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Background:
The use of vitamin-K antagonists in pediatric patients is rare and information on quality and safety of the treatment with acenocoumarol and phenprocoumon is limited.
Objectives:
To assess the quality, safety and effectiveness during the first year of acenocoumarol and phenprocoumon treatment in pediatric patients in the Netherlands....
Context in source publication
Context 1
... total, 573 pediatric patients who used a VKA, were identified and invited in writing to participate in the study. We were able to get in contact with 485 patients, and of these patients, 213 gave informed consent. Of these patients, 172 started with acenocoumarol, 34 with phenprocoumon and seven with warfarin (see Fig. 1). Seventeen acenocoumarol and two phenprocoumon patients were excluded as a result of an unknown start date and/or no (valid) available INR measurements dur- ing the first year of VKA use. Furthermore, the seven patients who started on warfarin were excluded. Table 2 provides an overview of the characteristics of the aceno- coumarol ...
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Background: In January 2021, the Dutch vaccination programme against 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.
Aim...
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 f...
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 u...
Introduction:
Treatment with cannabis extracts for a variety of diseases has gained popularity. However, differences in herb-drug interaction potential of extracts from different plant sources are poorly understood. In this study, we provide a characterization of cannabis extracts prepared from four cannabis chemotypes and an in vitro assessment o...
Background:
Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not been analyzed in emergency situations.
Methods:
Phenprocoumon-treated patients with major bleeding or urgent surgery were included in a prospective, observational registry. Phenproc...
Citations
... Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID- 19), has played a crucial role in controlling the COVID-19 pandemic [1,2]. However, there are concerns regarding the potential interactions and side-effects of these vaccines, which have been associated with the development of coagulation disorders and thrombotic events [3][4][5]. ...
... In addition, AYAs who require anticoagulation tend to have severe medical conditions, comorbidities and thrombophilia [16], increasing the risk of (recurrent) venous thrombosis and bleeding or resulting in polypharmacy. Consequentially, anticoagulation stability is usually lower in AYAs compared to adult patients [17][18][19][20], making them potentially more prone to therapeutic instability after COVID-19 vaccination. ...
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.
... Most evidence supporting this approach has been developed in programs serving adult patients living within the clinic's local catchment area. A few pediatric-only and combined pediatric-adult programs have reported improved care using this and other approaches [1][2][3][4][5][6][7][8][9][11][12][13][14]. Because of its narrow therapeutic index, warfarin efficacy and safety are dependent upon maintaining the international normalized ratio (INR) within the therapeutic range defined by underlying indication. ...
Background:
Evidence-based anticoagulation programs usually serve a local, adult patient population. Here we report outcomes for a regional combined pediatric-adult program.
Aims:
The aims of this study were: (1) Compare the pre- vs. post-implementation quality of therapy (% time in therapeutic range (%TTR) and compliance). (2) Assess anticoagulant-relevant outcomes (bleeding and thrombotic complications).
Methods:
Data were collected for the years 2014-2019. Rosendaal linear interpolation was used to calculate %TTR. Bleeding complications were categorized using ISTH-SSC standard nomenclature and new thrombotic events were reviewed.
Results:
The patients were divided into a long-term warfarin group (N = 308), 80.2% of whom had cardiac-related therapeutic indications (median age 24y), and a second group (N = 114) comprised of short-term and non-warfarin long-term anticoagulation (median age 16y). Median %TTR for those on long-term warfarin was 78.9%. The incidence of major and clinically relevant non-major bleeding events was 1.65 and 2.43 /100 person-years of warfarin use, respectively. Thromboembolism (TE) incidence was 0.78/100 patient-years of warfarin use. Neither bleeding nor thrombosis was associated with %TTR (p = 0.48). Anticoagulant indication was the only variable associated with bleeding risk (p = 0.005). The second group had no on-therapy TE events but 7.9% experienced bleeding. Complete data were available for a randomly sampled pre-program warfarin group (N = 26). Median %TTR improved from 17.5 to 87% pre- vs. post-implementation. Similarly, compliance (defined as ≥ 1 INR/month) improved by 34.3%.
Conclusions:
In conclusion, this program significantly improved and sustained %TTR and compliance. The lack of association between bleeding and thrombosis events and %TTR may be related to the high median %TTR (> 70%) achieved by this approach.
... Our INR self-monitoring and VKA education programme starts immediately after VKA initiation, during a potential period of unstable health status, with repeated VKA dose adjustments. INR tests and dose adjustments are commonly repeated more often during the first weeks or months following VKA initiation, with frequent out-of-range INR values [35], which may impact QoL. For example, VKA dose adjustments are usually more difficult to perform in infants and young children because of high sensitivity to viral infection and diet changes. ...
... Indeed, the mean TTR over this 3-month period of time was 76%, which is similar to the overall TTR in this study (78%), and close to the overall TTR reported previously (81%) [11]. Similar studies reported a mean TTR value of 50% immediately after VKA initiation in children [35], and a TTR increase from 54% in the first month to 75% after the first 3 months in adults [36]. ...
Background
Managing oral anticoagulant therapy with vitamin K antagonists remains challenging in paediatric medicine.
