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Thrombosis and Haemostasis Mar 2022In January 2021, the Dutch vaccination program against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started. Clinical studies have shown that...
BACKGROUND
In January 2021, the Dutch vaccination program against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications.
AIMS
This article investigates whether the BNT162b2 vaccine affects anticoagulation control in outpatients using vitamin K antagonists (VKAs).
METHODS
A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. International normalized ratio (INR) results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination.
RESULTS
A total of 3,148 outpatient VKA users were included, with a mean age (standard deviation) of 86.7 (8.7) years, of whom 43.8% were male, 67.0% used acenocoumarol, and 33.0% phenprocoumon. We observed a decrease of 8.9% of INRs within range in the standard intensity group (target INR 2.0-3.0). There was both an increased risk of supratherapeutic (odds ratio [OR] = 1.34 [95% confidence interval [CI] 1.08-1.67]) and subtherapeutic levels (OR = 1.40 [95% CI 1.08-1.83]) after first vaccination. In the high-intensity group (target INR 2.5-3.5), the risk of a supratherapeutic INR was 2.3 times higher after first vaccination (OR = 2.29 [95% CI 1.22-4.28]) and 3.3 times higher after second vaccination (OR = 3.25 [95% CI 1.06-9.97]).
CONCLUSION
BNT162b2 was associated with an immediate negative effect on anticoagulation control in patients treated with VKAs, so it is advisable to monitor the INR shortly after vaccination, even in stable patients.
Topics: Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; BNT162 Vaccine; Blood Coagulation; Drug Monitoring; Female; Humans; International Normalized Ratio; Male; Netherlands; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vaccination; Vitamin K
PubMed: 35245945
DOI: 10.1055/s-0042-1742628 -
Frontiers in Pharmacology 2020Vitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and...
BACKGROUND
Vitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and acenocoumarol. These drugs have a narrow therapeutic margin and high inter-individual response variability due to clinical and pharmacogenetic variables.
OBJECTIVE
The authors aim to develop an algorithm comprised of clinical and genetic factors to explain the variability in the therapeutic dose of acenocoumarol among Chilean patients.
METHODOLOGY
DNA was obtained from 304 patients as a discovery cohort with an international normalized ratio (INR) range of 2.0-3.0. The non-genetic (demographic and clinical) variables were also recorded. Genotype analyses were performed using real-time PCR for (), (), () () () (), (), and ().
RESULTS
The clinical variables that significantly influenced the weekly therapeutic dose of VKA were age, sex, body mass index (BMI), and initial INR, collectively accounting for 19% of the variability, and the genetic variables with a significant impact were (), (), and (), explaining for another 37% of the variability.
CONCLUSION
We developed an algorithm that explains 49.99% of the variability in therapeutic VKA dosage in the Chilean population studied. Factors that significantly affected the dosage included , , and polymorphisms, as well as age, sex, BMI, and initial INR.
PubMed: 32327994
DOI: 10.3389/fphar.2020.00325 -
Drugs & Aging Jul 2020Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age... (Review)
Review
A Structured Literature Review and International Consensus Validation of FORTA Labels of Oral Anticoagulants for Long-Term Treatment of Atrial Fibrillation in Older Patients (OAC-FORTA 2019).
INTRODUCTION
Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019.
METHODS
A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA.
RESULTS
A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p < 0.05) and the proposed FORTA classes were confirmed in all cases during the first round (consensus coefficient > 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A.
CONCLUSION
OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age.
Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Consensus Development Conferences as Topic; Dabigatran; Europe; Female; Humans; Long-Term Care; Male; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Vitamin K; Warfarin
PubMed: 32500503
DOI: 10.1007/s40266-020-00771-0 -
Biomedica : Revista Del Instituto... Sep 2021We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of...
We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of acenocoumarol, as well as other values reported as uncoagulable, forcing the discontinuation and restart of treatment more than once. Expected and stable INR levels were achieved after more than 30 days of treatment, surprisingly with half the recommended dose for a patient of her age and weight. We decided to conduct a retrospective pharmacogenomic analysis including nucleotide genetic polymorphisms (SNPs) with different degrees of association with the dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853, and rs1057910 (CYP2C9 gene) using TaqMan® RT-PCR. The patient was homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2),a genetic profile strongly associated with a requirement of lower AVK doses as shown by national and international evidence. In conclusion, the pharmacogenetic analysis confirmed that this patient’s genetic conditions, involving low expression of the VKA therapeutic target, required a lower dose than that established in clinical protocols as recommended by the Food and Drug Administration (FDA) and the PharmGKB® for coumarin drugs. A previous genotypic analysis of the patient would have allowed reaching the therapeutic range sooner, thus avoiding potential bleeding risks. This shows the importance of pharmacogenetic analyses for highly variable treatments with a narrow therapeutic range.
