Journal articles on the topic 'Fundamental hemostasis'
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1
Kondratiev, M. V., A. S. Petrova, A. S. Gryzunova, S. N. Lavrentiev, N. I. Zakharova, O. F. Serova, V. A. Krasnova, and K. B. Zhybanisheva. "Changes in primary and secondary hemostasis as a predictor of adverse neonatal outcomes in birth asphyxia." Voprosy praktičeskoj pediatrii 18, no. 1 (2023): 103–10. http://dx.doi.org/10.20953/1817-7646-2023-1-103-110.
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The hemostatic system is complex and evolves continuously since gestation and well into the adult years, in a process known as “developmental hemostasis”. This article presents information about the functioning of the hemostatic system in normal and pathological conditions (birth asphyxia) in newborns, reflects fundamental differences in hemostatic functioning during the neonatal period and the possibilities in maintaining normal hemostasis in conditions of physiological deficiency of both clotting factors and the anticoagulant system. The article highlights various methods of diagnosing the hemostatic system used in neonatology. The so-called global hemostasis tests are being introduced into neonatal practice. The study of hemostasis using thromboelastography technique allows to correct for the patient's real body temperature and estimate both the interaction of platelets and clotting factors and examine the plasma hemostasis component in isolation. The effects of neonatal asphyxia and therapeutic hypothermia procedures on the hemostatic system are poorly understood. This review article attempts to summarize the data available in the world scientific literature concerning this problem. Key words: newborns, developing hemostasis, asphyxia, hypoxic-ischemic encephalopathy, thromboelastography, coagulation, therapeutic hypothermia
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Romantsov, Mikhail N., Eugene F. Cherednikov, Aleksandr Anatolevich Glukhov, and Constantine O. Fursov. "New technologies of endoscopic hemostasis in a treatment protocol of patients with gastroduodenal ulcer bleeding." Vestnik of Experimental and Clinical Surgery 11, no. 1 (April 8, 2018): 16–23. http://dx.doi.org/10.18499/2070-478x-2018-11-1-16-23.
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Relevance of research. Acute gastroduodenal bleeding is remaining a difficult and largely unsolved problem up to day. The fundamental importance in treating this category of patients is an endoscopic hemostasis. The decisive point in this problem is the most stable hemostasis and preventing a recurrence of a hemorrhage. In this regard, the search of new solutions and the development of known methods of treatment of the gastroduodenal ulcer bleeding is an important issue.
Aim of research. To evaluate the effectiveness of the treatment protocol of patients with the gastroduodenal ulcer bleeding by applying combined endoscopic insufflations of hemostatic agents and a diovin as an integral part of a complex therapy.
Materials and methods. The research is based on results of treatment of the patients with the gastroduodenal ulcer bleeding being in a medical setting at the departments of surgery at Voronezh city clinical emergency hospital №1. During the treatment of the main group (59 patients) there was used an integrated approach with the usage of powdered hemostatic agents of gelplastan and lyophilisate NovoSeven in combination with diovin in the endoscopic treatment of gastroduodenal ulcer bleeding. There were used the traditional well-known methods of the endoscopic hemostasis without the usage of hemostatic agents and absorbent grains in treatment of the control group (56 patients).
Results and discussion. The evaluation of results of patients’ treatment with gastroduodenal ulcer bleeding was performed according to the figures of the final hemostasis, the frequency of recurrent bleeding, the prevention of emergency operations, the rates of mortality, the duration of hospitalization. The developed protocol of the patients’ treatment with gastroduodenal ulcer bleeding with the usage of combined the endoscopic insufflation of two hemostatics and diovin makes it possible to achieve the maximum persistent hemostasis at 94.9% of patients, to reduce the risk of recurrent hemorrhages by 2.5 times, to prevent emergency operations and, as a result, to reduce the lethality.
Conclusion. The usage of new technologies of endoscopic hemostasis by the hemostatic pneumoinsufflation gelplastan and lyophilisate NovoSeven in combination with diovin in the treatment of patients with gastroduodenal ulcer bleeding allows to reduce the risk of recurrent hemorrhage from 12,5% to 5,01% (by 2,5 times), to prevent emergency operations, to reduce the lethality from 3,65% to 1,7% (by 2,1 times) and to reduce the period of staying in the hospital from 10,2 to 7,4 bed days (p<0.05).
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Scridon, Alina. "Platelets and Their Role in Hemostasis and Thrombosis—From Physiology to Pathophysiology and Therapeutic Implications." International Journal of Molecular Sciences 23, no. 21 (October 23, 2022): 12772. http://dx.doi.org/10.3390/ijms232112772.
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Hemostasis is a physiological process critical for survival. Meanwhile, thrombosis is amongst the leading causes of death worldwide, making antithrombotic therapy one of the most crucial aspects of modern medicine. Although antithrombotic therapy has progressed tremendously over the years, it remains far from ideal, and this is mainly due to the incomplete understanding of the exceptionally complex structural and functional properties of platelets. However, advances in biochemistry, molecular biology, and the advent of ‘omics’ continue to provide crucial information for our understanding of the complex structure and function of platelets, their interactions with the coagulation system, and their role in hemostasis and thrombosis. In this review, we provide a comprehensive view of the complex role that platelets play in hemostasis and thrombosis, and we discuss the major clinical implications of these fundamental blood components, with a focus on hemostatic platelet-related disorders and existing and emerging antithrombotic therapies. We also emphasize a number of questions that remain to be answered, and we identify hotspots for future research.
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Davis, Jessica, Stephen Caldwell, and Nicolas Intagliata. "Coagulation Pathways, Hemostasis, and Thrombosis in Liver Failure." Seminars in Respiratory and Critical Care Medicine 39, no. 05 (October 2018): 598–608. http://dx.doi.org/10.1055/s-0038-1673658.
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AbstractAchieving hemostasis, preventing and treating thrombosis, and laboratory measurement of the hemostatic pathways constitute the core elements of managing the critically ill patient with liver failure. Uncontrolled bleeding in acutely decompensated cirrhosis and acute-on-chronic liver failure is probably the most familiar clinical challenge to intensivists. Bleeding in these patients can be broadly divided into pressure-driven (portal hypertension-related) bleeding with only limited dependence on hemostatic pathways and intractable mucosal/wound bleeding, which is much more directly related to a severely disturbed hemostatic system with imbalances in the coagulation cascade and the fibrinolytic system. Both types of bleeding can occur simultaneously and may even coexist with inappropriate thrombosis such as portal vein thrombosis or venous thromboembolism. Due to the fundamental role of the liver in coagulation factor synthesis and its direct and indirect regulation of nearly all aspects of the hemostatic system, laboratory measurements of coagulation pathways also constitute key aspects of all prognostic scores that guide clinical decisions and forecast optimal interventions in both acute and chronic forms of liver failure.
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Starlinger, Patrick, James P. Luyendyk, and Dafna J. Groeneveld. "Hemostasis and Liver Regeneration." Seminars in Thrombosis and Hemostasis 46, no. 06 (September 2020): 735–42. http://dx.doi.org/10.1055/s-0040-1715450.
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AbstractThe liver is unique in its remarkable regenerative capacity, which enables the use of liver resection as a treatment for specific liver diseases, including removal of neoplastic liver disease. After resection, the remaining liver tissue (i.e, liver remnant) regenerates to maintain normal hepatic function. In experimental settings as well as patients, removal of up to two-thirds of the liver mass stimulates a rapid and highly coordinated process resulting in the regeneration of the remaining liver. Mechanisms controlling the initiation and termination of regeneration continue to be discovered, and many of the fundamental signaling pathways controlling the proliferation of liver parenchymal cells (i.e., hepatocytes) have been uncovered. Interestingly, while hemostatic complications (i.e., bleeding and thrombosis) are primarily thought of as a complication of surgery itself, strong evidence suggests that components of the hemostatic system are, in fact, powerful drivers of liver regeneration. This review focuses on the clinical and translational evidence supporting a link between the hemostatic system and liver regeneration, and the mechanisms whereby the hemostatic system directs liver regeneration discovered using experimental settings.
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White, J. G. "Morphological and Functional Aspects of Cellular Hemostatic Mechanisms." Hämostaseologie 16, no. 02 (April 1996): 78–87. http://dx.doi.org/10.1055/s-0038-1656643.
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SummaryTransmission, scanning and low-voltage, high resolution scanning electron microscopy have provided fundamental knowledge of relationships between plate-let structure and function. In combination with ultrastructural cytochemistry and immunocytochemistry, basic aspects of shape change, pseudopod extension, internal transformation, secretion, adhesion, aggregation, spreading, hemostatic plug formation and thrombus development have been defined. The morphological events of the platelet reaction in hemostasis have been linked to biochemical alterations. The result is a comprehensive picture of cellular aspects of hemosta-sis. This knowledge provides a basis for designing programs of treatment for heart attacks, strokes and other occlusive vascular disorders, as well as for their prevention.
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Thattaliyath, Bijoy, Matthew Cykowski, and Pudur Jagadeeswaran. "Young thrombocytes initiate the formation of arterial thrombi in zebrafish." Blood 106, no. 1 (July 1, 2005): 118–24. http://dx.doi.org/10.1182/blood-2004-10-4118.
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The zebrafish system is an excellent vertebrate genetic model to study hemostasis and thrombosis because saturation mutagenesis screens can identify novel genes that play a role in this vital physiologic pathway. To study hemostatic mutations, it is important to understand the physiology of zebrafish hemostasis and thrombosis. Previously, we identified zebrafish thrombocytes and have shown that they participate in arterial thrombus formation. Here, we recognized 2 populations of thrombocytes distinguishable by DiI-C18 (DiI) staining. DiI+ thrombocytes have a high density of adhesive receptors and are functionally more active than DiI– thrombocytes. We classified DiI+ thrombocytes as young and DiI– thrombocytes as mature thrombocytes. We found young and mature thrombocytes each formed independent clusters and that young thrombocytes clustered first. We have also shown that young thrombocytes initiate arterial thrombus formation. We propose that due to the increased adhesive receptor density on young thrombocytes, they adhere first to the subendothelial matrix, get activated rapidly, release agonists, and recruit more young thrombocytes, which further release more agonists. This increase in agonists activates the less active mature thrombocytes, drawing them to the growing thrombus. Since arterial thrombus formation is a fundamental hemostatic event, this mechanism may be conserved in mammals and may open new avenues for prevention of arterial thrombosis.
