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Thrombosis and Haemostasis Jun 2017The biochemical characterisation of the proteolytic pathways that constitute blood coagulation was one of the most relevant achievements in biomedical research during... (Review)
Review
The biochemical characterisation of the proteolytic pathways that constitute blood coagulation was one of the most relevant achievements in biomedical research during the second half of the 20th century. Understanding these pathways was of crucial importance for improving global health through application in haemostasis and thrombosis pathologies. Immediately after the cloning of the genes corresponding to these proteins, mutations were discovered in them that were associated with imbalances in haemostasis. Later, the importance of coagulation pathways in other pathological processes was demonstrated, such as in atherosclerosis and inflammation, both essential processes involved in vascular disease. In the present review we evaluate the concepts that have allowed us to reach the integrated vision on coagulation that we have today. The thrombo-inflammation model encompassing these aspects includes a pivotal role for the proteases of the coagulation pathway as well as the regulatory proteins thereof. These concepts illustrate the importance of the coagulation cascade in cardiovascular pathology, not only in thrombotic processes, but also in atherosclerotic processes and in the response to ischaemia-reperfusion injury, making it a central mechanism in cardiovascular disease.
Topics: Blood Coagulation; Blood Coagulation Factors; Cardiovascular Diseases; Hemostasis; Humans; Mutation; Peptide Hydrolases; Proteolysis; Reperfusion Injury; Thrombosis
PubMed: 28594052
DOI: 10.1160/TH17-02-0079 -
American Journal of Physiology.... Aug 2018Liver is the primary source of numerous proteins that are critical for normal function of the blood coagulation cascade. Because of this, diseases of the liver,... (Review)
Review
Liver is the primary source of numerous proteins that are critical for normal function of the blood coagulation cascade. Because of this, diseases of the liver, particularly when affiliated with severe complications like cirrhosis, are associated with abnormalities of blood clotting. Although conventional interpretation has inferred cirrhosis as a disorder of uniform bleeding risk, it is now increasingly appreciated as a disease wherein the coagulation cascade is precariously rebalanced. Moreover, prothrombotic risk factors are also associated with a more rapid progression of fibrosis in humans, suggesting that coagulation proteases participate in disease pathogenesis. Indeed, strong evidence drawn from experimental animal studies indicates that components of the coagulation cascade, particularly coagulation factor Xa and thrombin, drive profibrogenic events, leading to hepatic fibrosis. Here, we concisely review the evidence supporting a pathologic role for coagulation in the development of liver fibrosis and the potential mechanisms involved. Further, we highlight how studies in experimental animals may shed light on emerging clinical evidence, suggesting that beneficial effects of anticoagulation could extend beyond preventing thrombotic complications to include reducing pathologies like fibrosis.
Topics: Animals; Blood Coagulation; Blood Coagulation Factors; Humans; Liver Cirrhosis
PubMed: 29723040
DOI: 10.1152/ajpgi.00402.2017 -
Military Medical Research 2016Traumatic injury is one of the leading causes of death, with uncontrolled hemorrhage from coagulation dysfunction as one of the main potentially preventable causes of... (Review)
Review
Traumatic injury is one of the leading causes of death, with uncontrolled hemorrhage from coagulation dysfunction as one of the main potentially preventable causes of the mortality. Hypothermia, acidosis, and resuscitative hemodilution have been considered as the significant contributors to coagulation manifestations following trauma, known as the lethal triad. Over the past decade, clinical observations showed that coagulopathy may be present as early as hospital admission in some severely injured trauma patients. The hemostatic dysfunction is associated with higher blood transfusion requirements, longer hospital stay, and higher mortality. The recognition of this early coagulopathy has initiated tremendous interest and effort in the trauma community to expand our understanding of the underlying pathophysiology and improve clinical treatments. This review discusses the current knowledge of coagulation complications following trauma.
