The delicate biochemistry of coagulation and anticoagulation is greatly affected by deviations from the optimal temperature required for the interactions between various coagulation enzymes, cellular ...receptors, and intracellular mechanisms. Hyperthermia will lead to a prothrombotic state and, if sufficiently severe such as in heatstroke, a consumption coagulopathy, which will clinically manifest with the simultaneous appearance of intravascular thrombotic obstruction and an increased bleeding tendency. Hypothermia slows down the coagulation process, but as this seems to be adequately balanced by impairment of anticoagulant and fibrinolytic processes, its clinical effects are modest; however, hypothermia may be modestly linked to a somewhat higher risk of localized thrombosis. Restoration of a normal body temperature in patients affected by hyper- or hypothermia is the cornerstone for the management of associated coagulation derangements.
Disseminated intravascular coagulation (DIC) is a condition characterized by systemic activation of coagulation, potentially leading to thrombotic obstruction of small and midsize vessels, thereby ...contributing to organ dysfunction. At the same time, ongoing consumption of platelets and coagulation proteins results in thrombocytopenia and low concentrations of clotting factors, which may cause profuse hemorrhagic complications. DIC is always secondary to an underlying condition, such as severe infections, solid or hematologic malignancies, trauma, or obstetric calamities. A reliable diagnosis of DIC can be made through simple scoring algorithms based on readily available routine hemostatic parameters. The cornerstone of supportive treatment of this coagulopathy is management of the underlying condition. Additionally, administration of heparin may be useful, and restoration of physiological anticoagulants has been suggested, but has not been proven successful in improving clinically relevant outcomes so far. In patients with major bleeding or at risk for hemorrhagic complications, administration of platelet concentrates, plasma, or coagulation factor concentrates should be considered.
ABSTRACT Cancer may be complicated by the occurrence of disseminated intravascular coagulation (DIC). DIC is characterized by a widespread and intravascular activation of coagulation (leading to ...intravascular fibrin deposition) and simultaneous consumption of coagulation factors and platelets (potentially resulting in bleeding). Clinically, DIC in cancer has in general a less fulminant presentation than the types of DIC complicating sepsis and trauma. A more gradual, but also more chronic, systemic activation of coagulation can proceed subclinically. Eventually this process may lead to exhaustion of platelets and coagulation factors and bleeding (for example at the site of the tumor) may be the first clinical symptom indicating the presence of DIC. In some cases, the clinical presentation of DIC in cancer may be reminiscent of thrombotic microangiopathies, which is understandable in view of the role of endothelium in both conditions. The therapeutic cornerstone of DIC is treatment of the underlying disorder but supportive treatment, specifically aimed at the hemostatic system may be required.
Recent studies have reported a high prevalence of thrombotic events in coronavirus disease 2019. However, the significance of thromboembolic complications has not been widely appreciated. The purpose ...of this review is to provide current knowledge of this serious problem.
Narrative review.
Online search of published medical literature through PubMed using the term "COVID-19," "SARS," "acute respiratory distress syndrome," "coronavirus," "coagulopathy," "thrombus," and "anticoagulants."
Articles were chosen for inclusion based on their relevance to coagulopathy and thrombosis in coronavirus disease 2019, and anticoagulant therapy. Reference lists were reviewed to identify additional relevant articles.
Coronavirus disease 2019 is associated with a strikingly high prevalence of coagulopathy and venous thromboembolism that may contribute to respiratory deterioration. Monitoring coagulation variables is important, as abnormal coagulation tests are related to adverse outcomes and may necessitate adjuvant antithrombotic interventions. In the initial phase of the infection, D-dimer and fibrinogen levels are increased, while activated partial prothrombin time, prothrombin time, and platelet counts are often relatively normal. Increased D-dimer levels three times the upper limit of normal may trigger screening for venous thromboembolism. In all hospitalized patients, thromboprophylaxis using low-molecular-weight heparin is currently recommended. The etiology of the procoagulant responses is complex and thought to be a result of specific interactions between host defense mechanisms and the coagulation system. Although the coagulopathy is reminiscent of disseminated intravascular coagulation and thrombotic microangiopathy, it has features that are markedly distinct from these entities.
Severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 frequently induces hypercoagulability with both microangiopathy and local thrombus formation, and a systemic coagulation defect that leads to large vessel thrombosis and major thromboembolic complications, including pulmonary embolism in critically ill hospitalized patients. D-dimers and fibrinogen levels should be monitored, and all hospitalized patients should undergo thromboembolism prophylaxis with an increase in therapeutic anticoagulation in certain clinical situations.
Coagulation and sepsis Levi, Marcel, MD; van der Poll, Tom, MD
Thrombosis research,
01/2017, Letnik:
149
Journal Article
Recenzirano
Abstract Severe sepsis is almost invariably associated with systemic activation of coagulation. There is ample evidence that demonstrates a wide-ranging cross-talk between hemostasis and ...inflammation, which is probably implicated in the pathogenesis of organ dysfunction in patients with sepsis. Inflammation not only leads to initiation and propagation of coagulation activity, but coagulation also markedly influences inflammation. Molecular mechanisms that play a role in inflammation-induced effects on coagulation have been recognized in much detail. Pro-inflammatory cells and cyto- and chemokines can activate the coagulation system and downregulate crucial physiological anticoagulant mechanisms. Initiation of coagulation activation and consequent thrombin generation is caused by expression of tissue factor on activated monocytes and endothelial cells and is ineffectually offset by tissue factor pathway inhibitor. At the same time, endothelial-associated anticoagulant pathways, in particular the protein C system, is impaired by pro-inflammatory cytokines. Also, fibrin removal is severely obstructed by inactivation of the endogenous fibrinolytic system, mainly as a result of upregulation of its principal inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin generation and impaired break down lead to deposition of (micro)vascular clots, which may contribute to tissue ischemia and ensuing organ dysfunction. The foundation of the management of coagulation in sepsis is the explicit and thorough treatment of the underlying disorder by antibiotic treatment and source control measures. Adjunctive strategies focused at the impairment of coagulation, including anticoagulants and restoration of physiological anticoagulant mechanisms, may supposedly be indicated and have been found advantageous in experimental and initial clinical trials.
Many severe illnesses with a systemic impact may cause activation of coagulation. While systemic activation of coagulation leads to a coagulopathy that follows many common activation pathways and ...failure of endogenous regulatory anticoagulant systems, underlying conditions may utilize distinctive pathogenetic routes and may vary in clinical manifestations of the coagulopathy. The coagulation derangement associated with hematological malignancies and the coagulopathy of coronavirus disease 2019 (COVID‐19) clearly demonstrate such differences. Malignancies are associated with venous thromboembolism due to the biological effect of malignant cells, frequent medical interventions, or the presence of indwelling vascular catheters. The underlying pathogenesis of cancer‐associated coagulopathy relies on tissue factor‐mediated activation of coagulation, cytokine‐controlled defective anticoagulant pathways, fibrinolytic changes, and dysfunctional endothelium. There is an additional risk caused by anti‐cancer agents including chemotherapy and immunotherapy. The underlying pathogenetic factor that contributes to the thrombotic risk associated with chemotherapy is endothelial cell injury (or loss of protection of endothelial integrity, for example, by vascular endothelial growth factor inhibition). In addition, individual anti‐cancer agents may have specific prothrombotic effects. One of the remarkable features of severe COVID‐19 infections is a coagulopathy that mimics but is not identical to the disseminated intravascular coagulation and thrombotic microangiopathy and has been identified as a strong marker for an adverse outcome. Severe COVID‐19 infections cause inflammation‐induced changes in coagulation in combination with severe endothelial cell injury. This coagulopathy likely contributes to pulmonary microvascular thrombosis, bronchoalveolar fibrin deposition (which is a hallmark of acute respiratory distress syndrome) and venous thromboembolic complications.
Thrombotic complications and coagulopathy frequently occur in COVID-19. However, the characteristics of COVID-19-associated coagulopathy (CAC) are distinct from those seen with bacterial ...sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC), with CAC usually showing increased D-dimer and fibrinogen levels but initially minimal abnormalities in prothrombin time and platelet count. Venous thromboembolism and arterial thrombosis are more frequent in CAC compared to SIC/DIC. Clinical and laboratory features of CAC overlap somewhat with a hemophagocytic syndrome, antiphospholipid syndrome, and thrombotic microangiopathy. We summarize the key characteristics of representative coagulopathies, discussing similarities and differences so as to define the unique character of CAC.
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