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Journal of Multidisciplinary Healthcare 2022During the last few years, a progressive higher proportion of patients have had upper gastrointestinal bleeding (UGIB) related to antithrombotic therapy. The...
INTRODUCTION
During the last few years, a progressive higher proportion of patients have had upper gastrointestinal bleeding (UGIB) related to antithrombotic therapy. The introduction of direct oral anticoagulant (DOAC) and COVID-19 pandemic may change the incidence, mortality, and follow-up, especially in patients at high risk of bleeding.
PATIENTS AND METHODS
We studied the use of anti-thrombotic therapy (AT) in patients with upper gastrointestinal bleeding for 5 years (January 2017-December 2021) including Covid-19 pandemic period (March 2020-December 2021). We analyzed mortality rate, rebleeding rate and need for transfusion in patients with AT therapy compared with those without AT therapy and risk factors for mortality, and also the incidence of gastrointestinal bleeding in patients admitted for COVID-19 infection.
RESULTS
A total of 824 patients were admitted during Covid-19 pandemic period and 1631 before pandemic period; a total of 426 cases of bleeding were recorded in patients taking antithrombotic therapy and the frequency of antithrombotic therapy in patients with UGIB was higher in pandemic period (24.39% versus 13.8%). Unadjusted mortality was 12.21%, similar with patients with no antithrombotic treatment but age-adjusted mortality was 9.62% (28% lower). The rate of endoscopy was similar but fewer therapeutic procedures were required. Mean Hb level was 10% lower, and more than 60% of patients required blood transfusion.
CONCLUSION
Mortality was similar compared with patients with no antithrombotic therapy, fewer therapeutic endoscopies were performed and similar rebleeding rate and emergency surgery were noted. Hb level was 10% lower and a higher proportion of patients required blood transfusions. Mortality was higher in DOAC treatment group compared with VKA patients but with no statistical significance. The rate of upper gastrointestinal bleeding in Covid-19 positive hospitalized cases was 0.58%. The mortality risk in multivariate analysis was associated with GB score, with no endoscopy performed, with obscure and variceal bleeding and with LMWH versus VKA therapy.
PubMed: 36425876
DOI: 10.2147/JMDH.S380500 -
Blood Nov 2018Warfarin, acenocoumarol, phenprocoumon, and fluindione are commonly prescribed oral anticoagulants for the prevention and treatment of thromboembolic disorders. These...
Warfarin, acenocoumarol, phenprocoumon, and fluindione are commonly prescribed oral anticoagulants for the prevention and treatment of thromboembolic disorders. These anticoagulants function by impairing the biosynthesis of active vitamin K-dependent coagulation factors through the inhibition of vitamin K epoxide reductase (VKOR). Genetic variations in VKOR have been closely associated with the resistant phenotype of oral anticoagulation therapy. However, the relative efficacy of these anticoagulants, their mechanisms of action, and their resistance variations among naturally occurring VKOR mutations remain elusive. Here, we explored these questions using our recently established cell-based VKOR activity assay with the endogenous VKOR function ablated. Our results show that the efficacy of these anticoagulants on VKOR inactivation, from most to least, is: acenocoumarol > phenprocoumon > warfarin > fluindione. This is consistent with their effective clinical dosages for stable anticoagulation control. Cell-based functional studies of how each of the 27 naturally occurring VKOR mutations responds to these 4 oral anticoagulants indicate that phenprocoumon has the largest resistance variation (up to 199-fold), whereas the resistance of acenocoumarol varies the least (<14-fold). Cell-based kinetics studies show that fluindione appears to be a competitive inhibitor of VKOR, whereas warfarin is likely to be a mixed-type inhibitor of VKOR. The anticoagulation effect of these oral anticoagulants can be reversed by the administration of a high dose of vitamin K, apparently due to the existence of a different enzyme that can directly reduce vitamin K. These findings provide new insights into the selection of oral anticoagulants, their effective dosage management, and their mechanisms of anticoagulation.
Topics: Administration, Oral; Anticoagulants; Cell Line; Drug Resistance; Enzyme Inhibitors; Humans; Phenindione; Point Mutation; Vitamin K; Vitamin K Epoxide Reductases; Warfarin
PubMed: 30089628
DOI: 10.1182/blood-2018-05-846592 -
British Journal of Clinical Pharmacology May 2018Warfarin-related nephropathy.
ADVERSE EVENT
Warfarin-related nephropathy.
DRUG IMPLICATED
Warfarin.
