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Pathogenesis of disseminated intravascular coagulation. DIC is characterized by systemic activation of blood coagulation, which results in generation and deposition of fibrin, leading to microvascular thrombi contributing to multi-organ dysfunction. Furthermore, consumption of clotting factors and platelets can result in life-threatening hemorrhage.
Source publication
Abstract Coronavirus disease 2019 (COVID-19) is a highly contagious disease that appeared in China in December 2019 and spread rapidly around the world. Several patients with severe COVID-19 infection can develop a coagulopathy according to the ISTH criteria for disseminated intravascular coagulopathy (DIC) with fulminant activation of coagulation,...
Citations
... Elevated levels of clotting markers are important for determining the prognosis of patients with COVID-19, as infection with SARS-CoV-2 can lead to severe conditions and thrombus formation [6,15]. Assessment of blood clotting factors, including pro-clotting factors such as fibrinogen, prothrombin, and factors XI, XII, and XIII, and natural anticoagulants such as antithrombin is critical in understanding the pathophysiological processes underlying the development of COVID-19 and its complications. ...
Background
Because severe acute respiratory syndrome coronarivus 2 (SARS-CoV-2) leads to severe conditions and thrombus formation, evaluation of the coagulation markers is important in determining the prognosis and phenotyping of patients with COVID-19.
Methods
In a prospective study that included 213 COVID-19 patients admitted to the intensive care unit (ICU) the levels of antithrombin, C-reactive protein (CRP); factors XI, XII, XIII; prothrombin and D-dimer were measured. Spearman’s correlation coefficient was used to assess the pairwise correlations between the biomarkers. Hierarchical and non-hierarchical cluster analysis was performed using the levels of biomarkers to identify patients´ phenotypes. Multivariate binary regression was used to determine the association of the patient´s outcome with clinical variables and biomarker levels.
Results
The levels of factors XI and XIII were significantly higher in patients with less severe COVID-19, while factor XIII and antithrombin levels were significantly associated with mortality. These coagulation biomarkers were associated with the in-hospital survival of COVID-19 patients over and above the core clinical factors on admission. Hierarchical cluster analysis showed a cluster between factor XIII and antithrombin, and this hierarchical cluster was extended to CRP in the next step. Furthermore, a non-hierarchical K-means cluster analysis was performed, and two phenotypes were identified based on the CRP and antithrombin levels independently of clinical variables and were associated with mortality.
Conclusion
Coagulation biomarkers were associated with in-hospital survival of COVID-19 patients. Lower levels of factors XI, XII and XIII and prothrombin were associated with disease severity, while higher levels of both CRP and antithrombin clustered with worse prognosis. These results suggest the role of coagulation abnormalities in the development of COVID-19 and open the perspective of identifying subgroups of patients who would benefit more from interventions focused on regulating coagulation.
... Several factors play a role in modulating the platelet response. It has been shown that inflammatory diseases can lead to alterations in platelet function [15]. Indeed, platelets play a major role in the pathogenesis of acute coronary syndromes. ...
