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1.
Int J Biol Macromol ; 192: 1040-1057, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1466382

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent responsible for the Coronavirus Disease-2019 (COVID-19) pandemic, has infected over 185 million individuals across 200 countries since December 2019 resulting in 4.0 million deaths. While COVID-19 is primarily associated with respiratory illnesses, an increasing number of clinical reports indicate that severely ill patients often develop thrombotic complications that are associated with increased mortality. As a consequence, treatment strategies that target COVID-associated thrombosis are of utmost clinical importance. An array of pharmacologically active compounds from natural products exhibit effects on blood coagulation pathways, and have generated interest for their potential therapeutic applications towards thrombotic diseases. In particular, a number of snake venom compounds exhibit high specificity on different blood coagulation factors and represent excellent tools that could be utilized to treat thrombosis. The aim of this review is to provide a brief summary of the current understanding of COVID-19 associated thrombosis, and highlight several snake venom compounds that could be utilized as antithrombotic agents to target this disease.


Subject(s)
COVID-19/blood , Fibrinolytic Agents/pharmacology , Snake Venoms/pharmacology , Thrombosis/drug therapy , Thrombosis/virology , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/pathology , Humans , Pandemics , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity
2.
JCI Insight ; 6(17)2021 09 08.
Article in English | MEDLINE | ID: covidwho-1413722

ABSTRACT

Neutrophil-mediated activation and injury of the endothelium play roles in the pathogenesis of diverse disease states ranging from autoimmunity to cancer to COVID-19. Neutralization of cationic proteins (such as neutrophil extracellular trap-derived [NET-derived] histones) with polyanionic compounds has been suggested as a potential strategy for protecting the endothelium from such insults. Here, we report that the US Food and Drug Administration-approved polyanionic agent defibrotide (a pleiotropic mixture of oligonucleotides) directly engages histones and thereby blocks their pathological effects on endothelium. In vitro, defibrotide counteracted endothelial cell activation and pyroptosis-mediated cell death, whether triggered by purified NETs or recombinant histone H4. In vivo, defibrotide stabilized the endothelium and protected against histone-accelerated inferior vena cava thrombosis in mice. Mechanistically, defibrotide demonstrated direct and tight binding to histone H4 as detected by both electrophoretic mobility shift assay and surface plasmon resonance. Taken together, these data provide insights into the potential role of polyanionic compounds in protecting the endothelium from thromboinflammation with potential implications for myriad NET- and histone-accelerated disease states.


Subject(s)
Fibrinolytic Agents/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Polydeoxyribonucleotides/pharmacology , Thrombosis/drug therapy , Animals , Extracellular Traps/drug effects , Extracellular Traps/metabolism , Fibrinolytic Agents/therapeutic use , Histones/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Male , Mice , Mice, Inbred C57BL , Polydeoxyribonucleotides/therapeutic use , Pyroptosis
3.
Int J Mol Sci ; 22(15)2021 Aug 03.
Article in English | MEDLINE | ID: covidwho-1346502

ABSTRACT

Thrombosis is a life-threatening disease with a high mortality rate in many countries. Even though anti-thrombotic drugs are available, their serious side effects compel the search for safer drugs. In search of a safer anti-thrombotic drug, Quantitative Structure-Activity Relationship (QSAR) could be useful to identify crucial pharmacophoric features. The present work is based on a larger data set comprising 1121 diverse compounds to develop a QSAR model having a balance of acceptable predictive ability (Predictive QSAR) and mechanistic interpretation (Mechanistic QSAR). The developed six parametric model fulfils the recommended values for internal and external validation along with Y-randomization parameters such as R2tr = 0.831, Q2LMO = 0.828, R2ex = 0.783. The present analysis reveals that anti-thrombotic activity is found to be correlated with concealed structural traits such as positively charged ring carbon atoms, specific combination of aromatic Nitrogen and sp2-hybridized carbon atoms, etc. Thus, the model captured reported as well as novel pharmacophoric features. The results of QSAR analysis are further vindicated by reported crystal structures of compounds with factor Xa. The analysis led to the identification of useful novel pharmacophoric features, which could be used for future optimization of lead compounds.