THE PATIENT
A 31-year-old female, managed with warfarin for rheumatic heart disease with atrial fibrillation.
EVIDENCE THAT LINKS THE DRUG TO THE EVENT
There were no alternative causes of nephropathy that could have caused the adverse event in this patient.
MANAGEMENT
Shifting the drug from warfarin to acenocoumarol.
MECHANISM
Difference in renal elimination between warfarin and acenocoumarol.
IMPLICATION FOR THERAPY
Clinicians should be aware of this rare adverse effect of warfarin, and acenocoumarol can be considered as an alternative therapy for this condition.
HYPOTHESES TO BE TESTED
Further prospectively designed studies are needed to consider acenocoumarol as an alternative therapy in warfarin-related nephropathy.
Topics: Acenocoumarol; Adult; Anticoagulants; Atrial Fibrillation; Female; Humans; Kidney Diseases; Rheumatic Heart Disease; Warfarin
PubMed: 29424022
DOI: 10.1111/bcp.13541 -
Journal of Cardiology Mar 2017Cardiac catheterization in anticoagulated patients is usually performed after the anticoagulation has been withdrawn, at least in the previous 48h, and sometimes... (Observational Study)
Observational Study
BACKGROUND
Cardiac catheterization in anticoagulated patients is usually performed after the anticoagulation has been withdrawn, at least in the previous 48h, and sometimes bridging therapy with heparin is used.
METHODS
A prospective observational study including 489 patients undergoing transradial catheterization was conducted. A total of 140 patients were under acenocoumarol (group A) and they were compared with the remainder (group B) for complications after the procedure (bleeding and vascular access complications).
RESULTS
Patients in group A were older (74±12 years vs. 68±17 years, p<0.01) and the main indication for anticoagulation was atrial fibrillation (58.6%). No complications occurred during the procedures. There were no acute bleedings just after the bandage removal. During the first 24h, only 3 (2.1%) radial occlusions in group A and 2 (0.6%) in group B (p=0.14) were recorded. Hematomas between 5 and 10cm appeared in 5% of the group A vs. 4.6% in group B. During the 1-month follow-up period, one more radial occlusion in each group was recorded and there were 4 (1.1%) additional mild hematomas in group B and none in group A (p=0.48).
CONCLUSIONS
Performing a transradial diagnostic cardiac catheterization without removal of the oral chronic anticoagulation appears safe in patients under acenocumarol therapy.
Topics: Aged; Anticoagulants; Cardiac Catheterization; Female; Hematoma; Heparin; Humans; Male; Prospective Studies; Radial Artery
PubMed: 27234220
DOI: 10.1016/j.jjcc.2016.04.015 -
Basic & Clinical Pharmacology &... Nov 2016This study aimed to describe the impact of implementing a protocol on the perioperative management of patients admitted for hip fracture treated with antithrombotics. A... (Observational Study)
Observational Study
This study aimed to describe the impact of implementing a protocol on the perioperative management of patients admitted for hip fracture treated with antithrombotics. A protocol was designed based on the recommendations from the American College of Chest Physicians (ACCP). After its implementation (May 2012), information on antithrombotic management was collected from admission to 3 months after surgery in retrospective (October 2011-March 2012) and prospective (October 2012-March 2013) cohorts. Patients' thromboembolic risk was classified into high, moderate or low according to the ACCP categories. A total of 113 and 101 cases were included in the retrospective and prospective cohorts, respectively. No differences in age, gender, American Society of Anaesthesiology score or thrombotic risk categories were observed between cohorts. Most patients were treated with aspirin or triflusal (55.1% and 48.1% in each cohort, respectively), clopidogrel (24.5% and 26.6%) or acenocoumarol (16.3% and 20.2%). In moderate to high thromboembolic risk patients, a higher rate of bridging therapy with full doses of enoxaparin (18.5% and 50%, p = 0.04 before and 9.1% and 43.7%, p = 0.02 after surgery) and a lower rate of aspirin discontinuation (76% and 55.3%, p = 0.03) were observed in the prospective cohort. Both cohorts had a similar percentage of cases with bleeding (68.1% and 68.3%) and thrombotic events (11.5% and 13%). No differences in the timing between surgery and the discontinuation or resumption of antithrombotics were noted. After the protocol implementation, aspirin was less often stopped and bridging therapy with therapeutic doses of enoxaparin was used more often. However, interruption and resumption times of antithrombotics remained almost unchanged. In order to achieve these goals, more efforts should be made to implement the protocol in clinical practice.