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Ono, Akiko, Erik Westein, Sarah Hsiao, Warwick S. Nesbitt, Justin R. Hamilton, Simone M. Schoenwaelder, and Shaun P. Jackson. "Identification of a fibrin-independent platelet contractile mechanism regulating primary hemostasis and thrombus growth." Blood 112, no. 1 (July 1, 2008): 90–99. http://dx.doi.org/10.1182/blood-2007-12-127001.
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Abstract A fundamental property of platelets is their ability to transmit cytoskeletal contractile forces to extracellular matrices. While the importance of the platelet contractile mechanism in regulating fibrin clot retraction is well established, its role in regulating the primary hemostatic response, independent of blood coagulation, remains ill defined. Real-time analysis of platelet adhesion and aggregation on a collagen substrate revealed a prominent contractile phase during thrombus development, associated with a 30% to 40% reduction in thrombus volume. Thrombus contraction developed independent of thrombin and fibrin and resulted in the tight packing of aggregated platelets. Inhibition of the platelet contractile mechanism, with the myosin IIA inhibitor blebbistatin or through Rho kinase antagonism, markedly inhibited thrombus contraction, preventing the tight packing of aggregated platelets and undermining thrombus stability in vitro. Using a new intravital hemostatic model, we demonstrate that the platelet contractile mechanism is critical for maintaining the integrity of the primary hemostatic plug, independent of thrombin and fibrin generation. These studies demonstrate an important role for the platelet contractile mechanism in regulating primary hemostasis and thrombus growth. Furthermore, they provide new insight into the underlying bleeding diathesis associated with platelet contractility defects.
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Tarasova, L. N. "Zubairov D.M. Molecular basis of blood coagulation and thrombosis. - Kazan, 2000 - Circulation 1000 copies. - 364 p." Kazan medical journal 82, no. 5 (October 15, 2001): 413–14. http://dx.doi.org/10.17816/kazmj84133.
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The book by Prof. D.M. Zubairov is devoted to the actual problem - the study of molecular and regulatory mechanisms of hemostasis and their disorders. The publication of this fundamental scientific work of an authoritative scientist, known not only in our country but also abroad, is very timely.
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Jain, Mukesh. "Kruppel-Like Factors in Thrombosis and Hemostasis." Blood 132, Supplement 1 (November 29, 2018): SCI—45—SCI—45. http://dx.doi.org/10.1182/blood-2018-99-109558.
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Abstract Armed with the appreciation that the blood and vascular system share common origins and cooperate to ensure fundamental processes (e.g. blood flow/fluidity, oxygen/nutrient delivery, immunity) essential for organismal survival, we posited that shared molecular pathways may be operative in coordinating the function of both systems. Over the past 2 decades, studies from our group and others have identified a family of transcription factors termed Kruppel-like factors (KLFs) as essential for development, differentiation, and function of cellular constituents of both the hematopoietic and vascular systems. In this presentation, discussion will focus on the role KLFs in control of endothelium and myeloid cell biology in physiology and disease. Specifically, cellular and in vivo evidence will be discussed implicating KLFs as master regulators of all cardinal endothelial functions (permeability, vasoreactivity, blood fluidity, and inflammation). Further, studies demonstrating KLF-control of myeloid cell development, subset specification, and pro-inflammatory activation will be reviewed with particular emphasis on results of efforts altering myeloid KLFs in the context of acute (e.g. bacterial infection, sepsis) and chronic (e.g. atherosclerosis, arterial/venous thrombosis) inflammatory processes. Correlative studies in human subjects will be presented. And finally, insights into how targeting KLFs can be exploited for therapeutic gain will be discussed. Disclosures No relevant conflicts of interest to declare.
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Hugel, Bénédicte, M. Carmen Martínez, Corinne Kunzelmann, and Jean-Marie Freyssinet. "Membrane Microparticles: Two Sides of the Coin." Physiology 20, no. 1 (February 2005): 22–27. http://dx.doi.org/10.1152/physiol.00029.2004.
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Microparticles are plasma membrane-derived vesicles shed from stimulated cells, in the broad sense of the term. Their presence is interpreted by proximal or remote cells in fundamental physiological processes including intercellular communication, hemostasis, and immunity. On the other hand, variations of their number or characteristics are frequently observed in pathophysiological situations.
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Belousov, Andrey. "Contemporary Paradigm of Anticoagulant and Antiplatelet Therapy: Revolutionary Approaches to Assessing Blood Coagulation in the Laboratory and Using Instrumental Methods." Journal of Hematology and Transfusion 11, no. 1 (January 24, 2024): 1–11. http://dx.doi.org/10.47739/2333-6684.hematology.1118.
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Statement of the Problem: Impairment of the blood coagulation system remains a relevant issue in clinical practice. A striking example of this is the fact that despite the administration of anticoagulant therapy, up to 35% of COVID-19 patients were hospitalized in the intensive care unit with thromboembolic complications. Prophylactic and therapeutic methods for the hemostatic system, recommended by various protocols, have a general nature. Moreover, they introduce dissonance into the clinical clarity of appropriate anticoagulant and antiplatelet use and fail to provide practitioners with the necessary fundamental knowledge to understand the aspects of clinical tactics for correcting the hemostatic system. Uncertainties remain regarding how to correctly choose a specific anticoagulant and determine its effective dose based on individual clinical and laboratory data, which laboratory markers of the coagulation system should be investigated, and whether they always reflect the true picture of hemostasis. Methodology and Theoretical Orientation: This article briefly presents the main aspects of the functioning of the blood coagulation system, points of application for pharmacological agents, and provides objective information for clinicians about the mechanisms of action of major anticoagulants and antiplatelets. Effective and practical methods for assessing the hemostatic system are recommended. Findings: The proper correction of the hemostatic system can only be carried out by a highly qualified specialist - a clinical transfusiologist, who possesses a comprehensive understanding of the functioning of the coagulation and anticoagulation systems, the platelet and fibrinolysis systems, knows the points of application and mechanisms of action of the pharmacological agents and blood components used, and takes into account internal and external factors that influence hemostasis. Conclusion and Significance: Empirical prescription of anticoagulant and antiplatelet therapies, based solely on instructions and clinical protocols without objective comprehensive analysis of the hemostatic components, is not only ineffective but also life-threatening for the patient. Hemostasiogram (coagulogram) and D-dimer measurements cannot serve as the sole determining markers for monitoring the coagulation system. Evaluation of the blood coagulation system should only be carried out based on a comprehensive analysis of hemostasiogram data, complete blood count, thromboelastography (TEG), and data from all relevant systems.
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Kantsurova, M. R., A. N. Rymashevsky, and R. S. Sapronov. "Features of the state of a woman’s reproductive function after previously undergoing organ-preserving surgical hemostasis." Medical Herald of the South of Russia 11, no. 2 (June 30, 2020): 117–21. http://dx.doi.org/10.21886/2219-8075-2020-11-2-117-121.
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Today one of the main state tasks in the Russian Federation is to save people, which cannot be implemented without increasing the birth rate. Despite the fact that maternal mortality tends to decrease, bleeding remains one of the leading causes of death of women during pregnancy, childbirth and the postpartum period, so the fight against bleeding is one of the fundamental tasks in obstetric practice. The existing standards of step-by-step medical care for obstetric bleeding are successfully applied in practical health care, but the state of a woman’s reproductive function after the use of surgical hemostasis has not been sufficiently studied. This article presents an overview of a clinical case of reproductive function preservation in a 38-year-old woman after undergoing surgical hemostasis due to obstetric bleeding in the anamnesis.
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Khaliulin, A. V., O. A. Gusyakova, A. V. Kozlov, and A. I. Gabrilchak. "METABOLISM PROCESSES AND MECHANISMS OF REGULATION OF PLATELET ACTIVITY (REVIEW OF LITERATURE)." Russian Clinical Laboratory Diagnostics 64, no. 3 (April 29, 2019): 164–69. http://dx.doi.org/10.18821/0869-2084-2019-64-3-164-169.
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Platelets play fundamental role in ensuring the hemostatic function in blood. In addition to this canonical function, the blood plates play angiotrophic, immunological, transport role, participate in the activation of plasma hemostasis, retraction of a blood clot, and can record circulating immune complexes. The review article presents current data on the structure and conjugation of molecular rearrangements of platelet ultrastructures associated with the functioning of an open canalicular platelet system, a dense tubular system, and a platelet cytoplasmic membrane. The main types of resting platelet metabolism, and the processes underlying the activation of platelets associated with the enhancement of carbohydrate and fatty acid catabolism are characterized, as well as some signaling pathways that regulate processes of induction of platelet aggregation. The data show the value of lipid components of activated platelet membranes, including phospholipids of various classes, glycolipids and cholesterol. The role of regulatory processes associated with the non-covalent modification of certain platelet proteins with fatty acids is reflected. Fundamental questions of platelet metabolism are relevant nowadays and require a combined approach of studying them, which can potentially solve many problems of clinical laboratory diagnostics, pathobiochemistry, and pharmacology. In preparing the review, we used sources from international and russian databases: Scopus, Web of Science, RSCI.
