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Blood Reviews Mar 2021Haemostasis stops bleeding at the site of vascular injury and maintains the integrity of blood vessels through clot formation. This regulated physiological process... (Review)
Review
Haemostasis stops bleeding at the site of vascular injury and maintains the integrity of blood vessels through clot formation. This regulated physiological process consists of complex interactions between endothelial cells, platelets, von Willebrand factor and coagulation factors. Haemostasis is initiated by a damaged vessel wall, followed with a rapid adhesion, activation and aggregation of platelets to the exposed subendothelial extracellular matrix. At the same time, coagulation factors aggregate on the procoagulant surface of activated platelets to consolidate the platelet plug by forming a mesh of cross-linked fibrin. Platelets and coagulation mutually influence each other and there are strong indications that, thanks to the interplay between platelets and coagulation, haemostasis is far more effective than the two processes separately. Clinically this is relevant because impaired interaction between platelets and coagulation may result in bleeding complications, while excessive platelet-coagulation interaction induces a high thrombotic risk. In this review, platelets, coagulation factors and the complex interaction between them will be discussed in detail.
Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Disease Susceptibility; Hemostasis; Humans; Platelet Activation; Platelet Aggregation; Platelet Membrane Glycoproteins; Protein Binding
PubMed: 32682574
DOI: 10.1016/j.blre.2020.100733 -
International Journal of Environmental... Aug 2021Hypothermia in trauma patients is a common condition. It is aggravated by traumatic hemorrhage, which leads to hypovolemic shock. This hypovolemic shock results in a... (Review)
Review
Hypothermia in trauma patients is a common condition. It is aggravated by traumatic hemorrhage, which leads to hypovolemic shock. This hypovolemic shock results in a lethal triad of hypothermia, coagulopathy, and acidosis, leading to ongoing bleeding. Additionally, hypothermia in trauma patients can deepen through environmental exposure on the scene or during transport and medical procedures such as infusions and airway management. This vicious circle has a detrimental effect on the outcome of major trauma patients. This narrative review describes the main factors to consider in the co-existing condition of trauma and hypothermia from a prehospital and emergency medical perspective. Early prehospital recognition and staging of hypothermia are crucial to triage to proper care to improve survival. Treatment of hypothermia should start in an early stage, especially the prevention of further cooling in the prehospital setting and during the primary assessment. On the one hand, active rewarming is the treatment of choice of hypothermia-induced coagulation disorder in trauma patients; on the other hand, accidental or clinically induced hypothermia might improve outcomes by protecting against the effects of hypoperfusion and hypoxic injury in selected cases such as patients suffering from traumatic brain injury (TBI) or traumatic cardiac arrest.
Topics: Blood Coagulation Disorders; Heart Arrest; Hemorrhage; Humans; Hypothermia; Rewarming; Wounds and Injuries
PubMed: 34444466
DOI: 10.3390/ijerph18168719 -
Physiological Reviews Jan 2013Hemostasis encompasses the tightly regulated processes of blood clotting, platelet activation, and vascular repair. After wounding, the hemostatic system engages a... (Review)
Review
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.
Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factor Inhibitors; Blood Coagulation Factors; Blood Platelets; Cell Communication; Feedback, Physiological; Hemostasis; Humans; Platelet Activation; Signal Transduction
PubMed: 23303912
DOI: 10.1152/physrev.00016.2011 -
Anesthesiology May 2020
Review
Topics: Animals; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Humans; Inflammation Mediators; Sepsis
PubMed: 32044801
DOI: 10.1097/ALN.0000000000003122 -
Journal of Thrombosis and Haemostasis :... Aug 2016Mild inherited bleeding disorders are relatively common in the general population. Despite recent advances in diagnostic approaches, mild inherited bleeding disorders... (Review)
Review
Mild inherited bleeding disorders are relatively common in the general population. Despite recent advances in diagnostic approaches, mild inherited bleeding disorders still pose a significant diagnostic challenge. Hemorrhagic diathesis can be caused by disorders in primary hemostasis (von Willebrand disease, inherited platelet function disorders), secondary hemostasis (hemophilia A and B, other (rare) coagulant factor deficiencies) and fibrinolysis, and in connective tissue or vascular formation. This review summarizes the currently available diagnostic methods for mild bleeding disorders and their pitfalls, from structured patient history to highly specialized laboratory diagnosis. A comprehensive framework for a diagnostic approach to mild inherited bleeding disorders is proposed.
