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Biomedicine & Pharmacotherapy =... Sep 2023Rivaroxaban is a direct inhibitor of factor Xa, a member of direct oral anticoagulant group of drugs (DOACs). Despite being a widely extended alternative to vitamin K...
Rivaroxaban is a direct inhibitor of factor Xa, a member of direct oral anticoagulant group of drugs (DOACs). Despite being a widely extended alternative to vitamin K antagonists (i.e., acenocoumarol, warfarin) the interindividual variability of DOACs is significant, and may be related to adverse drug reaction occurrence or drug inefficacy, namely hemorrhagic or thromboembolic events. Since there is not a consistent analytic practice to monitor the anticoagulant activity of DOACs, previously reported polymorphisms in genes coding for proteins responsible for the activation, transport, or metabolism of DOACs were studied. The study population comprised 60 healthy volunteers, who completed two randomized, crossover bioequivalence clinical trials between two different rivaroxaban formulations. The effect of food, sex, biogeographical origin and 55 variants (8 phenotypes and 47 single nucleotide polymorphisms) in drug metabolizing enzyme genes (such as CYP2D6, CYP2C9, NAT2) and transporters (namely, ABCB1, ABCG2) on rivaroxaban pharmacokinetics was tested. Individuals dosed under fasting conditions presented lower t (2.21 h vs 2.88 h, β = 1.19, R =0.342, p = 0.012) compared to fed volunteers. NAT2 slow acetylators presented higher AUC corrected by dose/weight (AUC/DW; 8243.90 vs 7698.20 and 7161.25 h*ng*mg /ml*kg, β = 0.154, R =0.250, p = 0.044), higher C/DW (1070.99 vs 834.81 and 803.36 ng*mg /ml*kg, β = 0.245, R =0.320, p = 0.002), and lower t (2.63 vs 3.19 and 4.15 h, β = -0.346, R =0.282, p = 0.047) than NAT2 rapid and intermediate acetylators. No other association was statistically significant. Thus, slow NAT2 appear to have altered rivaroxaban pharmacokinetics, increasing AUC and C. Nonetheless, further research should be conducted to verify NAT2 involvement on rivaroxaban pharmacokinetics and to determine its clinical significance.
Topics: Humans; Rivaroxaban; Healthy Volunteers; Anticoagulants; Polymorphism, Single Nucleotide; Phenotype; Arylamine N-Acetyltransferase
PubMed: 37385211
DOI: 10.1016/j.biopha.2023.115058 -
Journal of Comparative Effectiveness... Aug 2023Healthcare resources usage and costs associated to nonvalvular atrial fibrillation (NVAF) were analyzed in Spain. This is an observational and retrospective study on... (Observational Study)
Observational Study
Healthcare resources usage and costs associated to nonvalvular atrial fibrillation (NVAF) were analyzed in Spain. This is an observational and retrospective study on patients with NVAF who started their treatment with apixaban or acenocoumarol between 1 January 2015 and 31 December 2017. 2160 patients treated with apixaban were paired (1:1) with patients treated with acenocoumarol (propensity score matching). Apixaban reduced the incidence of strokes and systemic embolisms, minor and major bleedings and deaths, versus acenocoumarol. Apixaban led to reductions of 80, 55 and 43% in costs related to nursing visits, hospitalizations, and emergency visits, respectively, leading to annual cost savings of €274/patient, from the perspective of society. Our results suggested that apixaban is a cost-effective alternative for patients with NVAF.
Topics: Humans; Acenocoumarol; Atrial Fibrillation; Anticoagulants; Spain; Retrospective Studies; Pyridones; Stroke; Delivery of Health Care; Rivaroxaban
PubMed: 37489950
DOI: 10.57264/cer-2023-0007 -
Journal of Physiology and Pharmacology... Aug 2023Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the...
Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be important therapeutic agents. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to determine whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 μg/kg) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of AP was assessed immediately after the last dose of cerulein, as well as at days 1, 2, 3, 5, and 10 after AP induction. Treatment with warfarin dose-dependently increased international normalized ratio (INR) and attenuated the severity of pancreatitis in histological examination and accelerated pancreatic recovery. These effects were accompanied with a faster reduction in the AP-evoked increase in serum activity of amylase and lipase, the serum concentration of pro-inflammatory interleukin-1β, and the plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight (an index of pancreatic edema) and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 μg/kg. We conclude that treatment with warfarin accelerated regeneration of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.
Topics: Rats; Male; Animals; Pancreatitis; Warfarin; Ceruletide; Rats, Wistar; Acenocoumarol; Acute Disease; Pancreas
PubMed: 37865961
DOI: 10.26402/jpp.2023.4.08 -
Cureus Jan 2024Acenocoumarol is one of the most common drugs used as a part of the management of patients undergoing cardiac surgery. Linezolid, on the other hand, is an antibiotic...