Aims
This study aimed to assess the correlation between time in therapeutic range and quality of life in children participating in a non-selective International Normalised Ratio self-monitoring and vitamin K antagonist education programme.
Methods
Children aged from 2 to 18 years and receiving vitamin K antagonist therapy were eligible for this prospective multicentre study. Clinical and demographic data were collected. Health-related quality of life was assessed using the PedsQL™ 4.0 questionnaire. Correlations between quality of life scores and time in therapeutic range were measured.
Results
A total of 121 children were included in the study (mean age 9.6 ± 4.9 years). Cardiac conditions were the predominant indication for vitamin K antagonists. The mean time in therapeutic range was 0.78 ± 0.15 overall, and 0.76 ± 0.24 over the 3-month period before quality of life assessment. The mean total quality of life score was 76.2 ± 18 in self reports, 71.4 ± 22 in mother reports and 73.5 ± 19 in father reports. The time in therapeutic range correlated with the total quality of life scores in self reports (r = 0.22; P = 0.04), mother reports (r = 0.23; P = 0.02) and father reports (r = 0.28; P = 0.02). The time in therapeutic range predominantly correlated with school functioning in self reports (r = 0.38; P = 0.002) and mother reports (r = 0.40; P < 0.001), and with physical functioning in father reports (r = 0.28; P = 0.03).
Conclusions
Time in therapeutic range correlated with quality of life in children participating in a non-selective International Normalised Ratio self-monitoring and vitamin K antagonist education programme. Regular assessment of quality of life in patient education programmes contributes towards understanding the concerns and needs of patients.
... The doses recommended in the guide- lines seem to be safe, but are not yet optimal, with per- centages of time in which the INR is within the therapeutic range (time in therapeutic range [TTR]) of around⁓ 50% during the first year of treatment [7]. Within the cohort of the Children Anticoagulation and Pharma- cogenetics Study, we obtained similar results within the first 3 months of acenocoumarol use (54.6%), and higher percentages after the first 3 months of use (> 64%) [8]. ...
Background
The large variability in dose requirement of vitamin K antagonists is well known. For warfarin, pediatric dosing algorithms have been developed to predict the right dose for a patient, however not for acenocoumarol.
Objectives
To develop dosing algorithms for pediatric patients on acenocoumarol with and without genetic information.
Methods
The Children Anticoagulation and Pharmacogenetics Study (CAPS) was designed as a multicenter retrospective follow‐up study in Dutch anticoagulation clinics and children's hospitals. Pediatric patients who used acenocoumarol between 1995 and 2014 were selected for inclusion. Clinical information and saliva samples for genotyping of CYP2C9, VKORC1, CYP4F2, CYP2C18 and CYP3A4 were collected. Linear regression was used to analyze their association with the log mean stable dose. A stable period was defined as ≥3 consecutive International Normalized Ratio measurements within therapeutic range over a period of ≥3 weeks.
Results
In total 175 patients were included in the study of whom 86 patients had a stable period and no missing clinical information (clinical cohort; median age 8.9 years and 49% female). Of 80 of these 86 patients genetic information was also available (genetic cohort). The clinical algorithm, containing body surface area and indication, explained 45.0% of the variability in dose requirement of acenocoumarol. By adding the genotypes of VKORC1, CYP2C9, and CYP2C18 to the algorithm it increased to 61.8%.
Conclusions
These findings show that clinical factors had the largest impact on the required dose of acenocoumarol in pediatric patients. Nevertheless, genetic factors, and especially VKORC1, also explained a significant part of the variability.
This article is protected by copyright. All rights reserved.
Thromboembolic disease rates are increasing in pediatric patients. Anticoagulation is prescribed for treatment and prevention of thromboembolic disease. While nonadherence to anticoagulation regimens predicts poor health outcomes in adults, data in anticoagulated pediatric patients are limited. We systematically reviewed the rates, outcomes, and predictors of anticoagulation nonadherence in the pediatric population. Out of a total of 3581 unique articles identified for review, 17 studies met inclusion criteria. These studies primarily evaluated patients with cardiac disease treated with vitamin K antagonists. Overall nonadherence rates varied from 3% to 42%, based upon population, definition of adherence, and measurement strategy. Patient age, goal international normalized ratio (INR), and number of concurrent potentially interacting medications correlated with nonadherence. Data examining the relationship between nonadherence and health outcomes were included in only two studies. Limitations of current literature, as well as critical knowledge gaps that require future study, are discussed.
Aim:
To study the effects of clinical and genetic factors on the phenprocoumon dose requirement in pediatric patients and to develop a dosing algorithm.
Methods:
Pediatric patients who used phenprocoumon were invited to participate in a retrospective follow-up study. Clinical information and genotypes of genetic variations in CYP2C9, VKORC1, CYP4F2, CYP2C18 and CYP3A4 were collected and tested with linear regression for association with phenprocoumon dose requirement.
Results:
Of the 41 patients included in the analysis, age, VKORC1, CYP2C9*2/*3 and CYP3A4*1B were statistically significantly associated with dose requirement, and together explained 80.4% of the variability in phenprocoumon dose requirement.
Conclusion:
Our study reveals that age and genetic variations explain a significant part of the variability in phenprocoumon dose requirement in pediatric patients.
