Management of anticoagulation in clinical practice

This thesis describes various aspects of the anticoagulation management of patients with atrial fibrillation and venous thromboembolism. In this thesis, we focus on the management of direct oral anticoagulants (DOACs). Direct oral anticoagulants inhibit one specific clotting factor and are also known as Non-Vitamin K Antagonist Oral Anticoagulants or Novel Oral Anticoagulants (NOACs). Currently, four different DOACs are available in the Netherlands. Apixaban, edoxaban and rivaroxaban inhibit clotting factor Xa (factor Xa inhibitors) and dabigatran inhibits factor IIa (thrombin inhibitor). There are several clinical indications for oral anticoagulants, of which atrial fibrillation and venous thromboembolism are the most common. The overall aim of the research described in this thesis is to optimize management of oral anticoagulation in clinical practice. The first part of this thesis focusses on the management of oral anticoagulation in non-acute clinical settings and the second part of this thesis on the management of oral anticoagulation-related bleeding complications

Diagnostic accuracy of four different D-dimer assays: a post-hoc analysis of the YEARS study

Introduction: For exclusion of pulmonary embolism (PE) clinical decision rules in combination with a D-dimer assay are applied. Currently available D-dimer assays are not standardized and it is unknown whether these differences have an impact on diagnostic management of suspected PE. Therefore, the aim is to explore differences between D-dimer assays and their impact on diagnostic outcome. Methods: Data from all patients included in the YEARS study were collected. The YEARS study is a prospective, multicentre, cohort outcome study evaluating 3462 patients with suspected PE in which four different D-dimer assays were applied (Liatest, Innovance, Tinaquant, Vidas). Median D-dimer concentrations were calculated for each D-dimer assay. Sensitivity, specificity, PPV and NPV for detection of PE of all four assays were determined in patients without YEARS items and in those with >1 YEARS items (i.e. symptomatic deep vein thrombosis, haemoptysis, and whether PE is the most likely diagnosis). Results: A total of 1323, 1100, 768 and 271 D-dimer concentrations were collected using the Liatest Innovance, Tinaquant and Vidas assay, respectively. Median D-dimer concentrations differed significantly between assays, with lowest values in the Tinaquant assay. In patients without YEARS items using a cutoff level of 1000 ng/mL, the NPV varied from 99,5 to 100%. In patients with >1 YEARS items using a 500 ng/mL cutoff, the NPV varied from 97,0 to 100% depending on the assay. Conclusions: The overall high NPV for all assays demonstrates the clinical value of the D-dimer assay. However, these results confirm differences between D-dimer assays, which have an impact on follow-up imaging. This emphasizes the need for standardization of D-dimer assays.Experimentele farmacotherapi

Current practice patterns of outpatient management of acute pulmonary embolism: A post-hoc analysis of the YEARS study

Background: Studies have shown the safety of home treatment of patients with pulmonary embolism (PE) at low risk of adverse events. Management studi

Non-invasive early exclusion of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: the InShape II study

Background The current diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is unacceptably long, causing loss of quality-adjusted life years and excess mortality. Validated screening strategies for early CTEPH diagnosis are lacking. Echocardiographic screening among all PE survivors is associated with overdiagnosis and cost-ineffectiveness. We aimed to validate a simple screening strategy for excluding CTEPH early after acute PE, limiting the number of performed echocardiograms. Methods In this prospective, international, multicentre management study, consecutive patients were managed according to a screening algorithm starting 3 months after acute PE to determine whether echocardiographic evaluation of pulmonary hypertension (PH) was indicated. If the 'CTEPH prediction score' indicated high pretest probability or matching symptoms were present, the 'CTEPH rule-out criteria' were applied, consisting of ECG reading and N-terminalpro-brain natriuretic peptide. Only if these results could not rule out possible PH, the patients were referred for echocardiography. Results 424 patients were included. Based on the algorithm, CTEPH was considered absent in 343 (81%) patients, leaving 81 patients (19%) referred for echocardiography. During 2-year follow-up, one patient in whom echocardiography was deemed unnecessary by the algorithm was diagnosed with CTEPH, reflecting an algorithm failure rate of 0.29% (95% CI 0% to 1.6%). Overall CTEPH incidence was 3.1% (13/424), of whom 10 patients were diagnosed within 4 months after the PE presentation. Conclusions The InShape II algorithm accurately excluded CTEPH, without the need for echocardiography in the overall majority of patients. CTEPH was identified early after acute PE, resulting in a substantially shorter diagnostic delay than in current practice.Cardiolog

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

International audienceIn 2018, the International Council for Standardization in Haematology (ICSH) published a consensus document providing guidance for laboratories on measuring direct oral anticoagulants (DOACs). Since that publication, several significant changes related to DOACs have occurred, including the approval of a new DOAC by the Food and Drug Administration, betrixaban, and a specific DOAC reversal agent intended for use when the reversal of anticoagulation with apixaban or rivaroxaban is needed due to life-threatening or uncontrolled bleeding, andexanet alfa. In addition, this ICSH Working Party recognized areas where additional information was warranted, including patient population considerations and updates in point-of-care testing. The information in this manuscript supplements our previous ICSH DOAC laboratory guidance document. The recommendations provided are based on (1) information from peer-reviewed publications about laboratory measurement of DOACs, (2) contributing author's personal experience/expert opinion and (3) good laboratory practice

Direct oral anticoagulant blood level monitoring in daily practice

Introduction: Routine monitoring is not required in direct oral anticoagulant (DOAC) treatment, yet it is frequently performed. Guidance on the interpretation and management of DOAC level measurements is lacking and it is key to investigate which patients would benefit from monitoring. Our aims were to investigate why DOAC levels are requested and if they lead to changes in anticoagulant management. Methods: We retrospectively collected all clinically requested DOAC levels from 2012 until 2019 in two Dutch academic hospitals. Clinical data with regard to the first DOAC level of every patient was collected by chart review. Primary outcomes were settings, indications and changes in anticoagulant management of DOAC level measurement. In addition, we compared demographic and clinical characteristics in patients with and without changes in anticoagulant management. Results: In total, we included 604 DOAC levels. The majority was requested in an outpatient setting by the department of internal medicine. In 270 (45%) cases we identified a patient specific indication, with evaluation of DOAC accumulation being the most frequently requested. Of all 604 DOAC levels, 159 (26%) were followed by changes in anticoagulation management. The large majority of changes occurred in patients that had a patient specific indication. Patients who underwent changes were older and had more comorbidity than patients who did not (n ​= ​445). Conclusion: Almost half of the DOAC levels with a specific indication for monitoring were followed by a change in anticoagulant management. Future studies should investigate the relation between DOAC levels, the changes in anticoagulant management and clinical outcomes