Topics: Blood Coagulation; Blood Coagulation Disorders; Hemorrhage; Humans; Wounds and Injuries
PubMed: 27895932
DOI: 10.1186/s40779-016-0105-2 -
Lancet (London, England) Jan 2022
Topics: Anticoagulants; Blood Coagulation; COVID-19; Humans; SARS-CoV-2
PubMed: 34921757
DOI: 10.1016/S0140-6736(21)02503-4 -
Interplay between coagulation and inflammation in cancer: Limitations and therapeutic opportunities.Cancer Treatment Reviews Jan 2022Advances in understanding the molecular mechanisms of tumor progression have achieved impressive progress in the treatment of cancer and so-called immune checkpoint... (Review)
Review
Advances in understanding the molecular mechanisms of tumor progression have achieved impressive progress in the treatment of cancer and so-called immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Indeed, antibody-based drugs blocking immune escape of tumor cells by modulation of T cell responses are increasingly utilized for a wide range of tumor entities. Nonetheless, response rates remain limited, and the development of secondary resistance is a common problem. In addition, by increasing the immune response a variety of severe side effects are provoked. Next to autoimmune responses, activation of the complement system and skin toxicity, an increased incidence for thrombotic complications has been observed associated with an increased mortality rate. Based on this, it can be postulated that the interplay of coagulation with inflammation in the tumor microenvironment is relevant for each step in the tumor life cycle. This review focuses on the coagulation as central player fostering mechanisms associated with tumor progression. Thus, a better understanding of the molecular pathways involved in the complex interaction of circulating tumor cells, the plasmatic coagulation and immune cells may help to improve therapeutic concepts reducing mortality and morbidity associated with cancer.
Topics: Anticoagulants; Blood Coagulation; Heparin, Low-Molecular-Weight; Humans; Immune Checkpoint Inhibitors; Inflammation; Neoplasms; Thrombosis; Tumor Escape
PubMed: 34922151
DOI: 10.1016/j.ctrv.2021.102322 -
Blood Apr 2021
Topics: Blood Coagulation; Humans; Neoplasms; Oncogenes; Thrombosis
PubMed: 33856444
DOI: 10.1182/blood.2020009967 -
Internal and Emergency Medicine Nov 2020The overflow of studies in the recent literature on COVID-19 often gives provisional or contradictory results and therefore deserves pauses of reflection and...
The overflow of studies in the recent literature on COVID-19 often gives provisional or contradictory results and therefore deserves pauses of reflection and reconsideration. In fact, knowledges of pathophysiology of this new disease are still in development and hence originate discussions and interpretations. Regarding the role of blood coagulation and fibrinolysis, these mechanisms should be considered as crucial especially in severe cases. It is proposed to consider two distinct phenotypes of thrombotic manifestations: the current "thromboembolic type" also occurring in other kinds of sepsis, and the diffuse micro-thrombotic type, prevailing in the lungs but sometimes extending to other organs. Both types can induce severe disease and are potentially lethal. The micro-thrombotic pattern, more specific for COVID-19, results from a massive activation of coagulation strictly coupled with a hyper-intense inflammatory and immune reaction. This results in widespread occlusive thrombotic micro-angiopathy with destruction of alveoli and obstructive neoangiogenesis. The involvement of fibrinolysis, often neglected, confers a double faceted process of activation/inhibition, finally conducive to a fibrinolytic shutdown that reinforces persistence of micro-thrombi. Considering these peculiar mechanisms, it seems evident that both prophylactic and therapeutic effects of current anti-thrombotic drugs cannot be taken for granted and need therefore new specific and rigorous controlled trials.
