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thrombus stability

Diana A Gorog
The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications...
March 17, 2018: Journal of Thrombosis and Thrombolysis
Frédéric Adam, Alexandre Kauskot, Mathieu Kurowska, Nicolas Goudin, Isabelle Munoz, Jean-Claude Bordet, Jian-Dong Huang, Marijke Bryckaert, Alain Fischer, Delphine Borgel, Geneviève de Saint Basile, Olivier D Christophe, Gaël Ménasché
OBJECTIVE: Platelet secretion is crucial for many physiological platelet responses. Even though several regulators of the fusion machinery for secretory granule exocytosis have been identified in platelets, the underlying mechanisms are not yet fully characterized. APPROACH AND RESULTS: By studying a mouse model (cKO [conditional knockout]Kif5b ) lacking Kif5b (kinesin-1 heavy chain) in its megakaryocytes and platelets, we evidenced unstable hemostasis characterized by an increase of blood loss associated to a marked tendency to rebleed in a tail-clip assay and thrombus instability in an in vivo thrombosis model...
March 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Sadaaki Horiguchi, Hisako Ono, Hiroyuki Shirato, Toshimitsu Kawakami, Shiho Yabuki, Naomi Morita, Nozomu Shirasugi
In our varicose vein center, on a trial basis, among the patients with asymptomatic calf deep vein thrombosis (CDVT) we carefully selected the patients for varicose vein surgery using the requirements as follows; 1) the patients had varicose veins with incompetent saphenous veins, 2) sequential examination including DUS confirmed stability and clinical insignificance of asymptomatic CDVT, 3) the patients do not have any risk factors for DVT such as a coagulation profile disorder (antithrombin deficiency, protein C deficiency, protein S deficiency, or antiphospholipid syndrome) or malignancies, 4) surgery is possible under local anesthesia alone, and 5) the patients can understand the concept of asymptomatic CDVT and undergo the surgery on their own will and informed consent...
December 25, 2017: Annals of Vascular Diseases
László Balogh, Éva Katona, Zoltán A Mezei, Judit Kállai, Réka Gindele, István Édes, László Muszbek, Zoltán Papp, Zsuzsanna Bereczky
Factor XIII (FXIII) stabilizes and protects the fibrin network. Its role in myocardial infarction (MI) is still to be clarified. To evaluate the association of FXIII levels with MI in young patients and to investigate how the FXIII-A p.Val34Leu, FXIII-B p.His95Arg, and IVS11, c.1952 + 144 C>G (Intron K) polymorphisms influence FXIII levels and MI risk. Patients with ST elevation MI below 40 years of age (MI, n = 119), age-matched clinical controls (CC, n = 101) without MI and coronary artery disease, and healthy controls (HC, n = 120) were investigated for FXIII activity, FXIII-A2 B2 , FXIII-B concentrations and for the polymorphisms...
February 26, 2018: Molecular and Cellular Biochemistry
Michal Bijak, Rafal Szelenberger, Angela Dziedzic, Joanna Saluk-Bijak
Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly reduces the risk of peripheral artery disease, myocardial infarction, ischemic stroke, and vascular death. Recent studies demonstrated the inhibition of ADP-induced blood platelet activation by three major compounds of the flavonolignans group: silybin, silychristin, and silydianin...
February 10, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Alexander D Malkin, Sang-Ho Ye, Evan J Lee, Xiguang Yang, Yang Zhu, Lara J Gamble, William J Federspiel, William R Wagner
Respiratory assist devices, that utilize ∼2 m2 of hollow fiber membranes (HFMs) to achieve desired gas transfer rates, have been limited in their adoption due to such blood biocompatibility limitations. This study reports two techniques for the functionalization and subsequent conjugation of zwitterionic sulfobetaine (SB) block copolymers to polymethylpentene (PMP) HFM surfaces with the intention of reducing thrombus formation in respiratory assist devices. Amine or hydroxyl functionalization of PMP HFMs (PMP-A or PMP-H) was accomplished using plasma-enhanced chemical vapor deposition...
February 9, 2018: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Brit Long, Jennifer Robertson, Alex Koyfman, Kurian Maliel, Justin R Warix
BACKGROUND: Atrial fibrillation (AF) is an abnormal heart rhythm which may lead to stroke, heart failure, and death. Emergency physicians play a role in diagnosing AF, managing symptoms, and lessening complications from this dysrhythmia. OBJECTIVE: This review evaluates recent literature and addresses ED considerations in the management of AF. DISCUSSION: Emergency physicians should first assess patient clinical stability and evaluate and treat reversible causes...