Topics: Anticoagulants; Child; Female; Genotype; Humans; Pharmacogenomic Testing; Polymorphism, Single Nucleotide; Retrospective Studies; Vitamin K Epoxide Reductases
PubMed: 34559488
DOI: 10.7705/biomedica.5840 -
Patient Preference and Adherence 2022Cardiovascular diseases are one of the major causes of mortality at the global level. They account for approximately 17.9 million deaths per year. Warfarin and...
Effectiveness of a Nursing Intervention Module on Adherence, Knowledge, Quality of Life, and Complications Among Patients Receiving Anticoagulation therapy-a Randomized Controlled Trial Protocol.
BACKGROUND
Cardiovascular diseases are one of the major causes of mortality at the global level. They account for approximately 17.9 million deaths per year. Warfarin and acenocoumarol are the commonly used oral anticoagulants to treat and prevent thromboembolic disorders in patients with cardiovascular diseases. In India, approximately 2-2.5 million patients with rheumatic heart disease are receiving oral anticoagulation therapy. Additionally, this therapy is provided for stroke prevention in the case of atrial fibrillation and the treatment of valvular heart disease, stroke, and deep vein thrombosis. As the therapeutic range of these drugs is narrow and is affected by many factors, their use is challenging. This study aims to evaluate the effectiveness of a nursing intervention module in terms of adherence to therapy, knowledge, quality of life, and complications among patients receiving oral anticoagulation therapy. Furthermore, this study will address factors that affect adherence and the risk for bleeding by using a randomized controlled trial design.
METHODS
This single-blind, single-center, randomized controlled trial will focus on adherence to oral anticoagulation therapy. A total of 320 patients who are on oral anticoagulation therapy will be randomized into blocks and allocated to either the intervention or standard care group. The intervention will comprise the use of a nursing intervention module that includes a booklet, log sheet, and decision aid on oral anticoagulation therapy adherence. Outcome measures, that is, knowledge regarding oral anticoagulation therapy, adherence, complications, and quality of life, will be assessed at the baseline and during follow-ups.
DISCUSSION
Patient safety can be best achieved through patients' adherence to medication dose and monitoring of blood test values. Thromboembolic and bleeding complications are likely to occur when either the patient does not adhere to the treatment or the therapeutic range of the international normalized ratio is not maintained. This study will assess the nonadherence behavior and the effectiveness of a nursing intervention module toward adherence behavior.
TRIAL REGISTRATION
This research project is registered under the Clinical Trial Registry of India (CTRI/2019/06/019610).
PubMed: 35903081
DOI: 10.2147/PPA.S365585 -
Revista Medica de Chile Sep 2020Vitamin K antagonist medications (VKA) are essential for the prevention of thromboembolic events, but their effectiveness is influenced by multiple factors, such as the...
BACKGROUND
Vitamin K antagonist medications (VKA) are essential for the prevention of thromboembolic events, but their effectiveness is influenced by multiple factors, such as the type of medication chosen.
AIM
To evaluate the efficacy in anticoagulant control of the bioequivalent and non-bioequivalent drugs of acenocoumarol compared to the reference drug. To evaluate the efficacy of warfarin bioequivalents available in Chile. To contrast the overall anticoagulant control efficacy between acenocoumarol and warfarin.
MATERIAL AND METHODS
The results of 69333 outpatient oral anticoagulation controls were analyzed. Patient were separated in groups according to the drug that they used. Subsequently, the proportions of controls outside the range for each of acenocoumarol and warfarin bioequivalent drugs were compared. Acenocoumarol non-bioequivalent drugs were also compared with the reference drug. Acenocoumarol was compared with warfarin.