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Avtaeva, Yu N., I. S. Melnikov, S. A. Vasiliev, and Z. A. Gabbasov. "The role of von Willebrand factor in hemostasis pathology." Aterotromboz = Atherothrombosis 12, no. 2 (January 14, 2023): 79–102. http://dx.doi.org/10.21518/2307-1109-2022-12-2-79-102.
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Von Willebrand factor (VWF) is a multimeric plasma glycoprotein present in endothelial cells, megakaryocytes, platelets, and connective tissue. It mediates platelet adhesion in small arteries. VWF also binds and protects coagulation factor VIII from degradation. Moreover, VWF is involved in inflammatory response, linking hemostasis and inflammation. VWF multimers and platelets attached to damaged or activated endothelium mediate leukocyte recruitment, facilitating local inflammatory response. At shear rates above 5000 s–1, VWF molecules are capable of hydrodynamic activation that changes their conformation from globular to fibrillar. Therefore, VWF plays a key role in cellular hemostasis at high shear rates. Acquired and inherited disfunction, defective synthesis or increased proteolysis of VWF multimers lead to bleeding, as in von Willebrand disease or Heyde syndrome. Pathological activation of VWF may lead to the development of thrombotic complications of coronary artery disease. COVID-19, especially severe form, is characterized by prothrombotic shift in pulmonary vascular bed. Following endothelial damage, VWF plasma level rises and ADAMTS-13 activity decreases. In patients with COVID-19, a change in the VWF/ADAMTS-13 ratio is associated with an increase in the risk of thromboembolic complications. Therefore, assessment of hydrodynamic activation of VWF under flow conditions may be valuable in fundamental research and laboratory diagnostics.
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Pezzino, Salvatore, Tonia Luca, Mariacarla Castorina, Stefano Puleo, Saverio Latteri, and Sergio Castorina. "Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines." Life 14, no. 1 (January 7, 2024): 93. http://dx.doi.org/10.3390/life14010093.
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The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it one of the most prevalent chronic liver disorders. MASLD encompasses a range of liver pathologies, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) with inflammation, hepatocyte damage, and fibrosis. Interestingly, the liver exhibits close intercommunication with fatty tissue. In fact, adipose tissue could contribute to the etiology and advancement of MASLD, acting as an endocrine organ that releases several hormones and cytokines, with the adipokines assuming a pivotal role. The levels of adipokines in the blood are altered in people with MASLD, and recent research has shed light on the crucial role played by adipokines in regulating energy expenditure, inflammation, and fibrosis in MASLD. However, MASLD disease is a multifaceted condition that affects various aspects of health beyond liver function, including its impact on hemostasis. The alterations in coagulation mechanisms and endothelial and platelet functions may play a role in the increased vulnerability and severity of MASLD. Therefore, more attention is being given to imbalanced adipokines as causative agents in causing disturbances in hemostasis in MASLD. Metabolic inflammation and hepatic injury are fundamental components of MASLD, and the interrelation between these biological components and the hemostasis pathway is delineated by reciprocal influences, as well as the induction of alterations. Adipokines have the potential to serve as the shared elements within this complex interrelationship. The objective of this review is to thoroughly examine the existing scientific knowledge on the impairment of hemostasis in MASLD and its connection with adipokines, with the aim of enhancing our comprehension of the disease.
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Gawaz, Meinrad, and Sebastian Vogel. "Platelets in tissue repair: control of apoptosis and interactions with regenerative cells." Blood 122, no. 15 (October 10, 2013): 2550–54. http://dx.doi.org/10.1182/blood-2013-05-468694.
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Abstract Besides mediating primary hemostasis and thrombosis, platelets play a critical role in tissue repair and regeneration. They regulate fundamental mechanisms involved in the healing process including cellular migration, proliferation, and angiogenesis. Control of apoptosis/cell survival and interaction with progenitor cells, which are clinically relevant but poorly understood aspects of platelets in tissue repair, will be highlighted in this review. Gaining deeper insight into the less well-characterized molecular mechanisms is necessary to develop new therapeutic platelet-based options.
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SATOH, Kohji. "Fundamental studies on application of Nd-YAG laser to oral surgery. Hemostasis of movable oral mucous membrane." Japanese Journal of Oral & Maxillofacial Surgery 34, no. 11 (1988): 2359–74. http://dx.doi.org/10.5794/jjoms.34.2359.
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Ware, Jerry, and Shashank Jain. "Platelet Glycoprotein 1b-1X in Hemostasis and Malignancy." Blood 112, no. 11 (November 16, 2008): sci—21—sci—21. http://dx.doi.org/10.1182/blood.v112.11.sci-21.sci-21.
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Abstract The platelet paradigm in hemostasis and thrombosis involves an initiation step dependent upon platelet membrane receptors binding to ligands on a damaged or inflamed vascular surface. Once bound to the surface, platelets provide a unique microenvironment supporting the accumulation of more platelets and the elaboration of a fibrin-rich network produced by coagulation factors. This paradigm has been established from decades of research. The platelet-specific receptor, glycoprotein (GP) Ib-IX, is critical in this process and can initiate the formation of a platelet-rich thrombus by tethering the platelet to a thrombogenic surface. Several ligands binding to GP Ib-IX have been identified, but von Willebrand factor (vWF) and the resultant GP Ib-IX/vWF axis has emerged as a major initiator of platelet thrombus formation in the arterial circulation. Newer, emerging data supports a role for platelets in pathological events beyond the prevention of blood loss. We have obtained data supporting the hypothesis that platelet GP Ib-IX contributes to malignancy. Knockout and transgenic mouse colonies have been generated in our laboratory and bred to C57BL/6J animals to generate several congenic strains (> 10 generation backcrosses) with dysfunctional platelet GP Ib-IX. These colonies have been used to characterize tumor metastasis and primary tumor growth in syngeneic models where the host animals are immunocompetent. The results demonstrate platelet GP Ib-IX contributes to tumorigenesis, as a functional absence of GP Ib-IX correlates with a significant reduction in the number of metastatic foci using models of experimental metastasis. In addition, an absence of GP Ib-IX significantly reduces primary tumor burden. A second series of experiments has determined that platelet GP VI, a key activation receptor on the surface of platelets also contributes to progression of experimental metastasis. The importance of metastasis in the prognosis for recovery from cancer can not be over-emphasized. Indeed, the spread of metastatic disease represents a fundamental change in significantly shortening the lifespan of patients with breast cancer. Thus, understanding the molecules that regulate metastasis identifies potential targets for therapeutic intervention that could significantly improve the prognosis for the breast cancer patient. Several decades of prior work in hemostasis and thrombosis has placed this project in a position to quickly provide new information and understanding on the links between hemostasis and cancer.
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Chen, Kuo, Mikhail Y. Sinelnikov, Vladimir N. Nikolenko, Igor V. Reshetov, Yu Cao, Zhi Li, Ekaterina V. Kochurova, et al. "The Use of Fibrin-based Tissue Adhesives for Breast in Reconstructive and Plastic Surgery." Current Topics in Medicinal Chemistry 19, no. 32 (January 8, 2020): 2985–90. http://dx.doi.org/10.2174/1568026619666191112101448.
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Background: Breast plastic surgery is a rapidly evolving field of medicine. The modern view of surgical trends reflects the desire to minimize complications and introduce advanced technologies. These always will be priorities for surgeons. Reconstructive surgery, a branch of plastic surgery focusing on restoration of lost functional and aesthetic component, seeks to enhance psychological rehabilitation and improves the quality of life, as well as aesthetic recovery. Objective: This review addresses the action of fibrin agents and their effect on the quality of surgical hemostasis. Discussion and Conclusion: The fundamental goals for the surgeon are to perform a minimally traumatic intervention and to prevent any form of complication. Achieving complete hemostasis is an intraoperative necessity. Timely prevention of bleeding and hemorrhagic phenomena can affect not only the outcome of the operation, but also the incidence of postoperative complications. Topics include the integrity of microvascular anastomoses, tissue adhesion, and the incidence of seromas and hematomas associated with fibrin glue usage. The literature on fibrin adhesives with respect to prevention of postoperative complications, and the effectiveness with active drainage also are analyzed.
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Ohkubo, Y. Zenmei, and Jesper J. Madsen. "Uncovering Membrane-Bound Models of Coagulation Factors by Combined Experimental and Computational Approaches." Thrombosis and Haemostasis 121, no. 09 (July 2, 2021): 1122–37. http://dx.doi.org/10.1055/s-0040-1722187.
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AbstractIn the life sciences, including hemostasis and thrombosis, methods of structural biology have become indispensable tools for shedding light on underlying mechanisms that govern complex biological processes. Advancements of the relatively young field of computational biology have matured to a point where it is increasingly recognized as trustworthy and useful, in part due to their high space–time resolution that is unparalleled by most experimental techniques to date. In concert with biochemical and biophysical approaches, computational studies have therefore proven time and again in recent years to be key assets in building or suggesting structural models for membrane-bound forms of coagulation factors and their supramolecular complexes on membrane surfaces where they are activated. Such endeavors and the proposed models arising from them are of fundamental importance in describing and understanding the molecular basis of hemostasis under both health and disease conditions. We summarize the body of work done in this important area of research to drive forward both experimental and computational studies toward new discoveries and potential future therapeutic strategies.
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Jahan, Nusrat, Md Sowaib Ibne Mahbub, Byong-Taek Lee, and Sang Ho Bae. "In Vivo and In Vitro Investigation of a Novel Gelatin/Sodium Polyacrylate Composite Hemostatic Sponge for Topical Bleeding." Journal of Functional Biomaterials 14, no. 5 (May 10, 2023): 265. http://dx.doi.org/10.3390/jfb14050265.
