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1.
Clin Appl Thromb Hemost ; 29: 10760296231180865, 2023.
Article in English | MEDLINE | ID: covidwho-20240789

ABSTRACT

OBJECTIVE: During the first wave of the SARS-CoV-2 pandemic, management of anticoagulation therapy in hospitalized patients with atrial fibrillation (AF) was simplified to low-molecular-weight heparin (LMWH) followed by oral anticoagulation, mainly owing to the risk of drug-drug interactions. However, not all oral anticoagulants carry the same risk. METHODS: Observational, retrospective, and multicenter study that consecutively included hospitalized patients with AF anticoagulated with LMWH followed by oral anticoagulation or edoxaban concomitantly with empirical COVID-19 therapy. Time-to-event (mortality, total bleeds, and admissions to ICU) curves, using an unadjusted Kaplan-Meier method and Cox regression model adjusted for potential confounders were constructed. RESULTS: A total of 232 patients were included (80.3 ± 7.7 years, 50.0% men, CHA2DS2-VASc 4.1 ± 1.4; HAS-BLED 2.6 ± 1.0). During hospitalization, patients were taking azithromycin (98.7%), hydroxychloroquine (89.7%), and ritonavir/lopinavir (81.5%). The mean length of hospital stay was 14.6 ± 7.2 days, and total follow-up was 31.6 ± 13.4 days; 12.9% of patients required admission to ICU, 18.5% died, and 9.9% had a bleeding complication (34.8% major bleeding). Length of hospital stay was longer in patients taking LMWH (16.0 ± 7.7 vs 13.3 ± 6.5 days; P = .005), but mortality and total bleeds were similar in patients treated with edoxaban and those treated with LMWH followed by oral anticoagulation. CONCLUSIONS: Mortality rates, arterial and venous thromboembolic complications, and bleeds did not significantly differ between AF patients receiving anticoagulation therapy with edoxaban or LMWH followed by oral anticoagulation. However, the duration of hospitalization was significantly lower with edoxaban. Edoxaban had a similar therapeutic profile to LMWH followed by oral anticoagulation and may provide additional benefits.


Subject(s)
Atrial Fibrillation , COVID-19 , Stroke , Male , Humans , Female , Heparin, Low-Molecular-Weight , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Retrospective Studies , COVID-19/complications , SARS-CoV-2 , Anticoagulants , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Stroke/etiology , Heparin
2.
Adv Ther ; 2022 Oct 16.
Article in English | MEDLINE | ID: covidwho-2312848

ABSTRACT

Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent conditions with a significant healthcare burden, and represent the main indications for anticoagulation. Direct oral anticoagulants (DOACs) are the first choice treatment of AF/VTE, and have become the most prescribed class of anticoagulants globally, overtaking vitamin K antagonists (VKAs). Compared to VKAs, DOACs have a similar or better efficacy/safety profile, with reduced risk of intracerebral hemorrhage (ICH), while the risk of major bleeding and other bleeding harms may vary depending on the type of DOAC. We have critically reviewed available evidence from randomized controlled trials and observational studies regarding the risk of bleeding complications of DOACs compared to VKAs in patients with AF and VTE. Special patient populations (e.g., elderly, extreme body weights, chronic kidney disease) have specifically been addressed. Management of bleeding complications and possible resumption of anticoagulation, in particular after ICH and gastrointestinal bleeding, are also discussed. Finally, some suggestions are provided to choose the optimal DOAC to minimize adverse events according to individual patient characteristics and bleeding risk.

3.
Farmacia Hospitalaria ; 47(1):20-25, 2023.
Article in English, Spanish | EMBASE | ID: covidwho-2292560

ABSTRACT

Objective: Adverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. Method(s): Observational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Result(s): 10,799 patients visited the emergency department and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 +/- 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24, 95% CI: 1.47-7.13, p = 0.003, in Charlson comorbidity index 4-6;and aOR 20.07, 95% CI: 6.87-58.64, p = 0.000, in Charlson comorbidity index >= 10). Conclusion(s): The prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.Copyright © 2022 Sociedad Espanola de Farmacia Hospitalaria (S.E.F.H)