This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an overview of the effects of major hypolipidemic drugs on platelet function. Indeed, growing evidence supports the view that statins, ezetimibe, PCSK9 inhibitors, inclisiran, and icosapent ethyl also act as antithrombotics. It is known that platelets play a key role not only in the acute phase of coronary syndromes but also in the early phase of atherosclerotic plaque formation. The goal of cholesterol-lowering therapy is to reduce cardiovascular events. The direct effects of cholesterol-lowering drugs are widely described in the literature. Lowering LDL-c (low-density lipoprotein cholesterol) by 1 mmol/L results in a 22–23% reduction in cardiovascular risk. Numerous studies have examined the direct antithrombotic effects of these drugs on platelets, endothelium, monocytes, and smooth muscle cells, and thus, potentially independent of blood LDL-cholesterol reduction. We reviewed in vitro and in vivo studies evaluating the complex interaction between hypercholesterolemia, hypertriglyceridemia, platelet function, and related drug treatments. First, we discussed the role of statins in modulating platelet activation. Discontinuation of statin therapy was associated with increased cardiovascular events with increased ox-LDL, P-selectin, and platelet aggregation. The effect of PCSK9-I (inhibitors of proprotein convertase subtilisin/kexin type 9, PCSK9 involved in the degradation of LDL receptors in the liver) was associated with a statistically significant reduction in platelet reactivity, calculated in P2Y12 reaction units (PRU), in the first 14 days and no difference at 30 days compared to placebo. Finally, in patients with hypertriglyceridemia, the REDUCE-IT study showed that icosapent ethyl (an ethyl ester of eicosapentaenoic acid that reduces triglyceride synthesis and improves triglyceride clearance) resulted in a 25% reduction in ischemic events and cardiovascular death. However, to date, there is not yet clear clinical evidence that the direct antithrombotic effects of the drugs may have a beneficial impact on outcomes independently from the reduction in LDL-C or triglycerides.
... Conventional blood glucose control is clearly not the perfect method for reducing mortality in COVID-19 patients with T2D, as it does not address the main reasons for deterioration [10,11]. Studies have shown that thrombosis is an important cause of both COVID-19 and T2D mortality [12][13][14][15], with patients typically experiencing thrombosis within days or weeks after contracting COVID-19 pneumonia [16]. Therefore, the development of thrombosis or hypercoagulability in COVID-19 patients with T2D has raised concerns. ...
SARS-CoV-2 can directly or indirectly damage endothelial cells. Endothelial injury, especially phosphatidylserine (PS) exposure on the outer membrane of cells, can more easily promote thrombosis. Type 2 diabetes(T2D) patients were more susceptible to COVID-19, they had more severe symptoms, higher risk of thrombotic complications, and longer duration of post-COVID-19 sequelae. This review provided a detailed overview of the mechanisms underlying endothelial dysfunction in T2D patients with COVID-19 (including long COVID), which may be influenced by hyperglycemia, hypoxia, and pro-inflammatory environments. The mechanisms of thrombosis in T2D patients with COVID-19 are also explored, particularly the effects of increased numbers of PS-exposing particles, blood cells, and endothelial cells on hypercoagulability. Given the high risk of thrombosis in T2D patients with COVID-19, early antithrombotic therapy can both minimize the impact of the disease on patients and maximize the chances of improvement, thereby alleviating patient suffering. We provided detailed guidance on antithrombotic drugs and dosages for mild, moderate, and severe patients, emphasizing that the optimal timing of thromboprophylaxis is a critical factor in influencing prognosis. Considering the potential interactions between antidiabetic, anticoagulant, and antiviral drugs, we proposed practical and comprehensive management recommendations to supplement the incomplete efficacy of vaccines in the diabetic population, reduce the incidence of post-COVID-19 sequelae, and improve patient quality of life.
... There were 181 patients (90.5%) below 60 years old and 19 patients (9.5%) above 60 years old. Concordant with other studies, 34,35 most of the patients were males (56.8%). ...
... Non-survivors had significantly higher levels of D-dimer, prolonged prothrombin time (PT), and decreased platelet counts compared to survivors [94]. Similar results were also obtained in another research [95]. The study of Zhu demonstrated a high prevalence of coagulopathy in patients with severe COVID-19 [96]. ...
Coronavirus disease 2019 (COVID-19) is a severe respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Heart failure (HF) is associated with a worse prognosis for patients with this viral infection, highlighting the importance of early detection and effective treatment strategies. HF can also be a consequence of COVID-19-related myocardial damage. To optimise the treatment of these patients, one needs to understand the interactions between this disease and viruses. Until now, the validity of the screening for cardiovascular complications after COVID-19 has not been confirmed. There were also no patients in whom such diagnostics seemed appropriate. Until appropriate recommendations are made, diagnosis procedures must be individualised based on the course of the acute phase and clinical symptoms reported or submitted after COVID-19. Clinical phenomena are the criteria for determining the recommended test panel. We present a structured approach to COVID-19 patients with heart involvement.
