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2.
Clin Appl Thromb Hemost ; 27: 10760296211066945, 2021.
Article in English | MEDLINE | ID: covidwho-1574469

ABSTRACT

INTRODUCTION: Argatroban is licensed for patients with heparin-induced thrombocytopenia and is conventionally monitored by activated partial thromboplastin time (APTT) ratio. The target range is 1.5 to 3.0 times the patients' baseline APTT and not exceeding 100 s, however this baseline is not always known. APTT is known to plateau at higher levels of argatroban, and is influenced by coagulopathies, lupus anticoagulant and raised FVIII levels. It has been used as a treatment for COVID-19 and Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). Some recent publications have favored the use of anti-IIa methods to determine the plasma drug concentration of argatroban. METHODS: Plasma of 60 samples from 3 COVID-19 patients and 54 samples from 5 VITT patients were tested by APTT ratio and anti-IIa method (dilute thrombin time dTT). Actin FS APTT ratios were derived from the baseline APTT of the patient and the mean normal APTT. RESULTS: Mean APTT ratio derived from baseline was 1.71 (COVID-19), 1.33 (VITT) compared to APTT ratio by mean normal 1.65 (COVID-19), 1.48 (VITT). dTT mean concentration was 0.64 µg/ml (COVID-19) 0.53 µg/ml (VITT) with poor correlations to COVID-19 baseline APTT ratio r2 = 0.1526 p <0.0001, mean normal r2 = 0.2188 p < 0.0001; VITT baseline APTT ratio r2 = 0.04 p < 0.001, VITT mean normal r2 = 0.0064 p < 0.001. CONCLUSIONS: We believe that dTT is a superior method to monitor the concentration of argatroban, we have demonstrated significant differences between APTT ratios and dTT levels, which could have clinical impact. This is especially so in COVID-19 and VITT.


Subject(s)
Arginine/analogs & derivatives , COVID-19/drug therapy , Partial Thromboplastin Time/methods , Pipecolic Acids/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Sulfonamides/therapeutic use , Thrombocytopenia/drug therapy , Thrombosis/drug therapy , Aged , Arginine/pharmacology , Arginine/therapeutic use , COVID-19/complications , Female , Humans , Male , Middle Aged , Pipecolic Acids/pharmacology , Platelet Aggregation Inhibitors/pharmacology , SARS-CoV-2 , Sulfonamides/pharmacology , Thrombocytopenia/chemically induced , Thrombosis/chemically induced
3.
J Thromb Thrombolysis ; 53(2): 273-281, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1401065

ABSTRACT

SARS-CoV-2 represents the causative agent of the current pandemic (COVID-19). The drug repurposing technique is used to search for possible drugs that can bind to SARS-CoV-2 proteins and inhibit viral replication. In this study, the FDA-approved antiplatelets are tested against the main protease and spike proteins of SARS-CoV-2 using in silico methods. Molecular docking and molecular dynamics simulation are used in the current study. The results suggest the effectiveness of vorapaxar, ticagrelor, cilostazol, cangrelor, and prasugrel in binding the main protease (Mpro) of SARS-CoV-2. At the same time, vorapaxar, ticagrelor, and cilostazol are the best binders of the spike protein. Therefore, these compounds could be successful candidates against COVID-19 that need to be tested experimentally.


Subject(s)
Antiviral Agents , Platelet Aggregation Inhibitors , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , COVID-19/drug therapy , Cilostazol , Coronavirus 3C Proteases/antagonists & inhibitors , Humans , Lactones , Molecular Docking Simulation , Molecular Dynamics Simulation , Platelet Aggregation Inhibitors/pharmacology , Pyridines , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Ticagrelor
4.
Drug Dev Res ; 82(8): 1075-1078, 2021 12.
Article in English | MEDLINE | ID: covidwho-1380379