4.
Hamostaseologie ; 43(Supplement 1):S25-S26, 2023.
Article in English | EMBASE | ID: covidwho-2266863

ABSTRACT

Introduction Edoxaban is a non-vitamin K dependent oral anticoagulant (NOAC) licensed for venous thromboembolism (VTE) treatment or stroke prevention in atrial fibrillation (SPAF). Major surgical procedures are not uncommon in anticoagulated patients but data on perioperative edoxaban management are scarce. Method Using data from the prospective DRESDEN NOAC REGISTRY we extracted data on major surgical procedures in patients who took edoxaban within the preceding 7 days. Periinterventional edoxaban management patterns and rates of outcome events were evaluated until day 30 after procedure. Results Between 2011 and 2021, 3448 procedures were identified in edoxaban patients, including 287 (8.3 %) major procedures. Overall, patient characteristics were comparable for major and non-major procedures, but significant differences existed with regard to gender, concomitant antiplatelet therapies and the proportion of patients with a CHA2DS2-VASc score >= 2 (Table 1). Major procedures consisted of orthopaedic/trauma surgery (44.3 %);open pelvic, abdominal or thoracic surgery (30.4 %), central nervous system surgery and procedures (13.9 %), vascular surgery (9.1 %) and extensive wound revision surgery (2.4 %). A scheduled interruption of edoxaban was observed in 284/287 major procedures (99 %) with a total median edoxaban interruption time of 11.0 days (25- 75th percentile 5.0-18.0 days). Heparin bridging was documented in 183 procedures (46 prophylactic dosages, 111 intermediate and 26 therapeutic dosages). Overall, 7 (2.4 %;95 %-CI 1.2 %-4.9 %) major cardiovascular events (5 VTE, 2 arterial thromboembolic events) occurred and 63 bleeding events were observed in 287 major procedures (22.0 %;95 %-CI 17.6 %-2.71 %), comprising of 38 ISTH major bleeding events (13.2 %;95 %-CI 9.8 %-17.7 %) and 25 ISTH CRNM bleedings (8.7 %;95 %-CI 6.0 %-12.5 %). Rates of major cardiovascular events with or without heparin bridging were comparable (6/183;3.3 %;95 %-CI 1.5 %-7.0 % vs. 1/36;2.8 %;95 %-CI 0.5 %-14.2 %;p = 0.7173). ISTH major bleeding occurred numerically more frequent in patients receiving heparin bridging (30/183;16.4 %;95 %-CI 11.7 %-22.4 %) versus procedures without heparin bridging (2/36;5.6 %;95 %-CI 1.5 %-18.1 %;p = 0.1542) (Fig. 1). Within 30 days of follow up, 6 patients died (2.1 %;95 %-CI 1.0 %-4.5 %) with causes of death being a ruptured truncus coeliacus following palliative angioplasty for an infiltrating pancreas cancer (ruled as fatal bleeding), septic organ failure, pneumocystis jirovecii pneumonia, COVID-19-pneumonia, septic complications following clipping of a ruptured cerebrovascular aneurism or terminal malignant disease. No fatal cardiovascular event occurred. Conclusion Within the limitations of our study design, periprocedural edoxaban management seems effective and safe in routine care. Use of heparin bridging seems to have limited effects on reducing vascular events but may increase bleeding risk. (Table Presented).

5.
Journal of the American Pharmacists Association ; 63(1):151-157.e2, 2023.
Article in English | EMBASE | ID: covidwho-2245152

ABSTRACT

Background: The University of Kentucky HealthCare Anticoagulation Clinic at the Gill Heart and Vascular Institute in Lexington, Kentucky, designed and implemented a drive-up clinic for warfarin management with the goal to minimize person-to-person exposure during the coronavirus disease 2019 (COVID-19) pandemic. Objective: The purpose of this study was to evaluate the effect on warfarin management in a pharmacist-led anticoagulation service when transitioned from an in-person clinic to a drive-up clinic during the COVID-19 pandemic. Methods: This is a retrospective observational cohort study of 68 patients seen in the University of Kentucky HealthCare Anticoagulation Clinic on warfarin therapy for any indication. Patients were included if they had scheduled visits at least 3 times in the period 6 months before, during, and after the initiation of the drive-up clinic. The primary outcome is the difference in time in therapeutic range (TTR) before and during the drive-up clinic. Results: The difference between the mean TTR in period 1 (69.1% ± 23.2%) and period 2 (69.6% ± 19.2%) was not statistically significant (P = 0.882). The mean TTR in period 3 (70.5% ± 20.8%) did not differ in statistical significance from either period 1 (P = 0.688) or period 2 (P = 0.746). Safety outcomes including reported bleeding events and emergency department visits or hospital admissions for bleeding or thrombotic events were consistently low across each period. Conclusion: The results of this study illustrate that a drive-up clinic for warfarin management may be a reasonable alternative approach to providing care for outpatient anticoagulant management and may support nontraditional clinic models for long-term management of anticoagulation and other chronic disease states.