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Designing a functional and efficient blood-clotting agent is a major challenge. In this research, hemostatic scaffolds (GSp) were prepared from the superabsorbent, inter-crosslinked polymer sodium polyacrylate (Sp) bound to a natural protein gelatin (G) loaded with thrombin (Th) by a cost-effective freeze-drying method. Five compositions were grafted (GSp0.0, Gsp0.1, GSp0.2, GSp0.3, GSp0.3-Th) where the concentration of Sp varied but the ratios of G remained the same. The fundamental physical characteristics that increased the amounts of Sp with G gave synergistic effects after interacting with thrombin. Due to the presence of superabsorbent polymer (SAP) swelling capacities in GSp0.3 and GSp0.3-Th surge forward 6265% and 6948%, respectively. Pore sizes became uniform and larger (ranging ≤ 300 μm) and well-interconnected. The water-contact angle declined in GSp0.3 and GSp0.3-Th to 75.73 ± 1.097 and 75.33 ± 0.8342 degrees, respectively, thus increasing hydrophilicity. The pH difference was found to be insignificant as well. In addition, an evaluation of the scaffold in in vitro biocompatibility with the L929 cell line showed cell viability >80%, so the samples were nontoxic and produced a favorable environment for cell proliferation. The composite GSp0.3-Th revealed the lowest HR (%) (2.601%), and the in vivo blood-clotting time (s) and blood loss (gm) supported hemostasis. Overall, the results showed that a novel GSp0.3-Th scaffold can be a potential candidate as a hemostatic agent.
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Hognon, Cécilia, Emmanuelle Bignon, Guillaume Harle, Nadège Touche, Stéphanie Grandemange, and Antonio Monari. "The Iron Maiden. Cytosolic Aconitase/IRP1 Conformational Transition in the Regulation of Ferritin Translation and Iron Hemostasis." Biomolecules 11, no. 9 (September 9, 2021): 1329. http://dx.doi.org/10.3390/biom11091329.
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Maintaining iron homeostasis is fundamental for almost all living beings, and its deregulation correlates with severe and debilitating pathologies. The process is made more complicated by the omnipresence of iron and by its role as a fundamental component of a number of crucial metallo proteins. The response to modifications in the amount of the free-iron pool is performed via the inhibition of ferritin translation by sequestering consensus messenger RNA (mRNA) sequences. In turn, this is regulated by the iron-sensitive conformational equilibrium between cytosolic aconitase and IRP1, mediated by the presence of an iron–sulfur cluster. In this contribution, we analyze by full-atom molecular dynamics simulation, the factors leading to both the interaction with mRNA and the conformational transition. Furthermore, the role of the iron–sulfur cluster in driving the conformational transition is assessed by obtaining the related free energy profile via enhanced sampling molecular dynamics simulations.
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Stroukov, D. V., A. G. Vasilev, and Yu S. Alexandrovich. "Quick model of septic shock in rats." Regional blood circulation and microcirculation 15, no. 1 (March 30, 2016): 73–77. http://dx.doi.org/10.24884/1682-6655-2016-15-1-73-77.
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Modeling septic shock by means of administration of living bacteria is a minimum invasive adequate model for reproduction of this pathologic process, however there is a few data on effectiveness of this model in rats on the basis of direct measurement of hemodynamic parameters. The goal of the study was to elaborate a simple and convenient model of septic shock by intravenous infusion of living bifidobacteria. Indexes of central hemodynamics evaluated by direct method were analyzed in the study as well as endothelial function of blood vessels assessed by measuring concentration of NO, vessels' endothelial growth factor-A and tissue plasminogen activator. Dysfunction of hemostasis was also estimated by measuring fibrinogen level and soluble complexes of fibrin monomer. Intravenous infusion of living bifidobacteria caused development of severe septic shock by 15th minute after administration with valid decrease of all systemic hemodynamics' parameters. Marked hemodynamic disturbancies combined with development of endothelial dysfunction and hemostatic mechanisms' increased activity. The present model is absolutely safe; it can be easily reproduced in a research or training laboratory and it can be used for fundamental research of septic shock, for pre-clinical tests of drugs as well as for educational purposes.
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AOKI, NOBUO. "Hemorrhagic disease and thrombosis.Advance of diagnosis and medical treatment.1.Fundamental matter for diagnosis.1.Hemostasis : mechanism of thrombogenesis." Nihon Naika Gakkai Zasshi 80, no. 6 (1991): 817–21. http://dx.doi.org/10.2169/naika.80.817.
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Versteeg, Henri H., Johan W. M. Heemskerk, Marcel Levi, and Pieter H. Reitsma. "New Fundamentals in Hemostasis." Physiological Reviews 93, no. 1 (January 2013): 327–58. http://dx.doi.org/10.1152/physrev.00016.2011.
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Hemostasis encompasses the tightly regulated processes of blood clotting, platelet activation, and vascular repair. After wounding, the hemostatic system engages a plethora of vascular and extravascular receptors that act in concert with blood components to seal off the damage inflicted to the vasculature and the surrounding tissue. The first important component that contributes to hemostasis is the coagulation system, while the second important component starts with platelet activation, which not only contributes to the hemostatic plug, but also accelerates the coagulation system. Eventually, coagulation and platelet activation are switched off by blood-borne inhibitors and proteolytic feedback loops. This review summarizes new concepts of activation of proteases that regulate coagulation and anticoagulation, to give rise to transient thrombin generation and fibrin clot formation. It further speculates on the (patho)physiological roles of intra- and extravascular receptors that operate in response to these proteases. Furthermore, this review provides a new framework for understanding how signaling and adhesive interactions between endothelial cells, leukocytes, and platelets can regulate thrombus formation and modulate the coagulation process. Now that the key molecular players of coagulation and platelet activation have become clear, and their complex interactions with the vessel wall have been mapped out, we can also better speculate on the causes of thrombosis-related angiopathies.
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Starke, Richard D., Francesco Ferraro, Koralia E. Paschalaki, Nicola H. Dryden, Thomas A. J. McKinnon, Rachel E. Sutton, Elspeth M. Payne, et al. "Endothelial von Willebrand factor regulates angiogenesis." Blood 117, no. 3 (January 20, 2011): 1071–80. http://dx.doi.org/10.1182/blood-2010-01-264507.
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AbstractThe regulation of blood vessel formation is of fundamental importance to many physiological processes, and angiogenesis is a major area for novel therapeutic approaches to diseases from ischemia to cancer. A poorly understood clinical manifestation of pathological angiogenesis is angiodysplasia, vascular malformations that cause severe gastrointestinal bleeding. Angiodysplasia can be associated with von Willebrand disease (VWD), the most common bleeding disorder in man. VWD is caused by a defect or deficiency in von Willebrand factor (VWF), a glycoprotein essential for normal hemostasis that is involved in inflammation. We hypothesized that VWF regulates angiogenesis. Inhibition of VWF expression by short interfering RNA (siRNA) in endothelial cells (ECs) caused increased in vitro angiogenesis and increased vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2)–dependent proliferation and migration, coupled to decreased integrin αvβ3 levels and increased angiopoietin (Ang)–2 release. ECs expanded from blood-derived endothelial progenitor cells of VWD patients confirmed these results. Finally, 2 different approaches, in situ and in vivo, showed increased vascularization in VWF-deficient mice. We therefore identify a new function of VWF in ECs, which confirms VWF as a protein with multiple vascular roles and defines a novel link between hemostasis and angiogenesis. These results may have important consequences for the management of VWD, with potential therapeutic implications for vascular diseases.
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Serebrennikova, Svetlana N. "INFLAMMATION AS A FUNDAMENTAL PATHOLOGICAL PROCESS: LECTURE 1 (ALTERATION, VASCULAR REACTIONS)." Baikal Medical Journal 2, no. 2 (June 10, 2023): 53–64. http://dx.doi.org/10.57256/2949-0715-2023-2-53-64.
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Inflammation is the most widespread pathological process in medical practice. Inflammation is the basis of the vast majority of diseases. In this connection, the topic is actual for any medical student, as well as a doctor of any specialty. Local signs of inflammation (redness, swelling, heat, pain, dysfunction) were described more than two thousand years ago. Like any typical pathological process, inflammation includes protective and damaging reactions. Their knowledge is very important for understanding the pathogenesis of inflammatory diseases. The first part of the lecture describes the causes and mechanisms leading to the development of inflammation, as well as the consequences of tissue damage (acidosis, hyperonkia, hyperosmia, synthesis and release of inflammatory mediators). Inflammatory mediators are biologically active substances those regulate all reactions in the focus of inflammation. Various cells (neutrophils, macrophages, lymphocytes, endothelial cells, hepatocytes, etc.) can be sources of mediators. By origin, mediators are divided into cell-derived (biogenic amines, derivatives of arachidonic acid, lysosomal enzymes and reactive oxygen species, cytokines) and plasma-derived (components of the complement system, kinins and the hemostasis system). There are pro-inflammatory mediators (they increase inflammatory response) and anti-inflammatory ones. Under the influence of inflammatory mediators, changes in microcirculatory blood flow begin (vasospasm, arterial hyperemia, venous congestion, stasis) and exudation develops. Exudation is caused by an increase in the permeability of microvessels, its mechanisms are different. The composition of the exudate is determined by the cause of the inflammation and degree of tissue damage, the spectrum and amount of chemoattractants influence the type of exudate as well. The main types of exudates are serous, purulent, fibrinous, hemorrhagic, ichorous, catarrhal.
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Vulliamy, Paul, Scarlett Gillespie, Paul C. Armstrong, Harriet E. Allan, Timothy D. Warner, and Karim Brohi. "Histone H4 induces platelet ballooning and microparticle release during trauma hemorrhage." Proceedings of the National Academy of Sciences 116, no. 35 (August 12, 2019): 17444–49. http://dx.doi.org/10.1073/pnas.1904978116.