Topics: Blood Coagulation; Blood Platelet Disorders; Blood Platelets; Coagulants; Fibrinolysis; Genetic Testing; Hematology; Hemophilia A; Hemophilia B; Hemorrhage; Hemorrhagic Disorders; Hemostasis; Humans; Mutation; von Willebrand Diseases
PubMed: 27208505
DOI: 10.1111/jth.13368 -
Journal of Thrombosis and Haemostasis :... Jun 2019Trauma remains a leading cause of death worldwide, and most early preventable deaths in both the civilian and military settings are due to uncontrolled hemorrhage,... (Review)
Review
Trauma remains a leading cause of death worldwide, and most early preventable deaths in both the civilian and military settings are due to uncontrolled hemorrhage, despite paradigm advances in modern trauma care. Combined tissue injury and shock result in hemostatic failure, which has been identified as a multidimensional molecular, physiologic and clinical disorder termed trauma-induced coagulopathy (TIC). Understanding the biology of TIC is of utmost importance, as it is often responsible for uncontrolled bleeding, organ failure, thromboembolic complications, and death. Investigations have shown that TIC is characterized by multiple phenotypes of impaired hemostasis due to altered biology in clot formation and breakdown. These coagulopathies are attributable to tissue injury and shock, and encompass underlying endothelial, immune and inflammatory perturbations. Despite the recognition and identification of multiple mechanisms and mediators of TIC, and the development of targeted treatments, the mortality rates and associated morbidities due to hemorrhage after injury remain high. The purpose of this review is to examine the past and present understanding of the multiple distinct but highly integrated pathways implicated in TIC, in order to highlight the current knowledge gaps and future needs in this evolving field, with the aim of reducing morbidity and mortality after injury.
Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Endothelium; Exsanguination; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Protein C; Shock, Hemorrhagic; Wounds and Injuries
PubMed: 30985957
DOI: 10.1111/jth.14450 -
Journal of Thrombosis and Haemostasis :... Mar 2021Cardiopulmonary bypass (CPB) has allowed for significant surgical advancements, but accompanying risks can be significant and must be expertly managed. One of the... (Review)
Review
Cardiopulmonary bypass (CPB) has allowed for significant surgical advancements, but accompanying risks can be significant and must be expertly managed. One of the foremost risks is coagulopathic bleeding. Increasing levels of bleeding in cardiac surgical patients at the time of separation from CPB are associated with poor outcomes and mortality. CPB-associated coagulopathy is typically multifactorial and rarely due to inadequate reversal of systemic heparin alone. The components of the bypass circuit induce systemic inflammation and multiple disturbances of the coagulation and fibrinolytic systems. Anticipating coagulopathy is the first step in managing it, and specific patient and procedural risk factors have been identified as predictors of excessive bleeding. Medication management pre-procedure is critical, as patients undergoing cardiac surgery are commonly on anticoagulants or antiplatelet agents. Important adjuncts to avoid transfusion include antifibrinolytics, and perfusion practices such as red cell salvage, sequestration, and retrograde autologous priming of the bypass circuit have varying degrees of evidence supporting their use. Understanding the patient's coagulation status helps target product replacement and avoid larger volume transfusion. There is increasing recognition of the role of point-of-care viscoelastic and functional platelet testing. Common pitfalls in the management of post-CPB coagulopathy include overdosing protamine for heparin reversal, imperfect laboratory measures of thrombin generation that result in normal or near-normal laboratory results in the presence of continued bleeding, and delayed recognition of surgical bleeding. While challenging, the effective management of CPB-associated coagulopathy can significantly improve patient outcomes.
Topics: Blood Coagulation; Blood Coagulation Disorders; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Heparin; Humans
PubMed: 33251719
DOI: 10.1111/jth.15195 -
American Journal of Health-system... Feb 2022To provide an overview of current literature on the pathophysiology of sepsis, with a focus on mediators of endothelial injury and organ dysfunction. (Review)
Review
PURPOSE
To provide an overview of current literature on the pathophysiology of sepsis, with a focus on mediators of endothelial injury and organ dysfunction.