RESULTS
Acenocoumarol bioequivalent drugs and the reference drug had a similar proportion of controls outside the range (Odds ratios (OR) 0.812; 0.969; 0.974 and 0.963). Non-bioequivalent drugs had a higher proportion than the reference drug (OR 1.561 and 2.037). Both warfarin brands have a similar proportion of controls outside of the range (OR 1.050). Acenocoumarol compared to warfarin had a significant higher proportion of controls outside the range (OR 1.191).
CONCLUSIONS
The pharmacological presentation of vitamin K antagonists could influence anticoagulant control. Therefore, it is not prudent to switch these presentations frequently.
Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Chile; Humans; Thromboembolism; Vitamin K
PubMed: 33399700
DOI: 10.4067/S0034-98872020000901254 -
International Journal of Environmental... Feb 2021Bleeding complications in patients undergoing antiplatelet and/or anticoagulant therapy have been one of the main concerns in dental practice. Upon the introduction of...
BACKGROUND
Bleeding complications in patients undergoing antiplatelet and/or anticoagulant therapy have been one of the main concerns in dental practice. Upon the introduction of new antiplatelet and anticoagulant drugs, there is a search for new protocols that respond to a secure treatment. The aim of the present study was to evaluate bleeding complications in anticoagulated and antiplatelet-treated patients after performing simple dental extractions, in a period of 4 years.
MATERIAL AND METHODS
147 clinical records of anticoagulated and/or antiplatelet-treated patients undergoing a simple dental extraction over a period of 4 years (October 2015 to September 2019) were studied. Within the sample, 63 patients were antiplatelet-treated, 83 were anticoagulated, and 1 patient was under both therapies. Within the anticoagulated patients, 70 took classic anticoagulants and 14 new oral anticoagulants (NOACs). Quantitative data were studied with arithmetic mean and standard deviation (SD). The chi-square test was used for the qualitative variables. ANOVA tests were used to compare age and anticoagulated or antiplatelet-treated patients. Statistical significance was determined when < 0.05.
RESULTS
From the 418 dental extractions performed, five severe bleeding complications took place in three patients (2.11%). From the five events, four were in patients treated with NOACs (1.68%) and one occurred in a patient anticoagulated with acenocoumarol (0.42%; = 0.003).
CONCLUSIONS
Considering the results of this retrospective clinical study, we can conclude that bleeding complications in anticoagulated and/or antiplatelet-treated patients after tooth extractions were low, with a higher incidence recorded in patients treated with NOACs, followed by classic anticoagulants, and there were no complications in antiplatelet-treated patients.
Topics: Administration, Oral; Anticoagulants; Dental Offices; Humans; Platelet Aggregation Inhibitors; Retrospective Studies; Tooth Extraction
PubMed: 33567762
DOI: 10.3390/ijerph18041609 -
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 -
PloS One 2020Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability...
BACKGROUND
Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability to be maximally safe and effective. Switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control.
AIMS
We assessed whether switching from acenocoumarol to phenprocoumon improves the time in the therapeutic range (TTR) and INR variability.
METHODS AND RESULTS
In a retrospective cohort with data on 236,957 patients-years of VKA management from two first-line anticoagulation clinics in the Netherlands, we identified 124 patients in target range 2-3, 269 patients in target range 2-3.5 and 98 patients in target range 2.5-3.5 who switched from acenocoumarol to phenprocoumon. They were matched in a 1:2 ratio to non-switching controls using propensity score matching. Over the first 180 days after a switch, switchers' TTR declined 5 (95% CI 1 to 10), 10 (95% CI 7 to 13) and 5 (95% CI 0 to 11) percentage points relative to non-switchers, in target ranges 2-3, 2-3.5 and 2.5-3.5. Anticoagulation was more often supra-therapeutic in switchers, and switchers had a higher INR variability. In the following 180 days, TTR in switchers became 1 (95% CI -4 to 6), 4 (95% CI 0 to 7) and 6 (95% CI 1 to 12) percentage points better than in non-switchers. Switchers' INRs were much more stable than non-switchers'.
CONCLUSION
Eventually, a switch from acenocoumarol to phenprocoumon leads to a higher TTR and a lower INR variability. However, this is preceded by a transition period with opposite effects. An improved conversion algorithm could possibly shorten the transition period. Until then, physicians and patients should decide whether switching is worth the increased risk during the transition phase.
Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Humans; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Retrospective Studies; Risk; Treatment Outcome; Venous Thromboembolism; Vitamin K
PubMed: 32649714
DOI: 10.1371/journal.pone.0235639 -
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