January 30, 2018: American Journal of Emergency Medicine
H M H Spronk, T Padro, J E Siland, J H Prochaska, J Winters, A C van der Wal, J J Posthuma, G Lowe, E d'Alessandro, P Wenzel, D M Coenen, P H Reitsma, W Ruf, R H van Gorp, R R Koenen, T Vajen, N A Alshaikh, A S Wolberg, F L Macrae, N Asquith, J Heemskerk, A Heinzmann, M Moorlag, N Mackman, P van der Meijden, J C M Meijers, M Heestermans, T Renné, S Dólleman, W Chayouâ, R A S Ariëns, C C Baaten, M Nagy, A Kuliopulos, J J Posma, P Harrison, M J Vries, H J G M Crijns, E A M P Dudink, H R Buller, Y M C Henskens, A Själander, S Zwaveling, O Erküner, J W Eikelboom, A Gulpen, F E C M Peeters, J Douxfils, R H Olie, T Baglin, A Leader, U Schotten, B Scaf, H M M van Beusekom, L O Mosnier, L van der Vorm, P Declerck, M Visser, D W J Dippel, V J Strijbis, K Pertiwi, A J Ten Cate-Hoek, H Ten Cate
Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1...
February 2018: Thrombosis and Haemostasis
Sravya Kattula, James R Byrnes, Sara M Martin, Lori A Holle, Brian C Cooley, Matthew J Flick, Alisa S Wolberg
The transglutaminase factor XIII (FXIII) stabilizes clots against mechanical and biochemical disruption and is essential for hemostasis. In vitro and in vivo models of venous thrombosis demonstrate that FXIII mediates clot size by promoting red blood cell (RBC) retention. However, the key source of FXIII and whether FXIII activity can be reduced to suppress thrombosis without imposing deleterious hemostatic consequences are 2 critical unresolved questions. FXIII is present in multiple compartments, including plasma (FXIIIplasma ) as a heterotetramer of A2 and B2 subunits and platelets (FXIIIplt ) as an A2 homodimer...
January 9, 2018: Blood Advances
Wen-Zhe Fan, Ying-Qiang Zhang, Wang Yao, Yu Wang, Guo-Sheng Tan, Yong-Hui Huang, Jian-Yong Yang, Jia-Ping Li
PURPOSE: To evaluate the utility of emergent transcatheter arterial embolization for spontaneously ruptured hepatocellular carcinoma (HCC) in patients with Child-Pugh class C (CPC) liver cirrhosis presenting hemorrhagic shock. MATERIALS AND METHODS: A study of all 94 patients was retrospectively conducted from January 2006 to January 2016. Sixty patients underwent conservative treatment (control group) and 34 underwent embolization. RESULTS: Embolization provided better stabilization of hemodynamic status than conservative treatment (91...
December 14, 2017: Journal of Vascular and Interventional Radiology: JVIR
Lei Xing, Erika Yamamoto, Tomoyo Sugiyama, Haibo Jia, Lijia Ma, Sining Hu, Chao Wang, Yingchun Zhu, Lulu Li, Maoen Xu, Huimin Liu, Krzysztof Bryniarski, Jingbo Hou, Shaosong Zhang, Hang Lee, Bo Yu, Ik-Kyung Jang
BACKGROUND: The initial EROSION study (Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography-Based Management in Plaque Erosion) demonstrated that patients with acute coronary syndrome caused by plaque erosion might be stabilized with aspirin and ticagrelor without stenting for ≤1 month. However, a long-term evaluation of outcomes is lacking. The aim of this study was to assess whether the initial benefit of noninterventional therapy for patients with acute coronary syndrome caused by plaque erosion is maintained for ≤1 year...
December 2017: Circulation. Cardiovascular Interventions
I Induruwa, M Moroi, A Bonna, J-D Malcor, J-M Howes, E A Warburton, R W Farndale, S M Jung
Essentials Glycoprotein VI (GPVI) binds collagen, starting thrombogenesis, and fibrin, stabilizing thrombi. GPVI-dimers, not monomers, recognize immobilized fibrinogen and fibrin through their D-domains. Collagen, D-fragment and D-dimer may share a common or proximate binding site(s) on GPVI-dimer. GPVI-dimer-fibrin interaction supports spreading, activation and adhesion involving αIIbβ3. SUMMARY: Background Platelet collagen receptor Glycoprotein VI (GPVI) binds collagen, initiating thrombogenesis, and stabilizes thrombi by binding fibrin...
February 2018: Journal of Thrombosis and Haemostasis: JTH
Mohammed Makkawi, David Howells, Mark D Wright, Denise E Jackson
Tumor-suppressing subchromosomal transferable fragment cDNA 6 (TSSC6) expression is restricted to hematopoietic organs and tissues where it plays a role in hematopoietic-cell function. The ADP purinergic receptor P2Y12 is mainly expressed by platelets with important clinical significance as a target for several clinically approved antithrombotic agents. We have previously shown a physical association between P2Y12 and TSSC6 in platelets. Hence our aim was to investigate whether this physical association is translated to functional effects...
January 2018: Thrombosis Research
Emanuele Bertaglia, Matteo Anselmino, Alessandro Zorzi, Vincenzo Russo, Elisabetta Toso, Francesco Peruzza, Antonio Rapacciuolo, Federico Migliore, Fiorenzo Gaita, Umberto Cucchini, Marcello De Divitiis, Sabino Iliceto, Giuseppe Stabile
AIMS: Despite optimal oral anticoagulation with vitamin K antagonist, left atrial (LA) thrombus could be detected in the left appendage (LAA) in >2% of patients with atrial fibrillation (AF) and CHA2 DS2 -VASc score≥1 but few data are available for patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). We evaluated the occurrence and predictors of LA thrombi by means of transesophageal echocardiography (TOE) in consecutive patients with non-valvular AF who received for at least 3weeks Apixaban, Dabigatran, or Rivaroxaban...
