conservative treatment (serial angioembolisation and bisphosphonates). Later intralesional curettage was done as the patient started developing bladder and bowel disturbances after two sessions of angioembolisation. Six months later patient again presented with pain at the primary lesion site and bilateral limb swelling. Imaging revealed recurrence of the disease and tumor thrombus extending into the inferior vena cava up to the subhepatic region. Conclusion: Treatment of sacral GCT (Giant Cell Tumor) poses a unique challenge to the treating surgeon because of the close proximity of vital neurovascular structures, viscera and associated complications related to the disease. Tumor thrombi are a very rare phenomenon associated with giant cell tumors of the bone. High index of suspicion and multimodality approach is the key in treating such challenging tumors and their complications. PMID:27299100

  16. Effects of acute systemic administration of TiO2, ZnO, SiO2, and Ag nanoparticles on hemodynamics, hemostasis and leukocyte recruitment.

    PubMed

    Haberl, Nadine; Hirn, Stephanie; Holzer, Martin; Zuchtriegel, Gabriele; Rehberg, Markus; Krombach, Fritz

    2015-01-01

    It has been suggested that engineered nanomaterials (ENM), once arrived in the circulation, may affect the cardiovascular system. The aim of this in vivo study was to screen major cardiovascular effects of acute systemic administration of a panel of five nanomaterials, TiO2 anatase (NM-101), TiO2 rutile (NM-104), ZnO (NM-110), SiO2 (NM-200) and Ag (NM-300). Mice were anesthetized and the ENM were injected at a dose of 1 mg/kg via a catheter placed in the left femoral artery. Hemodynamic parameters were determined by invasive measurement of blood pressure and non-invasive measurement of heart rate. Ten minutes after injection of the ENM, the formation of light/dye-induced thrombi was assessed in the cremasteric microcirculation by intravital microscopy. In addition, the numbers of rolling, firmly adherent and transmigrated leukocytes were recorded in postcapillary cremasteric venules over a time period of 120 min after injection of ENM by intravital microscopy. The systemic administration of a single dose of the ENM tested did not dramatically alter hemodynamic parameters or affect early steps of leukocyte recruitment. However, the presence of circulating TiO2 anatase, but not of TiO2 rutile, SiO2, ZnO or Ag nanoparticles, significantly accelerated thrombus formation in the murine microcirculation. Moreover, TiO2 anatase but not TiO2 rutile nanoparticles increased murine platelet aggregation in vitro. Taken together, only one of the five systemically administered ENM, TiO2 anatase, affected hemostasis, whereas none of the ENM tested in this screening study dramatically modulated hemodynamic parameters or early steps of leukocyte recruitment. PMID:25670207

  17. [Acute aortic syndrome].

    PubMed

    Nienaber, Christoph A

    2016-06-01

    Acute aortic syndrome is the common denominator for acute events to the aortic wall and encompasses dissection of the aorta, intramural hematoma, formation of aortic ulcers and trauma to the aorta with an annual incidence of up to 35 cases/100.000 between 65 and 75 years of age. Both, inflammation and/or microtrauma at the level of the aortic media layer, and a genetic disposition are promoting elements of AAS, while the extent and anatomic involvement of the ascending aorta call for either surgical resection/repair in the proximal part of the aorta, or an endovascular solution for pathologies in the distal aorta; in all cases of dissection (regardless of location) reconstruction/realignment has been proven to portend better long-term outcomes (in addition to medical management of blood pressure). PMID:27254622

  18. Acute Kidney Injury Associated with Renal Cell Carcinoma Complicated by Renal Vein and Inferior Vena Cava Involvement.

    PubMed

    Sugase, Taro; Akimoto, Tetsu; Kubo, Taro; Imai, Toshimi; Otani-Takei, Naoko; Miki, Takuya; Takeda, Shin-Ichi; Nukui, Akinori; Muto, Shigeaki; Morita, Tatsuo; Nagata, Daisuke

    2016-01-01

    Acute kidney injury (AKI) is caused by diverse pathologies, although it may occasionally result from concurrent renal efflux disturbances. We herein describe a case of AKI in a patient complicated by renal cell carcinoma (RCC) with renal vein and inferior vena cava (IVC) involvement. A neoplastic thrombus which disrupted the blood flow in the renal vein appeared to play a role in the rapid decline in the renal function. Such a scenario has rarely been mentioned in the previous literature describing the cases of RCC complicated by AKI. Concerns regarding the diagnostic and therapeutic strategies for RCC are also discussed. PMID:27580548

  19. Effect of ambient particulate matter expousre on hemostasis

    EPA Science Inventory

    Epidemiological studies have linked levels of particulate matter (PM) in ambient air to cardiovascular mortality and hospitalizations for myocardial infarction (MI) and stroke. Thrombus formation plays a primary role in potentiating acute cardiovascular events, and this study was...

  20. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  1. Contrast-enhanced sonothrombolysis in a porcine model of acute peripheral arterial thrombosis and prevention of anaphylactic shock.

    PubMed

    Nederhoed, Johanna H; Slikkerveer, Jeroen; Meyer, Klaas W; Wisselink, Willem; Musters, René J P; Yeung, Kak K

    2014-03-01

    Acute peripheral arterial thrombosis can be threatening to life and limb. Dissolution of the thrombus local catheter-directed intra-arterial infusion of fibrinolytic agents such as urokinase is the standard therapy for thrombosis; however, this method is time-intensive, and amputation of the affected limb is still needed in 10-30% of cases. Furthermore, thrombolytic therapy carries the risk of bleeding complications. The use of small gas-filled bubbles, or ultrasound contrast agents (UCAs), in combination with ultrasound has been investigated as an improved thrombolytic therapy in acute coronary and cerebral arterial thrombosis. The authors describe a porcine model of acute peripheral arterial occlusion to test contrast-enhanced sonothrombolysis approaches that combine ultrasound, UCAs and fibrinolytic agents and recommend a strategy for preventing severe allergic reactions to UCAs in the pigs. PMID:24552914

  2. Prolonged Intraoperative Cardiac Resuscitation Complicated by Intracardiac Thrombus in a Patient Undergoing Orthotopic Liver Transplantation.

    PubMed

    Kim, Sang; DeMaria, Samuel; Cohen, Edmond; Silvay, George; Zerillo, Jeron

    2016-09-01

    We report the case of successful resuscitation after prolonged cardiac arrest during orthotopic liver transplantation. After reperfusion, the patient developed ventricular tachycardia, complicated by intracardiac clot formation and massive hemorrhage. Transesophageal echocardiography demonstrated stunned and nonfunctioning right and left ventricles, with developing intracardiac clots. Treatment with heparin, massive transfusion and prolonged cardiopulmonary resuscitation ensued for 51 minutes. Serial arterial blood gases demonstrated adequate oxygenation and ventilation during cardiopulmonary resuscitation. Cardiothoracic surgery was consulted for potential use of extracorporeal membrane oxygenation, however, the myocardial function improved and the surgery was completed without further intervention. On postoperative day 6, the patient was extubated without neurologic or cardiac impairment. The patient continues to do well 2 years posttransplant, able to perform independent daily activities of living and his previous job. This case underscores the potential for positive outcomes with profoundly prolonged, effective advanced cardiovascular life support in patients who experience postreperfusion syndrome. PMID:27233818

  3. The formation and design of the 'Acute Admission Database'- a database including a prospective, observational cohort of 6279 patients triaged in the emergency department in a larger Danish hospital

    PubMed Central

    2012-01-01

    Background Management and care of the acutely ill patient has improved over the last years due to introduction of systematic assessment and accelerated treatment protocols. We have, however, sparse knowledge of the association between patient status at admission to hospital and patient outcome. A likely explanation is the difficulty in retrieving all relevant information from one database. The objective of this article was 1) to describe the formation and design of the 'Acute Admission Database', and 2) to characterize the cohort included. Methods All adult patients triaged at the Emergency Department at Hillerød Hospital and admitted either to the observationary unit or to a general ward in-hospital were prospectively included during a period of 22 weeks. The triage system used was a Danish adaptation of the Swedish triage system, ADAPT. Data from 3 different data sources was merged using a unique identifier, the Central Personal Registry number; 1) Data from patient admission; time and date, vital signs, presenting complaint and triage category, 2) Blood sample results taken at admission, including a venous acid-base status, and 3) Outcome measures, e.g. length of stay, admission to Intensive Care Unit, and mortality within 7 and 28 days after admission. Results In primary triage, patients were categorized as red (4.4%), orange (25.2%), yellow (38.7%) and green (31.7%). Abnormal vital signs were present at admission in 25% of the patients, most often temperature (10.5%), saturation of peripheral oxygen (9.2%), Glasgow Coma Score (6.6%) and respiratory rate (4.8%). A venous acid-base status was obtained in 43% of all patients. The majority (78%) had a pH within the normal range (7.35-7.45), 15% had acidosis (pH < 7.35) and 7% had alkalosis (pH > 7.45). Median length of stay was 2 days (range 1-123). The proportion of patients admitted to Intensive Care Unit was 1.6% (95% CI 1.2-2.0), 1.8% (95% CI 1.5-2.2) died within 7 days, and 4.2% (95% CI 3.7-4.7) died within

  4. Acute wiiitis representing as thrombosis of the inferior vena cava and left pelvic veins.

    PubMed

    Brodmann, M; Gary, T; Hafner, F; Eller, P; Deutschmann, H; Pilger, E; Seinost, G

    2015-08-01

    Deep venous thrombosis as a result of venous wall injury provoked by trauma is a common finding. It often occurs in patients with sportive overstraining, caused by over fatigue of the body structures. In 2007, the entity of "acute wiiitis" was first described in a letter to the New England Journal of Medicine. Acute wiiitis sums up all affections, mainly skeletal and muscle affections, provoked by playing Nintendo Wii, a very common and loved video-game system. Deep venous thrombosis as a consequence of Nintendo Wii has not been described so far. We present a patient with a massive free floating thrombus of the left pelvic veins originating from the gluteal veins and reaching into the inferior vena cava after playing Nintendo Wii. PMID:24681523

  5. Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder

    PubMed Central

    Bispo, Miguel; Valente, Ana; Maldonado, Rosário; Palma, Rui; Glória, Helena; Nóbrega, João; Alexandrino, Paula

    2009-01-01

    Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure. PMID:19533818

  6. Prognostic biomarkers in acute coronary syndrome.

    PubMed

    Salvagno, Gian Luca; Pavan, Chiara

    2016-07-01

    The acute coronary syndrome (ACS) is a leading cause of death around the globe. Beside a still high mortality rate, additional complications of ACS include arrhythmias, left ventricular mural thrombus, cardiac fibrosis, heart failure (HF), cardiogenic shock, mitral valve dysfunction, aneurysms, up to cardiac rupture. Despite many prognostic tools have been developed over the past decades, efforts are still ongoing to identify reliable and predictive biomarkers, which may help predict the prognosis of these patients and especially the risk of HF. Recent evidence suggests that the value of a discrete number of biomarkers of myocardial fibrosis, namely the soluble form of suppression of tumorigenicity 2 (sST2) and galectin-3 (GAL-3), may be predictive of HF and death in patients with ACS. Interestingly, the already promising predictive value of these biomarkers when measured alone was shown to be consistently magnified when combined with other and well-established cardiac biomarkers such natriuretic peptides and cardiac troponins. This article is hence aimed to review the current knowledge about cardiac biomarkers of fibrosis and adverse remodeling. PMID:27500159