6.
BMC Chem ; 16(1): 102, 2022 Nov 23.
Article in English | MEDLINE | ID: covidwho-2139389

ABSTRACT

A precise, sensitive eco-friendly, simple, rapid, and derivative spectrofluorimetric method was developed to quantify edoxaban tosylate monohydrate in pure form and pharmaceutical dosage form. Sudden death due to pulmonary embolism as a consequence of coronavirus infection (covid-19) is an emerging problem. As a result, the world health organization introduced new guidelines to treat patients with COVID-19 with oral anticoagulants. Edoxaban tosylate monohydrate is an oral anticoagulant that doesn't require hospitalization after dose adjustment. This spectrofluorimetric method relies on the derivatization by 9-fluorenyl methyl chloroformate at room temperature in borate buffer pH 9.0. After excitation at 265 nm, the product is highly fluorescent at 309 nm. Many experimental factors influencing the reaction's stability and development were thoroughly investigated and optimized. The method validation was evaluated by using ICH guidelines and showed high precision and accuracy with an average percent recovery of 101.46% ± 1.02. The linear range was 5.0-50.0 ng/mL with a correlation coefficient of 0.9999, the LOD was 1.5 ng/mL, and the LOQ was 4.5 ng/mL. The green assessment of the method was achieved utilizing the eco-scale and the Green Analytical Procedure Index. There was no significant difference between the results of the suggested method and those of the reported method according to Statistical analysis.

7.
Chest ; 162(4):A786, 2022.
Article in English | EMBASE | ID: covidwho-2060688

ABSTRACT

SESSION TITLE: Rare Cases of Nervous System and Thrombotic Complication Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Rivaroxaban is a dose-dependent inhibitor of factor Xa. It is approved by the FDA to help reduce the risk of blood clots. Although bioavailability is not significantly affected at lower doses (80-100%), bioavailability at higher doses (≥15 mg) is as low as 66% when given without food [1] [3]. Here, we present a patient with poor oral intake who developed deep vein thrombosis (DVT) while on high dose Xarelto. CASE PRESENTATION: Our patient was a 48-year-old male with a history of pulmonary embolism diagnosed two months prior to admission (on 20 mg rivaroxaban daily at home) and morbid obesity who presented with dyspnea, fever, and decreased appetite. His viral PCR was positive for COVID-19, and CT angiogram showed multifocal ground glass opacities but was negative for pulmonary embolism. He was severely hypoxic on room air and required noninvasive ventilatory support in the intensive care unit. He was treated with remdesivir, dexamethasone, and baricitinib. His food intake was extremely poor due to near continuous use of noninvasive ventilation and decreased appetite. A nasogastric (NG) tube was offered, but the patient declined and elected to continue diminished oral feedings. He was able to take all of his home medications including rivaroxaban during this time. On day four, clinical nutrition was consulted because he had 3% loss of body weight. On day seven, the patient developed a fever of 101.6° F. Ultrasound of his lower extremities revealed acute DVTs in his left popliteal vein, posterior tibial vein, and peroneal vein. His anticoagulation was switched to full-dose enoxaparin and a NG tube was placed. On day ten, he was intubated due to worsening hypoxia. Unfortunately, the patient deteriorated into multiorgan failure and died on day seventeen. DISCUSSION: The latest expert guidelines suggest that direct oral anticoagulants (DOAC) should be used over vitamin K antagonists (VKA) in patients with acute venous thromboembolism (VTE) due to lower rates of major bleeding and recurrent VTE as well as convenience. Although VKAs are preferred in situations with extreme weight and renal impairment, DOACs have been proven to be effective for the large majority of patients [2]. Unlike rivaroxaban, the bioavailabilities of other DOACs like apixaban, edoxaban, and dabigatran are all unaffected by food and should be preferred in patients with tenuous oral intake [3]. It is well known that COVID-19 can produce a hypercoagulable state. This factor, combined with our patient's predisposition to blood clots and poor appetite, ended up precipitating new onset VTEs in his left leg despite rivaroxaban therapy. CONCLUSIONS: In patients with decreased oral intake, DOACs other than rivaroxaban should be considered. Patients should be briefed on the importance of taking high dose rivaroxaban with food. Our goal is to bring awareness to providers about this significant pharmacodynamic property of rivaroxaban. Reference #1: Mueck W, Stampfuss J, Kubitza D, Becka M. Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet. 2014 Jan;53(1):1-16. doi: 10.1007/s40262-013-0100-7. PMID: 23999929;PMCID: PMC3889701. Reference #2: Stevens SM, Woller SC, Baumann Kreuziger L, Bounameaux H, Doerschug K, Geersing GJ, Huisman MV, Kearon C, King CS, Knighton AJ, Lake E, Murin S, Vintch JRE, Wells PS, Moores LK. Executive Summary: Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report. Chest. 2021 Dec;160(6):2247-2259. doi: 10.1016/j.chest.2021.07.056. Epub 2021 Aug 2. PMID: 34352279. Reference #3: Lexicomp Online. Copyright © 1978-2022 Lexicomp, Inc. DISCLOSURES: No relevant relationships by Rishika Bajaj No relevant relationships by Ann Hylton No relevant relationships by Roger McSharry No relevant relationships by Krupa Solanki