Subject(s)
Fibrinolytic Agents/pharmacology , Heterocyclic Compounds/pharmacology , Thrombosis/drug therapy , Fibrinolytic Agents/chemistry , Heterocyclic Compounds/chemistry , Humans , Models, Molecular , Quantitative Structure-Activity Relationship
4.
Cerebrovasc Dis ; 50(5): 551-559, 2021.
Article in English | MEDLINE | ID: covidwho-1238619

ABSTRACT

INTRODUCTION: The COVID-19 pandemic resulted in significant healthcare reorganizations, potentially striking standard medical care. We investigated the impact of the COVID-19 pandemic on acute stroke care quality and clinical outcomes to detect healthcare system's bottlenecks from a territorial point of view. METHODS: Crossed-data analysis between a prospective nation-based mandatory registry of acute stroke, Emergency Medical System (EMS) records, and daily incidence of COVID-19 in Catalonia (Spain). We included all stroke code activations during the pandemic (March 15-May 2, 2020) and an immediate prepandemic period (January 26-March 14, 2020). Primary outcomes were stroke code activations and reperfusion therapies in both periods. Secondary outcomes included clinical characteristics, workflow metrics, differences across types of stroke centers, correlation analysis between weekly EMS alerts, COVID-19 cases, and workflow metrics, and impact on mortality and clinical outcome at 90 days. RESULTS: Stroke code activations decreased by 22% and reperfusion therapies dropped by 29% during the pandemic period, with no differences in age, stroke severity, or large vessel occlusion. Calls to EMS were handled 42 min later, and time from onset to hospital arrival increased by 53 min, with significant correlations between weekly COVID-19 cases and more EMS calls (rho = 0.81), less stroke code activations (rho = -0.37), and longer prehospital delays (rho = 0.25). Telestroke centers were afflicted with higher reductions in stroke code activations, reperfusion treatments, referrals to endovascular centers, and increased delays to thrombolytics. The independent odds of death increased (OR 1.6 [1.05-2.4], p 0.03) and good functional outcome decreased (mRS ≤2 at 90 days: OR 0.6 [0.4-0.9], p 0.015) during the pandemic period. CONCLUSION: During the COVID-19 pandemic, Catalonia's stroke system's weakest points were the delay to EMS alert and a decline of stroke code activations, reperfusion treatments, and interhospital transfers, mostly at local centers. Patients suffering an acute stroke during the pandemic period had higher odds of poor functional outcome and death. The complete stroke care system's analysis is crucial to allocate resources appropriately.


Subject(s)
Emergency Medical Services , Fibrinolytic Agents/pharmacology , SARS-CoV-2/pathogenicity , Stroke/virology , Humans , Prospective Studies , Spain/epidemiology , Stroke/diagnosis , Thrombolytic Therapy/methods , Time-to-Treatment
5.
Biomed Pharmacother ; 139: 111561, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1174103

ABSTRACT

Heparin is the earliest and most widely used anticoagulant and antithrombotic drug that is still used in a variety of clinical indications. Since it was discovered in 1916, after more than a century of repeated exploration, heparin has not been replaced by other drugs, but a great progress has been made in its basic research and clinical application. Besides anticoagulant and antithrombotic effects, heparin also has antitumor, anti-inflammatory, antiviral, and other pharmacological activities. It is widely used clinically in cardiovascular and cerebrovascular diseases, lung diseases, kidney diseases, cancer, etc., as the first anticoagulant medicine in COVID-19 exerts anticoagulant, anti-inflammatory and antiviral effects. At the same time, however, it also leads to a lot of adverse reactions, such as bleeding, thrombocytopenia, elevated transaminase, allergic reactions, and others. This article comprehensively reviews the modern research progress of heparin compounds; discusses the structure, preparation, and adverse reactions of heparin; emphasizes the pharmacological activity and clinical application of heparin; reveals the possible mechanism of the therapeutic effect of heparin in related clinical applications; provides evidence support for the clinical application of heparin; and hints on the significance of exploring the wider application fields of heparin.