ABSTRACT

One of the most remarkable results in 2019 is the reduced prevalence and death of children from coronavirus infection (COVID-19). In 2019, a worldwide pandemic impacted around 0.1 billion individuals, with over 3.5 million mortality reported in the literature. There is minimal knowledge on SARS-CoV-2 infection immunological responses in kids. Studies have been focused mostly on adults and children since the course of pediatric sickness is often short. In adults, severe COVID-19 is related to an excessive inflammatory reaction. Macrophages and monocytes are well known to contribute to this systemic response, although numerous lines are indicative of the importance of neutrophils. An increased number of neutrophils and neutrophil to lymphocyte ratios are early signs of SARS-CoV-2 and a worse prognosis. In this study that it is crucial to monitor PAR2 and PAR4 expression and function (since nursing children have elevated levels) and the inhibiting the normal physiology through the use of anticoagulants may exacerbate the problem in adults. Thus, in COVID-19 infection, we propose the use of antiplatelet (thromboxane A2 inhibitors), if required rather than anticoagulants (FXa and thrombin Inhibitors).


Subject(s)
COVID-19/metabolism , Receptor, PAR-2/metabolism , Receptors, Thrombin/metabolism , Adult , Age Factors , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , Child , Humans , Lymphocyte Count , Neutrophils/immunology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use
5.
Open Heart ; 8(1)2021 06.
Article in English | MEDLINE | ID: covidwho-1261214

ABSTRACT

Although primarily affecting the respiratory system, COVID-19 causes multiple organ damage. One of its grave consequences is a prothrombotic state that manifests as thrombotic, microthrombotic and thromboembolic events. Therefore, understanding the effect of antiplatelet and anticoagulation therapy in the context of COVID-19 treatment is important. The aim of this rapid review was to highlight the role of thrombosis in COVID-19 and to provide new insights on the use of antithrombotic therapy in its management. A rapid systematic review was performed using preferred reporting items for systematic reviews. Papers published in English on antithrombotic agent use and COVID-19 complications were eligible. Results showed that the use of anticoagulants increased survival and reduced thromboembolic events in patients. However, despite the use of anticoagulants, patients still suffered thrombotic events likely due to heparin resistance. Data on antiplatelet use in combination with anticoagulants in the setting of COVID-19 are quite scarce. Current side effects of anticoagulation therapy emphasise the need to update treatment guidelines. In this rapid review, we address a possible modulatory role of antiplatelet and anticoagulant combination against COVID-19 pathogenesis. This combination may be an effective form of adjuvant therapy against COVID-19 infection. However, further studies are needed to elucidate potential risks and benefits associated with this combination.


Subject(s)
Anticoagulants/pharmacology , COVID-19 , Platelet Aggregation Inhibitors/pharmacology , Thromboembolism , COVID-19/blood , COVID-19/complications , COVID-19/drug therapy , Drug Therapy, Combination/methods , Humans , SARS-CoV-2 , Thromboembolism/etiology , Thromboembolism/prevention & control , Treatment Outcome
6.
Adv Ther ; 38(7): 3911-3923, 2021 07.
Article in English | MEDLINE | ID: covidwho-1258274

ABSTRACT

INTRODUTION: COVID-19 is associated with an increased risk of thrombotic events. However, the contribution of platelet reactivity (PR) to the aetiology of the increased thrombotic risk associated with COVID-19 remains unclear. Our aim was to evaluate PR in stable patients diagnosed with COVID-19 and hospitalized with respiratory symptoms (mainly dyspnoea and dry cough), in comparison with a control group comprised of non-hospitalized healthy controls. METHODS: Observational, case control study that included patients with confirmed COVID-19 (COVID-19 group, n = 60) and healthy individuals matched by age and sex (control group, n = 60). Multiplate electrode aggregometry (MEA) tests were used to assess PR with adenosine diphosphate (MEA-ADP, low PR defined as < 53 AUC), arachidonic acid (MEA-ASPI, low PR < 86 AUC) and thrombin receptor-activating peptide 6 (MEA-TRAP, low PR < 97 AUC) in both groups. RESULTS: The rates of low PR with MEA-ADP were 27.5% in the COVID-19 group and 21.7% in the control group (OR = 1.60, p = 0.20); with MEA-ASPI, the rates were, respectively, 37.5% and 22.5% (OR = 3.67, p < 0.001); and with MEA-TRAP, the incidences were 48.5% and 18.8%, respectively (OR = 9.58, p < 0.001). Levels of D-dimer, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) were higher in the COVID-19 group in comparison with the control group (all p < 0.05). Thromboelastometry was utilized in a subgroup of patients and showed a hypercoagulable state in the COVID-19 group. CONCLUSION: Patients hospitalized with non-severe COVID-19 had lower PR compared to healthy controls, despite having higher levels of D-dimer, fibrinogen, and PAI-1, and hypercoagulability by thromboelastometry. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04447131.