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Trauma hemorrhage is a leading cause of death and disability worldwide. Platelets are fundamental to primary hemostasis, but become profoundly dysfunctional in critically injured patients by an unknown mechanism, contributing to an acute coagulopathy which exacerbates bleeding and increases mortality. The objective of this study was to elucidate the mechanism of platelet dysfunction in critically injured patients. We found that circulating platelets are transformed into procoagulant balloons within minutes of injury, accompanied by the release of large numbers of activated microparticles which coat leukocytes. Ballooning platelets were decorated with histone H4, a damage-associated molecular pattern released in massive quantities after severe injury, and exposure of healthy platelets to histone H4 recapitulated the changes in platelet structure and function observed in trauma patients. This is a report of platelet ballooning in human disease and of a previously unrecognized mechanism by which platelets contribute to the innate response to tissue damage.
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Tikhomirova, I. A. "Blood Rheology and Microcirculation." Успехи физиологических наук 54, no. 1 (January 1, 2023): 3–25. http://dx.doi.org/10.31857/s0301179823010071.
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Abstract—The article discusses the features of the functioning of the microcirculation system, in particular, modern integrative ideas about the microcirculatory-tissue system, which provides blood supply and regulation of oxygen delivery in accordance with the metabolic needs of the tissue and organ. In this system, an important role belongs to the rheological properties of blood and the microrheological properties of erythrocytes, which act as intravasal regulators of microcirculation and have a significant impact on the functioning of the hemostasis system. In the implementation of the fundamental physiological function – oxygen supply to tissues matching their metabolic needs – erythrocytes play an active role, acting not only as a gas transporter, but also as a sensor of hypoxia and regulator of the endothelial vasodilatation function. The problems of dysfunction of the microcirculation and features of the rheological properties of blood in patients with severe COVID-19 are considered.
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Жданов, Александр Иванович, Андрей Анатольевич Иванов, Максим Сергеевич Шевелин, and Александр Сергеевич Брежнев. "IMPROVEMENT OF THROMBOTIC COMPLICATIONS PREVENTION AFTER OPERATIONS OF ENDOPROSTHETICS OF THE ABDOMINAL DEPARTMENT OF AORTA." СИСТЕМНЫЙ АНАЛИЗ И УПРАВЛЕНИЕ В БИОМЕДИЦИНСКИХ СИСТЕМАХ, no. 3() (September 30, 2020): 64–70. http://dx.doi.org/10.36622/vstu.2020.19.3.008.
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В статье представлены данные оригинального исследования по оптимизации антитромботической профилактики после хирургического лечения аневризм брюшного отдела аорты методом эндопротезирования. С этой целью произведен сравнительный анализ двух альтернативных друг другу подходов к предупреждению развития тромботических осложнений: 1) «традиционный подход» на основе использования препаратов дезагрегантов; 2) разработанная программа на основе использования препарата класса новых пероральных антикоагулянтов. Выдвинута научная гипотеза о том, что радикальная замена «традиционного подхода» на разработанную программу приведет к принципиальному снижению количества развивающихся послеоперационных тромботических осложнений. В независимых группах пациентов с использованием сравниваемых подходов к антитромботической профилактике произведена точная качественная и количественная оценка послеоперационных тромботических осложнений - тромбозов глубоких вен и тромбозов браншей протеза, а также ключевых клинико-лабораторных показателей системы гемостаза. После выполнения исследования было установлено, что принципиальная замена «традиционного подхода» на разработанную программу действительно приводит к принципиальному снижению уровня тромботических осложнений. При этом не происходит критических «сдвигов» как в сосудисто-тромбоцитарном, так и в коагуляционном звене системы гемостаза, и тем самым не создаются повышенный риск кровотечений. Полученные результаты имеют высокий уровень статистической значимости, что позволяет рекомендовать их к широкому использованию в практике сосудистой хирургии The article presents data from an original study on optimizing antithrombotic prophylaxis after surgical treatment of abdominal aortic aneurysms by endoprosthetics. To this end, a comparative analysis of two alternative approaches to preventing thrombotic complications has been made: 1) the «traditional approach» based on the use of disaggregant preparations; 2) a developed program based on the use of a drug of the class of new oral anticoagulants. A scientific hypothesis is put forward that the radical replacement of the “traditional approach” with the developed program will lead to a fundamental reduction in the number of developing postoperative thrombotic complications. In independent groups of patients, using the compared approaches to antithrombotic prophylaxis, an accurate qualitative and quantitative assessment of postoperative thrombotic complications - deep vein thrombosis and prosthetic branches thrombosis, as well as key clinical and laboratory parameters of the hemostasis system was performed. After carrying out the study, it was found that a fundamental replacement of the «traditional approach» with the developed program does lead to a fundamental decrease in the level of thrombotic complications. In this case, there are no critical «shifts» both in the vascular-platelet and in the coagulation unit of the hemostatic system, and thus there is no increased risk of bleeding. The results obtained have a high level of statistical significance, which allows us to recommend them for widespread use in the practice of vascular surgery
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Pantelic, Milos, Jelena Ljikar, Gordana Devecerski, and Jelena Karadzic. "Energy systems in surgery." Medical review 68, no. 11-12 (2015): 394–99. http://dx.doi.org/10.2298/mpns1512394p.
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Introduction. The systems of energy in surgery are applied in order to achieve better and more effective performing of procedures. Whereas various energy sources, including electricity, ultrasound, laser and argon gas, may be used, the fundamental principle involves tissue necrosis and hemostasis by heating. Electro Surgery. Electro Surgery is a surgical technique by which surgical procedures are performed by focused heating of the tissue using devices based on high-frequency currents. It represents one of the most frequently used energy systems in laparoscopy. Ultrasound Energy. The basic principle of operation of the ultrasound surgical instruments is the usage of low-frequency mechanic vibrations (ultrasound energy within the range of 20-60 kHz) for cutting and coagulation of tissue. Laser. Laser is the abbreviation for Light Amplification by Stimulated Emission of Radiation, aimed at increasing light by stimulated emission of radiation and it is the name of the instrument which generates coherent beam of light. Argon Plasma Coagulation. It has been in use since 1991 for endoscopic hemostasis. It uses highfrequency electric current and ionized gas argon. The successful application of devices depends on the type of surgical procedure, training of the surgeon and his knowledge about the device. Surgeons do not agree on the choice of device which would be optimal for a certain procedure. Conclusion. The whole team in the operating room must have the basic knowledge of the way an energy system works so as to provide a safe and effective treatment of patients. The advantages and shortcomings of different systems of energy have to be taken into account while we use a special mode.
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Pokrovskaya, Irina D., Smita Joshi, Michael Tobin, Rohan Desai, Maria A. Aronova, Jeffrey A. Kamykowski, Guofeng Zhang, Sidney W. Whiteheart, Richard D. Leapman, and Brian Storrie. "SNARE-dependent membrane fusion initiates α-granule matrix decondensation in mouse platelets." Blood Advances 2, no. 21 (November 6, 2018): 2947–58. http://dx.doi.org/10.1182/bloodadvances.2018019158.
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Abstract Platelet α-granule cargo release is fundamental to both hemostasis and thrombosis. Granule matrix hydration is a key regulated step in this process, yet its mechanism is poorly understood. In endothelial cells, there is evidence for 2 modes of cargo release: a jack-in-the-box mechanism of hydration-dependent protein phase transitions and an actin-driven granule constriction/extrusion mechanism. The third alternative considered is a prefusion, channel-mediated granule swelling, analogous to the membrane “ballooning” seen in procoagulant platelets. Using thrombin-stimulated platelets from a set of secretion-deficient, soluble N-ethylmaleimide factor attachment protein receptor (SNARE) mutant mice and various ultrastructural approaches, we tested predictions of these mechanisms to distinguish which best explains the α-granule release process. We found that the granule decondensation/hydration required for cargo expulsion was (1) blocked in fusion-protein-deficient platelets; (2) characterized by a fusion-dependent transition in granule size in contrast to a preswollen intermediate; (3) determined spatially with α-granules located close to the plasma membrane (PM) decondensing more readily; (4) propagated from the site of granule fusion; and (5) traced, in 3-dimensional space, to individual granule fusion events at the PM or less commonly at the canalicular system. In sum, the properties of α-granule decondensation/matrix hydration strongly indicate that α-granule cargo expulsion is likely by a jack-in-the-box mechanism rather than by gradual channel-regulated water influx or by a granule-constriction mechanism. These experiments, in providing a structural and mechanistic basis for cargo expulsion, should be informative in understanding the α-granule release reaction in the context of hemostasis and thrombosis.
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Thekke Veedu, Sruthi, Meghna U. Naik, John C. Kostyak, and Ulhas P. Naik. "Junctional Adhesion Molecule a (JAM-A) Associates with CD36 upon Platelet Activation and Cytoskeleton in a Phosphorylation-Dependent Manner to Promote Platelet-Platelet Contacts." Blood 142, Supplement 1 (November 28, 2023): 2568. http://dx.doi.org/10.1182/blood-2023-190993.