Subject(s)
Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Drugs, Essential , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/therapeutic use , Heparin/pharmacology , Heparin/therapeutic use , Animals , COVID-19/drug therapy , Cardiovascular Diseases/drug therapy , Cerebrovascular Disorders/drug therapy , Humans , Kidney Diseases/drug therapy , Lung Injury/drug therapy
6.
J Thromb Thrombolysis ; 52(3): 766-771, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1172396

ABSTRACT

Patients critically ill with COVID-19 are at risk for thrombotic events despite prophylactic anticoagulation. Impaired fibrinolysis has been proposed as an underlying mechanism. Our objective was to determine if fibrinolysis stimulated by tissue plasminogen activator (tPA) differed between COVID patients and controls. Plasma from 14 COVID patients on prophylactic heparin therapy was obtained and compared with heparinized plasma from 14 different healthy donors to act as controls. Kaolin activated thromboelastography with heparinase was utilized to obtain baseline measurements and then repeated with the addition of 4 nM tPA. Baseline fibrinogen levels were higher in COVID plasma as measured by maximum clot amplitude (43.6 ± 6.9 mm vs. 23.2 ± 5.5 mm, p < 0.0001) and Clauss assay (595 ± 135 mg/dL vs. 278 ± 44 mg/dL, p < 0.0001). With the addition of tPA, fibrinolysis at 30 min after MA (LY30%) was lower (37.9 ± 16.5% vs. 58.9 ± 18.3%, p = 0.0035) and time to 50% lysis was longer (48.8 ± 16.3 vs. 30.5 ± 15.4 min, p = 0.0053) in the COVID-19 samples. Clotting times and rate of fibrin polymerization ('R' or 'α' parameters) were largely the same in both groups. Clot from COVID patients contains a higher fibrin content compared to standard controls and shows resistance to fibrinolysis induced by tPA. These findings suggest the clinical efficacy of thrombolytics may be reduced in COVID-19 patients.


Subject(s)
COVID-19/blood , Fibrinolysis/drug effects , Fibrinolytic Agents/pharmacology , Thrombelastography , Tissue Plasminogen Activator/pharmacology , COVID-19/diagnosis , Case-Control Studies , Critical Illness , Humans , Kinetics
7.
Molecules ; 26(7)2021 Mar 26.
Article in English | MEDLINE | ID: covidwho-1154457

ABSTRACT

The current COronaVIrus Disease 19 (COVID-19) pandemic caused by SARS-CoV-2 infection is enormously affecting the worldwide health and economy. In the wait for an effective global immunization, the development of a specific therapeutic protocol to treat COVID-19 patients is clearly necessary as a short-term solution of the problem. Drug repurposing and herbal medicine represent two of the most explored strategies for an anti-COVID-19 drug discovery. Clove (Syzygium aromaticum L.) is a well-known culinary spice that has been used for centuries in folk medicine in many disorders. Interestingly, traditional medicines have used clove since ancient times to treat respiratory ailments, whilst clove ingredients show antiviral and anti-inflammatory properties. Other interesting features are the clove antithrombotic, immunostimulatory, and antibacterial effects. Thus, in this review, we discuss the potential role of clove in the frame of anti-COVID-19 therapy, focusing on the antiviral, anti-inflammatory, and antithrombotic effects of clove and its molecular constituents described in the scientific literature.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antiviral Agents/pharmacology , COVID-19 , Fibrinolytic Agents/pharmacology , Syzygium/chemistry , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Antiviral Agents/chemistry , COVID-19/drug therapy , COVID-19/prevention & control , Herbal Medicine/methods , Humans , Phytochemicals/chemistry , Phytochemicals/pharmacology , Plants, Medicinal/chemistry
8.
J Thromb Haemost ; 18(12): 3296-3308, 2020 12.
Article in English | MEDLINE | ID: covidwho-1066732