Topics: Blood Coagulation; COVID-19; Coronavirus Infections; Fibrinolysis; Humans; Pandemics; Pneumonia, Viral; Thrombolytic Therapy
PubMed: 32748128
DOI: 10.1007/s11739-020-02443-8 -
Journal of Clinical Laboratory Analysis May 2021Platelets play a pivotal role in hemostasis. Activated platelets are classified into two groups, according to their agonist response: aggregating and procoagulant... (Review)
Review
Platelets play a pivotal role in hemostasis. Activated platelets are classified into two groups, according to their agonist response: aggregating and procoagulant platelets. Aggregating platelets consist of activated integrin αIIbβ3 and stretch out pseudopods to further attract platelets to the site of injury by connecting with fibrinogen. They mainly gather in the core of the thrombus and perform a secretory function, such as releasing adenosine diphosphate (ADP). Procoagulant platelets promote the formation of thrombin and fibrin by interacting with coagulation factors and can thus be considered as the connector between primary and secondary hemostasis. In addition to their functions in blood coagulation, procoagulant platelets play a proinflammatory role by releasing platelet microparticles and inorganic polyphosphate. Considering these important functions of procoagulant platelets, this subpopulation warrants detailed study to analyze their potential in preventing human diseases. This review summarizes the generation and important characteristics of procoagulant platelets, as well as their potential for preventing the adverse effects associated with current antiplatelet therapies.
Topics: Apoptosis; Biomarkers; Blood Coagulation; Blood Platelets; Humans; Necrosis
PubMed: 33709517
DOI: 10.1002/jcla.23750 -
Clinical Cardiology Apr 1990Recent advances in the understanding of blood coagulation provide strong evidence that exposure of tissue factor is the "match" which initiates blood coagulation. A... (Review)
Review
Recent advances in the understanding of blood coagulation provide strong evidence that exposure of tissue factor is the "match" which initiates blood coagulation. A novel plasma protease inhibitor, called EPI or LACI, effectively extinguishes this "match," leaving Factors IXa, VIII, X, V, and II to function as a "fuse." Activated Factors IX, X, and II are controlled by heparin-enhancable protease inhibitors. Activated Factors VIII and V are destroyed by the protein C/S system. Fibrinolysis is largely cell-based and controlled by differential secretion of plasminogen activators and plasminogen activator inhibitors.
Topics: Blood Coagulation; Factor VII; Fibrinolysis; Humans; Lipoproteins; Thromboplastin
PubMed: 2191814
DOI: No ID Found -
Medical Principles and Practice :... 2009This is a review of less well-known aspects of thrombophilia and hypercoagulability as they relate to thrombosis. Thrombosis is an abnormal fibrin clot that develops in... (Review)
Review
This is a review of less well-known aspects of thrombophilia and hypercoagulability as they relate to thrombosis. Thrombosis is an abnormal fibrin clot that develops in circulating blood with clinical symptoms of one or more arterial and/or venous obstructions exclusively identified by imaging techniques. The terms thrombophilia and hypercoagulability are often used indiscriminately when they are in fact separate entities. Thrombophilia is an inherited or acquired clinical phenotype manifesting in selected individuals as a greater risk to develop recurrent thrombosis at a younger age than the general population, with considerable differences in the magnitude of risks among individuals in the same family with the same thrombophilic gene defect. Hypercoagulability is a laboratory phenotype whereby in vivo activation of clotting, fibrinolysis, endothelial cells and platelets is identified in vitro by specialized clotting techniques and by specific antibodies directed at biomarkers of clotting activation and damaged vasculature. Hypercoagulability may be provoked by drugs to treat bleeding in hemophilia, by sepsis, inflammation, surgery, blood stasis, atherosclerosis, and it manifests selectively in inherited and acquired thrombophilia. A chronology of the discovery of acquired and inherited thrombophilia puts in perspective the data analyzed in two representative large family studies that address whether venous and arterial thrombosis are a necessary outcome in thrombophilia, and the question, whether patients with inherited antithrombin, protein C and protein S deficiencies need to be treated after a first episode of thrombosis. The liberal use of case vignettes emphasizes a close relationship and the distinction between thrombosis, thrombophilia and hypercoagulability.
Topics: Blood Coagulation; Humans; Thrombophilia; Thrombosis
PubMed: 19797918
DOI: 10.1159/000235891