  7. Prognostic biomarkers in acute coronary syndrome

    PubMed Central

    Pavan, Chiara

    2016-01-01

    The acute coronary syndrome (ACS) is a leading cause of death around the globe. Beside a still high mortality rate, additional complications of ACS include arrhythmias, left ventricular mural thrombus, cardiac fibrosis, heart failure (HF), cardiogenic shock, mitral valve dysfunction, aneurysms, up to cardiac rupture. Despite many prognostic tools have been developed over the past decades, efforts are still ongoing to identify reliable and predictive biomarkers, which may help predict the prognosis of these patients and especially the risk of HF. Recent evidence suggests that the value of a discrete number of biomarkers of myocardial fibrosis, namely the soluble form of suppression of tumorigenicity 2 (sST2) and galectin-3 (GAL-3), may be predictive of HF and death in patients with ACS. Interestingly, the already promising predictive value of these biomarkers when measured alone was shown to be consistently magnified when combined with other and well-established cardiac biomarkers such natriuretic peptides and cardiac troponins. This article is hence aimed to review the current knowledge about cardiac biomarkers of fibrosis and adverse remodeling. PMID:27500159

  8. The Quest for Arterial Recanalization in Acute Ischemic Stroke-The Past, Present and the Future

    PubMed Central

    L.L.Yeo, Leonard; Sharma, Vijay K

    2013-01-01

    Ischemic stroke is one of the major causes of mortality and long-term disability. In the recent past, only very few treatment options were available and a considerable proportion of stroke survivors remained permanently disabled. However, over the last 2 decades rapid advances in acute stroke care have resulted in a corresponding improvement in mortality rates and functional outcomes. In this review, we describe the evolution of systemic thrombolytic agents and various interventional devices, their current status as well as some of the future prospects. We reviewed literature pertaining to acute ischemic stroke reperfusion treatment. We explored the current accepted treatment strategies to attain cerebral reperfusion via intravenous modalities and compare and contrast them within the boundaries of their clinical trials. Subsequently we reviewed the trials for interventional devices for acute ischemic stroke, categorizing them into thrombectomy devices, aspiration devices, clot disruption devices and thrombus entrapment devices. Finally we surveyed several of the alternative reperfusion strategies available. We also shed some light on the controversies surrounding the current strategies of treatment of acute ischemic stroke. Acute invasive interventional strategies continue to improve along with the noninvasive modalities. Both approaches appear promising. We conducted a comprehensive chronological review of the existing treatments as well as upcoming remedies for acute ischemic stroke. PMID:23864913

  9. Single Photon Emission Computed Tomography-Based Three-Dimensional Conformal Radiotherapy for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

    SciTech Connect

    Shirai, Shintaro; Sato, Morio Suwa, Kazuhiro; Kishi, Kazushi; Shimono, Chigusa; Kawai, Nobuyuki; Tanihata, Hirohiko; Minamiguchi, Hiroki; Nakai, Motoki

    2009-03-01

    Purpose: To evaluate the safety and efficacy of three-dimensional conformal radiotherapy (3D-CRT) using single photon emission computed tomography (SPECT) in unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods and Materials: Patients with HCC with PVTT in the first branch and/or main trunk were selected for this study. The optimal beam directions for 3D-CRT were explored using a Tc-99m-galactosyl human serum albumin SPECT image for guidance. The SPECT image was classified as either wedge type or localized type. The clinical target volume to a total dose of 45 or 50 Gy per 18-20 fractions included the main tumor and PVTT in the wedge type and PVTT alone in the localized type. Results: Twenty-six patients were enrolled: 18 with wedge type and 8 with localized type. Mean tumor size was 7.1 cm (range, 4.4-12.3 cm). Clinical target volumes of wedge type vs. localized type were 111.2 cm{sup 3} vs. 48.4 cm{sup 3} (p = 0.010), respectively. Mean dose to normal liver and mean dose to functional liver were 1185 cGy and 988 cGy (p = 0.001) in wedge type and 1046 cGy and 1043 cGy (p = 0.658) in localized type, respectively. Despite an incidence of Child-Pugh B and C of 57.7%, no patients experienced radiation-induced liver disease. The progression of PVTT was inhibited, with an incidence of 92.2%; survival rates at 1 and 2 years were 44% and 30%, respectively. Conclusion: Single photon emission computed tomography-based 3D-CRT enables irradiation of both the main tumor and PVTT with low toxicity and promising survival.

  10. Effect of Thrombus Composition and Viscosity on Sonoreperfusion Efficacy in a Model of Micro-Vascular Obstruction.

    PubMed

    Black, John J; Yu, Francois T H; Schnatz, Rick G; Chen, Xucai; Villanueva, Flordeliza S; Pacella, John J

    2016-09-01

    Distal embolization of micro-thrombi during stenting for myocardial infarction causes micro-vascular obstruction (MVO). We have previously shown that sonoreperfusion (SRP), a microbubble (MB)-mediated ultrasound (US) therapy, resolves MVO from venous micro-thrombi in vitro in saline. However, blood is more viscous than saline, and arterial thrombi that embolize during stenting are mechanically distinct from venous clot. Therefore, we tested the hypothesis that MVO created with arterial micro-thrombi are more resistant to SRP therapy compared with venous micro-thrombi, and higher viscosity further increases the US requirement for effective SRP in an in vitro model of MVO. Lipid MBs suspended in plasma with adjusted viscosity (1.1 cP or 4.0 cP) were passed through tubing bearing a mesh with 40-μm pores to simulate a micro-vascular cross-section; upstream pressure reflected thrombus burden. To simulate MVO, the mesh was occluded with either arterial or venous micro-thrombi to increase upstream pressure to 40 mmHg ± 5 mmHg. Therapeutic long-tone-burst US was delivered to the occluded area for 20 min. MB activity was recorded with a passive cavitation detector. MVO caused by arterial micro-thrombi at either blood or plasma viscosity resulted in less effective SRP therapy compared to venous thrombi. Higher viscosity further reduced the effectiveness of SRP therapy. The passive cavitation detector showed a decrease in inertial cavitation when viscosity was increased, while stable cavitation was affected in a more complex manner. Overall, these data suggest that arterial thrombi may require higher acoustic pressure US than venous thrombi to achieve similar SRP efficacy; increased viscosity decreases SRP efficacy; and both inertial and stable cavitation are implicated in observed SRP efficacy. PMID:27207018

  11. Combination of Transarterial Chemoembolization and Three-Dimensional Conformal Radiotherapy for Hepatocellular Carcinoma With Inferior Vena Cava Tumor Thrombus

    SciTech Connect

    Koo, Ja Eun; Kim, Jong Hoon; Lim, Young-Suk

    2010-09-01

    Purpose: To evaluate the effects of transarterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (CRT) in patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT). Methods and Materials: A total of 42 consecutive patients who underwent TACE and CRT (TACE+CRT group) for the treatment of HCC with IVCTT were prospectively enrolled from July 2004 to October 2006. As historical controls, 29 HCC patients with IVCTT who received TACE alone (TACE group) between July 2003 and June 2004 were included. CRT was designed to target only the IVCTT and to deliver a median total dose of 45 Gy (range, 28-50 Gy). Results: Most baseline characteristics of the two groups were similar (p > 0.05). The response and progression-free rates of IVCTT were significantly higher in the TACE+CRT group than in the TACE group (42.9% and 71.4% vs. 13.8% and 37.9%, respectively; p < 0.01 for both rates). Overall, patient survival was significantly higher in the TACE+CRT group than in the TACE group (p < 0.01), with a median survival time of 11.7 months and 4.7 months, respectively. Treatment with TACE+CRT (hazard ratio [HR] = 0.38; 95% confidence interval [CI], 0.20-0.71), progression of IVCTT (HR = 4.05; 95% CI, 2.00-8.21), Child-Pugh class B (HR = 3.44; 95% CI, 1.79-6.61), and portal vein invasion (HR = 2.31; 95% CI, 1.19-4.50) were identified as independent predictors of mortality by multivariable analysis. Conclusions: The combination of TACE and CRT is more effective in the control of IVCTT associated with HCC and improves patient survival compared with TACE alone.

  12. The efficacy and safety of postoperative adjuvant transarterial embolization and radiotherapy in hepatocellular carcinoma patients with portal vein tumor thrombus

    PubMed Central

    Bai, Tao; Chen, Jie; Xie, Zhi-Bo; Wu, Fei-Xiang; Wang, Si-Da; Liu, Jun-Jie; Li, Le-Qun

    2016-01-01

    Objective This study aims to find out the safety and efficiency of postoperative adjuvant transarterial chemoembolization (TACE) and radiotherapy (RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Methods From 2009 to 2010, a total of 92 HCC patients with PVTT were enrolled in this retrospective study. Patients were divided into three groups according to their adjuvant therapies (conservative group, n=51; TACE group, n=31; RT group, n=10). Results In our analysis, median survival in patients with postoperative adjuvant TACE (21.91±3.60 months) or RT (14.53±1.61 months) was significantly longer than patients with hepatectomy alone (8.99±1.03 months). But the difference between adjuvant TACE and RT was of no significance (P=0.716). Also a similar result could be observed in median disease-free survival: conservative group (6.51±1.44 months), TACE group (13.98±3.38 months), and RT group (14.03±2.40 months). Treatment strategies (hazard ratio [HR] =0.411, P<0.001) and PVTT type (HR =4.636, P<0.001) were the independent prognostic factors for overall survival. Similarly, the risk factors were the same when multivariate analysis was conducted in disease-free survival (treatment strategies, HR =0.423, P<0.001; PVTT type, HR =4.351, P<0.001) and recurrence (treatment strategies, HR =0.459, P=0.030; PVTT type, HR =2.908, P=0.047). Patients with PVTT type I had longer overall survival than patients with PVTT type II (median survival: 18.43±2.88 months vs 11.59±1.45 months, P=0.035). Conclusion Postoperative adjuvant TACE and RT may be a choice for HCC patients with PVTT. PMID:27390524

  13. Acute diarrhea.

    PubMed

    Barr, Wendy; Smith, Andrew

    2014-02-01

    Acute diarrhea in adults is a common problem encountered by family physicians. The most common etiology is viral gastroenteritis, a self-limited disease. Increases in travel, comorbidities, and foodborne illness lead to more bacteria-related cases of acute diarrhea. A history and physical examination evaluating for risk factors and signs of inflammatory diarrhea and/or severe dehydration can direct any needed testing and treatment. Most patients do not require laboratory workup, and routine stool cultures are not recommended. Treatment focuses on preventing and treating dehydration. Diagnostic investigation should be reserved for patients with severe dehydration or illness, persistent fever, bloody stool, or immunosuppression, and for cases of suspected nosocomial infection or outbreak. Oral rehydration therapy with early refeeding is the preferred treatment for dehydration. Antimotility agents should be avoided in patients with bloody diarrhea, but loperamide/simethicone may improve symptoms in patients with watery diarrhea. Probiotic use may shorten the duration of illness. When used appropriately, antibiotics are effective in the treatment of shigellosis, campylobacteriosis, Clostridium difficile, traveler's diarrhea, and protozoal infections. Prevention of acute diarrhea is promoted through adequate hand washing, safe food preparation, access to clean water, and vaccinations. PMID:24506120

  14. Sinusitis (acute)

    PubMed Central

    2008-01-01

    Introduction Acute sinusitis is defined pathologically, by transient inflammation of the mucosal lining of the paranasal sinuses lasting less than 4 weeks. Clinically, it is characterised by nasal congestion, rhinorrhoea, facial pain, hyposmia, sneezing, and, if more severe, additional malaise and fever. It affects 1−5% of the adult population each year in Europe. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with clinically diagnosed acute sinusitis, and with radiologically or bacteriologically confirmed acute sinusitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (amoxicillin, co-amoxiclav, doxycycline, cephalosporins, macrolides, different doses [amoxicillin, co-amoxiclav, doxycycline, cephalosporins, macrolides], long-course regimens), antihistamines, cephalosporins or macrolides, decongestants (xylometazoline, phenylephrine, pseudoephedrine), doxycycline, saline nasal washes, steam inhalation, and topical corticosteroids (intra-nasal). PMID:19450327