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Background: Platelets play a fundamental role inmaintaining hemostasis. Stability of hemostatic plug is crucial for arresting blood loss during vascular breach. JAM-A is a member of the immunoglobulin superfamily that restricts α IIbβ 3 to its low affinity state by recruiting CSK to the α IIbβ 3-c-Src complex in resting platelets. Agonist-induced inside-out signaling causes JAM-A to dissociate from the α IIbβ 3-Src complex, thus facilitating activation of α IIbβ 3 and outside-in signaling. However, the function of JAM-A in the process of hemostasis is poorly understood. Aim: To evaluate the role of JAM-A in activated platelets and on hemostasis. Methods: Washed human platelets were used in these studies. Full-length cytoplasmic domain of JAM-A (cyto JAM-A) and JAM-A cytoplasmic domain lacking C-terminal PDZ-domain-binding motif (ΔPDZ cyto JAM-A) were expressed as GST-fusion proteins in bacteria using pGEX4T-1 vector. GST-fusion proteins were purified using glutathione beads. Pull-down assays were performed by incubating glutathione GST-fusion proteins beads with lysates of washed human platelets (4×10 8/mL). GST beads alone without the fusion proteins were used as a control. Immunoprecipitation studies were performed using washed human platelets (4x10 8/mL) lysed with CHAPS lysis buffer and precleared by using Protein G Sepharose beads. Specific primary antibodies and isotype specific IgGs (control) were used for immunoprecipitation followed by western blotting. To identify protein complexes two-dimensional blue-native polyacrylamide gel electrophoresis was performed in which protein complexes were first separated based on their size (1 st dimension) and individual proteins in each complex were separated using SDS PAGE (2 nd dimension). JAM-A S 284 phosphorylation was detected using anti-Phospho-S 284. Rap1 activation assay was performed by pull-down GTP-bound Rap1 following the manufacturer's instructions. Results: CD9 and α IIbβ 3 co-immunoprecipitated with JAM-A from resting platelet lysates suggesting that CD9 is a part of the JAM-A/α IIbβ 3 complex. In a pull-down assay recombinant full-length JAM-A cytoplasmic tail fused with GST, but not JAM-A tail lacking the PDZ domain motif fused with GST pull-down CD9 and α IIbβ 3 from resting platelet lysates suggesting that PDZ-domain binding motif of JAM-A is responsible for its interaction with CD9/α IIbβ 3 complex. Interestingly, platelet activation resulted in the dissociation of JAM-A from the CD9/α IIbβ 3 complex as seen by loss of interaction between JAM-A and CD9/α IIbβ 3 in co-immunoprecipitation and blue-native PAGE assays. It is reported that platelet activation results in rapid phosphorylation of JAM-A on S 284 in a PKC-dependent manner. We found that S 284 phosphorylated JAM-A associates with CD36 and this complex moves to the Triton X-100 insoluble cytoskeletal fraction upon platelet activation suggesting that phosphorylation of JAM-A may assist its localization to cytoskeleton. Interestingly, we found that induction of conformational change in α IIbβ 3 using Mn 2+ (10μM) activates JAM-A S 284 phosphorylation. Furthermore, Mn 2+ also induced a robust activation of Rap1, a key signaling molecule involved in junctional assembly. Both JAM-A phosphorylation and Rap1 activation were significantly ( P<0.05) inhibited by a pan PKC inhibitor, bisindolylmaleimide (10μM) suggesting that S 284 phosphorylated JAM-A/CD36 complex may support junctional assembly within the platelet plug. Conclusion: JAM-A, through its cytoplasmic domain, associates with α IIbβ 3 and CD9 in resting platelets. Upon platelet activation JAM-A rapidly dissociates from this complex and is phosphorylated on S 284. Phosphorylated JAM-A then associates with CD36 and cytoskeleton leading to activation of Rap1, a protein important in junctional assembly between platelets within a hemostatic plug.
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Degen, Jay L., and Joseph S. Palumbo. "Thrombin Control Mechanisms and Thrombin Targets in Cancer Biology." Blood 118, no. 21 (November 18, 2011): SCI—17—SCI—17. http://dx.doi.org/10.1182/blood.v118.21.sci-17.sci-17.
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Abstract SCI-17 A link between hemostasis and cancer has been recognized for more than a century, but the last decade has seen substantial strides in understanding the mechanisms by which hemostatic system components actively contribute to the malignant phenotype. The expression of procoagulants, such as tissue factor (TF), by tumor cells has been shown to be a poor prognostic factor in clinical studies and a crucial determinant of metastasis in animal models. While TF expressed by tumor cells likely plays a multifaceted role in cancer biology, a substantial body of evidence indicates that tumor cell-associated and circulating hemostatic system components (e.g., prothrombin, fibrinogen, platelets) play a cooperative role in supporting metastasis. The capacity of tumor cells to generate thrombin has been proposed to support metastasis through several mechanisms, including tumor cell proliferation, stable adhesion, regulation of apoptosis, and escape from innate immune surveillance mechanisms. More recently, the fundamental importance of endothelial regulators of thrombin activity in metastasis was established through studies of tumor dissemination in mice expressing mutant forms of thrombomodulin (TM). Mice expressing a TM derivative with reduced thrombin affinity (TMPro) exhibited a profoundly prometastatic phenotype relative to wild-type (WT) mice. The TMPro mutation was shown to support metastasis by promoting the survival of tumor cell emboli newly localized to the lung. The impact of the TMPro mutation on metastasis was dependent on tumor cell-associated tissue factor, prothrombin, thrombin function, and platelets. In contrast, mice expressing a mutant form of TM lacking the lectin-like domain (TMLed) that were shown previously to have altered immune function but normal thrombin affinity, exhibited metastatic potential comparable to wild-type mice. These studies further highlight the importance of the hemostatic system in metastasis and demonstrate that apart from tumor cell-associated and circulating procoagulants, TM-mediated regulation of hemostatic function strongly influences tumor cell metastatic success. In addition, recent studies of inflammation-driven cancer have revealed that the role of hemostatic factors in tumor biology is not limited to later phases of malignant progression, such as metastasis. Fibrin(ogen)-mediated regulation of leukocyte function was shown to support tumor development and tumor proliferation in a murine model of inflammation-driven colon cancer. Recent advances in our understanding of the role of hemostatic factors in cancer biology demonstrate that this system of proteins can be important in multiple phases of malignant progression, and underscore the potential utility of targeting selected coagulation factors as a novel adjunct therapy in the treatment of cancer. Disclosures: Palumbo: Novo Nordisk Corporation: Research Funding.
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Renné, Thomas. "In Vivo Roles for Factor XII." Blood 116, no. 21 (November 19, 2010): SCI—19—SCI—19. http://dx.doi.org/10.1182/blood.v116.21.sci-19.sci-19.
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Abstract Abstract SCI-19 The coagulation system is critical for limiting blood loss at a site of injury (hemostasis), but may also contribute to thrombotic disease. The model of a coagulation balance represents these two sides of the same coin. Thrombosis may occur in the venous or arterial circulation, causing pulmonary embolism or myocardial infarction and stroke, collectively the most common causes of death in the developed world. Recent data from genetically altered mouse models have challenged the dogma of a coagulation balance. Deficiency of coagulation factor XII (Hageman factor), a serine protease, which initiates the intrinsic pathway of coagulation, severely impairs thrombus formation but is not associated with any excessive bleedings in humans or in mice. Targeting factor XII protects from occlusive disease in experimental animal models. Individuals with hereditary deficiency in the factor XII substrate factor XI are largely protected form ischemic stroke and deep-vein thrombosis. These findings indicate that fibrin-forming mechanisms, which operate during pathologic thrombus formation, involve pathways distinct from those proceeding during normal hemostasis. As the factor XII-driven contact system selectively contributes to thrombosis, but not to hemostasis, inhibition of the system offers novel anticoagulation strategies associated with minimal or no bleeding risk. In contrast to factor XII deficiency states, a single missense mutation (Thr328Lys) in the coagulation protein is associated with a life-threatening swelling disease, hereditary angioedema type III. Pharmacological factor XII inhibitors interfered both with pathological thrombosis and edema formation suggesting broad medical implications. Factor XII is activated in vivo by platelet-released inorganic polyphosphate, a linear polymer of 60–100 phosphate residues that directly bound to the coagulation factor. Polyphosphates-driven factor XII activation triggered release of the inflammatory mediator bradykinin. Polyphosphates increased vascular permeability and induced skin edema formation in mice and animals deficient in factor XII or bradykinin receptors were resistant to polyphosphates-induced leakage. Polyphosphates were procoagulant via the intrinsic pathway of coagulation. Ablation of intrinsic coagulation pathway proteases factors XII and XI protected mice from polyphosphate-triggered lethal pulmonary embolism. Targeting polyphosphates with phosphatases interfered with procoagulant activity of activated platelets and blocked platelet-induced thrombosis in mice. Addition of polyphosphates restored defective plasma clotting of Hermansky-Pudlak Syndrome patients, who platelet lack storage organelles for polyphosphates. The data identify polyphosphates as the endogenous activator of factor XII having fundamental roles in platelet-driven proinflammatory and procoagulant disorders. Disclosures: No relevant conflicts of interest to declare.
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Lotta, Luca Andrea, Giacomo Tuana, Jin Yu, Ida Martinelli, Mark Wang, Fuli Yu, Serena Maria Passamonti, et al. "Rare Coding Single Nucleotide Variants of ADAMTS13 Are Associated with Deep Vein Thrombosis in a Next-Generation Sequencing Association Study." Blood 120, no. 21 (November 16, 2012): 107. http://dx.doi.org/10.1182/blood.v120.21.107.107.