ABSTRACT

BACKGROUND: It is long established that von Willebrand factor (VWF) is central to hemostasis and thrombosis. Endothelial VWF is stored in cell-specific secretory granules, Weibel-Palade bodies (WPBs), organelles generated in a wide range of lengths (0.5-5.0 µm). WPB size responds to physiological cues and pharmacological treatment, and VWF secretion from shortened WPBs dramatically reduces platelet and plasma VWF adhesion to an endothelial surface. OBJECTIVE: We hypothesized that WPB-shortening represented a novel target for antithrombotic therapy. Our objective was to determine whether compounds exhibiting this activity do exist. METHODS: Using a microscopy approach coupled to automated image analysis, we measured the size of WPB bodies in primary human endothelial cells treated with licensed compounds for 24 hours. RESULTS AND CONCLUSIONS: A novel approach to identification of antithrombotic compounds generated a significant number of candidates with the ability to shorten WPBs. In vitro assays of two selected compounds confirm that they inhibit the pro-hemostatic activity of secreted VWF. This set of compounds acting at a very early stage of the hemostatic process could well prove to be a useful adjunct to current antithrombotic therapeutics. Further, in the current SARS-CoV-2 pandemic, with a considerable fraction of critically ill COVID-19 patients affected by hypercoagulability, these WPB size-reducing drugs might also provide welcome therapeutic leads for frontline clinicians and researchers.


Subject(s)
Fibrinolytic Agents/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Organelle Size/drug effects , Weibel-Palade Bodies/drug effects , Cells, Cultured , Drug Evaluation, Preclinical , Drug Repositioning , Hemostasis/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/pathology , Humans , Weibel-Palade Bodies/metabolism , Weibel-Palade Bodies/pathology , von Willebrand Factor/genetics , von Willebrand Factor/metabolism
9.
Mar Drugs ; 19(1)2021 Jan 10.
Article in English | MEDLINE | ID: covidwho-1033055

ABSTRACT

Microalgae are at the start of the food chain, and many are known producers of a significant amount of lipids with essential fatty acids. However, the bioactivity of microalgal lipids for anti-inflammatory and antithrombotic activities have rarely been investigated. Therefore, for a sustainable source of the above bioactive lipids, the present study was undertaken. The total lipids of microalga Chlorococcum sp., isolated from the Irish coast, were fractionated into neutral-, glyco-, and phospho-lipids, and were tested in vitro for their anti-inflammatory and antithrombotic activities. All tested lipid fractions showed strong anti-platelet-activating factor (PAF) and antithrombin activities in human platelets (half maximal inhibitory concentration (IC50) values ranging ~25-200 µg of lipid) with the highest activities in glyco- and phospho-lipid fractions. The structural analysis of the bioactive lipid fraction-2 revealed the presence of specific sulfoquinovosyl diacylglycerols (SQDG) bioactive molecules and the HexCer-t36:2 (t18:1/18:1 and 18:2/18:0) cerebrosides with a phytosphingosine (4-hydrosphinganine) base, while fraction-3 contained bioactive phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecules. These novel bioactive lipids of Chlorococcum sp. with putative health benefits may indicate that marine microalgae can be a sustainable alternative source for bioactive lipids production for food supplements and nutraceutical applications. However, further studies are required towards the commercial technology pathways development and biosafety analysis for the use of the microalga.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Fibrinolytic Agents/chemistry , Fibrinolytic Agents/pharmacology , Lipids/chemistry , Lipids/pharmacology , Microalgae/chemistry , Antithrombins/pharmacology , Blood Platelets/drug effects , Fatty Acids/chemistry , Fatty Acids/pharmacology , Humans , Platelet Activating Factor/antagonists & inhibitors , Platelet Aggregation/drug effects , Water Microbiology
10.
Biomed Pharmacother ; 132: 110886, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-866443