Topics: Aged, 80 and over; Anticoagulants; Evidence-Based Medicine; Female; Hemorrhage; Hip Fractures; Humans; Male; Perioperative Care; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prospective Studies; Retrospective Studies; Spain; Thromboembolism
PubMed: 27151175
DOI: 10.1111/bcpt.12615 -
BMJ Case Reports Apr 2021Acute intoxication with a vitamin K antagonist may cause serious coagulopathy. We report the accidental ingestion of a high dose of acenocoumarol in a young child. Two...
Acute intoxication with a vitamin K antagonist may cause serious coagulopathy. We report the accidental ingestion of a high dose of acenocoumarol in a young child. Two intravenous administrations of 5 mg of vitamin K, in combination with fast and repeated administration of activated charcoal and sodium sulfate, were sufficient to prevent coagulopathy and related symptoms, despite a confirmed elevated blood acenocoumarol concentration (260 µg/L).
Topics: Acenocoumarol; Anticoagulants; Blood Coagulation Disorders; Child; Eating; Humans; Vitamin K
PubMed: 33795273
DOI: 10.1136/bcr-2020-240365 -
Annales de Biologie Clinique Oct 2017Eating patterns, food intake and type of alimentation vary greatly during the month of ramadan. Furthermore, fasting, which practiced during the month of ramadan, can... (Clinical Trial)
Clinical Trial
Eating patterns, food intake and type of alimentation vary greatly during the month of ramadan. Furthermore, fasting, which practiced during the month of ramadan, can have an impact on drug's metabolism. These two factors, fasting and eating habits changes during the month of ramadan, may impact acenocoumarol anticoagulant effect, translated by variations of INR values. The aim of our study was to see ramadan fasting effects on INR variations in patients treated by acenocoumarol. A prospective monocentric study was conducted during the ramadan month on fasting outpatients that were treated by acenocoumarol. Baseline INR values (e.i. most recent available value before the month of ramadan) were compared to INR values obtained during the month of ramadan. All patients were monitored for signs of secondary haemorrhagic complications linked to treatment by anti-vitamin K (AVK). Thirty patients were included in the study with a sex ratio 1. Patients mean age was 65 years. Around two thirds of the patients were treated by AVK for atrial fibrillation. The majority of patients (94%) have been treated by AVK for more than a year. Mean INR was significantly higher during the month of ramadan than baseline (3.51 vs 2.52; p< 0.0001). There were also more overdoses during the month of ramadan than baseline (9 vs. 0; p=0.014). The increased INR values highlights the need of a close monitoring of INR values during the month of ramadan, particularly in patients with a high haemorrhagic risk.
Topics: 4-Hydroxycoumarins; Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Fasting; Female; Hemorrhage; Humans; Indenes; Islam; Male; Middle Aged; Tunisia; Vitamin K
PubMed: 28958959
DOI: 10.1684/abc.2017.1264 -
Thrombosis Journal 2015Behçet's disease (BD) is a rare vasculitis in sub-Saharan Africa. Vascular thrombosis, especially venous, is common in this condition and also constitutes a basic...
INTRODUCTION
Behçet's disease (BD) is a rare vasculitis in sub-Saharan Africa. Vascular thrombosis, especially venous, is common in this condition and also constitutes a basic diagnostic criterion. Its affection of the superior vena cava is rather rare with only a few cases described in the literature.
CASE REPORT
A 42-year-old male patient was seen at consultation presenting with a pulsatile, warm and slightly painful right latero-cervical swelling extending to the supraclavicular fossa with the presence of collateral venous circulation for three weeks prior to presentation associated with a mild headache. There were oral and genital ulcerations and erythematous skin lesions associated with a history of inflammatory recurrent arthralgia. Chest computed tomo-angiography showed cruoric internal jugular vein thrombosis extending to the superior vena cava with significant venous collateral circulation. The patient was treated with prednisolone (1 mg/kg/day) and colchicine (2 mg/day), as well as anticoagulation with heparin and vitamin K antagonist (Acenocoumarol) with regular INR monitoring. Clinical evolution was favorable during hospitalization, with residual discrete right supraclavicular swelling. There was no bleeding associated with anticoagulants use.
CONCLUSION
The case stresses the importance of maintaining a high degree of suspicion for Behçet's disease in all cases of venous thrombosis.
PubMed: 25667567
DOI: 10.1186/s12959-015-0039-z -
Journal of Physiology and Pharmacology... Feb 2019Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and...
Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and vitamin K antagonists (VKAs) can improve plasma clot viscoelastic properties. We studied four age- and sex-matched groups: 25 healthy controls, 15 VTE patients taking rivaroxaban 20 mg/day (blood concentration, 145 (67 - 217) ng/ml), 15 VTE patients taking VKA (INR: 2 - 3), and 15 VTE patients who stopped oral anticoagulant therapy (OAT). Using a hybrid rheometier the storage (G') and loss (G") moduli were evaluated in citrated plasma after addition of 5 pmol/l tissue factor. Fiber thickness within clots was assessed using scanning electron microscopy. Higher G' but not G" was observed for VTE patients taking rivaroxaban (+34%; post hoc, P = 0.029) compared to controls. As reflected by lower G' and G", patients taking rivaroxaban (-19% and -30%; post hoc, P = 0.0013 and P < 0.0001, respectively) formed less stiff and viscous clots compared to VTE patients after OAT withdrawal, also after adjustment for fibrinogen. VTE patients treated with rivaroxaban and VKA had similar clot viscoelastic properties (post hoc, P = 0.85 for G' and P = 0.29 for G"). G' and G" correlated with plasma rivaroxaban concentrations (r = -0.67, P = 0.005 and r = -0.59, P = 0.021, respectively), and the time from the last dose of rivaroxaban intake (r = 0.59, P = 0.02 and r = 0.58, P = 0.022, respectively). G' and G" showed no association with INR in patients on VKAs. G' or G" were not associated with fibrin diameter on scanning electron microscopy images in either group. Our preliminary study shows that both rivaroxaban and VKA improve clot viscoelastic properties in VTE patients, which might contribute to their antithrombotic effects. G' and G" may reflect specific clot physical features, beyond key plasma clot characteristics, which highlights benefits from comprehensive plasma clot analysis in patients with thrombotic diseases.
Topics: Acenocoumarol; Adult; Anticoagulants; Elasticity; Factor Xa Inhibitors; Female; Fibrin; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Venous Thromboembolism; Viscosity; Vitamin K; Warfarin
PubMed: 31019123
DOI: 10.26402/jpp.2019.1.05 -
Drug Discoveries & Therapeutics Dec 2015Coumarin derivatives such as warfarin and acenocoumarol are used in various disorders such as deep venous thrombosis, pulmonary embolism, atrial fibrillation and...
Coumarin derivatives such as warfarin and acenocoumarol are used in various disorders such as deep venous thrombosis, pulmonary embolism, atrial fibrillation and artificial heart valves. They have improved prognosis of patients with thromboembolic disease. An individual's response to coumarins depends on several factors. The non-genetic factors include age, gender, body mass index, diet and interacting drugs. Among the genetic factors, the cytochrome P450 system and vitamin K epoxide reductase complex subunit 1 play a key role in drug metabolism. This was a prospective hospital based study in which allele and genotypic frequencies of CYP2C9 gene polymorphisms; 430C>T and 1075A>C and VKORC1 gene polymorphisms; 1639G>A, 9041G>A and 6009C>T in 106 alleles of north Indian patients with valve replacement on acenocoumarol were determined and their effect on acenocoumarol dosing was studied. To the best of our knowledge, this is first report of VKORC1 9041G>A and 6009C>T gene polymorphisms and their effect on acenocoumarol dosing from north India. In 53 patients with valve replacement on acenocoumarol with stable INR, the allele frequency of CYP2C9*2 and CYP2C9*3 gene polymorphisms was 0.05 and 0.17 respectively and that of VKORC1 *2,*3 and *4 gene polymorphisms was 0.15, 0.72 and 0.11 respectively. The presence of CYP2C9*3 or VKORC1*2 gene polymorphism were associated with decrease in acenocoumarol dose requirements (p values 0.03 and 0.02 respectively).This study confirmed the association of lower mean weekly dosages of acenocoumarol in patients with CYP2C9*3 and VKORC1*2 gene polymorphisms. An unusually high frequency of 9041A polymorphism in VKORC1 was found in study population.
Topics: Acenocoumarol; Adult; Anticoagulants; Cytochrome P-450 CYP2C9; Female; Gene Frequency; Haplotypes; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Logistic Models; Male; Middle Aged; Polymorphism, Genetic; Prospective Studies; Vitamin K Epoxide Reductases
PubMed: 26781925
DOI: 10.5582/ddt.2015.01066