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Abstract Abstract 107 The considerable genetic predisposition to deep vein thrombosis (DVT) is only partially accounted for by known genetic risk variants. Genome-wide association studies investigating hundreds of thousands of common single nucleotide variants (SNVs) identified a number of associations, but missing heritability remains. Rare (i.e. minor allele frequency below 1%) and low-frequency (i.e. minor allele frequency below 5%) SNVs of the coding area may be responsible for at least part of this missing heritability. In order to investigate this, we sequenced 700,000 base pairs of genomic DNA including the protein coding exons and intron-exon boundaries of 186 hemostatic/pro-inflammatory genes. Indexed genomic DNA libraries were co-captured on NimbleGen HD2 2.1M-probe chips and capture products were sequenced on SOLiD 4 platforms. More than 70 billion base-pairs of raw sequence data were produced to sequence the target area with a median redundancy of 45X in 94 thrombophilia-negative patients with DVT and 98 controls. Most of the 4366 SNVs identified were rare, novel and nonsynonymous indicating pathogenetic potential. We tested the association of coding SNVs in the ADAMTS13 and VWF genes, encoding two interconnected proteins with fundamental roles in hemostasis. Sequencing of the two genes yielded 109 variants, 108 SNVs and a c.8241_8442del frameshift deletion in exon 51 of VWF. Being a carrier of rare coding (prevalence in DVT: 17% [n=16]; prevalence in controls 4% [n=4]; odds ratio [OR]: 4.8; 95% confidence interval [CI]: 1.6–15.0), rare nonsynonymous (prevalence in DVT: 11% [n=10]; prevalence in controls 3% [n=3]; OR: 3.8; 95% CI: 1.0–14.2) or low-frequency coding (prevalence in DVT: 36% [n=34]; prevalence in controls 23% [n=23]; OR: 1.9; 95% CI: 1.0–3.5) SNVs of ADAMTS13 was associated with DVT. Carrying rare or low-frequency SNVs of VWF was not associated with DVT. The 11 different rare missense variants of ADAMTS13 found in DVT patients had never been described in association with congenital thrombotic thrombocytopenic purpura. Patients carrying at least one ADAMTS13 mutation of the categories associated with DVT had lower plasmatic levels of ADAMTS13 activity compared to patients without mutations. The change in ADAMTS13 activity was −7% (95% CI: −24 to 10%) for patients with rare coding ADAMTS13 mutations, −12% (95% CI: −30 to 6%) for patients with rare nonsynonymous mutations and −29% (95% CI: −52 to −6%) for patients with missense mutations predicted to be damaging for protein function by SIFT. Our results uncover for the first time a link between ADAMTS13, an important regulator of hemostasis implicated in microvascular thrombosis, and DVT. Disclosures: No relevant conflicts of interest to declare.
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Iskander, Gaby P., and Eugene Y. Cheng. "FUNDAMENTALS OF NORMAL HEMOSTASIS." Anesthesiology Clinics of North America 17, no. 4 (December 1999): 715–31. http://dx.doi.org/10.1016/s0889-8537(05)70130-9.
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Kanova, Marcela, and Pavel Kohout. "Serotonin—Its Synthesis and Roles in the Healthy and the Critically Ill." International Journal of Molecular Sciences 22, no. 9 (May 3, 2021): 4837. http://dx.doi.org/10.3390/ijms22094837.
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Serotonin (5-hydroxytryptamine, 5-HT) plays two important roles in humans—one central and the other peripheral—depending on the location of the 5-HT pools of on either side of the blood-brain barrier. In the central nervous system it acts as a neurotransmitter, controlling such brain functions as autonomic neural activity, stress response, body temperature, sleep, mood and appetite. This role is very important in intensive care, as in critically ill patients multiple serotoninergic agents like opioids, antiemetics and antidepressants are frequently used. High serotonin levels lead to altered mental status, deliria, rigidity and myoclonus, together recognized as serotonin syndrome. In its role as a peripheral hormone, serotonin is unique in controlling the functions of several organs. In the gastrointestinal tract it is important for regulating motor and secretory functions. Apart from intestinal motility, energy metabolism is regulated by both central and peripheral serotonin signaling. It also has fundamental effects on hemostasis, vascular tone, heart rate, respiratory drive, cell growth and immunity. Serotonin regulates almost all immune cells in response to inflammation, following the activation of platelets.
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Brown, Edward, Leo M. Carlin, Claus Nerlov, Cristina Lo Celso, and Alastair W. Poole. "Multiple membrane extrusion sites drive megakaryocyte migration into bone marrow blood vessels." Life Science Alliance 1, no. 2 (May 2018): e201800061. http://dx.doi.org/10.26508/lsa.201800061.
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Platelets, cells central to hemostasis and thrombosis, are formed from parent cell megakaryocytes. Although the process is highly efficient in vivo, our ability to generate them in vitro is still remarkably inefficient. We proposed that greater understanding of the process in vivo is needed and used an imaging approach, intravital correlative light electron microscopy, to visualize platelet generation in bone marrow in the living mouse. In contrast to current understanding, we found that most megakaryocytes enter the sinusoidal space as large protrusions rather than extruding fine proplatelet extensions. The mechanism for large protrusion migration also differed from that of proplatelet extension. In vitro, proplatelets extend by sliding of dense bundles of microtubules, whereas in vivo our data showed the absence of microtubule bundles in the large protrusion, but the presence of multiple fusion points between the internal membrane and the plasma membrane, at the leading edge of the protruding cell. Mass membrane fusion, therefore, drives megakaryocyte large protrusions into the sinusoid, significantly revising our understanding of the fundamental biology of platelet formation in vivo.
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Senis, Yotis A., Michael G. Tomlinson, Stuart Ellison, Alexandra Mazharian, Jenson Lim, Yan Zhao, Kristin N. Kornerup, et al. "The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis." Blood 113, no. 20 (May 14, 2009): 4942–54. http://dx.doi.org/10.1182/blood-2008-08-174318.
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Abstract Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase–linked and G protein–coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced in CD148-deficient platelets, resulting in a global hyporesponsiveness to agonists that signal through SFKs, including collagen and fibrinogen. G protein–coupled receptor responses to thrombin and other agonists were also marginally reduced. These results highlight CD148 as a global regulator of platelet activation and a novel antithrombotic drug target.
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Ghoshal, Kakali, and Maitree Bhattacharyya. "Overview of Platelet Physiology: Its Hemostatic and Nonhemostatic Role in Disease Pathogenesis." Scientific World Journal 2014 (2014): 1–16. http://dx.doi.org/10.1155/2014/781857.
Full textAbstract:
Platelets are small anucleate cell fragments that circulate in blood playing crucial role in managing vascular integrity and regulating hemostasis. Platelets are also involved in the fundamental biological process of chronic inflammation associated with disease pathology. Platelet indices like mean platelets volume (MPV), platelets distributed width (PDW), and platelet crit (PCT) are useful as cheap noninvasive biomarkers for assessing the diseased states. Dynamic platelets bear distinct morphology, whereαand dense granule are actively involved in secretion of molecules like GPIIb , IIIa, fibrinogen, vWf, catecholamines, serotonin, calcium, ATP, ADP, and so forth, which are involved in aggregation. Differential expressions of surface receptors like CD36, CD41, CD61 and so forth have also been quantitated in several diseases. Platelet clinical research faces challenges due to the vulnerable nature of platelet structure functions and lack of accurate assay techniques. But recent advancement in flow cytometry inputs huge progress in the field of platelets study. Platelets activation and dysfunction have been implicated in diabetes, renal diseases, tumorigenesis, Alzheimer’s, and CVD. In conclusion, this paper elucidates that platelets are not that innocent as they keep showing and thus numerous novel platelet biomarkers are upcoming very soon in the field of clinical research which can be important for predicting and diagnosing disease state.
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Brondijk, T. Harma C., Talitha de Ruiter, Joost Ballering, Hans Wienk, Robert Jan Lebbink, Hugo van Ingen, Rolf Boelens, Richard W. Farndale, Linde Meyaard, and Eric G. Huizinga. "Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI." Blood 115, no. 7 (February 18, 2010): 1364–73. http://dx.doi.org/10.1182/blood-2009-10-246322.
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Abstract Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), one of the most widely spread immune receptors, attenuates immune cell activation when bound to specific sites in collagen. The collagen-binding domain of LAIR-1 is homologous to that of glycoprotein VI (GPVI), a collagen receptor crucial for platelet activation. Because LAIR-1 and GPVI also display overlapping collagen-binding specificities, a common structural basis for collagen recognition would appear likely. Therefore, it is crucial to gain insight into the molecular interaction of both receptors with their ligand to prevent unwanted cross-reactions during therapeutic intervention. We determined the crystal structure of LAIR-1 and mapped its collagen-binding site by nuclear magnetic resonance (NMR) titrations and mutagenesis. Our data identify R59, E61, and W109 as key residues for collagen interaction. These residues are strictly conserved in LAIR-1 and GPVI alike; however, they are located outside the previously proposed GPVI collagen-binding site. Our data provide evidence for an unanticipated mechanism of collagen recognition common to LAIR-1 and GPVI. This fundamental insight will contribute to the exploration of specific means of intervention in collagen-induced signaling in immunity and hemostasis.
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Chang, Jae Chan. "Novel Classification of Thrombotic Disorders Based on Molecular Hemostasis and Thrombogenesis Producing Primary and Secondary Phenotypes of Thrombosis." Biomedicines 10, no. 11 (October 26, 2022): 2706. http://dx.doi.org/10.3390/biomedicines10112706.
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Thrombosis, the common and deadliest disorder among human diseases, develops as a result of the intravascular hemostasis following an intravascular injury, which can be caused by a variety of trauma, non-traumatic insults or clinical illnesses. Thrombosis can occur at any location of the vascular system supplied by blood from the heart to large and smallest arterial and venous systems and may affect the function and anatomy of the organ and tissue. It more commonly occurs in the smaller circulatory system of the vascular tree such as arterioles and capillaries, and venules of the organs, especially in the brain, lungs, heart, pancreas, muscle and kidneys, and sinusoids of the liver. Thrombosis has been referred as the disease of “blood clots”, which concept is incompletely defined, but represents many different hemostatic diseases from microthrombosis to fibrin clot disease, macrothrombosis, and combined micro-macrothrombosis. Thrombosis is produced following an intravascular injury via one or more combination of four different mechanisms of thrombogenesis: microthrombogenesis, fibrinogenesis, macrothrombogenesis and micro-macrothrombogenesis initiated by normal physiological hemostasis in vivo. The clinical phenotype expression of thrombosis is determined by: (1) depth of the intravascular wall injury, (2) extent of the injury affecting the vascular tree system, (3) physiological character of the involved vascular system, (4) locality of the vascular injury, and (5) underlying non-hemostatic conditions interacting with hemostasis. Recent acquisition of “two-path unifying theory” of hemostasis and “two-activation theory of the endothelium” has opened a new frontier in science of medicine by identifying the pathophysiological mechanism of different thrombotic disorders, and also contributing to the better understanding of many poorly defined human diseases, including different phenotypes of stroke and cardiovascular disease, trauma, sepsis and septic shock, multiorgan dysfunction syndrome, and autoimmune disease, and others. Reviewed are the fundamentals in hemostasis, thrombogenesis and thrombosis based on hemostatic theories, and proposed is a novel classification of thrombotic disorders.