Acenocoumarol is one of the most common drugs used as a part of the management of patients undergoing cardiac surgery. Linezolid, on the other hand, is an antibiotic prescribed post-operatively. Reports of any interaction between the two are very few. Here, we are presenting four case reports of patients admitted to the Cardio Thoracic and Vascular Surgery Department of a tertiary healthcare center in North East India. Drug-drug interactions can lead to long-term and life-threatening effects, and also hamper the management of patients post-operatively. Due to the limited literature, assessing such interactions is difficult. The cases reported here were treated with fresh frozen plasma, and the patients responded well to the treatment and were discharged without further complications.
PubMed: 38264177
DOI: 10.7759/cureus.52753 -
Archivio Italiano Di Urologia,... Oct 2023Renal artery infarction (RI) is the presence of blood clot in the main renal artery or its branches causing complete or partial obstruction of the blood supply. Its...
AIM
Renal artery infarction (RI) is the presence of blood clot in the main renal artery or its branches causing complete or partial obstruction of the blood supply. Its etiology is either related with disorders of the renal vasculature or with cardiovascular diseases. Recently, the SARSCoV- 2 virus is an emerging cause of thromboembolic events and the incidence of RI is anticipated to increase after the pandemic.
METHODS
A systematic review based on COVID-19 associated RI was conducted.
PROTOCOL
A systematic review of the Medline/Pubmed and Scopus databases was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (the PRISMA statement). Search strategy and information sources: A hand-search was performed using the terms "SARS-Cov-2" OR "COVID-19" AND "renal thrombosis" OR "renal infarction" OR "renal "thromboembolism".
ELIGIBILITY CRITERIA
all types of publications (case reports, case series, letters to the editor, short communications) were evaluated for relevance. Inclusion criteria were: confirmed SARS-Cov-2 infection irrespectively of the age, diagnosis of RI during or after the onset of viral infection, and exclusion of other potential causes of thromboembolic event except of SARS-Cov-2. Patients with renal transplantation were also considered. Study criteria selection: after checking for relevance based on the title and the abstract, the full texts of the selected papers were retrieved and were further evaluated. Duplicated and irrelevant cases were excluded. Any disagreement was resolved by consensus with the involvement of a third reviewer. Quality of studies: The assessment of the quality case reports was based on four different domains: selection, ascertainment, casualty and reporting. Each paper was classified as "Good", "Moderate" and "Poor" for any of the four domains. Data extractions: Crucial data for the conduct of the study were extracted including: age, sex, time from SARS-Cov-2 infection till RI development, medical history, previous or current antithrombotic protection or treatment, laterality and degree of obstruction, other sites of thromboembolism, treatment for thromboembolism and SARS-Cov-2 and final outcome.
DATA ANALYSIS
methods of descriptive statistics were implicated for analysis and presentation of the data.
RESULTS
The systematic review retrieved 35 cases in 33 reports. In most cases, RI was diagnosed within a month from the SARSCov- 2 infection albeit 17 out of 35 patients were receiving or had recently received thromboprophylaxis. Right, left, bilateral and allograft obstruction was diagnosed in 7, 15, 8 and 5 patients respectively. 17 cases experienced additional extrarenal thromboembolism primarily in aorta, spleen, brain and lower limbs. Low molecular weight heparins (LMWH) (usually 60-80 mg enoxaparine bid) was the primary treatment, followed by combinations of unfractionated heparin and salicylic acid, apixaban and rivaraxaban, warfarin, acenocoumarol or clopidogrel. Kidney replacement therapy was offered to five patients while invasive therapies with thrombus aspiration or catheter directed thrombolysis were performed in two. Regarding the outcomes, five of the patients died. The total renal function was preserved in 17 cases and renal impairment with or without hemodialysis was recorded in 5 patients, two of them having lost their kidney allografts.
LIMITATIONS
The majority of included studies are of moderate quality. The results and the conclusions are based on case-reports only and crucial data are dissimilarly presented or missing through the relevant publications.
CONCLUSIONS
Thromboprophylaxis may not offer adequate protection against SARS-Cov-2 induced thrombosis. Most patients could be effectively treated with conservative measures, while in more severe cases aggressive treatment could be recommended.
IMPLICATIONS OF KEY FINDINGS
Therapeutic doses of LMWH could be considered for protection against RI in SARS-Cov-2 cases. Interventional treatment could be offered in a minority of more severe cases after carful balancing the risks and benefits.