8.
Res Pract Thromb Haemost ; 6(4): e12735, 2022 May.
Article in English | MEDLINE | ID: covidwho-1905946
9.
Electrophoresis ; 43(15): 1617-1625, 2022 08.
Article in English | MEDLINE | ID: covidwho-1825938

ABSTRACT

The incidence of thrombotic complications in SARS-CoV-2 infections has become a global concern; thus, anticoagulants are an integral part of the treatment. Edoxaban (EDX) is an oral anticoagulant suitable for pharmacologic thromboprophylaxis. Herein, two novel analytical methods for EDX determination in tablets are developed and validated using capillary zone electrophoresis (CZE) and high-performance liquid chromatography (HPLC). Operating conditions such as the electrolyte's concentration and pH value, injection time, volume, and the capillary temperature, were optimized. The methods were successfully validated by establishing the linearity, intra- and inter-day precisions (relative standard deviation [%]), accuracy, and robustness. Adequate separation of excipients and degradation products of EDX generated by stress degradation conditions demonstrated the stability-indicating capability of the methods. The analytical procedures were linear in the range of 25-125 µg/ml (r > 0.999), with the limits of detection and quantification of 3.26 and 10.87 µg/ml for CZE and 0.740 and 2.78 µg/ml for HPLC. Although both methodologies are suitable for determining EDX in tablets, CZE provides a greener alternative due to low-cost analysis using less organic solvents and minimizing waste generation.


Subject(s)
COVID-19 , Venous Thromboembolism , Anticoagulants , Chromatography, High Pressure Liquid/methods , Electrophoresis, Capillary/methods , Humans , Pyridines , Reproducibility of Results , SARS-CoV-2 , Tablets , Thiazoles
10.
Biomolecules ; 12(4)2022 04 17.
Article in English | MEDLINE | ID: covidwho-1792832

ABSTRACT

Edoxaban is a direct oral anticoagulant (DOAC) that has been recently indicated for the treatment of pulmonary embolism (PE) in SARS-CoV-2 infections. Due to its pharmacokinetic variability and a narrow therapeutic index, the safe administration of the drug requires its therapeutic drug monitoring (TDM) in patients receiving the treatment. In this work, we present a label-free method for the TDM of edoxaban by surface enhanced Raman spectroscopy (SERS). The new method utilises the thiol chemistry of the drug to chemisorb its molecules onto a highly sensitive SERS substrate. This leads to the formation of efficient hotspots and a strong signal enhancement of the drug Raman bands, thus negating the need for a Raman reporter for its SERS quantification. The standard samples were run with a concentration range of 1.4 × 10-4 M to 10-12 M using a mobile phase comprising of methanol/acetonitrile (85:15 v/v) at 291 nm followed by the good linearity of R2 = 0.997. The lowest limit of quantification (LOQ) by the SERS method was experimentally determined to be 10-12 M, whereas LOQ for HPLC-UV was 4.5 × 10-7 M, respectively. The new method was used directly and in a simple HPLC-SERS assembly to detect the drug in aqueous solutions and in spiked human blood plasma down to 1 pM. Therefore, the SERS method has strong potential for the rapid screening of the drug at pathology labs and points of care.