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Khemichian, Saro, and Norah A. Terrault. "Thrombopoietin Receptor Agonists in Patients with Chronic Liver Disease." Seminars in Thrombosis and Hemostasis 46, no. 06 (August 20, 2020): 682–92. http://dx.doi.org/10.1055/s-0040-1715451.
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AbstractThrombocytopenia is one of the most common hematologic complications in cirrhosis. Despite limited data linking platelet count and bleeding risk in patients with cirrhosis, the use of platelets transfusions for invasive procedures has been a common practice. Recently, thrombopoietin (TPO) receptor agonists have been approved for use in patients with chronic liver disease (CLD) undergoing invasive procedures. The aim of this study was to review current literature on bleeding risk in patients with cirrhosis and the use of platelet transfusions and TPO receptor agonists in the context of invasive procedures. PubMed search was conducted to find articles relating to cirrhosis, thrombocytopenia, and new novel treatments for this condition. Search terms included CLD, cirrhosis, thrombocytopenia, bleeding, thrombosis, coagulopathy, hemostasis, and TPO receptor agonists. Romiplostim, eltrombopag, avatrombopag, and lusutrombopag are approved TPO receptor agonists, with avatrombopag and lusutrombopag specifically approved for use in patients with CLD undergoing invasive procedures. In patients with platelet counts < 50,000/mm3, avatrombopag and lusutrombopag increased the platelet counts above this threshold in the majority of treated patients and reduced the frequency of platelet transfusions. At the approved doses, incidence of thrombosis was not increased and therapies were well tolerated. Studies were not powered to assess whether risk of bleeding complications was reduced and the fundamental question of whether correction of thrombocytopenia is warranted in patients undergoing invasive procedures remains unanswered. The use of TPO receptor agonists has resulted in less requirement for platelet transfusions. In patients with cirrhosis undergoing invasive procedures for whom platelet transfusion is planned, TPO receptor agonists are an alternative and avoid the risks associated with transfusions. However, there is need for a thoughtful approach to manage bleeding risk in patients with cirrhosis undergoing procedures, with the consideration of a comprehensive hemostatic profile, the severity of portal hypertension, and the complexity of the invasive procedure to guide decisions regarding transfusions or use of TPO receptor agonists.
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Naik, Meghna U., and Ulhas P. Naik. "Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen." Blood 102, no. 10 (November 15, 2003): 3629–36. http://dx.doi.org/10.1182/blood-2003-05-1703.
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AbstractPlatelet spreading on the subendothelium in response to vascular injury is fundamental to the regulation of physiologic hemostasis. Previously, we have shown that, when bound to glycoprotein IIb (GPIIb), calcium- and integrin-binding protein (CIB) regulates platelet spreading on immobilized fibrinogen (Fg). In this study, we investigated the signaling events that occur downstream of CIB in the absence of signaling that occurs as a result of granular secretion. Using Chinese hamster ovary (CHO) cells as a model, we demonstrate that CIB induces cell migration. Immunofluorescence analysis of CIB localization indicates that endogenous CIB accumulates in areas of focal adhesions, and its overexpression up-regulates the formation of focal adhesion complexes compared with control cells. Immunoprecipitation analysis indicates that CIB associates with focal adhesion kinase (FAK), a key regulator in focal complex formation, and up-regulates its activity. Overexpression of dominant-negative FAK, FRNK, along with CIB in CHO cells completely inhibits CIB-induced cell migration. Further, confirmation of these data in the platelet system indicates that CIB and FAK associate throughout all stages of platelet spreading but only on Fg binding to GPIIb/IIIa. Taken together, our results suggest that CIB regulates platelet spreading through the regulation of FAK activation. (Blood. 2003;102: 3629-3636)
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David, Victor, Barbara Barbosa Succar, João Alfredo de Moraes, Roberta Ferreira Gomes Saldanha-Gama, Christina Barja-Fidalgo, and Russolina Benedeta Zingali. "Recombinant and Chimeric Disintegrins in Preclinical Research." Toxins 10, no. 8 (August 7, 2018): 321. http://dx.doi.org/10.3390/toxins10080321.
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Disintegrins are a family of small cysteine-rich peptides, found in a wide variety of snake venoms of different phylogenetic origin. These peptides selectively bind to integrins, which are heterodimeric adhesion receptors that play a fundamental role in the regulation of many physiological and pathological processes, such as hemostasis and tumor metastasis. Most disintegrins interact with integrins through the RGD (Arg-Gly-Asp) sequence loop, resulting in an active site that modulates the integrin activity. Some variations in the tripeptide sequence and the variability in its neighborhood result in a different specificity or affinity toward integrin receptors from platelets, tumor cells or neutrophils. Recombinant forms of these proteins are obtained mainly through Escherichia coli, which is the most common host used for heterologous expression. Advances in the study of the structure-activity relationship and importance of some regions of the molecule, especially the hairpin loop and the C-terminus, rely on approaches such as site-directed mutagenesis and the design and expression of chimeric peptides. This review provides highlights of the biological relevance and contribution of recombinant disintegrins to the understanding of their binding specificity, biological activities and therapeutic potential. The biological and pharmacological relevance on the newest discoveries about this family of integrin-binding proteins are discussed.
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La Terra, Salvatore Luca. "What Factors can have an impact on the wound Healing Process from an oral surgery perspective? A Review." SVOA Dentistry 5, no. 1 (February 9, 2024): 33–45. http://dx.doi.org/10.58624/svoade.2024.05.0167.
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Wound healing is a complex and dynamic process that involves a series of intricately regulated phases, each contributing to the restoration of tissue integrity. This comprehensive review dives into the fundamental aspects of wound healing, exploring the physiological mechanisms, phases, and influencing factors. The review begins with describing the significance of wound healing and navigates through sequential phases, such as hemostasis and inflammation, proliferation, remodelling, wound classification and closure techniques, thus providing insights into the diverse strategies employed in clinical settings. Much focus lies to bone healing, addressing both primary and secondary healing mechanisms, as well as the bone healing in extraction sockets. A significant segment of the review explores the factors affecting wound healing, which are categorized into local, surgical, and systemic factors encompassing ageing, diabetes mellitus, hormonal changes, immunocompromised conditions, medications, smoking, alcohol consumption, obesity, and nutrition deficiency. A synthesis of the reviewed content highlights the interplay of these factors in the ‘wound healing’ process. Understanding these elements is imperative for clinicians and researchers alike to develop effective therapeutic interventions tailored to individual patient needs. This review serves as a valuable resource for those seeking a comprehensive understanding of the intricate dynamics of wound healing in the human body.
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Riley, Jeffrey B., Bruce E. Searles, Edward M. Darling, Dawn M. Oles, and Hani Aiash. "The Effectiveness of Three Different Curricular Models to Teach Fundamental ECMO Specialist Skills to Entry Level Perfusionists." Journal of ExtraCorporeal Technology 53, no. 4 (December 2021): 245–50. http://dx.doi.org/10.1051/ject/202153245.
Full textAbstract:
The dramatic increase in the use of extracorporeal membrane oxygenation (ECMO) over the last decade with the concomitant need for ECMO competent perfusionists has raised questions of how well perfusion education programs are preparing entry-level perfusionists to participate in ECMO. While all perfusion schools teach ECMO principles, there is no standardized or systematic approach to the delivery of didactic knowledge and clinical skills in ECMO. Given this variability of ECMO education across and within perfusion schools, the CES-A exam may provide a metric for comparing curricular approaches. The purpose of this study is to examine three different curricular approaches to prepare new perfusion graduates to master the Adult ECMO Specialist Certification exam (CES-A). We examined three different curricular approaches to prepare new perfusion graduates to master the Adult ECMO Specialist Certification exam (CES-A). We hypothesized that there would be no difference in CES-A pass rate, exam score, Rasch measure, and item category scores between SUNY Cardiovascular Perfusion Program (CVP) graduates who completed SUNY’s ECMO Capstone experience (Group III) and CVP graduates who did not select the ECMO Capstone experience (Group II). Further, we studied the performance of a third group of new graduates from an external program that does not offer formal ECMO courses or an ECMO Capstone experience (Group I). Every perfusion graduate in all groups passed the adult ECMO specialist exam. The graduates who as students completed an ECMO Capstone experience (Group III) scored higher on the exam and significantly higher on four exam categories: coagulation and hemostasis (p = .058), lab analysis point of care (p = .035), and monitor patient and circuit (p = .073), and the safety and failure modes (p = .017). Overall the median graduate Rasch measures ranked with Group III demonstrating the highest measure to Group I the lowest measures (not significant at p = .085). There is a positive educational effect due to CVP graduates completion of the ECMO Capstone experience compared to the program standard ECMO-related curricula in the two perfusion programs participating in this study. From this observation a structured ECMO simulation-based program appears to be equally effective as a traditional, typical lecture-only, clinical perfusion preceptorship, while demonstrating a more satisfactory experience with a higher reported case experience. In this study the standard perfusionist education curriculum prepared the new graduate to be successful on the CES-A exam. The three curricular approaches appear to prepare perfusionist graduates to be successful on the Adult ECMO Specialist exam.
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Cruz, Lisa. "Clinical Hematology and Fundamentals of Hemostasis." American Journal of Clinical Pathology 108, no. 5 (November 1, 1997): 599.2–599. http://dx.doi.org/10.1093/ajcp/108.5.599a.
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