Background
Routine monitoring of direct oral anticoagulant (DOAC) levels is not recommended but may be useful in certain clinical situations. There is a knowledge gap regarding the clinical use of ...DOAC levels in Australian hospitals.
Aims
To evaluate the clinical settings, indications and changes to anticoagulant management associated with DOAC levels in a tertiary hospital in Northern Tasmania, Australia.
Methods
Patients with one or more DOAC levels (dabigatran, rivaroxaban or apixaban) requested between January 2017 and December 2022 were identified. Retrospective chart review was performed to evaluate the clinical settings, indications, adequacy of request information and changes to clinical management associated with the measurement of DOAC levels.
Results
One hundred and twenty‐nine DOAC measurements (54 rivaroxaban, 66 apixaban and nine dabigatran) were performed in 98 patients between January 2017 and December 2022. Annual requests for DOAC levels increased significantly between 2017 and 2019 and remained stable between 2020 and 2021 but declined in 2022. Overall, the most common indication for a DOAC level was renal impairment, followed by bleeding and recurrent thrombosis. Approximately 25% of requests were for acute bleeding with a reversal/haemostatic agent given in 45% of patients, while 10% were prior to urgent surgery. Measurement of DOAC levels was associated with a change in management in 50% of cases. 10% of requests did not specify anticoagulant history.
Conclusion
Trends in requests for DOAC levels have changed over time. Clinician education regarding the importance of providing specific anticoagulant history is essential. Future prospective studies investigating the clinical utility of DOAC levels in different clinical settings are needed.
•Long-term benefits of anticoagulants for oldest-old stroke survivors were investigated.•Over one-year period, all recurrent stroke was ischemic rather than hemorrhagic.•Long-term anticoagulant ...therapy for oldest-old stroke survivors may be justified.
Long-term anticoagulant therapy in oldest-old persons poses the risk of bleeding complications. The aim of this study was to evaluate the long-term benefits of anticoagulant therapy for oldest-old stroke survivors with AF.
Patients with atrial fibrillation (AF) who were 90 years of age or older and were prescribed an anticoagulant on discharge were identified from a set of data from a prospective follow-up registry of 1,484 consecutive patients admitted for ischemic stroke or transient ischemic attack over a 4-year period beginning in 2014. The outcome measures were stroke and death following discharge.
Of the 77 identified patients with AF who were 90 years of age or older, 71 were prescribed an anticoagulant (median age 93 years, 73% women). Thirty-nine patients were given a direct oral anticoagulant (DOAC) (median age 92 years, 69% women), and 32 were given warfarin (median age 93 years, 78% women). During the follow-up period (median 466 days), 9 patients (13%) had stroke recurrence (recurrence rate: 14%/year), and 25 patients (35%) died (mortality rate: 33%/year). The type of all recurrent strokes was ischemic, and no fatal bleeding occurred. There was no difference in the incidence of recurrent strokes according to anticoagulant type (DOAC 15%/year, warfarin 13%/year, P = 0.743), but a higher proportion of patients on warfarin died (21% vs. 47%, P = 0.002).
Given that a higher proportion of oldest-old stroke survivors with AF on anticoagulant therapy have recurrent ischemic stroke rather than hemorrhagic stroke, long-term anticoagulant therapy may be justified for secondary stroke prevention.
For more than a decade, US laboratories have failed to implement solutions to help their clinicians in managing complex situations or patients on direct oral anticoagulants (DOACs). The problem may ...find different origins, among which is the position of the Food and Drug Administration, which categorized these drugs as monitoring‐ and measurement‐free, whereas other regulatory bodies like the European Medicines Agency or the Therapeutic Goods Administration in Australia were more conservative on the principle that the absence of proof (of monitoring/measurement benefits) is not proof of an absence (of monitoring/measurement needs). Pivotal clinical studies that led to the approval of DOACs were presented as devoid of such testing, although some companies considered monitoring as a solution to improve their benefit/risk ratio. In this JTH In Clinics issue, we report more than a decade of development that has permitted the activation of smart laboratory solutions to qualify or quantify DOACs and discuss myths and misconceptions around technical and regulatory requirements that support the current reluctance of implementing these technologies in most US laboratories. Use of DOACs is ever expanding, with DOAC prescriptions now exceeding those of other anticoagulants, including vitamin K antagonists, in some geographies. As this use increases, the likely need to measure DOAC exposure will also increase. Measurement of DOACs does not represent any technical difficulty. That these laboratory tests are not available in some locations suggests disparities in patient care, and we suggest it is time to address such inequalities.