Subject(s)
COVID-19 Drug Treatment , Metal Nanoparticles , Drug Monitoring , Gold/chemistry , Humans , Metal Nanoparticles/chemistry , Pharmaceutical Preparations , Pyridines , SARS-CoV-2 , Thiazoles
11.
Electroanalysis ; : 8, 2022.
Article in English | Web of Science | ID: covidwho-1680319

ABSTRACT

During COVID-19 pandemic, coagulopathy have been reported as a potential threat to most infected patients. Edoxaban (EDX) is a direct oral anticoagulant that is recently added to most COVID-19 treatment protocols either as therapy or prophylaxis. Herein, a novel nanoparticles modified glassy carbon potentiometric sensor was developed for the selective quantitation of EDX in human plasma. The electrochemical performance of the proposed sensor was assessed and compared to nanoparticle free sensor. An enhancement in electrode performance including: detection limit (3.39 x 10(-6) mol L-1), response time (8.0 +/- 2.0 s) and improved selectivity. The proposed sensor was able to determine EDX in pure form, pharmaceutical formulation and human plasma.

12.
Italian Journal of Medicine ; 15(3):12, 2021.
Article in English | EMBASE | ID: covidwho-1567335

ABSTRACT

Background: Venous thromboembolism, arterial thrombosis and thrombotic microangiopathy substantially contribute to increased morbidity and mortality in CoViD-19. We report a case of 56-year old man that presented with stroke and was found to have CoViD- 19 pneumonia complicated by pulmonary embolism (PE). Description of the case: A 55-year-old man with history of hypertension presented to the emergency department after a transient loss of consciousness. He was found to have left lateral hemianopia and lower right quadrantanopsia and head CT confirmed bilateral stroke in the posterior cerebral artery territory. MR angiography excluded atherosclerosis/dissection of the vertebral and basilar artery and a positive nasopharingeal swab PCR test revealed SARS-CoV-2 infection. The patient was admitted and ASA 100 mg and enoxaparin 40 mg per day were started. He experienced dry cough and fever and 10 days after admission presented atypical chest pain. CT Angiography revealed multiple confined ground glass opacities with segmental bilateral PE. Therapeutic dose of enoxaparin was started and after 5 days switched to edoxaban 60 mg per day. The patient progressively recovered and a complete work up excluded patent foramen ovale and any other cause predisponing to combined presence of venous and arterial thrombosis Conclusions: CoViD-19 has presented many diagnostic challanges in patients with neurologic and respiratory findings: thromboembolic disease may even be the initial or unique presentation. The early recognition of these phenotipes of the disease play a dramatic role in the CoViD-19 management.

13.
Int J Pharm ; 608: 121122, 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1433361

ABSTRACT

Herein, we demonstrated the development and characterization of a dry powder inhaler (DPI) formulation of edoxaban (EDX); and investigated the in-vitro anticoagulation effect for the management of pulmonary or cerebral coagulopathy associated with COVID-19 infection. The formulations were prepared by mixing the inhalable micronized drug with a large carrier lactose and dispersibility enhancers, leucine, and magnesium stearate. The drug-excipient interaction was studied using X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) methods. The drug and excipients showed no physical inter particulate interaction. The in-vitro drug aerosolization from the developed formulation was determined by a Twin Stage Impinger (TSI) at a flow rate of 60 ± 5 L /min. The amount of drug deposition was quantified by an established HPLC-UV method. The fine particle fraction (FPF) of EDX API from drug alone formulation was 7%, whereas the formulations with excipients increased dramatically to almost 7-folds up to 47%. The developed DPI formulation of EDX showed a promising in-vitro anticoagulation effect at a very low concentration. This novel DPI formulation of EDX could be a potential and effective inhalation therapy for managing pulmonary venous thromboembolism (VTE) associated with COVID-19 infection. Further studies are warranted to investigate the toxicity and clinical application of the inhaled EDX DPI formulation.