  15. Sinusitis (acute)

    PubMed Central

    2011-01-01

    Introduction Acute sinusitis is defined pathologically, by transient inflammation of the mucosal lining of the paranasal sinuses lasting less than 4 weeks. Clinically, it is characterised by nasal congestion, rhinorrhoea, facial pain, hyposmia, sneezing, and, if more severe, additional malaise and fever. It affects 1% to 5% of the adult population each year in Europe. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with clinically diagnosed acute sinusitis, and in people with radiologically or bacteriologically confirmed acute sinusitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (amoxicillin, amoxicillin–clavulanic acid [co-amoxiclav], doxycycline, cephalosporins, macrolides; different doses, long-course regimens), antihistamines, decongestants (xylometazoline, phenylephrine, pseudoephedrine), saline nasal washes, steam inhalation, and topical corticosteroids (intranasal). PMID:22189346

  16. Effectiveness of Integrating Delayed Computed Tomography Angiography Imaging for Left Atrial Appendage Thrombus Exclusion into the Care of Patients Undergoing Ablation of Atrial Fibrillation

    PubMed Central

    Bilchick, Kenneth C.; Mealor, Augustus; Gonzalez, Jorge; Norton, Patrick; Zhuo, David; Mason, Pamela; Ferguson, John D.; Malhotra, Rohit; Mangrum, J. Michael; Darby, Andrew E.; DiMarco, John; Hagspiel, Klaus; Dent, John; Kramer, Christopher M.; Stukenborg, George J.; Salerno, Michael

    2015-01-01

    Background Computed tomography angiography (CTA) can identify and rule out left atrial appendage (LAA) thrombus when delayed imaging is also performed. Objective In patients referred for CTA for pulmonary vein anatomy prior to ablation of atrial fibrillation or atypical left atrial flutter (AF), we sought to determine the effectiveness of a novel clinical protocol for integrating results of CTA delayed imaging of the LAA into pre-procedure care. Methods After making delayed imaging of the LAA part of our routine pre-ablation CTA protocol, we integrated early reporting of pre-ablation CTA LAA imaging results into clinical practice as part of a formal protocol in June 2013. We then analyzed the effectiveness of this protocol by evaluating 320 AF ablation patients with CTA imaging during 2012–2014. Results Among CTA patients with delayed LAA imaging, the sensitivity and negative predictive values for LAA thrombus with intracardiac echocardiography (ICE) or transesophageal echocardiograms (TEEs) as the reference standard were both 100%. ICE during ablation confirmed absence of thrombus in patients with a negative CTA or negative TEE. No patients with either a negative CTA or an equivocal CTA combined with a negative TEE had strokes or transient ischemic attacks. Overall, the need for TEEs decreased from 57.5% to 24.0% during the 3-year period as a result of the CTA protocol. Conclusions Clinical integration of CTA with delayed LAA imaging into the care of patients having catheter ablation of AF is feasible, safe, and effective. Such a protocol could be applied broadly to improve patient care. PMID:26341605

  17. Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion

    SciTech Connect

    Hou Jiazhou; Zeng Zhaochong; Zhang Jianying; Fan Jia; Zhou Jian; Zeng Mengsu

    2012-10-01

    Purpose: The present study evaluates the influence of portal vein (PV) vs. inferior vena cava (IVC) tumor thrombosis sites on the effectiveness of external-beam radiation therapy (EBRT) in advanced hepatocellular carcinoma (HCC) with macrovascular invasion. Methods and Materials: We retrospectively reviewed 181 HCC patients with PV and/or IVC tumor thrombi who were referred for EBRT at our institution between 2000 and 2009. EBRT was designed to focus on the tumor thrombi with or without primary intrahepatic tumors to deliver a median total conventional dose of 50 Gy (range, 30-60 Gy). Predictors of survival were identified using univariate and multivariate analyses. Results: The median survival was 10.2, 7.4, 17.4, and 8.5 months for patients with PV branch, PV trunk, IVC, and PV plus IVC tumor thrombosis, respectively. Unfavorable pretreatment predictors were associated by multivariate analysis with lower albumin and higher {alpha}-fetoprotein levels, poorer Child-Pugh liver function classification, multiple intrahepatic foci, lymph node metastases, thrombus location, less chance to receive post-EBRT transarterial chemoembolization (TACE) and the two-dimensional EBRT technique. In comparison to patients with PV tumor thrombosis, patients with IVC thrombi had a higher occurrence of solitary intrahepatic lesions (p = 0.027), well-controlled intrahepatic tumors (p < 0.001), and a better response to EBRT (p < 0.001), and they were more likely to receive post-EBRT TACE (p = 0.033). Conclusions: In HCC, patients with IVC thrombus treated with EBRT had a better response rate and longer survival than those with PV thrombus.

  18. Effective use of gemcitabine in the treatment of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas with portal vein tumor thrombus.

    PubMed

    Yoshioka, Masato; Uchinami, Hiroshi; Watanabe, Go; Takahashi, Tomokazu; Nakagawa, Yasuhiko; Andoh, Hideaki; Yoshioka, Toshiaki; Nanjo, Hiroshi; Yamamoto, Yuzo

    2012-01-01

    A 74-year-old woman had an undifferentiated carcinoma with osteoclast-like giant cells (UCWOGC) in the body of the pancreas with massive portal vein tumor thrombus (PVTT). Because the PVTT progressed so rapidly into the right portal branch, the patient first underwent distal pancreatectomy and tumor thrombectomy to prevent life-threatening portal venous obstruction. Although a recurrent PVTT had developed early postoperatively, systemic gemcitabine treatment was so effective that it induced complete remission 5 months after the initiation of chemotherapy. The patient continued to be in complete response for 12 months, and has survived for 19 months since surgery. PMID:22892493

  19. Case-Control Study of Platelet Glycoprotein Receptor Ib and IIb/IIIa Expression in Patients with Acute and Chronic Cerebrovascular Disease

    PubMed Central

    Kraft, Peter; Drechsler, Christiane; Gunreben, Ignaz; Heuschmann, Peter Ulrich; Kleinschnitz, Christoph

    2015-01-01

    Background Animal models have been instrumental in defining thrombus formation, including the role of platelet surface glycoprotein (GP) receptors, in acute ischemic stroke (AIS). However, the involvement of GP receptors in human ischemic stroke pathophysiology and their utility as biomarkers for ischemic stroke risk and severity requires elucidation. Aims To determine whether platelet GPIb and GPIIb/IIIa receptors are differentially expressed in patients with AIS and chronic cerebrovascular disease (CCD) compared with healthy volunteers (HV) and to identify predictors of GPIb and GPIIb/IIIa expression. Methods This was a case—control study of 116 patients with AIS or transient ischemic attack (TIA), 117 patients with CCD, and 104 HV who were enrolled at our University hospital from 2010 to 2013. Blood sampling was performed once in the CCD and HV groups, and at several time points in patients with AIS or TIA. Linear regression and analysis of variance were used to analyze correlations between platelet GPIb and GPIIb/IIIa receptor numbers and demographic and clinical parameters. Results GPIb and GPIIb/IIIa receptor numbers did not significantly differ between the AIS, CCD, and HV groups. GPIb receptor expression level correlated significantly with the magnitude of GPIIb/IIIa receptor expression and the neutrophil count. In contrast, GPIIb/IIIa receptor numbers were not associated with peripheral immune-cell sub-population counts. C-reactive protein was an independent predictor of GPIIb/IIIa (not GPIb) receptor numbers. Conclusions Platelet GPIb and GPIIb/IIIa receptor numbers did not distinguish between patient or control groups in this study, negating their potential use as a biomarker for predicting stroke risk. PMID:25748430

  20. [Acute myocarditis].

    PubMed

    Combes, Alain

    2012-06-01

    Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent-onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option. PMID:22515999

  1. [Acute myocarditis].

    PubMed

    Combes, Alain

    2013-05-01

    Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option. PMID:23789482

  2. Acute cerebellar ataxia

    MedlinePlus

    Cerebellar ataxia; Ataxia - acute cerebellar; Cerebellitis; Post-varicella acute cerebellar ataxia; PVACA ... Acute cerebellar ataxia in children, especially younger than age 3, may occur several weeks after an illness caused by a virus. ...

  3. Ear infection - acute

    MedlinePlus

    Otitis media - acute; Infection - inner ear; Middle ear infection - acute ... Casselbrandt ML, Mandel EM. Acute otitis media and otitis media with effusion. In: Flint PW, Haughey BH, Lund V, et al, eds. Cummings Otolaryngology: Head & Neck Surgery . 6th ed. ...

  4. Iodine-125 Seeds Strand for Treatment of Tumor Thrombus in Inferior Vena Cava: An Experimental Study in a Rabbit Model

    SciTech Connect

    Zhang, Wen Yan, Zhiping Luo, Jianjun Fang, Zhuting Wu, Linlin Liu, QingXin Qu, Xudong Liu, Lingxiao Wang, Jianhua

    2013-10-15

    Objective: The purpose of this study was to establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT) and to evaluate the effect of linear iodine-125 seeds strand in treating implanted IVCTT. Methods: Tumor cell line VX{sub 2} was inoculated subcutaneously into New Zealand rabbit to develop the parent tumor. The tumor strip was inoculated into inferior vena cava (IVC) to establish the IVCTT model. The IVCTT was confirmed by multidetector computed tomography (MDCT) after 2 weeks. Twelve rabbits with IVCTT were randomly divided into two groups. Treatment group (group T; n = 6) underwent Iodine-125 seeds brachytherapy, and the control group (group C; n = 6) underwent blank seeds strand. The blood laboratory examination (including blood routine examination, hepatic and renal function), body weight, survival time, and IVCTT volume by MDCT were monitored. All rabbits were dissected postmortem, and the therapeutic effects were evaluated on the basis of histopathology. The proliferating cell nuclear antigen index (PI) and apoptosis index (AI) of IVCTT were compared between two groups. T test, Wilcoxon rank test, and Kaplan-Meier survival curve analysis were used. Results: The success rate of establishing IVCTT was 100 %. The body weight loss and cachexia of rabbits in group C appeared earlier than in group T. Body weight in the third week, the mean survival time, PI, AI in groups T and C were 2.23 {+-} 0.12 kg, 57.83 {+-} 8.68 days, (16.73 {+-} 5.18 %), (29.47 {+-} 7.18 %), and 2.03 {+-} 0.13 kg, 43.67 {+-} 5.28 days, (63.01 {+-} 2.01 %), (6.02 {+-} 2.93 %), respectively. There were statistically significant differences between group T and group C (P < 0.05). The IVCTT volume of group T was remarkably smaller than that of group C. Conclusions: Injecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish IVCTT animal model. The linear Iodine-125 seeds strand brachytherapy was a safe and effective method for treating IVCTT

  5. Multimodality Treatment for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Large-Scale, Multicenter, Propensity Mathching Score Analysis.