Subject(s)
COVID-19 , Blood Platelets , Case-Control Studies , Humans , Platelet Aggregation , Platelet Aggregation Inhibitors/pharmacology , SARS-CoV-2
7.
Med Hypotheses ; 147: 110480, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1174424

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus is now considered a global public health threat. The primary focus has been on reducing the viral spread and treating respiratory symptoms; as time goes on, the impact of COVID-19 on neurological and haemostatic systems becomes more evident. The clinical data suggest that platelet hyperactivity plays a role in the pathology of COVID-19 from its onset and that platelets may serve critical functions during COVID-19 progression. Hyperactivation of blood platelets and the coagulation system are emerging as important drivers of inflammation and may be linked to the severity of the 'cytokine storm' induced in severe cases of COVID-19, in which disseminated intravascular coagulation, and platelet hyperactivity are associated with poor prognosis and increased risk of mortality. We propose that targeting platelet hyperactivity in the early stages of COVID-19 infection may reduce the immunothrombotic complications of COVID-19 and subdue the systemic inflammatory response. Lowering baseline platelet activity may be of particular importance for higher-risk groups. As an alternative to antiplatelet drugs, an inappropriate intervention in public health, we propose that the dietary antiplatelet agent Fruitflow®, derived from tomatoes, may be considered a suitable therapy. Fruitflow® contains antiplatelet and anti-inflammatory compounds that target the mechanisms of platelet activation specific to COVID-19 and can be considered a safe and natural antiplatelet regime.


Subject(s)
Blood Platelets/cytology , COVID-19/blood , Lycopersicon esculentum , Plant Extracts/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Anti-Inflammatory Agents , Blood Coagulation , Blood Pressure , COVID-19/complications , Disease Progression , Humans , Immunoglobulin G , Inflammation/pathology , Models, Theoretical , Platelet Activation , Prognosis , Thrombosis
8.
Br J Pharmacol ; 177(21): 4971-4974, 2020 11.
Article in English | MEDLINE | ID: covidwho-998832

ABSTRACT

In the search to rapidly identify effective therapies that will mitigate the morbidity and mortality of COVID-19, attention has been directed towards the repurposing of existing drugs. Candidates for repurposing include drugs that target COVID-19 pathobiology, including agents that alter angiotensin signalling. Recent data indicate that key findings in COVID-19 patients include thrombosis and endotheliitis. Activation of proteinase-activated receptor 1 (PAR1), in particular by the serine protease thrombin, is a critical element in platelet aggregation and coagulation. PAR1 activation also impacts on the actions of other cell types involved in COVID-19 pathobiology, including endothelial cells, fibroblasts and pulmonary alveolar epithelial cells. Vorapaxar is an approved inhibitor of PAR1, used for treatment of patients with myocardial infarction or peripheral arterial disease. We discuss evidence for a possible beneficial role for vorapaxar in the treatment of COVID-19 patients and other as-yet non-approved antagonists of PAR1 and proteinase-activated receptor 4 (PAR4). LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.