Topics: Humans; SARS-CoV-2; COVID-19; Heparin, Low-Molecular-Weight; Anticoagulants; Heparin; Renal Artery; Venous Thromboembolism; Thrombosis; Infarction
PubMed: 37791549
DOI: 10.4081/aiua.2023.11625 -
Biomolecules Jun 2023Acute pancreatitis (AP) is a severe disease with high morbidity and mortality in which inflammation and coagulation play crucial roles. The development of inflammation...
Acute pancreatitis (AP) is a severe disease with high morbidity and mortality in which inflammation and coagulation play crucial roles. The development of inflammation leads to vascular injury, endothelium and leukocytes stimulation, and an increased level of tissue factor, which results in the activation of the coagulation process. For this reason, anticoagulants may be considered as a therapeutic option in AP. Previous studies have shown that pretreatment with heparin, low-molecular-weight heparin (LMWH), or acenocoumarol inhibits the development of AP. The aim of the present study was to check if pretreatment with warfarin affects the development of edematous pancreatitis evoked by cerulein. Warfarin (90, 180, or 270 µg/kg/dose) or saline were administered intragastrically once a day for 7 days consecutively before the induction of AP. AP was evoked by the intraperitoneal administration of cerulein. The pre-administration of warfarin at doses of 90 or 180 µg/kg/dose reduced the histological signs of pancreatic damage in animals with the induction of AP. Additionally, other parameters of AP, such as an increase in the serum activity of lipase and amylase, the plasma concentration of D-dimer, and interleukin-1β, were decreased. In addition, pretreatment with warfarin administered at doses of 90 or 180 µg/kg/dose reversed the limitation of pancreatic blood flow evoked by AP development. Warfarin administered at a dose of 270 µg/kg/dose did not exhibit a preventive effect in cerulein-induced AP. Conclusion: Pretreatment with low doses of warfarin inhibits the development of AP evoked by the intraperitoneal administration of cerulein.
Topics: Rats; Animals; Pancreatitis; Warfarin; Ceruletide; Rats, Wistar; Heparin, Low-Molecular-Weight; Acute Disease; Inflammation
PubMed: 37371528
DOI: 10.3390/biom13060948 -
Journal of Medical Case Reports Jun 2023Cerebral cardiac embolism accounts for an increasing proportion of ischemic strokes and transient ischemic attacks. Calcified cerebral emboli are rare and mostly...
BACKGROUND
Cerebral cardiac embolism accounts for an increasing proportion of ischemic strokes and transient ischemic attacks. Calcified cerebral emboli are rare and mostly iatrogenic secondary to heart or aorta catheterization. However, spontaneous cerebral calcified embolism in the case of calcified aortic valve is very rare and there are less than 10 case reports in the literature. And a more interesting fact is that such an event, in the context of calcified mitral valve disease, has never been reported, at least to our knowledge. We are reporting a case of spontaneous calcified cerebral embolism revealing a calcified rheumatic mitral valve stenosis.
CASE PRESENTATION
We report a case of a 59 year-old Moroccan patient, with a history of rheumatic fever at the age of 14 and no history of recent cardiac intervention or aortic/carotid manipulation, who was admitted to the emergency department after a transient ischemic attack. Physical examination at admission found normal blood pressure of 124/79 mmHg and heart rate of 90 bpm. A 12-lead electrocardiogram showed an atrial fibrillation, no other anomalies. Unenhanced cerebral computed tomography imaging was performed, revealing calcified material inside both middle cerebral arteries. Transthoracic echocardiography was performed, showing severe mitral leaflets calcification with a severe mitral stenosis, probably due to rheumatic heart disease. Cervical arteries Duplex was normal. A vitamin K antagonist (acenocoumarol) was prescribed, targeting an international normalized ratio of 2-3 and mitral valve replacement surgery was performed using mechanical prosthesis. Short- and long-term health, with a 1-year follow-up, were good and the patient did not experience any stroke.
CONCLUSION
Spontaneous calcified cerebral emboli secondary to mitral valve leaflet calcifications is an extremely rare condition. Replacement of the valve is the only option to prevent recurrent emboli and outcomes are still to be determined.
Topics: Humans; Middle Aged; Mitral Valve Stenosis; Intracranial Embolism; Heart Valve Diseases; Mitral Valve; Echocardiography; Embolism
PubMed: 37330507
DOI: 10.1186/s13256-023-03982-2 -
Cureus Mar 2024Aortic stenosis is the most common heart valve disease, especially among the elderly. Symptomatic aortic valve stenosis is linked to a poor prognosis and a high...
Reversing the Tide: A Case of a Mechanical Aortic Valve Recipient Lost to Follow-up, Education on Rivaroxaban Contraindications, and the Vital Role of Acenocoumarol in Preventing Valve Thrombosis.