    PubMed

    Wang, Kang; Guo, Wei Xing; Chen, Min Shan; Mao, Yi Lei; Sun, Bei Cheng; Shi, Jie; Zhang, Yao Jun; Meng, Yan; Yang, Ye Fa; Cong, Wen Ming; Wu, Meng Chao; Lau, Wan Yee; Cheng, Shu Qun

    2016-03-01

    The optimal treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains controversial. We aimed to investigate the best treatment for patients with HCC with PVTT. From January 2002 to January 2014, the data from all consecutive patients with HCC with PVTT who underwent surgical treatment (ST),TACE,TACE combined with sorafenib (TACE-Sor), or TACE combined with radiotherapy (TACE-RT) in the 4 largest tertiary hospitals in China were analyzed retrospectively. The patients were divided into 3 subtypes according to the extent of PVTT in the portal vein (type I-III). The primary endpoint was overall survival (OS). A total of 1580 patients with HCC with PVTT were included in the study. The median survival times (MST) for ST (n = 745) for type I, II, and III patients (95% CI) were 15.9 (13.3-18.5), 12.5 (10.7-14.3), and 6.0 (4.3-7.7) months, respectively. The corresponding figures for patients after TACE (n = 604) were 9.3 (5.6-12.9), 4.9 (4.1-5.7), and 4.0 (3.1-4.9), respectively; for patients after TACE-Sor (n = 113) 12.0 (6.6-17.4), 8.9 (6.7-11.1), and 7.0 (3.0-10.9), respectively; and for patients after TACE-RT (n = 118) 12.2 (0-24.7), 10.6 (6.8-14.5), and 8.9 (5.2-12.6), respectively. Comparison among the different treatments for the 3 subtypes of PVTT patients after propensity score (PS) matching showed the effectiveness of ST to be the best for type I and type II PVTT patients, and TACE-RT was most beneficial for type III patients. Treatment was an independent risk factor of OS. ST was the best treatment for type I and II PVTT patients with Child-Pugh A and selected B liver function. TACE-RT should be given to type III PVTT patients. PMID:26986115

  6. Early Platelet Dysfunction: An Unrecognized Role in the Acute Coagulopathy of Trauma

    PubMed Central

    Wohlauer, Max V.; Moore, Ernest E.; Thomas, Scott; Sauaia, Angela; Evans, Ed; Harr, Jeffrey; Silliman, Christopher C.; Ploplis, Victoria; Castellino, Francis J.; Walsh, Mark

    2012-01-01

    Background To determine the prevalence of platelet dysfunction, using an end-point of assembly into a stable thrombus, following severe injury. Background: Although the current debate on acute traumatic coagulopathy (ATC) has focused on the consumption or inhibition of coagulation factors, the question of early platelet dysfunction in this setting remains unclear. Study Design Prospective platelet function in assembly and stability of the thrombus was determined within 30 minutes of injury using whole blood samples from trauma patients at the point of care employing thrombelastography (TEG)-based platelet functional analysis. Results There were 51 patients in the study. There were significant differences in the platelet response between trauma patients and healthy volunteers such that there was impaired aggregation to these agonists. In trauma patients, the median ADP inhibition of platelet function was 86.1% (IQR: 38.6–97.7%), compared to 4.2 % (IQR 0–18.2%) in healthy volunteers. Following trauma, the impairment of platelet function in response to AA was 44.9% (IQR 26.6–59.3%), compared to 0.5% (IQR 0–3.02%) in volunteers (Wilcoxon non parametric test p<0.0001 for both tests). Conclusions In this study, we show that platelet dysfunction is manifest following major trauma, before significant fluid or blood administration. These data suggest a potential role for early platelet transfusion in severely injured patients at risk for postinjury coagulopathy. PMID:22520693

  7. Possible benefits of catheters with lateral holes in coronary thrombus aspiration: a computational study for different clot viscosities and vacuum pressures.

    PubMed

    Soleimani, Sajjad; Dubini, Gabriele; Pennati, Giancarlo

    2014-10-01

    According to a number of clinical studies, coronary aspiration catheters are useful tools to remove a thrombus (blood clot) blocking a coronary artery. However, these thrombectomy devices may fail to remove the blood clot entirely. Few studies have been devoted to a systematic analysis of factors affecting clot aspiration. The geometric characteristics of the aspiration catheter, the physical properties of the thrombus, and the applied vacuum pressure are crucial parameters. In this study, the aspiration of a blood clot blocking a coronary bifurcation is computationally simulated. The clot is modeled as a highly viscous fluid, and a two-phase (blood and clot) problem is solved. The effects of geometric variations in the tip of the coronary catheter, including lateral hole size and location, are investigated considering different aspiration pressures and clot viscosities. A Bird-Carreau model is adopted for blood viscosity, while a power law model is used to describe the clot rheology. Computational results for blood clot aspiration show that the presence of holes in the lateral part of the tip of the catheter can be beneficial depending on clot viscosity, hole features, and applied aspiration pressure. In general, the holes are beneficial when the clot viscosity is low, while aspiration catheters without any extra lateral holes exhibit better performance for higher clot viscosity. However, when higher aspiration pressures are applied, the catheters tend to behave relatively similarly in removing clots with various viscosities, reducing the role of the clot viscosity. PMID:24571089

  8. Non-Invasive Pulse Wave Analysis in a Thrombus-Free Abdominal Aortic Aneurysm after Implantation of a Nitinol Aortic Endograft.

    PubMed

    Georgakarakos, Efstratios; Argyriou, Christos; Georgiadis, George S; Lazarides, Miltos K

    2015-01-01

    Endovascular aneurysm repair has been associated with changes in arterial stiffness, as estimated by pulse wave velocity (PWV). This marker is influenced by the medical status of the patient, the elastic characteristics of the aneurysm wall, and the presence of intraluminal thrombus. Therefore, in order to delineate the influence of the endograft implantation in the early post-operative period, we conducted non-invasively pulse wave analysis in a male patient with an abdominal aortic aneurysm containing no intraluminal thrombus, unremarkable past medical history, and absence of peripheral arterial disease. The estimated parameters were the systolic and diastolic pressure calculated at the aortic level (central pressures), PWV, augmentation pressure (AP) and augmentation index (AI), pressure wave reflection magnitude (RM), and peripheral resistance. Central systolic and diastolic pressure decreased post-operatively. PWV showed subtle changes from 11.6 to 10.6 and 10.9 m/s at 1-week and 1-month, respectively. Accordingly, the AI decreased from 28 to 14% and continued to drop to 25%. The AP decreased gradually from 15 to 6 and 4 mmHg. The wave RM dropped from 68 to 52% at 1-month. Finally, the peripheral resistance dropped from 1.41 to 0.99 and 0.85 dyn × s × cm(-5). Our example shows that the implantation of an aortic endograft can modify the pressure wave reflection over the aortic bifurcation without causing significant alterations in PWV. PMID:26793712

  9. Non-Invasive Pulse Wave Analysis in a Thrombus-Free Abdominal Aortic Aneurysm after Implantation of a Nitinol Aortic Endograft

    PubMed Central

    Georgakarakos, Efstratios; Argyriou, Christos; Georgiadis, George S.; Lazarides, Miltos K.

    2016-01-01

    Endovascular aneurysm repair has been associated with changes in arterial stiffness, as estimated by pulse wave velocity (PWV). This marker is influenced by the medical status of the patient, the elastic characteristics of the aneurysm wall, and the presence of intraluminal thrombus. Therefore, in order to delineate the influence of the endograft implantation in the early post-operative period, we conducted non-invasively pulse wave analysis in a male patient with an abdominal aortic aneurysm containing no intraluminal thrombus, unremarkable past medical history, and absence of peripheral arterial disease. The estimated parameters were the systolic and diastolic pressure calculated at the aortic level (central pressures), PWV, augmentation pressure (AP) and augmentation index (AI), pressure wave reflection magnitude (RM), and peripheral resistance. Central systolic and diastolic pressure decreased post-operatively. PWV showed subtle changes from 11.6 to 10.6 and 10.9 m/s at 1-week and 1-month, respectively. Accordingly, the AI decreased from 28 to 14% and continued to drop to 25%. The AP decreased gradually from 15 to 6 and 4 mmHg. The wave RM dropped from 68 to 52% at 1-month. Finally, the peripheral resistance dropped from 1.41 to 0.99 and 0.85 dyn × s × cm−5. Our example shows that the implantation of an aortic endograft can modify the pressure wave reflection over the aortic bifurcation without causing significant alterations in PWV. PMID:26793712

  10. [Sustained complete remission with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP) for bilobar multiple hepatocellular carcinoma with portal venous tumor thrombus--a case report].

    PubMed

    Tanaka, Motofumi; Tominaga, Masahiro; Iwasaki, Takeshi; Fukumoto, Takumi; Kusunoki, Nobuya; Sugimoto, Takemi; Tsuchida, Shinobu; Kido, Masahiro; Takebe, Atsushi; Kinoshita, Hisoka; Ku, Yonson

    2005-10-01

    For patients with multiple bilobar hepatocellular carcinoma (m-HCC) and/or advanced portal venous tumor thrombus (Vp3, 4), there has been no effective therapy, and the survival of more than 6 months was exceptional. Under these circumstances, we have developed a dual treatment (dual Tx) that combines reductive hepatectomy with percutaneous isolated hepatic perfusion (PIHP) for such patients. This dual Tx offers the high-rate of mid- and long-term survival in a subset of patients who had previously a dismal prognosis. Herein, we report a patient with Vp4 m-HCC who was successfully treated with dual Tx and survived for more than 2 years with a complete remission of hepatic tumors. A 53-year-old man had main tumors in the right lobe liver and multiple bilobar intrahepatic metastases (IM) with portal venous tumor thrombus reaching the portal trunk. He underwent an extended right hepatectomy with portal venous tumor thrombectomy, and subsequently PIHP twice in a 3-month period after reductive hepatectomy. After dual Tx, he had sustained complete remission for more than 2 years. He died because of obstruction of the superior vena cava by recurrent tumors in the mediastinum. His clinical course after treatment strongly indicates that the dual Tx should become a major treatment option for patients with Vp3, 4 m-HCC. PMID:16315950

  11. Acute pain.

    PubMed

    Good, M

    1999-01-01

    The review of acute pain describes the problem of unresolved pain and its effects on the neural, autonomic, and immune systems. Conceptualizations and mechanisms of pain are reviewed as well as theories of pain management. Descriptive studies of patient and nurse factors that inhibit effective pain management are discussed, followed by studies of pharmacological and nonpharmacological interventions. Critical analysis reveals that most studies were atheoretical, and therefore, this proliferation of information lacked conceptual coherence and organization. Furthermore, the nature and extent of barriers to pain management were described, but few intervention studies have been devised, as yet, to modify the knowledge, beliefs, and attitudes of nurses and patients that are barriers to pain management. Although some of the complementary therapies have sufficient research support to be used in clinical pain management, the physiological mechanisms and outcomes need to be studied. It is critical at this time to design studies of interventions to improve assessment, decision making, attentive care, and patient teaching. PMID:10418655

  12. Acute Coronary Syndromes: Diagnosis and Management, Part II

    PubMed Central

    Kumar, Amit; Cannon, Christopher P.

    2009-01-01

    At the most severe end of the spectrum of acute coronary syndromes is ST-segment elevation myocardial infarction (STEMI), which usually occurs when a fibrin-rich thrombus completely occludes an epicardial coronary artery. The diagnosis of STEMI is based on clinical characteristics and persistent ST-segment elevation as demonstrated by 12-lead electrocardiography. Patients with STEMI should undergo rapid assessment for reperfusion therapy, and a reperfusion strategy should be implemented promptly after the patient's contact with the health care system. Two methods are currently available for establishing timely coronary reperfusion: primary percutaneous coronary intervention and fibrinolytic therapy. Percutaneous coronary intervention is the preferred method but is not always available. Antiplatelet agents and anticoagulants are critical adjuncts to reperfusion. This article summarizes the current evidence-based guidelines for the diagnosis and management of STEMI. This summary is followed by a brief discussion of the role of noninvasive stress testing in the assessment of patients with acute coronary syndrome and their selection for coronary revascularization. PMID:19880693

  13. Endovascular Mechanical Thrombectomy of an Occluded Superior Division Branch of the Left MCA for Acute Cardioembolic Stroke

    SciTech Connect

    Schumacher, H. C. Meyers, P. M.; Yavagal, D. R.; Harel, N. Y.; Elkind, M. S. V.; Mohr, J. P.; Pile-Spellman, J.