Subject(s)
Coronavirus Infections/drug therapy , Lactones/administration & dosage , Pneumonia, Viral/drug therapy , Pyridines/administration & dosage , Receptor, PAR-1/antagonists & inhibitors , Animals , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/virology , Drug Repositioning , Humans , Lactones/pharmacology , Pandemics , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/pharmacology , Pneumonia, Viral/virology , Pyridines/pharmacology , Receptor, PAR-1/metabolism , Receptors, Thrombin/antagonists & inhibitors , Receptors, Thrombin/metabolism , SARS-CoV-2
9.
Platelets ; 32(5): 582-590, 2021 Jul 04.
Article in English | MEDLINE | ID: covidwho-786866

ABSTRACT

Dual antiplatelet therapy (DAPT) is the basis of preventing stent thrombosis and ischemic events after percutaneous coronary intervention (PCI), but prolonging the duration of DAPT will increase the risk of bleeding. The optimal duration of DAPT after PCI remains controversial at present. The purpose of this meta-analysis was to investigate the efficacy and safety of short-term DAPT in patients undergoing PCI. PubMed, Embase, Cochrane and Web of science from inception to September 2019 were systematically searched. Randomized controlled trials were included to compare short term (3 months or less) with a standard 12-months DAPT in patients undergoing PCI. Random effect model and fixed effect model wereused to calculate the risk ratio (RR) and 95% confidence interval (CI) of each endpoint. This meta-analysis included 38479 patients undergoing PCI from 8 randomized clinical trials. No difference was observed in the risk of all-cause death (RR 0.92, 95% CI 0.80-1.06, P = 0.25), cardiovascular death (RR 0.88, 0.69-1.12, P = 0.29), myocardial infarction (RR 1.05, 0.94-1.19, P = 0.38), definite or probable stent thrombosis (RR 1.05, 0.80-1.36, P = 0.73), and stroke (RR 1.02, 0.80-1.30, P = 0.89) between short term and standard DAPT. The short-term DAPT could reduce the risk of major bleeding (RR 0.67, 0.48-0.94, P = 0.02) and any bleeding (RR 0.63, 0.48-0.82, P = 0.0005) compared with 12 months of DAPT. In conclusion, the short-term DAPT can reduce the risk of bleeding compared with standard DAPT, without increasing the risk of death or ischemia (Registered by PROSPERO, CRD42020153881).


Subject(s)
Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/therapeutic use , Female , Humans , Male , Platelet Aggregation Inhibitors/pharmacology , Randomized Controlled Trials as Topic , Time Factors , Treatment Outcome
10.
Turk Kardiyol Dern Ars ; 48(4): 410-424, 2020 06.
Article in English | MEDLINE | ID: covidwho-622990

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the effectiveness of plants used in the formulations of traditional Chinese medicine (TCM), which were also used in clinical trials to treat patients with the novel coronavirus COVID-19, and to assess their effects on the cardiovascular system. METHODS: A literature review of PubMed, ResearchGate, ScienceDirect, the Cochrane Library, and TCM monographs was conducted and the effects of the plants on the cardiovascular system and the mechanisms of action in COVID-19 treatment were evaluated. RESULTS: The mechanism of action, cardiovascular effects, and possible toxicity of 10 plants frequently found in TCM formulations that were used in the clinical treatment of COVID-19 were examined. CONCLUSION: TCM formulations that had been originally developed for earlier viral diseases have been used in COVID-19 treatment. Despite the effectiveness seen in laboratory and animal studies with the most commonly used plants in these formulations, the clinical studies are currently insufficient according to standard operating procedures. More clinical studies are needed to understand the safe clinical use of traditional plants.


Subject(s)
Cardiovascular System/drug effects , Coronavirus Infections/therapy , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Pneumonia, Viral/therapy , Animals , Anti-Arrhythmia Agents/pharmacology , Anti-Arrhythmia Agents/therapeutic use , Anti-Arrhythmia Agents/toxicity , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/toxicity , Anticholesteremic Agents/pharmacology , Anticholesteremic Agents/therapeutic use , Anticholesteremic Agents/toxicity , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/toxicity , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Antiviral Agents/toxicity , COVID-19 , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/therapeutic use , Calcium Channel Blockers/toxicity , Drug Interactions , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/toxicity , Humans , Pandemics , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/toxicity , Vasodilator Agents/pharmacology , Vasodilator Agents/therapeutic use , Vasodilator Agents/toxicity
11.
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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