Aortic stenosis is the most common heart valve disease, especially among the elderly. Symptomatic aortic valve stenosis is linked to a poor prognosis and a high mortality rate if left untreated. The only effective treatment for severe symptomatic aortic stenosis is aortic valve replacement using either a mechanical or a biological prosthesis. Mechanical valve prostheses, while highly durable, are thrombogenic, necessitating lifelong anticoagulation with oral anti-vitamin K agents, such as acenocoumarol. Conversely, bioprosthetic valves, though less durable, carry a minimal thrombogenic risk and do not require anticoagulation. Currently, there is no proven role for direct-acting oral anticoagulants (DOACs) in patients with mechanical heart valves due to insufficient clinical trial data regarding their safety in this patient population. Herein, we present the case of a 59-year-old female known to have aortic stenosis, who underwent surgical treatment with mechanical aortic valve replacement eight years ago. Post-surgery, acenocoumarol was initiated. However, 18 months prior to presenting at our institution, the patient started taking rivaroxaban (a DOAC) instead of acenocoumarol due to the unavailability of acenocoumarol during the ongoing economic crisis in Lebanon, without consulting her cardiologist. Although she was followed up by her general practitioner and reported having a mechanical valve, her son contradicted this, claiming she had a biological valve. After thorough investigations, including chest X-ray, echocardiography, and fluoroscopy, it was confirmed that the patient indeed had a normally functioning mechanical aortic valve. Immediate corrective measures were taken, starting with IV unfractionated heparin and acenocoumarol, targeting an International Normalized Ratio (INR) between 2.5 and 3, while educating the patient about her condition and the importance of adhering to acenocoumarol therapy.
PubMed: 38681325
DOI: 10.7759/cureus.57059 -
Thrombosis Research Aug 2023The European Medicine Agency has authorized COVID-19 vaccination in adolescents and young adults (AYAs) from 12 years onwards. In elderly vitamin K antagonist (VKA)...
INTRODUCTION
The European Medicine Agency has authorized COVID-19 vaccination in adolescents and young adults (AYAs) from 12 years onwards. In elderly vitamin K antagonist (VKA) users, COVID-19 vaccination has been associated with an increased risk of supra- and subtherapeutic INRs. Whether this association is also observed in AYAs using VKA is unknown. Our aim was to describe the stability of anticoagulation after COVID-19 vaccination in AYA VKA users.
MATERIALS AND METHODS
A case-crossover study was performed in a cohort of AYAs (12-30 years) using VKAs. The most recent INR results before vaccination, the reference period, were compared with the most recent INR after the first and, if applicable, second vaccination. Several sensitivity analyses were performed in which we restricted our analysis to stable patients and patients without interacting events.
RESULTS
101 AYAs were included, with a median age [IQR] of 25 [7] years, of whom 51.5 % were male and 68.3 % used acenocoumarol. We observed a decrease of 20.8 % in INRs within range after the first vaccination, due to an increase of 16.8 % in supratherapeutic INRs. These results were verified in our sensitivity analyses. No differences were observed after the second vaccination compared to before and after the first vaccination. Complications after vaccination occurred less often than before vaccination (9.0 vs 3.0 bleedings) and were non-severe.
CONCLUSIONS
the stability of anticoagulation after COVID-19 vaccination was decreased in AYA VKA users. However, the decrease might not be clinically relevant as no increase of complications nor significant dose adjustments were observed.
Topics: Humans; Male; Young Adult; Adolescent; Aged; Adult; Female; COVID-19 Vaccines; Cross-Over Studies; COVID-19; Anticoagulants; International Normalized Ratio; Vitamin K
PubMed: 37321159
DOI: 10.1016/j.thromres.2023.06.005 -
Cureus Feb 2024Warm antibody autoimmune hemolytic anemia (WAIHA) is a rare disease that leads to the destruction of red blood cells in the reticuloendothelial system through the...
Warm antibody autoimmune hemolytic anemia (WAIHA) is a rare disease that leads to the destruction of red blood cells in the reticuloendothelial system through the mediation of agglutinins (immunoglobulin G (IgG) type in most cases) that attach to the erythrocyte wall at 37 °C. The association of WAIHA and venous thromboembolism (VTE) seems to be higher than other hemolytic disorders classically associated with VTE and there is a current investigation aimed at clarifying this association and establishing some criteria to use anticoagulant treatment in patients with WAIHA. Despite this, WAIHA is a rare cause for the development of recurrent VTE under secondary prophylactic anticoagulant treatment, with only a few cases described in the literature. We present the case of a patient who developed a recurrence of deep vein thrombosis during a WAIHA episode despite treatment with acenocoumarol and a review of the literature.
PubMed: 38500896
DOI: 10.7759/cureus.54361