    2003-06-15

    Cardiac embolism accounts for a large proportion of ischemic stroke. Revascularization using systemic or intra-arterial thrombolysis is associated with increasing risks of cerebral hemorrhageas time passes from stroke onset. We report successful mechanicalthrombectomy from a distal branch of the middle cerebral artery (MCA)using a novel technique. A 72-year old man suffered an acute ischemic stroke from an echocardiographically proven ventricular thrombus due toa recent myocardial infarction. Intra-arterial administration of 4 mgrt-PA initiated at 5.7 hours post-ictus failed to recanalize an occluded superior division branch of the left MCA. At 6 hours,symptomatic embolic occlusion persisted. Mechanical extraction of the clot using an Attracter-18 device (Target Therapeutics, Freemont, CA) resulted in immediate recanalization of the MCA branch. Attracter-18 for acute occlusion of MCA branches may be considered in selected patients who fail conventional thrombolysis or are nearing closure of the therapeutic window for use of thrombolytic agents.

  14. Ultrasound enhanced thrombolysis in acute arterial ischemia.

    PubMed

    Tsivgoulis, Georgios; Culp, William C; Alexandrov, Andrei V

    2008-08-01

    In vitro and animal studies have shown that thrombolysis with intravenous tissue plasminogen activator (tPA) can be enhanced with ultrasound. Ultrasound delivers mechanical pressure waves to the clot, thus exposing more thrombus surface to circulating drug. Moreover, intravenous gaseous microspheres with ultrasound have been shown to be a potential alternative to fibrinolytic agents to recanalize discrete peripheral thrombotic arterial occlusions or acute arteriovenous graft thromboses. Small phase I-II randomized and non-randomized clinical trials have shown promising results concerning the potential applications of ultrasound-enhanced thrombolysis in the setting of acute cerebral ischemia. CLOTBUST was an international four-center phase II trial, which demonstrated that, in patients with acute ischemic stroke, transcranial Doppler (TCD) monitoring augments tPA-induced arterial recanalization (sustained complete recanalization rates: 38% vs. 13%) with a non-significant trend toward an increased rate of clinical recovery from stroke, as compared with placebo. The rates of symptomatic intracerebral hemorrhage (sICH) were similar in the active and placebo group (4.8% vs. 4.8%). Smaller single-center clinical trials using transcranial color-coded sonography (TCCD) reported recanalization rates ranging from 27% to 64% and sICH rates of 0-18%. A separate clinical trial evaluating the safety and efficacy of therapeutic low-frequency ultrasound was discontinued because of a concerning sICH rate of 36% in the active group. To further enhance the ability of tPA to break up thrombi, current ongoing clinical trials include phase II studies of a single beam 2 MHz TCD with perflutren-lipid microspheres. Moreover, potential enhancement of intra-arterial tPA delivery is being clinically tested with 1.7-2.1 MHz pulsed wave ultrasound (EKOS catheter) in ongoing phase II-III clinical trials. Intravenous platelet-targeted microbubbles with low-frequency ultrasound are currently

  15. Suprarenal inferior vena cava filter placement prior to transcatheter arterial embolization (TAE) of a renal cell carcinoma with large renal vein tumor thrombus: Prevention of pulmonary tumor emboli after TAE

    SciTech Connect

    Hirota, Shozo; Matsumoto, Shinnichi; Ichikawa, Satoshi; Tomita, Masaru; Koshino, Tukasa; Sako, Masao; Kono, Michio

    1997-03-15

    To prevent embolization of necrotic renal vein tumor after transcatheter embolization of a left renal cell carcinoma, we placed a suprarenal Bird's nest inferior vena cava filter. The patient tolerated the procedure well and had extensive tumor infarction including the tumor thrombus on 6-month follow-up computed tomography.

  16. Migration of a Central Venous Catheter in a Hemodialysis Patient Resulted in Left Atrial Perforation and Thrombus Formation Requiring Open Heart Surgery.

    PubMed

    Wong, Kevin; Marks, Barry A; Qureshi, Anwer; Stemm, Joseph J

    2016-07-01

    Central venous catheterization is widely used in patients on hemodialysis. A rare complication associated with the clinical use of central venous catheters is perforation of the heart or major vessels. We report a case of inadvertent perforation of the left atrium and thrombosis after the placement of a hemodialysis catheter in the right internal jugular vein. In such cases, surgical removal of the central venous catheter from perforation sites in the heart and vessel walls poses anesthetic challenges because of the high risk of pneumothorax, hemorrhage, arrhythmias, thrombosis, and death. PMID:27224040

  17. [Stroke from the Perspective of Neurologists (Part 2): Update in the Acute Therapy].

    PubMed

    Schur, Patrick; Luft, Andreas

    2016-05-11

    In the last praxis edition (9/2016) the article with the title “Neues in der Akutdiagnostik” reported about the relevant factors for the extension of thrombolytic procedures despite the usual inclusion criteria of thrombolysis. The rapid clinical and imaging identification of patients who benefit from endovascular therapy based on the “target mismatch” is an other key factor in the race against time. In addition the advantages of new mechanical devices allow to remove a thrombus quickly, completely and especially with better outcome. The recently published randomized controlled studies MR-CLEAN, EXTEND-IA, ESCAPE, SWIFT-PRIME and REVASCAT showed significant benefits of intra-arterial thrombolysis in patients with large artery occlusions. The following article discusses the state-of-the-art of the basic therapy and the major pathways of acute therapy. PMID:27167477

  18. Aggregation of red blood cells: From rouleaux to clot formation

    NASA Astrophysics Data System (ADS)

    Wagner, Christian; Steffen, Patrick; Svetina, Saša

    2013-06-01

    Red blood cells are known to form aggregates in the form of rouleaux. This aggregation process is believed to be reversible, but there is still no full understanding on the adhesion mechanism. There are at least two competing models, based either on bridging or on depletion. We review recent experimental results on the single cell level and theoretical analyses of the depletion model and of the influence of the cell shape on the adhesion strength. Another important aggregation mechanism is caused by activation of platelets. This leads to clot formation which is life-saving in the case of wound healing, but also a major cause of death in the case of a thrombus induced stroke. We review historical and recent results on the participation of red blood cells in clot formation.

  19. Stereotactic radiotherapy for the treatment of lung cancer with a giant left atrial tumor thrombus: A case report and literature review

    PubMed Central

    LI, YONG; LOU, JINRONG; QIU, SHUJUN; GUO, YUTIAN; PAN, MIANSHUN

    2016-01-01

    Lung cancer presenting with a giant atrial tumor thrombus is particularly rare. Surgical resection, aided by a cardiopulmonary bypass, is the standard treatment of choice if there is no distant metastasis. However, this form of surgery carries a high risk, with the subsequent patient prognosis being extremely poor. The current study describes the case of a 52-year-old man presenting with left lung squamous cell carcinoma that had extended into the left atrium. The patient was treated with stereotactic radiotherapy, and regarding the atrial disease, a complete response was achieved within 12 months. The present case demonstrates that stereotactic radiotherapy may be a beneficial palliative treatment for patients with stage IV lung cancer invading the left atrium. PMID:26998153

  20. THE IMPACT OF HISTOLOGY ON CLINICOPATHOLOGIC OUTCOMES FOR PATIENTS WITH RENAL CELL CARCINOMA AND VENOUS TUMOR THROMBUS: A MATCHED COHORT ANALYSIS

    PubMed Central

    Kaushik, Dharam; Linder, Brian J.; Thompson, R. Houston; Eisenberg, Manuel S.; Lohse, Christine M.; Cheville, John C.; Leibovich, Bradley C.; Boorjian, Stephen A.

    2013-01-01

    Objectives To evaluate the impact of tumor histology on clinicopathologic outcomes for patients with renal cell carcinoma (RCC) and venous tumor thrombus (VTT). Methods We identified 807 patients with RCC and VTT who underwent nephrectomy at our institution between 1970–2008. All pathologic specimens were re-reviewed by a single urologic pathologist. Patients with non-clear cell RCC (non-ccRCC) (n=56) were matched 1:2 to patients with clear cell RCC (ccRCC) VTT based onsymptoms at presentation, regional lymph node involvement, distant metastases, tumor thrombus level, nuclear grade and sarcomatoid differentiation. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Results The 56 patients with non-ccRCC VTT included 26 papillary, 11 chromophobe, 5 collecting duct tumors, and 14 RCC not otherwise specified. Compared to unmatched patients with ccRCC VTT (n=751), patients with non-ccRCC VTT presented with larger tumor size (p=0.02), higher nuclear grade (p=0.04), and more frequent sarcomatoid differentiation (p<0.001) and lymph node invasion (p<0.001). However, when patients with non-ccRCC were matched to patients with cc-RCC, no significant differences were noted with regard to 5-year metastases-free survival (41% versus 34%; p=0.24) or cancer-specific survival (25% versus 27%; p=0.97). Conclusions Non-ccRCC VTT is associated with a high rate of adverse pathologic features. Nevertheless, when matched to patients with ccRCC, patients with non-ccRCC VTT did not have increased rates of recurrence or adverse survival. Aggressive surgical resection represents the mainstay of treatment in these cases, while continued efforts to optimize a multimodal management approach to such patients remain necessary. PMID:23642851

  1. Acute kidney failure

    MedlinePlus

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  2. Acute arterial occlusion - kidney

    MedlinePlus

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidneys need a good blood supply. The main artery to the kidney is called the renal artery. ...

  3. Acute arterial occlusion - kidney

    MedlinePlus

    ... arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... often result in permanent kidney failure. Acute arterial occlusion of the renal artery can occur after injury ...

  4. Acute Lymphocytic Leukemia

    MedlinePlus

    ... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...

  5. CCL5 deficiency reduces neointima formation following arterial injury and thrombosis in apolipoprotein E-deficient mice.

    PubMed

    Czepluch, Frauke S; Meier, Julia; Binder, Claudia; Hasenfuss, Gerd; Schäfer, Katrin

    2016-08-01

    Activated platelets secrete different chemokines, among others CCL5, thereby triggering inflammatory cell recruitment into the vessel wall. Here, we investigated how CCL5 deficiency influences vascular remodeling processes. Experiments were performed in apolipoprotein E and CCL5 double deficient (ApoE(-/-)×CCL5(-/-)) mice, using ApoE(-/-)×CCL5(+/+) mice as controls. The ferric chloride model was applied to induce thrombosis at the site of carotid artery injury within minutes and the formation of a smooth muscle cell-rich neointima within 3weeks. In both groups, vascular injury resulted in thrombus formation. CCL5 deficiency did not alter thrombus resolution examined at day 7. Analysis at 21days revealed that CCL5 absence was associated with a significant reduction in the neointima area (p<0.05), neointima-to-media ratio (p<0.05) and lumen stenosis (p<0.05) compared to ApoE(-/-)×CCL5(+/+) mice. Immunohistochemical analysis of CCL5 receptors showed decreased CCR5 positive staining in ApoE(-/-)×CCL5(-/-) mice (p<0.01), whereas the amount of CCR1 (p=0.053) and Mac2-positive macrophages (p<0.05) was increased. The amount of SMA-positive smooth muscle cells was lower in ApoE(-/-) mice lacking CCL5 (p<0.05). Positive staining for Krüppel-like factor 4 (KLF4), an atheroprotective transcription factor, was increased in the neointima of ApoE(-/-)×CCL5(-/-) mice (p<0.05) and found to co-localize with smooth muscle cells. In summary, CCL5 deficiency resulted in reduced neointima formation after carotid artery injury and thrombosis. Hemodynamic and histochemical analyses suggested that this was not due to differences in thrombus formation or resolution. Possibly, the atheroprotective effect of CCL5 deficiency is mediated by KLF4 upregulation in smooth muscle cells. PMID:27337700

  6. Imaging of Acute Pancreatitis.

    PubMed

    Thoeni, Ruedi F

    2015-11-01

    Acute pancreatitis is an acute inflammation of the pancreas. Several classification systems have been used in the past but were considered unsatisfactory. A revised Atlanta classification of acute pancreatitis was published that assessed the clinical course and severity of disease; divided acute pancreatitis into interstitial edematous pancreatitis and necrotizing pancreatitis; discerned an early phase (first week) from a late phase (after the first week); and focused on systemic inflammatory response syndrome and organ failure. This article focuses on the revised classification of acute pancreatitis, with emphasis on imaging features, particularly on newly-termed fluid collections and implications for the radiologist. PMID:26526433

  7. Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke.