Subject(s)
Blood Coagulation Disorders/drug therapy , COVID-19 , Dry Powder Inhalers , Pyridines/administration & dosage , Thiazoles/administration & dosage , Administration, Inhalation , Aerosols , Blood Coagulation Disorders/virology , COVID-19/complications , Humans , Particle Size , Powders
14.
Expert Rev Clin Pharmacol ; 14(10): 1289-1294, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1360277

ABSTRACT

PURPOSE: We aimed to investigate the clinical performance of edoxaban for the treatment of pulmonary embolism (PE) in hospitalized COVID-19 patients. METHODS: We conducted a retrospective analysis selecting hospitalized patients with COVID-19 admitted to our Institution from 20 May 2020 to 20 November 2020 with computer tomography (CT) detected PE at admission, treated with edoxaban after initial parenteral therapy. Clinical outcomes were compared between patients with and without ARDS at admission and between those with and without CT confirmed PE resolution. RESULTS: 50 patients were included. Mean follow-up was 42.5 ± 10 days. No baseline differences were found between patients with ARDS (30%) and those without ARDS at admission. Patients with PE resolution (84%) were younger (P = 0.03), had a shorter duration of fondaparinux therapy (9.9 ± 3.8 vs 15.8 ± 7.5 days; P = 0.0015) and length of hospitalization (36 ± 8 vs 46 ± 9 days: P = 0.0023) compared with those without PE resolution. 2 patients experienced major bleedings. At multivariate analysis the time to edoxaban switch was the only predictor of the PE resolution (HR: 0.92; 95% C.I. 0.86 to 0.99). CONCLUSION: Edoxaban was an effective and safe treatment for acute PE in COVID-19 setting.


Subject(s)
COVID-19/complications , Factor Xa Inhibitors/therapeutic use , Pulmonary Embolism/drug therapy , Pyridines/therapeutic use , SARS-CoV-2 , Thiazoles/therapeutic use , Adult , Aged , Female , Fondaparinux/therapeutic use , Humans , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Pulmonary Embolism/etiology , Respiratory Distress Syndrome , Retrospective Studies
15.
Biomedicines ; 9(5)2021 Apr 22.
Article in English | MEDLINE | ID: covidwho-1202388

ABSTRACT

Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.

16.
J Clin Neurosci ; 79: 30-32, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-665630

ABSTRACT

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first reported in Wuhan, China in December 2019, and is ongoing pandemic. While a majority of patients with SARS-CoV-2 infection shows asymptomatic or mild disease, hospitalized patients can develop critical condition, such as pneumonia, sepsis, and respiratory failure. Some cases deteriorate into sever systemic disease and multiorgan failure. Many patients of severe COVID-19 show hypercoagulable state and complicate with venous thromboembolism and atrial thrombosis. We herein reported a case of COVID-19 who developed cerebral venous thrombosis (CVT) co-incidence with pulmonary thromboembolism (PTE). A 56-year-old Japanese man was presented with fever and malaise and diagnosed with COVID-19. He was treated with ciclesonide and azithromycin, but his respiratory condition deteriorated. Thus, systemic corticosteroids and favipiravir were initiated and these treatments resulted in afebrile state, improving malaise and respiratory failure. However, he suddenly developed severe headache and vomiting with increased concentration of D-dimer. Brain CT and MRI showed typical images of CVT in the left transvers sinus and CT pulmonary angiography showed PE. Administration of unfractionated heparin followed by edoxaban treatment reduced the levels of D-dimer and improved his clinical presentation and thrombosis. Monitoring coagulopathy is important in COVID-19 patients and in case of venous thromboembolism, including cerebral venous system, appropriate anticoagulant therapy should be initiated.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Intracranial Thrombosis/etiology , Pneumonia, Viral/complications , Venous Thrombosis/etiology , COVID-19 , Fibrin Fibrinogen Degradation Products/analysis , Heparin/therapeutic use , Humans , Intracranial Thrombosis/diagnostic imaging , Intracranial Thrombosis/drug therapy , Magnetic Resonance Imaging , Male , Middle Aged , Pandemics , Pyridines/therapeutic use , SARS-CoV-2 , Thiazoles/therapeutic use , Tomography, X-Ray Computed , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/drug therapy
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