ABSTRACT

Host excessive inflammatory immune response to SARS-CoV-2 infection is thought to underpin the pathogenesis of COVID-19 associated severe pneumonitis and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Once an immunological complication like cytokine storm occurs, anti-viral based monotherapy alone is not enough. Additional anti-inflammatory treatment is recommended. It must be noted that anti-inflammatory drugs such as JAK inhibitors, IL-6 inhibitors, TNF-α inhibitors, colchicine, etc., have been either suggested or are under trials for managing cytokine storm in COVID-19 infections. Natural astaxanthin (ASX) has a clinically proven safety profile and has antioxidant, anti-inflammatory, and immunomodulatory properties. There is evidence from preclinical studies that supports its preventive actions against ALI/ARDS. Moreover, ASX has a potent PPARs activity. Therefore, it is plausible to speculate that ASX could be considered as a potential adjunctive supplement. Here, we summarize the mounting evidence where ASX is shown to exert protective effect by regulating the expression of pro-inflammatory factors IL-1ß, IL-6, IL-8 and TNF-α. We present reports where ASX is shown to prevent against oxidative damage and attenuate exacerbation of the inflammatory responses by regulating signaling pathways like NF-ĸB, NLRP3 and JAK/STAT. These evidences provide a rationale for considering natural astaxanthin as a therapeutic agent against inflammatory cytokine storm and associated risks in COVID-19 infection and this suggestion requires further validation with clinical studies.


Subject(s)
COVID-19/drug therapy , Cytokines/antagonists & inhibitors , Fibrinolytic Agents/therapeutic use , SARS-CoV-2/drug effects , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/immunology , Cytokines/blood , Cytokines/immunology , Fibrinolytic Agents/pharmacology , Humans , Risk Factors , SARS-CoV-2/immunology , Xanthophylls/pharmacology , Xanthophylls/therapeutic use
11.
Eur Rev Med Pharmacol Sci ; 24(13): 7494-7496, 2020 07.
Article in English | MEDLINE | ID: covidwho-676179

ABSTRACT

Although most patients with coronavirus disease 2019 (COVID-19) have a good prognosis, in some cases, the disease progresses rapidly, and the mortality rate is high. Some evidence suggests that infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produces a 'cytokine storm', which is related to acute respiratory distress syndrome or multi-organ dysfunction leading to physiological deterioration and death. It is important to highlight the state of hypercoagulability that can be triggered, involving microvascular thrombosis and vascular occlusive events, which are relevant to such poor outcomes. At present, no specific antiviral drug or vaccine is available for SARS-CoV-2 infection, and current research is aimed at preventing and mitigating damage to the target organs, mainly the lungs. In seeking therapies for patients with COVID-19, immunomodulators, cytokine antagonists and early anti-coagulation therapies have been tested in attempts to reduce the mortality rate. Pentoxifylline, a non-specific phosphodiesterase inhibitor widely used to improve the rheological properties of blood, has beneficial anti-inflammatory properties and can significantly reduce the serum levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1, tumour necrosis factor-alpha, C-reactive protein and other immunoregulators. It has also been found to exert anti-thrombotic, antioxidant and anti-fibrogenic actions. These properties could help to prevent or mitigate the inflammatory response and hypercoagulability that develop with SARS-CoV-2 infection, decreasing multi-organ dysfunction manifesting primarily as acute lung injury.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , COVID-19 , Fibrinolytic Agents/pharmacology , Humans , Microbial Sensitivity Tests , Pandemics , Pentoxifylline/pharmacology , SARS-CoV-2
12.
Biomed Pharmacother ; 130: 110536, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-653483