    PubMed

    Martynov, Mikhail Yu; Gusev, Eugeny I

    2015-01-01

    Ischemic stroke is one of the leading causes of long-lasting disability and death. Two main strategies have been proposed for the treatment of ischemic stroke: restoration of blood flow by thrombolysis or mechanical thrombus extraction during the first few hours of ischemic stroke, which is one of the most effective treatments and leads to a better functional and clinical outcome. The other direction of treatment, which is potentially applicable to most of the patients with ischemic stroke, is neuroprotection. Initially, neuroprotection was mainly targeted at protecting gray matter, but during the past few years there has been a transition from a neuron-oriented approach toward salvaging the whole neurovascular unit using multimodal drugs. Citicoline is a multimodal drug that exhibits neuroprotective and neuroregenerative effects in a variety of experimental and clinical disorders of the central nervous system, including acute and chronic cerebral ischemia, intracerebral hemorrhage, and global cerebral hypoxia. Citicoline has a prolonged therapeutic window and is active at various temporal and biochemical stages of the ischemic cascade. In acute ischemic stroke, citicoline provides neuroprotection by attenuating glutamate exitotoxicity, oxidative stress, apoptosis, and blood-brain barrier dysfunction. In the subacute and chronic phases of ischemic stroke, citicoline exhibits neuroregenerative effects and activates neurogenesis, synaptogenesis, and angiogenesis and enhances neurotransmitter metabolism. Acute and long-term treatment with citicoline is safe and in most clinical studies is effective and improves functional outcome. PMID:27186142

  8. Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke

    PubMed Central

    Martynov, Mikhail Yu; Gusev, Eugeny I

    2015-01-01

    Ischemic stroke is one of the leading causes of long-lasting disability and death. Two main strategies have been proposed for the treatment of ischemic stroke: restoration of blood flow by thrombolysis or mechanical thrombus extraction during the first few hours of ischemic stroke, which is one of the most effective treatments and leads to a better functional and clinical outcome. The other direction of treatment, which is potentially applicable to most of the patients with ischemic stroke, is neuroprotection. Initially, neuroprotection was mainly targeted at protecting gray matter, but during the past few years there has been a transition from a neuron-oriented approach toward salvaging the whole neurovascular unit using multimodal drugs. Citicoline is a multimodal drug that exhibits neuroprotective and neuroregenerative effects in a variety of experimental and clinical disorders of the central nervous system, including acute and chronic cerebral ischemia, intracerebral hemorrhage, and global cerebral hypoxia. Citicoline has a prolonged therapeutic window and is active at various temporal and biochemical stages of the ischemic cascade. In acute ischemic stroke, citicoline provides neuroprotection by attenuating glutamate exitotoxicity, oxidative stress, apoptosis, and blood–brain barrier dysfunction. In the subacute and chronic phases of ischemic stroke, citicoline exhibits neuroregenerative effects and activates neurogenesis, synaptogenesis, and angiogenesis and enhances neurotransmitter metabolism. Acute and long-term treatment with citicoline is safe and in most clinical studies is effective and improves functional outcome. PMID:27186142

  9. Acute loss of consciousness.

    PubMed

    Tristán, Bekinschtein; Gleichgerrcht, Ezequiel; Manes, Facundo

    2015-01-01

    Acute loss of consciousness poses a fascinating scenario for theoretical and clinical research. This chapter introduces a simple yet powerful framework to investigate altered states of consciousness. We then explore the different disorders of consciousness that result from acute brain injury, and techniques used in the acute phase to predict clinical outcome in different patient populations in light of models of acute loss of consciousness. We further delve into post-traumatic amnesia as a model for predicting cognitive sequels following acute loss of consciousness. We approach the study of acute loss of consciousness from a theoretical and clinical perspective to conclude that clinicians in acute care centers must incorporate new measurements and techniques besides the classic coma scales in order to assess their patients with loss of consciousness. PMID:25702218

  10. Free-floating left atrial ball thrombus after mitral valve replacement with patent coronary artery bypass grafts: successful removal by a right minithoracotomy approach without aortic cross-clamp.

    PubMed

    Hisatomi, Kazuki; Hashizume, Koji; Tanigawa, Kazuyoshi; Miura, Takashi; Matsukuma, Seiji; Yokose, Shogo; Kitamura, Tessho; Shimada, Takashi; Eishi, Kiyoyuki

    2016-06-01

    A free-floating thrombus in the left atrium without attachment to either the atrial wall or the mitral valve is extremely rare. We describe a case in a 79-year-old woman with chronic atrial fibrillation and a recent stroke who had undergone mitral valve replacement 25 years previously and coronary artery bypass grafting 5 years previously. Redo cardiac surgery represents a clinical challenge due to a higher rate of peri-operative morbidity and mortality. Median re-sternotomy can be particularly difficult in patients with functioning coronary artery grafts, where the risk of graft injury is a significant concern. Prompt surgical intervention was carried out, and to avoid the challenge of re-sternotomy in this patient with two prior thoracotomies, we successfully removed the thrombus by a right minithoracotomy approach without aortic cross-clamping. There was no postoperative occurrence of a new stroke or aggravation of the pre-existing stroke. PMID:25098689

  11. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  12. Acute kidney injury due to decompression illness.

    PubMed

    Viecelli, Andrea; Jamboti, Jagadish; Waring, Andrew; Banham, Neil; Ferrari, Paolo

    2014-08-01

    Decompression illness is a rare but serious complication of diving caused by intravascular or extravascular gas bubble formation. We report the first case of acute kidney injury in a 27-year-old diver following three rapid ascents. He presented with transient neurological symptoms and abdominal pain followed by rapidly progressive acute kidney injury (creatinine peak 1210 µmol/L) due to arterial air emboli. He received supportive care and 100% oxygen followed by hyperbaric therapy and recovered fully. Arterial air emboli caused by rapid decompression can affect multiple organs including the kidneys. Early transfer to a hyperbaric unit is important as complications may present delayed. PMID:25852912

  13. Acute kidney injury due to decompression illness

    PubMed Central

    Viecelli, Andrea; Jamboti, Jagadish; Waring, Andrew; Banham, Neil; Ferrari, Paolo

    2014-01-01

    Decompression illness is a rare but serious complication of diving caused by intravascular or extravascular gas bubble formation. We report the first case of acute kidney injury in a 27-year-old diver following three rapid ascents. He presented with transient neurological symptoms and abdominal pain followed by rapidly progressive acute kidney injury (creatinine peak 1210 µmol/L) due to arterial air emboli. He received supportive care and 100% oxygen followed by hyperbaric therapy and recovered fully. Arterial air emboli caused by rapid decompression can affect multiple organs including the kidneys. Early transfer to a hyperbaric unit is important as complications may present delayed. PMID:25852912

  14. Characterisation of a novel cell line (CSQT-2) with high metastatic activity derived from portal vein tumour thrombus of hepatocellular carcinoma

    PubMed Central

    Wang, T; Hu, H S; Feng, Y X; Shi, J; Li, N; Guo, W X; Xue, J; Xie, D; Liu, S R; Wu, M C; Cheng, S Q

    2010-01-01

    Background: Portal vein tumour thrombus (PVTT) is highly associated with the progression and metastasis of hepatocellular carcinoma (HCC). However, there are no appropriate cell models of PVTT with which to study the biological and physiological characteristics of PVTT. Methods: Primary cell culture was performed by the use of a successive xenograft line called PVTT-#1, which was obtained from a 60-year-old male HCC patient accompanied by PVTT. Results: A successive cell line named CSQT-2 was established. The cell line showed aggressive phenotypes in terms of cell growth, survival, migration, xenograft and metastasis. Moreover, an orthotopic transplantation assay showed that PVTT can be generated in nude mice when CSQT-2 cells were inoculated in the liver and that it shows a typical migratory tendency in the vascular branches of portal vein. Moreover, the established CSQT-2 cells also showed varied expression of tumour-initiating cell (TIC) markers such as CD133, CD90 and EpCAM. Conclusion: Establishment of CSQT-2 may provide a suitable model with which to investigate the molecular mechanisms of PVTT-related HCC. PMID:20461085

  15. Platelet thrombosis in cardiac-valve prostheses

    SciTech Connect

    Dewanjee, M.K.

    1989-01-01

    The contribution of platelets and clotting factors in thrombosis on cardiovascular prostheses had been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and patients with indium-111, Technetium-99m labeled platelets, iodine-123, iodine-131 labeled fibrinogen, and In-111 and Tc-99m labeled antibody to the fibrinogen-receptor on the platelet- membrane, or fibrin. The early studies demonstrated that certain platelet-inhibitors, e.g. sulfinpyrazone, aspirin or aspirin- persantine increased platelet survival time with mechanical valves implanted in the baboon model and patients. Thrombus localization by imaging is possible for large thrombus on thrombogenic surface of prosthesis in the acute phase. The majority of thrombus was found in the sewing ring (Dacron) in the acute phase in both the mechanical and tissue valves. The amount of retained thrombus in both mechanical and tissue valves in our one-day study in the dog model was similar (< 1% if injected In-111 platelets = 5 billion platelets). As the fibrous ingrowth covered the sewing ring, the thrombus formation decreased significantly. Only a small amount of thrombus was found on the leaflets at one month in both the dog and calf models. 38 refs., 9 figs., 5 tabs.

  16. Acute Arterial Emergencies

    PubMed Central

    Dagnone, L. E.; Brown, P. M.

    1983-01-01

    The response of the primary care physician in the initial assessment and management of acute arterial injuries will often be the deciding factor in survival of life, limb or organ system. Most arterial emergencies occur as a result of trauma, disruption of vessel wall and/or occlusion of flow. The common clinical syndromes of acute arterial emergencies are injuries to and beyond the aorta, acute aortic dissection, ruptured aortic aneurysm, and thromboembolic occlusive arterial disease. The role of arteriography and the urgency of definitive surgical repair in acute arterial emergencies is summarized. PMID:21283323

  17. Multimodality Intravascular Imaging Assessment of Plaque Erosion versus Plaque Rupture in Patients with Acute Coronary Syndrome

    PubMed Central

    Kwon, Jee Eun; Mintz, Gary S.; Hong, Young Joon; Lee, Sung Yun; Kim, Ki Seok; Hahn, Joo-Yong; Kumar, Kaup Sharath; Won, Hoyoun; Hyeon, Seong Hyeop; Shin, Seung Yong; Lee, Kwang Je; Kim, Tae Ho; Kim, Chee Jeong; Kim, Sang Wook

    2016-01-01

    Background and Objectives We assessed plaque erosion of culprit lesions in patients with acute coronary syndrome in real world practice. Subjects and Methods Culprit lesion plaque rupture or plaque erosion was diagnosed with optical coherence tomography (OCT). Intravascular ultrasound (IVUS) was used to determine arterial remodeling. Positive remodeling was defined as a remodeling index (lesion/reference EEM [external elastic membrane area) >1.05. Results A total of 90 patients who had plaque rupture showing fibrous-cap discontinuity and ruptured cavity were enrolled. 36 patients showed definite OCT-plaque erosion, while 7 patients had probable OCT-plaque erosion. Overall, 26% (11/43) of definite/probable plaque erosion had non-ST elevation myocardial infarction (NSTEMI) while 35% (15/43) had ST elevation myocardial infarction (STEMI). Conversely, 14.5% (13/90) of plaque rupture had NSTEMI while 71% (64/90) had STEMI (p<0.0001). Among plaque erosion, white thrombus was seen in 55.8% (24/43) of patients and red thrombus in 27.9% (12/43) of patients. Compared to plaque erosion, plaque rupture more often showed positive remodeling (p=0.003) with a larger necrotic core area examined by virtual histology (VH)-IVUS, while negative remodeling was prominent in plaque erosion. Overall, 65% 28/43 of plaque erosions were located in the proximal 30 mm of a culprit vessel-similar to plaque ruptures (72%, 65/90, p=0.29). Conclusion Although most of plaque erosions show nearly normal coronary angiogram, modest plaque burden with negative remodeling and an uncommon fibroatheroma might be the nature of plaque erosion. Multimodality intravascular imaging with OCT and VH-IVUS showed fundamentally different pathoanatomic substrates underlying plaque rupture and erosion. PMID:27482258

  18. Acute phase reaction and acute phase proteins*

    PubMed Central

    Gruys, E.; Toussaint, M.J.M.; Niewold, T.A.; Koopmans, S.J.