Direct oral anticoagulants (DOACs) have overtaken vitamin K antagonists to become the most widely used method of anticoagulation for most indications. Their stable and predictable pharmacokinetics ...combined with relatively simple dosing, and the absence of routine monitoring has made them an attractive proposition for healthcare providers. Despite the benefits of DOACs as a class, important differences exist between individual DOAC drugs in respect of their pharmacokinetic and pharmacodynamic profiles with implications for dosing and reversal in cases of major bleeding.
This review summarizes the state of knowledge relating to the pharmacokinetics of dabigatran (factor IIa/thrombin inhibitor) and apixaban, edoxaban and rivaroxaban (factor Xa) inhibitors. We focus on pharmacokinetic differences between the drugs which may have clinically significant implications.
Patient-centered care necessitates a careful consideration of the pharmacokinetic and pharmacodynamic differences between DOACs, and how these relate to individual patient circumstances. Prescribers should be aware of the potential for pharmacokinetic drug interactions with DOACs which may influence prescribing decisions in patients with multiple comorbidities. In order to give an appropriate dose of DOAC drugs, accurate estimation of renal function using the Cockcroft-Gault formula using actual body weight is necessary. An increasing body of evidence supports the use of DOACs in patients who are obese, and this is becoming more routine in clinical practice.
Objectives
The aim of this clinical observational study was to assess the efficacy of L-PRF as a hemostatic agent in patients under treatment with vitamin K antagonists (VKAs) or direct oral ...anticoagulants (DOACs).
Materials and methods
Patients under oral anticoagulant therapy (VKA or DOACs) who needed a single simple tooth extraction were enrolled. L-PRF plug was positioned inside the alveolus and secured with non-absorbable sutures. Surgical time, pain-VAS, paracetamol intake, intra-operative, post-operative biological complications, and bleeding events have been registered.
Results
A total of 112 patients (59 patients for DOAC and 53 for VKA group) were enrolled. Post-operative bleeding was recorded in nine patients (17%) for VKA group and nine patients (15.3%) for DOACs group. None of the patients needed a medical support for managing of bleeding. Seven days after surgery, no cases of post-extractive complications occurred.
Conclusions
The use of L-PRF resulted in limited mild late post-operative bleedings without the need of medical intervention.
Clinical relevance
The use of L-PRF can be adopted for an uneventful post-operative curse in anticoagulated patients without chasing their therapy for single tooth extraction.
Background and Aim
Bleeding is an inevitable and often severe complication after endoscopic sphincterotomy (EST). We aimed to investigate the factors associated with post‐EST bleeding in patients ...treated with anticoagulants.
Methods
The data of patients who underwent EST at 15 hospitals between July 2015 and June 2017 were extracted. We investigated the incidence of post‐EST bleeding and risk factors for bleeding in patients treated with anticoagulants.
Results
One hundred forty‐nine patients undergoing EST who met the inclusion criteria were included in this study. The total‐EST bleeding (bleeding occurring during or after EST) rate did not differ between the heparin replacement (8.0%, 6/75) and continuation (16.6%, 2/12; P = 0.37) groups of warfarin users. The total‐EST‐bleeding rate in the heparin replacement group (12.9%, 4/31) was significantly higher than that in the continuation group (0%, 0/31; P = 0.016) in direct oral anticoagulant (DOAC) users. The rate of total‐EST bleeding with continuation of DOAC (0%, 0/31) was significantly lower with continuation of warfarin (16.6%, 2/12; P = 0.021). During‐EST bleeding (bleeding occurring during EST) (P = 0.0083) and precut (P = 0.033) were significant risk factors for post‐EST bleeding in all 149 patients. Heparin replacement was only a significant risk factor for total‐EST bleeding (P = 0.033) in DOAC users.