SUMMARY
Sepsis is a dysregulated response to infection that triggers cascades of interconnected systems. Sepsis has been a significant cause of mortality worldwide, and the recent viral pandemic that may produce severe sepsis and septic shock has been a major contributor to sepsis-related mortality. Understanding of the pathophysiology of sepsis has changed dramatically over the last several decades. Significant insight into the components of the inflammatory response that contribute to endothelial injury and trigger coagulation pathways has been achieved. Similarly, characterization of anti-inflammatory pathways that may lead to secondary infections and poor outcome has illustrated opportunities for improved therapies. Description of an increasing number of important mediators and pathways has occurred and may point the way to novel therapies to address immune dysregulation. Pharmacists will need a fundamental understanding of the overlapping pathways of the immune response to fully prepare for use of novel treatment options. While pharmacists typically understand coagulation cascade how to utilize anticoagulants, the issues in sepsis related coagulopathy and role of mediators such as cytokines and complement and role of activated platelets and neutrophils require a different perspective.
CONCLUSION
Pharmacists can benefit from understanding both the cellular and organ system issues in sepsis to facilitate assessment of potential therapies for risk and benefit.
Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Humans; Sepsis; Shock, Septic
PubMed: 34605875
DOI: 10.1093/ajhp/zxab380 -
Frontiers in Immunology 2022Infection with SARS-CoV-2, the causative agent of the Coronavirus disease 2019 (COVID-19) pandemic, causes respiratory problems and multifaceted organ dysfunction. A... (Review)
Review
Infection with SARS-CoV-2, the causative agent of the Coronavirus disease 2019 (COVID-19) pandemic, causes respiratory problems and multifaceted organ dysfunction. A crucial mechanism of COVID-19 immunopathy is the recruitment and activation of neutrophils at the infection site, which also predicts disease severity and poor outcomes. The release of neutrophil extracellular traps (NETs), occurring during a regulated form of neutrophil cell death known as NETosis, is a key effector function that mediates harmful effects caused by neutrophils. Abundant NETosis and NET generation have been observed in the neutrophils of many COVID-19 patients, leading to unfavorable coagulopathy and immunothrombosis. Moreover, excessive NETosis and NET generation are now more widely recognized as mediators of additional pathophysiological abnormalities following SARS-CoV-2 infection. In this minireview, we introduce subtypes of NET-producing neutrophils (e.g., low-density granulocytes) and explain the biological importance of NETs and the protein cargos of NETs in COVID-19. In addition, we discuss the mechanisms by which SARS-CoV-2 causes NETosis by upregulating viral processes (e.g., viral entry and replication) as well as host pro-NET mechanisms (e.g., proinflammatory mediator release, platelet activation, and autoantibody production). Furthermore, we provide an update of the main findings of NETosis and NETs in immunothrombosis and other COVID-19-related disorders, such as aberrant immunity, neurological disorders, and post COVID-19 syndromes including lung fibrosis, neurological disorder, tumor progression, and deteriorated chronic illness. Finally, we address potential prospective COVID-19 treatment strategies that target dysregulated NETosis and NET formation inhibition of NETosis and promotion of NET degradation, respectively.
Topics: Animals; Apoptosis; Blood Coagulation Disorders; COVID-19; Carcinogenesis; Extracellular Traps; Fibrosis; Humans; Lung; Neutrophils; SARS-CoV-2; Thromboinflammation
PubMed: 35309344
DOI: 10.3389/fimmu.2022.838011 -
Diagnosis (Berlin, Germany) Nov 2020Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized... (Review)
Review
Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized as a systemic disorder inducing a prothrombotic state. The molecular mechanisms underlying the hypercoagulable state seen in patients with COVID-19 is still incompletely understood, although it presumably involves the close link between inflammatory and hemostatic systems. The laboratory coagulation monitoring of severely ill COVID-19 patients is mandatory to identify those patients at increased thrombotic risk and to modulate thromboprophylaxis accordingly. In this review, we summarize the current understanding on the pathogenesis, epidemiology, clinical and laboratory features and management of coagulopathy associated with COVID-19.
Topics: Anticoagulants; Betacoronavirus; Blood Coagulation Disorders; COVID-19; Coronavirus Infections; Humans; Inflammation; Pandemics; Pneumonia, Viral; SARS-CoV-2; Severity of Illness Index; Thromboembolism; Thrombosis
PubMed: 32683333
DOI: 10.1515/dx-2020-0078