    2005-01-01

    A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations. PMID:16252337

  19. Resolution of Acute Inflammation In The Lung

    PubMed Central

    Levy, Bruce D.; Serhan, Charles N.

    2015-01-01

    Acute inflammation in the lung is essential to health. So too is its resolution. In response to invading microbes, noxious stimuli or tissue injury, an acute inflammatory response is mounted to protect the host. To limit inflammation and prevent collateral injury of healthy, uninvolved tissue, the lung orchestrates the formation of specialized pro-resolving mediators, specifically lipoxins, resolvins, protectins and maresins. These immunoresolvents are agonists for resolution that interact with specific receptors on leukocytes and structural cells to blunt further inflammation and promote catabasis. This process appears to be defective in several common lung diseases that are characterized by excess or chronic inflammation. Here, we review the molecular and cellular effectors of resolution of acute inflammation in the lung. PMID:24313723

  20. Resolution of acute inflammation in the lung.

    PubMed

    Levy, Bruce D; Serhan, Charles N

    2014-01-01

    Acute inflammation in the lung is essential to health. So too is its resolution. In response to invading microbes, noxious stimuli, or tissue injury, an acute inflammatory response is mounted to protect the host. To limit inflammation and prevent collateral injury of healthy, uninvolved tissue, the lung orchestrates the formation of specialized proresolving mediators, specifically lipoxins, resolvins, protectins, and maresins. These immunoresolvents are agonists for resolution that interact with specific receptors on leukocytes and structural cells to blunt further inflammation and promote catabasis. This process appears to be defective in several common lung diseases that are characterized by excess or chronic inflammation. Here, we review the molecular and cellular effectors of resolution of acute inflammation in the lung. PMID:24313723

  1. Pathobiochemical mechanisms during the acute phase response.

    PubMed

    Kleesiek, K; Greiling, H

    1984-01-01

    The acute phase response is characterised by the following sequence of principle phenomena: (1) an early local inflammatory reaction, (2) formation of inflammatory humoral factors inducing a systemic reaction, (3) stimulation of glycoprotein synthesis predominantly in the hepatocytes, and (4) an increase in the plasma concentration of acute phase proteins, when the rate of biosynthesis exceeds the degradation rate. Inflammatory mediators (lysosomal enzymes, oxygen derived radicals, prostaglandins) are mainly released during phagocytosis by granulocytes and macrophages. The signal reaching the hepatocytes is not yet clearly identified. A leukocyte endogenous mediator (LEM) released by macrophages is described. There is evidence that prostaglandins and probably proteinase alpha 2-macroglobulin complexes are also involved. The hepatic acute phase protein synthesis is modulated by hormones (insulin, cortisol, somatotropin). The biochemical events in the hepatocyte include an increase in protein synthesis and the regulatory control of the glycosylation of polypeptide precursors. The secreted glycoproteins serve variously as inhibitors or mediators of the inflammatory processes. PMID:6208159

  2. Acute kidney injury.

    PubMed

    Lang, Joanna; Zuber, Kim; Davis, Jane

    2016-04-01

    Acute kidney injury (AKI) complicates up to 20% of all hospital admissions. Responding to the increase in admissions, complications, mortality, morbidity, and cost of AKI, Kidney Disease: Improving Global Outcomes convened an expert panel to study the issue, review the literature, and publish guidelines to evaluate and treat patients with AKI in the acute setting. This article reviews those guidelines. PMID:27023656

  3. Acute Disseminated Encephalomyelitis.

    PubMed

    Gray, Matthew Philip; Gorelick, Marc H

    2016-06-01

    Acute disseminated encephalomyelitis is a primarily pediatric, immune-mediated disease characterized by demyelination and polyfocal neurologic symptoms that typically occur after a preceding viral infection or recent immunization. This article presents the pathophysiology, diagnostic criteria, and magnetic resonance imaging characteristics of acute disseminated encephalomyelitis. We also present evaluation and management strategies. PMID:27253358

  4. Poznan acute Astronomical Observatory

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    This Poznan acute Astronomical Observatory is a unit of the Adam Mickiewicz University, located in Poznan acute, Poland. From its foundation in 1919, it has specialized in astrometry and celestial mechanics (reference frames, dynamics of satellites and small solar system bodies). Recently, research activities have also included planetary and stellar astrophysics (asteroid photometry, catalysmic b...

  5. Concept Formation.

    ERIC Educational Resources Information Center

    Vaidya, Narendera

    This document, published in India by the Regional College of Education, deals with 13 subjects: the tough context (thinking), definitions of concept, functions of concept, the process of concept formation, discriminant learning, mediation process, second signalling system, factors affecting concept formation, studies in concept formation, the…

  6. Optimal medical therapy for secondary prevention after an acute coronary syndrome: 18-month follow-up results at a tertiary teaching hospital in South Korea

    PubMed Central

    Byeon, Hee Ja; Yang, Young-Mo; Choi, Eun Joo

    2016-01-01

    Background Acute coronary syndrome (ACS) is a fatal cardiovascular disease caused by atherosclerotic plaque erosion or rupture and formation of coronary thrombus. The latest guidelines for ACS recommend the combined drug regimen, comprising aspirin, P2Y12 inhibitor, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, β-blocker, and statin, at discharge after ACS treatment to reduce recurrent ischemic cardiovascular events. This study aimed to examine prescription patterns of secondary prevention drugs in Korean patients with ACS after hospital discharge, to access the appropriateness of secondary prevention drug therapy for ACS, and to evaluate whether to persistently use discharge medications for 18 months. Methods This study was retrospectively conducted with the patients who were discharged from the tertiary hospital, located in South Korea, after ACS treatment between September 2009 and August 2013. Data were collected through electronic medical record. Results Among 3,676 patients during the study period, 494 were selected based on inclusion and exclusion criteria. The regimen of aspirin + clopidogrel + β-blocker + angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker + statin was prescribed to 374 (75.71%) patients with ACS at discharge. Specifically, this regimen was used in 177 (69.69%) unstable angina patients, 44 (70.97%) non-ST-segment elevation myocardial infarction patients, and 153 (85.96%) ST-segment elevation myocardial infarction patients. Compared with the number of ACS patients with all five guideline-recommended drugs at discharge, the number of ACS patients using them 12 (n=169, 34.21%) and 18 (n=105, 21.26%) months after discharge tended to be gradually decreased. Conclusion The majority of ACS patients in this study received all five guideline-recommended medications at discharge from the hospital. However, the frequency of using all of them had been gradually decreased 3, 6, 12, and 18 months after

  7. Imaging Plaques to Predict and Better Manage Patients with Acute Coronary Events

    PubMed Central

    Garcia-Garcia, Hector M.; Jang, Ik-Kyung; Serruys, Patrick W.; Kovacic, Jason C.; Narula, Jagat; Fayad, Zahi A.

    2014-01-01

    Culprit lesions of patients who have had an acute coronary syndrome commonly are ruptured coronary plaques with superimposed thrombus. The precursor of such lesions is an inflamed thin-capped fibroatheroma. These plaques can be imaged by means of invasive techniques such as intravascular ultrasound (and derived techniques), optical coherence tomography and near-infrared spectroscopy. Very often these patients exhibit similar (multiple) plaques beyond the culprit lesion. These remote plaques can be assessed non invasively by computed tomography angiography and magnetic resonance imaging and also using invasive imaging. The detection of these remote plaques is not only feasible, but also in natural history studies have been associated with clinical coronary events. Different systemic pharmacological treatments have been studied (mostly statins) with modest success and therefore newer approaches are being tested. Local treatment for such lesions is in its infancy and larger, prospective and randomized trials are needed. This review will describe the pathological and imaging findings in culprit lesions of patients with acute coronary syndrome and as well as the assessment of remote plaques. In addition, the pharmacological and local treatment options will be reviewed. PMID:24902974

  8. Role of imaging in current acute ischemic stroke workflow for endovascular therapy.

    PubMed

    Menon, Bijoy K; Campbell, Bruce C V; Levi, Christopher; Goyal, Mayank

    2015-06-01

    Ischemic stroke is caused by a thrombus that blocks an intracranial artery. Brain tissue beyond the blocked artery survives for a variable period of time because of blood and nutrients received through tiny vessels called collaterals. Imaging the brain and the vasculature that supplies it is therefore a vital first step in treating patients with acute ischemic stroke. In this review, we focus on current evidence for imaging selection of patients for endovascular therapy in the context of the recently positive clinical trials, such as Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing Computed Tomography to Recanalization Times (ESCAPE), Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), and Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA). We discuss evidence for and use of the various imaging paradigms available. We discuss how to set up quick and efficient imaging protocols for patient selection and address common concerns about the use of imaging, including time spent, contrast, radiation, and other advantages and disadvantages. Finally, we briefly comment on how imaging can integrate itself within various health systems of care in the future, thereby potentially improving patient outcomes further. PMID:25944319

  9. Systematic review and meta-analysis of outcomes after liver resection in patients with hepatocellular carcinoma (HCC) with and without bile duct thrombus

    PubMed Central

    Navadgi, Suresh; Chang, Chi-Chun; Bartlett, Adam; McCall, John; Pandanaboyana, Sanjay

    2016-01-01

    Introduction This meta-analysis aimed to compare perioperative and survival outcomes in patients who underwent hepatectomy with and without Bile Duct Tumour Thrombus (BDTT). Methods A comprehensive search of Cochrane Library, PubMed, MEDLINE and EMBASE was performed to identify relevant articles. The perioperative, postoperative and long term outcomes were compared. Results Eleven studies including 6051 patients met the inclusion criteria. The perioperative outcomes were comparable between the 2 groups. The BDTT group had higher proportion poorly differentiated tumours (OR = 1.87, X2 = 10.00, df = 6, p = 0.002, I2 = 40%), Lymphovascular invasion (LVI) (OR = 4.85, X2 = 28.21, df = 9, p = <0.001, I2 = 68%) and Macrovascular invasion (MVI) (OR = 5.41, X2 = 8.73, df = 9, p = <0.001, I2 = 0%). There was no difference in 1 and 3 year survival, however 5-yr survival was poorer in the BDTT group (OR = 0.37, X2 = 37.04, df = 7, p = <0.001, I2 = 81%). The mean difference (MD) in overall survival in the BDTT group was −20 months [−32.31, −7.06], p = 0.002, I2 = 95%. Conclusion Patients with HCC with BDTT had more advanced stage HCC with adverse histological features including higher rates of MVI, LVI and poor differentiation. Hepatectomy in this group of patients offers similar survival at 3 years but inferior long-term survival and should be considered when feasible. PMID:27037199

  10. Differential Expression of Prognostic Proteomic Markers in Primary Tumour, Venous Tumour Thrombus and Metastatic Renal Cell Cancer Tissue and Correlation with Patient Outcome

    PubMed Central

    Laird, Alexander; O’Mahony, Fiach C.; Nanda, Jyoti; Riddick, Antony C. P.; O’Donnell, Marie; Harrison, David J.; Stewart, Grant D.