Conclusion
Heparin replacement was a significant risk factor for post‐EST bleeding in DOAC users; however, there was no significant difference between the bleeding rate of heparin replacement and that of continuation groups in patients taking warfarin. During EST and precut were significant risk factors for post‐EST bleeding in all patients treated with anticoagulants.
PURPOSE.The impact of a pharmacist-led direct oral anticoagulant (DOAC) service on prescription appropriateness and patient adherence was simultaneously evaluated.
METHODS.In this retrospective ...analysis, patients age 18 years or older for whom a DOAC was prescribed from September 20, 2013, through December 31, 2014, were identified through electronic medical record review of all DOAC prescriptions within the University of Michigan Health System. Patients had their DOAC therapy managed by a pharmacist-led DOAC service or by their physician (usual care). Primary endpoints included the percentage of patients who had appropriate DOAC therapy prescribed at baseline and at follow-up appointments at 3–6 months. Secondary endpoints included mean medication possession ratios (MPRs).
RESULTS.A total of 258 patients were included in the study, with 129 in each group. Patients in the pharmacist-led DOAC service were significantly more likely to have an appropriate combination of DOAC and dosage prescribed for their indication at baseline compared with the usual care group (p = 0.009), a finding that persisted at follow up (p = 0.016). There was no significant difference between groups in the number of patients determined to have an appropriate DOAC prescribed for an approved indication (independent of dose) in the pharmacist-led service (95.3%) versus usual care (93.0%) at baseline. Patients in the pharmacist-led service had a greater mean adjusted MPR compared with the usual care group (p = 0.0014) over a median follow-up period of 248 days.
CONCLUSION.A pharmacist-led DOAC service increased appropriate dosing of DOACs at baseline and follow up as well as patient adherence to therapy.
•An UHPLC-MS/MS was developed to simultaneously analyze 4 DOACs and a prodrug.•The method features simple sample preparation without extra consumables.•Nitrogen drying and reconstitution removed ...lipids with good recovery rates.•The assay can be used for therapeutic drug monitoring and pharmacokinetic studies.
Direct oral anticoagulants are widely used to treat and prevent thromboembolic disorders. With rising clinical application, monitoring concentrations of direct oral anticoagulants are necessary in certain clinical conditions. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of dabigatran etexilate, dabigatran, rivaroxaban, edoxaban, and apixaban, in human plasma. Protein precipitation with methanol was performed for sample preparation. The direct oral anticoagulants and internal standards were separated under gradient conditions using a C18 column, at an analytical run time of 8 min. The mobile phase was composed of 0.1% (v/v) formic acid in water (solvent A) and 0.1% (v/v) formic acid in acetonitrile (solvent B) at a flow rate of 0.3 mL/min. Mass detection was performed in multiple reaction monitoring using positive ionization mode. The method was validated over a range of 1.0–500 ng/mL for dabigatran etexilate, 0.1–500 ng/mL for dabigatran, and 0.5–500 ng/mL for edoxaban, rivaroxaban, and apixaban. The method detection limits of five analytes were in the range of 0.05–0.5 ng/mL. The lower limits of quantification of five analytes ranged from 0.1 to 1 ng/mL. The linearity (r2 values) was higher than 0.997. The accuracy of the low, medium, and high quality control samples were between 85.9 and 114%, and intra- and inter-day precision were below 9.47%. This validated method was successfully used to determine the plasma concentrations of rivaroxaban in 32 patients, and of dabigatran etexilate and dabigatran in 1 patient.
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