ABSTRACT

In the last three months, the whole scientific community has shifted its focus to the fight against the COVI-2 infection (COVID-19) trying to use different medications to save the patients' life. In some studies, the results were completely inconclusive, as in the case of chloroquine. However, the recent discovery on benefits deriving from use of such anticoagulants for Covid-19 patients, has increased the success of patients' treatment. Among lots of old and new drugs, PARP-inhibitors were not considered as possible option in the treatment of Covi-2 infection, being the latter able to induce the inflammatory and thrombotic cascades. Since PARP-inhibitors are able to reduce and block mechanisms leading to thrombosis and inflammation, they could be used as antithrombotic medications. Therefore, the present brief report is aimed to open the discussion on the potentials of PARP-inhibitors in non-oncological settings, like Covid-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/blood , Fibrinolytic Agents/therapeutic use , Pandemics , Pneumonia, Viral/blood , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Thrombophilia/drug therapy , Thrombosis/prevention & control , Anti-Inflammatory Agents/pharmacology , COVID-19 , Coronavirus Infections/complications , Drug Repositioning , Fibrinolytic Agents/pharmacology , Humans , Inflammation , Pneumonia, Viral/complications , Poly (ADP-Ribose) Polymerase-1/physiology , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerases/physiology , SARS-CoV-2 , Thrombophilia/etiology
13.
J Thromb Thrombolysis ; 51(1): 226-231, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-648995

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been linked to a higher risk of mortality compared to influenza, which is mainly due to severe secondary diseases, such as acute respiratory distress syndrome (ARDS). In turn, ARDS is characterized by an acute inflammation and an excessive activity of the coagulation cascade, rising the vulnerability for venous thromboembolic events. In order to investigate the relation of inflammation and the influence of coagulation factors on their release, human peripheral mononuclear blood cells (PBMCs) were treated with autologous serum, heparinized plasma and different doses of fibrin. Thereafter, the concentration of pro-inflammatory cytokines and chemokines in the secretome of PBMCs was measured by enzyme-linked immunosorbent assay. Our analyses revealed autologous serum to significantly increase the secretion of cytokines and chemokines after 24 h of incubation time. Furthermore, the addition of fibrin markedly increased the secretion of cytokines and chemokines by PBMCs in a dose-dependent manner. Consequently, in accordance with previous studies, our study outlines that anti-coagulation may constitute a promising tool for the treatment of SARS-CoV-2, reducing both, the cytokine storm, as well as the risk for thrombotic complications.


Subject(s)
Blood Coagulation , COVID-19/therapy , Cytokine Release Syndrome , Fibrin , Inflammation , Blood Coagulation/drug effects , Blood Coagulation/immunology , COVID-19/blood , COVID-19/drug therapy , COVID-19/immunology , Cells, Cultured , Chemokines/immunology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Dose-Response Relationship, Drug , Fibrin/immunology , Fibrin/pharmacology , Fibrinolytic Agents/pharmacology , Heparin/pharmacology , Humans , Immunization, Passive , Inflammation/blood , Inflammation/therapy , Leukocytes, Mononuclear/drug effects , SARS-CoV-2
14.
J Am Coll Cardiol ; 75(23): 2950-2973, 2020 06 16.
Article in English | MEDLINE | ID: covidwho-547082

ABSTRACT

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.


Subject(s)
Anticoagulants/pharmacology , Betacoronavirus/isolation & purification , Coronavirus Infections , Fibrinolytic Agents/pharmacology , Pandemics , Platelet Aggregation Inhibitors/pharmacology , Pneumonia, Viral , Thromboembolism , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Humans , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , SARS-CoV-2 , Thromboembolism/drug therapy , Thromboembolism/epidemiology , Thromboembolism/etiology , Thromboembolism/physiopathology , Treatment Outcome
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