... It can also be attributed to its nonspecific elevation in diabetes, some liver and kidney diseases, or because of fibrinolysis outside the vessel lumen [13][14][15][16]. Other plasma coagulation assays such as aPTT and PT were normal or hardly prolonged [17][18][19][20] and no reliable results were reported on their correlation with illness severity or thromboembolism presence. While fibrinogen levels are also generally elevated in patients, no substantial evidence of its role in plasma hypercoagulability were found yet [21]. ...
Background:
Blood coagulation abnormalities play a major role in COVID-19 pathophysiology. However, the specific details of hypercoagulation and anticoagulation treatment require investigation. The aim of this study was to investigate the status of the coagulation system by means of integral and local clotting assays in COVID-19 patients on admission to the hospital and in hospitalized COVID-19 patients receiving heparin thromboprophylaxis.
Methods:
Thrombodynamics (TD), thromboelastography (TEG), and standard clotting assays were performed in 153 COVID-19 patients observed in a hospital setting. All patients receiving treatment, except extracorporeal membrane oxygenation (ECMO) patients (n = 108), were administered therapeutic doses of low molecular weight heparin (LMWH) depending on body weight. The ECMO patients (n = 15) were administered unfractionated heparin (UFH).
Results:
On admission, the patients (n = 30) had extreme hypercoagulation by all integral assays: TD showed hypercoagulation in ~75% of patients, while TEG showed hypercoagulation in ~50% of patients. The patients receiving treatment showed a significant heparin response based on TD; 77% of measurements were in the hypocoagulation range, 15% were normal, and 8% remained in hypercoagulation. TEG showed less of a response to heparin: 24% of measurements were in the hypocoagulation range, 59% were normal and 17% remained in hypercoagulation. While hypocoagulation is likely due to heparin treatment, remaining in significant hypercoagulation may indicate insufficient anticoagulation for some patients, which is in agreement with our clinical findings. There were 3 study patients with registered thrombosis episodes, and all were outside the target range for TD parameters typical for effective thromboprophylaxis (1 patient was in weak hypocoagulation, atypical for the LMWH dose used, and 2 patients remained in the hypercoagulation range despite therapeutic LMWH doses).
Conclusion:
Patients with COVID-19 have severe hypercoagulation, which persists in some patients receiving anticoagulation treatment, while significant hypocoagulation is observed in others. The data suggest critical issues of hemostasis balance in these patients and indicate the potential importance of integral assays in its control.
... [129][130][131] In parallel, it emerged that coagulation and thrombosis are deeply involved in the clinical pathophysiology of COVID-19. 132 The thrombotic and procoagulation processes observed in COVID-19 share some similarities with atherothrombosis, strengthening the recent evidence suggesting a key role for purinergic receptors in atherothrombosis. 133 Gut microbiome and atherosclerosis: a tale of inflammation? ...
Atherosclerosis is the anatomo-pathological substrate of most cardio, cerebro and vascular diseases such as acute and chronic coronary syndromes, stroke and peripheral artery diseases. The pathophysiology of atherosclerotic plaque and its complications are under continuous investigation. In the last 2 decades our understanding on the formation, progression and complication of the atherosclerotic lesion has greatly improved and the role of immunity and inflammation is now well documented and accepted. The conventional risk factors modulate endothelial function determining the switch to a proatherosclerotic phenotype. From this point, lipid accumulation with an imbalance from cholesterol influx and efflux, foam cells formation, T-cell activation, cytokines release and matrix-degrading enzymes production occur. Lesions with high inflammatory rate become vulnerable and prone to rupture. Once complicated, the intraplaque thrombogenic material, such as the tissue factor, is exposed to the flowing blood, thus inducing coagulation cascade activation, platelets aggregation and finally intravascular thrombus formation that leads to clinical manifestations of this disease. Nonconventional risk factors, such as gut microbiome, are emerging novel markers of atherosclerosis. Several data indicate that gut microbiota may play a causative role in formation, progression and complication of atherosclerotic lesions. The gut dysbiosis-related inflammation and gut microbiota-derived metabolites have been proposed as the main working hypothesis in contributing to disease formation and progression. The current evidence suggest that the conventional and nonconventional risk factors may modulate the degree of inflammation of the atherosclerotic lesion, thus influencing its final fate. Based on this hypothesis, targeting inflammation seems to be a promising approach to further improve our management of atherosclerotic-related diseases.