December 15, 2017: International Journal of Cardiology
Maria Berndt, Sascha Prothmann, Christian Maegerlein, Paul Oberdieck, Claus Zimmer, Barbara Hegge, Jaroslav Pelisek, Lucas Schirmer, Holger Poppert, Tobias Boeckh-Behrens
OBJECTIVE: Especially since the establishment of mechanical thrombectomy as part of standard stroke therapy, artificial thrombi have become important in the training of interventionalists as well as for the development and testing of devices. So far, these in vitro clots have lacked direct comparisons with ex vivo thrombi. We therefore compared the histologic appearance of dynamically produced clots with that of stroke thrombi acquired during mechanical recanalization. METHODS: Thrombi of 145 consecutive patients with stroke with large-vessel occlusions were histologically compared with 10 artificial clots, dynamically created from human blood and pig's blood using a Chandler loop system...
February 2018: World Neurosurgery
Ecaterina Scărlătescu, Marcus D Lancé, Nathan J White, Stefan S Aramă, Dana R Tomescu
: The objectives of the study are to examine the effect of sepsis on the coagulation profile of patients having solid cancer and to test the hypothesis that septic patients with cancer have normal or increased hemostatic capacity despite prolonged standard coagulation tests (SCTs) compared with noninfected cancer patients. Patients with solid cancer were included in the study forming two groups: study group included patients with sepsis with minimum two organ dysfunctions and control group formed by noninfected cancer patients...
October 31, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Andre L Samson, Imala Alwis, Jessica A A Maclean, Pramith Priyananda, Brian Hawkett, Simone M Schoenwaelder, Shaun P Jackson
Clot retraction refers to the process whereby activated platelets transduce contractile forces onto the fibrin network of a thrombus, which over time increases clot density and decreases clot size. This process is considered important for promoting clot stability and maintaining blood vessel patency. Insights into the mechanisms regulating clot retraction at sites of vascular injury have been hampered by a paucity of in vivo experimental models. By pairing localized vascular injury with thrombin microinjection in the mesenteric circulation of mice, we have demonstrated that the fibrin network of thrombi progressively compacts over a 2-hour period...
December 7, 2017: Blood
Filippo Naso, Ugo Stefanelli, Edward Buratto, Giovanna Lazzari, Andrea Perota, Cesare Galli, Alessandro Gandaglia
BACKGROUND: Glutaraldehyde (GLA) has been used to crosslink bioprosthetic heart valve (BHVs) tissues to enhance their stability, besides ensuring a satisfactory degree of immunological tolerance. Unfortunately, GLA fixation does not guarantee a complete tissue biocompatibility of BHVs in currently used devices. The interaction between preformed human anti-alpha-Gal antibody and alpha-Gal antigens promotes the calcification of GLA-treated alpha-Gal-positive tissue. Recently, an alarming correlation between the presence of the alpha-Gal epitope and a premature BHVs degeneracy was reported...
October 2017: Tissue Engineering. Part A
Brian R Branchford, Timothy J Stalker, Luke Law, Gilbert Acevedo, Susan Sather, Christine Brzezinski, Katina M Wilson, Katherine Minson, Alisa B Lee-Sherick, Pavel Davizon-Castillo, Christopher Ng, Weihe Zhang, Keith B Neeves, Steven R Lentz, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Deborah DeRyckere, Lawrence F Brass, Douglas K Graham, Jorge A Di Paola
BACKGROUND: Gas6 signals through the TAM (TYRO-3, AXL, MERTK) receptor family mediating platelet activation and thrombus formation via activation of the aggregate-stabilizing αIIb β3 integrin. OBJECTIVE: Here we describe anti-thrombotic effects mediated by UNC2025, a small molecule MERTK tyrosine kinase inhibitor. METHODS: MERTK phosphorylation and downstream signaling were assessed by immunoblot. Light transmission aggregometry, flow cytometry, and microfluidic analysis were used to evaluate the impact of MERTK inhibition on platelet activation and stability of aggregate formation in vitro...
October 17, 2017: Journal of Thrombosis and Haemostasis: JTH
Diana A Gorog, Zahi A Fayad, Valentin Fuster
The spontaneous lysis of a coronary thrombus is a natural protective mechanism against lasting occlusion and downstream infarction. Thrombus stability is thus a direct determinant of clinical outcome. Compared with the extensive study of the crucial role of platelets, coagulation, and flow in arterial thrombosis, little attention has been paid to factors affecting thrombus stability, despite evidence linking impaired spontaneous fibrinolytic activity with acute coronary events. We summarize experimental evidence for the importance of thrombus stability and highlight the need for physiologically relevant tests to assess spontaneous disintegration/fibrinolysis of platelet-rich thrombi under arterial flow conditions, review techniques to assess thrombus stability in vitro, and describe novel imaging techniques to characterize thrombosis in vivo...
October 17, 2017: Journal of the American College of Cardiology
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