-
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 -
Journal of Hepatology Jun 2022Patients with cirrhosis frequently acquire complex changes in their haemostatic system including a decreased platelet count and decreased levels of various haemostatic... (Review)
Review
Patients with cirrhosis frequently acquire complex changes in their haemostatic system including a decreased platelet count and decreased levels of various haemostatic proteins. Although historically patients with cirrhosis were thought to have a haemostasis-related bleeding tendency, it is now widely accepted that the haemostatic system of patients with cirrhosis remains in balance as a result of simultaneous changes in pro- and anti-haemostatic systems. The concept of rebalanced haemostasis has led to changes in clinical management, although firm evidence from well-designed clinical studies is largely lacking. For example, many invasive procedures in patients with cirrhosis and a prolonged prothrombin time are now performed without prophylaxis with fresh frozen plasma. Conversely, clinicians have become more aware of the need for anti-thrombotic therapy, even in those patients with abnormal routine coagulation tests. This paper will outline recent advances in pathogenesis, prevention and treatment of both bleeding and thrombotic complications in patients with cirrhosis. Among other topics, we will discuss the haemostatic status of acutely ill patients with cirrhosis, the various causes of bleeding in patients with cirrhosis, and how best to prevent or treat bleeding. In addition, we will discuss the hypercoagulable features of patients with cirrhosis, new insights into the pathogenesis of portal vein thrombosis, and how best to prevent or treat thromboses.
Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Fibrosis; Hemorrhage; Hemostasis; Hemostatics; Humans; Liver Cirrhosis
PubMed: 35589251
DOI: 10.1016/j.jhep.2021.11.004 -
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 -
Anesthesiology May 2020
Review
Topics: Animals; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Humans; Inflammation Mediators; Sepsis
PubMed: 32044801
DOI: 10.1097/ALN.0000000000003122 -
Pathobiology : Journal of... 2021Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy... (Review)
Review
Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype. Initially, COVID-19 infection produces a prominent elevation of fibrinogen and D-dimer/fibrin(ogen) degradation products. This is associated with systemic hypercoagulability and frequent venous thromboembolic events. The degree of D-dimer elevation positively correlates with mortality in COVID-19 patients. COVID-19 also leads to arterial thrombotic events (including strokes and ischemic limbs) as well as microvascular thrombotic disorders (as frequently documented at autopsy in the pulmonary vascular beds). COVID-19 patients often have mild thrombocytopenia and appear to have increased platelet consumption, together with a corresponding increase in platelet production. Disseminated intravascular coagulopathy (DIC) and severe bleeding events are uncommon in COVID-19 patients. Here, we review the current state of knowledge of COVID-19 and hemostasis.
Topics: Blood Coagulation Disorders; Blood Platelets; COVID-19; Fibrin Fibrinogen Degradation Products; Humans; SARS-CoV-2; Thrombosis
PubMed: 33049751
DOI: 10.1159/000512007 -
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 -
British Journal of Anaesthesia Dec 2016Acute Traumatic Coagulopathy occurs immediately after massive trauma when shock, hypoperfusion, and vascular damage are present. Mechanisms for this acute coagulopathy... (Review)
Review
Acute Traumatic Coagulopathy occurs immediately after massive trauma when shock, hypoperfusion, and vascular damage are present. Mechanisms for this acute coagulopathy include activation of protein C, endothelial glycocalyx disruption, depletion of fibrinogen, and platelet dysfunction. Hypothermia and acidaemia amplify the endogenous coagulopathy and often accompany trauma. These multifactorial processes lead to decreased clot strength, autoheparinization, and hyperfibrinolysis. Furthermore, the effects of aggressive crystalloid administration, haemodilution from inappropriate blood product transfusion, and prolonged surgical times may worsen clinical outcomes. We review normal coagulation using the cell-based model of haemostasis and the pathophysiology of acute traumatic coagulopathy. Developed trauma systems reduce mortality, highlighting critical goals for the trauma patient in different phases of care. Once patients reach a trauma hospital, certain triggers reliably indicate when they require massive transfusion and specialized trauma care. These triggers include base deficit, international normalized radio (INR), systolic arterial pressure, haemoglobin concentration, and temperature. Early identification for massive transfusion is critically important, as exsanguination in the first few hours of trauma is a leading cause of death. To combat derangements caused by massive haemorrhage, damage control resuscitation is a technique that addresses each antagonist to normal haemostasis. Components of damage control resuscitation include damage control surgery, permissive hypotension, limited crystalloid administration, haemostatic resuscitation, and correction of hyperfibrinolysis.
Topics: Blood Coagulation Disorders; Blood Transfusion; Humans; Resuscitation; Shock; Wounds and Injuries
PubMed: 27940454
DOI: 10.1093/bja/aew328 -
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 -
Anesthesiology Mar 2021
Topics: Blood Coagulation Disorders; COVID-19; Fibrinolysis; Humans; SARS-CoV-2
PubMed: 33417671
DOI: 10.1097/ALN.0000000000003688