    2013-01-01

    Renal cell carcinoma (RCC) is the most deadly of urological malignancies. Metastatic disease affects one third of patients at diagnosis with a further third developing metastatic disease after extirpative surgery. Heterogeneity in the clinical course ensures predicting metastasis is notoriously difficult, despite the routine use of prognostic clinico-pathological parameters in risk stratification. With greater understanding of pathways involved in disease pathogenesis, a number of biomarkers have been shown to have prognostic significance, including Ki67, p53, vascular endothelial growth factor receptor 1 (VEGFR1) and ligand D (VEGFD), SNAIL and SLUG. Previous pathway analysis has been from study of the primary tumour, with little attention to the metastatic tumours which are the focus of targeted molecular therapies. As such, in this study a tissue microarray from 177 patients with primary renal tumour, renal vein tumour thrombus and/or RCC metastasis has been created and used with Automated Quantitative Analysis (AQUA) of immunofluorescence to study the prognostic significance of these markers in locally advanced and metastatic disease. Furthermore, this has allowed assessment of differential protein expression between the primary tumours, renal vein tumour thrombi and metastases. The results demonstrate that clinico-pathological parameters remain the most significant predictors of cancer specific survival; however, high VEGFR1 or VEGFD can predict poor cancer specific survival on univariate analysis for locally advanced and metastatic disease. There was significantly greater expression of Ki67, p53, VEGFR1, SLUG and SNAIL in the metastases compared with the primary tumours and renal vein tumour thrombi. With the exception of p53, these differences in protein expression have not been shown previously in RCC. This confirms the importance of proliferation, angiogenesis and epithelial to mesenchymal transition in the pathogenesis and metastasis of RCC. Importantly

  11. Catheter-Directed Thrombolysis via Small Saphenous Veins for Treating Acute Deep Venous Thrombosis

    PubMed Central

    Yang, Bin; Xu, Xiao-dong; Gao, Peng; Yu, Ji-Xiang; Li, Yu; Zhu, Ai-Dong; Meng, Ran-ran

    2016-01-01

    Background There is little data comparing catheter-directed thrombolysis (CDT) via small saphenous veins vs. systematic thrombolysis on complications and efficacy in acute deep venous thrombosis patients. The aim of our study was to compare the efficacy and safety of CDT via the small saphenous veins with systematic thrombolysis for patients with acute deep venous thrombosis (DVT). Material/Methods Sixty-six patients with acute DVT admitted from June 2012 to December 2013 were divided into 2 groups: 27 patients received systemic thrombolysis (ST group) and 39 patients received CDT via the small saphenous veins (CDT group). The thrombolysis efficiency, limb circumference differences, and complications such as post-thrombotic syndrome (PTS) in the 2 groups were recorded. Results The angiograms demonstrated that all or part of the fresh thrombus was dissolved. There was a significant difference regarding thrombolysis efficiency between the CDT group and ST group (71.26% vs. 48.26%, P=0.001). In both groups the postoperative limb circumference changes were higher compared to the preoperative values. The differences between postoperative limb circumferences on postoperative days 7 and 14 were significantly higher in the CDT group than in the ST group (all P<0.05). The incidence of postoperative PTS in the CDT group (17.9%) was significantly lower in comparison to the ST group (51.85%) during the follow-up (P=0.007). Conclusions Catheter-directed thrombolysis via the small saphenous veins is an effective, safe, and feasible approach for treating acute deep venous thrombosis. PMID:27552357

  12. Catheter-Directed Thrombolysis via Small Saphenous Veins for Treating Acute Deep Venous Thrombosis.

    PubMed

    Yang, Bin; Xu, Xiao-Dong; Gao, Peng; Yu, Ji-Xiang; Li, Yu; Zhu, Ai-Dong; Meng, Ran-Ran

    2016-01-01

    BACKGROUND There is little data comparing catheter-directed thrombolysis (CDT) via small saphenous veins vs. systematic thrombolysis on complications and efficacy in acute deep venous thrombosis patients. The aim of our study was to compare the efficacy and safety of CDT via the small saphenous veins with systematic thrombolysis for patients with acute deep venous thrombosis (DVT). MATERIAL AND METHODS Sixty-six patients with acute DVT admitted from June 2012 to December 2013 were divided into 2 groups: 27 patients received systemic thrombolysis (ST group) and 39 patients received CDT via the small saphenous veins (CDT group). The thrombolysis efficiency, limb circumference differences, and complications such as post-thrombotic syndrome (PTS) in the 2 groups were recorded. RESULTS The angiograms demonstrated that all or part of the fresh thrombus was dissolved. There was a significant difference regarding thrombolysis efficiency between the CDT group and ST group (71.26% vs. 48.26%, P=0.001). In both groups the postoperative limb circumference changes were higher compared to the preoperative values. The differences between postoperative limb circumferences on postoperative days 7 and 14 were significantly higher in the CDT group than in the ST group (all P<0.05). The incidence of postoperative PTS in the CDT group (17.9%) was significantly lower in comparison to the ST group (51.85%) during the follow-up (P=0.007). CONCLUSIONS Catheter-directed thrombolysis via the small saphenous veins is an effective, safe, and feasible approach for treating acute deep venous thrombosis. PMID:27552357

  13. Acute Hepatic Porphyria

    PubMed Central

    Bissell, D. Montgomery; Wang, Bruce

    2015-01-01

    The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting. PMID:26357631

  14. [PREVENTION AND CORRECTION OF PULMONARY COMPLICATIONS FOR SEVERE ACUTE PANCREATITIS].

    PubMed

    Fedorkiv, M B

    2015-06-01

    Increased of proinflammatory cytokines levels, including interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) on severe acute pancreatitis causes vasodilatation, increased permeability of the wall, accumulation of fluid in lung tissue and pleural sinuses. Transudate from acute parapancreatyc clusters of hot liquid and abdomen falls into the chest cavity through microscopic defects in the diaphragm due to the formation of pathological pleural-peritoneal connections or the relevant pressure gradient between the abdominal and pleural cavities. Remediation and removal of acute parapancreatyc clusters combined with the use of a multicomponent drug infusion therapy Cytoflavin provide a reduction in the frequency of pulmonary complications of acute pancreatitis from 48.3 to 31.0%. Use of the drug Cytoflavin reduces the severity of endogenous intoxication and mortality from acute lung injury from 12.9 to 6.1%. PMID:26521460

  15. Acute Lung Failure

    PubMed Central

    Mac Sweeney, Rob; McAuley, Daniel F.; Matthay, Michael A.

    2013-01-01

    Lung failure is the most common organ failure seen in the intensive care unit. The pathogenesis of acute respiratory failure (ARF) can be classified as (1) neuromuscular in origin, (2) secondary to acute and chronic obstructive airway diseases, (3) alveolar processes such as cardiogenic and noncardiogenic pulmonary edema and pneumonia, and (4) vascular diseases such as acute or chronic pulmonary embolism. This article reviews the more common causes of ARF from each group, including the pathological mechanisms and the principles of critical care management, focusing on the supportive, specific, and adjunctive therapies for each condition. PMID:21989697

  16. Acute porphyric disorders.

    PubMed

    Moore, A W; Coke, J M

    2000-09-01

    Acute porphyrias are classified into 3 distinct groups of rare genetic disorders of metabolic enzyme biosynthesis. Acute porphyrias can significantly impact multiple organ systems, which often provides a challenge to the dentist presented with such a patient. A case of hereditary coproporphyria is reported in a patient with many of the classical signs and symptoms. The patient also had complex dental needs that required special medical and pharmacotherapeutic modifications. The acute porphyrias are reviewed by the authors with presentation of this challenging case. Recommendations for other dental health care professionals encountering these patients are then presented. PMID:10982942

  17. A Coin-Like Peripheral Small Cell Lung Carcinoma Associated with Acute Paraneoplastic Axonal Guillain-Barre-Like Syndrome

    PubMed Central

    Jung, Ioan; Gurzu, Simona; Balasa, Rodica; Motataianu, Anca; Contac, Anca Otilia; Halmaciu, Ioana; Popescu, Septimiu; Simu, Iunius

    2015-01-01

    Abstract A 65-year-old previously healthy male heavy smoker was hospitalized with a 2-week history of progressive muscle weakness in the lower and upper extremities. After 10 days of hospitalization, urinary sphincter incompetence and fecal incontinence were added and tetraparesis was established. The computer-tomography scan examination revealed a massive right hydrothorax and multifocal solid acinar structures with peripheral localization in the left lung, which suggested pulmonary cancer. Bone marrow metastases were also suspected. Based on the examination results, the final diagnosis was acute paraneoplastic axonal Guillain-Barre-like syndrome. The patient died 3 weeks after hospitalization. At autopsy, bronchopneumonia and a right hydrothorax were confirmed. Several 4 to 5-mm-sized round peripherally located white nodules were identified in the left lung, without any central tumor mass. Under microscope, a coin-shaped peripheral/subpleural small cell carcinoma was diagnosed, with generalized bone metastases. A huge thrombus in the abdominal aorta and acute pancreatitis was also seen at autopsy. This case highlights the difficulty of diagnosis of lung carcinomas and the necessity of a complex differential diagnosis of severe progressive ascending neuropathies. This is the 6th reported case of small cell lung cancer-associated acute Guillain-Barre-like syndrome and the first report about an association with a coin-like peripheral pattern. PMID:26039124

  18. A coin-like peripheral small cell lung carcinoma associated with acute paraneoplastic axonal Guillain-Barre-like syndrome.

    PubMed

    Jung, Ioan; Gurzu, Simona; Balasa, Rodica; Motataianu, Anca; Contac, Anca Otilia; Halmaciu, Ioana; Popescu, Septimiu; Simu, Iunius

    2015-06-01

    A 65-year-old previously healthy male heavy smoker was hospitalized with a 2-week history of progressive muscle weakness in the lower and upper extremities. After 10 days of hospitalization, urinary sphincter incompetence and fecal incontinence were added and tetraparesis was established. The computer-tomography scan examination revealed a massive right hydrothorax and multifocal solid acinar structures with peripheral localization in the left lung, which suggested pulmonary cancer. Bone marrow metastases were also suspected. Based on the examination results, the final diagnosis was acute paraneoplastic axonal Guillain-Barre-like syndrome. The patient died 3 weeks after hospitalization. At autopsy, bronchopneumonia and a right hydrothorax were confirmed. Several 4 to 5-mm-sized round peripherally located white nodules were identified in the left lung, without any central tumor mass. Under microscope, a coin-shaped peripheral/subpleural small cell carcinoma was diagnosed, with generalized bone metastases. A huge thrombus in the abdominal aorta and acute pancreatitis was also seen at autopsy. This case highlights the difficulty of diagnosis of lung carcinomas and the necessity of a complex differential diagnosis of severe progressive ascending neuropathies. This is the 6th reported case of small cell lung cancer-associated acute Guillain-Barre-like syndrome and the first report about an association with a coin-like peripheral pattern. PMID:26039124

  19. Simultaneous measurement of thrombin generation and fibrin formation