... In COVID-19 patients, Plts, in addition to the liver, are predisposed to engage in procoagulant activities in the circulation and appear to be involved in the elevation of fibrinogen [17]. In rare cases, decreased fibrinogen levels have been observed in patients with severe COVID-19 due to the occurrence of DIC [69], which is associated with a poor prognosis [73]. ...
The coagulation, fibrinolytic, anticoagulation, and complement systems are in delicate balance with the vessel wall endothelium ensuring appropriate hemostasis. Coagulopathy in coronavirus disease 2019 (COVID-19) is not a simple disorder of one hemostatic component but a complicated process affecting most of the hemostasis system. COVID-19 disturbs the balance between the procoagulant systems and the regulatory mechanisms. Here, we investigate the effect of COVID-19 on key hemostatic components, including platelets, endothelial cells, coagulation factors, fibrinolytic system, anticoagulant protein system, and complement system, to improve our understanding of the pathophysiological processes underlying COVID-19 coagulopathy based on evidence.
... D-dimer has also been used as a prognostic monitor in COVID-19 patients, thus guiding management. Studies have shown that D-dimer was associated with disease severity [362][363][364][365][366][367], risk of adverse outcome (including death) [362][363][364]366,368] and thromboembolic risk [343,360,362]. Accordingly, it has been included in various risk classification scores. ...
... D-dimer has also been used as a prognostic monitor in COVID-19 patients, thus guiding management. Studies have shown that D-dimer was associated with disease severity [362][363][364][365][366][367], risk of adverse outcome (including death) [362][363][364]366,368] and thromboembolic risk [343,360,362]. Accordingly, it has been included in various risk classification scores. ...
D-dimer containing species are soluble fibrin degradation products derived from
plasmin-mediated degradation of cross-linked fibrin, i.e., ‘D-dimer’. D-dimer can hence
be considered a biomarker of in vivo activation of both coagulation and fibrinolysis,
the leading clinical application in daily practice of which is ruling out venous
thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of
VTE recurrence and helping define optimal duration of anticoagulation treatment in
VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening
those at enhanced risk of VTE. D-dimer assays should however be performed as
intended by regulatory agencies, as their use outside these indications might make
them a laboratory-developed test (LDT).
This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) dis-
cussing preanalytical variables affecting D-dimer measurement, (3) reviewing and
comparing the assays performance and some postanalytical variables (e.g., different
units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measure-
ment across different clinical settings, including pregnancy, cancer, and coronavirus
disease 2019 (COVID-19).
... Thus, 174 patients were admitted, most of whom were treated with antibiotics (n/N=157/174, 90%), chloroquine (n/N=131/174, 75%), and anticoagulation (n/N=154/174, 88%; either prophylactic [n=126] or therapeutic [n=28]) besides oxygen support. At that time, steroids (n/N=6/174, 3%) were not routinely prescribed.In line with previous studies,8 most patients with severe COVID-19 had elevated levels of D-dimer (n/N=62/64, 97%) and fibrinogen (n/N=55/62, 89%), whereas the activated partial thromboplastin time (n/N=52/71, 73%) and prothrombin time (n/N=56/70, 80%) were often normal (Table 1). Routine coagulation tests were not measured in patients with mild or moderate COVID-19. ...
