Urgent Need to Measure Effects of Direct Oral Anticoagulants
Bibliographic record
Abstract
anticoagulantT he direct oral anticoagulants (DOACs), which include dabigatran, rivaroxaban, apixaban, and edoxaban, were designed to be given in fixed doses without routine coagulation monitoring.When administered in this manner in trials that included >71 000 patients with atrial fibrillation 1 and >27 000 patients with venous thromboembolism, 2 the DOACs were at least as effective as vitamin K antagonists but were associated with less serious bleeding, particularly less intracranial bleeding.Eliminating coagulation monitoring simplifies anticoagulation therapy.This feature, together with their proven efficacy and safety, explains why guidelines give preference to the DOACs over vitamin K antagonists for stroke prevention in atrial fibrillation and for the treatment of venous thromboembolism.Although routine coagulation monitoring is unnecessary, there is an urgent need for readily and rapidly available tests to measure the DOACs.This need will increase with the introduction of costly reversal agents such as idarucizumab for dabigatran 3 and andexanet alfa for rivaroxaban, apixaban, and edoxaban. 4Idarucizumab is already licensed, and andexanet is undergoing regulatory review and could be approved later this year.What tests are currently available, and why do we need new ones?Although currently available global tests of coagulation such as the activated partial thromboplastin time (aPTT) and prothrombin time (PT) can be useful to assess the anticoagulant effects of dabigatran and some of the oral factor Xa inhibitors, respectively, the sensitivity of these tests is variable and reagent dependent. 5Regardless of reagent, the PT is less responsive to apixaban and edoxaban than to rivaroxaban.Unfortunately, because sensitivity to the DO-ACs is rarely considered when reagents are chosen, the utility of the tests may change when laboratories order new lots of reagents.This not only complicates interpretation of test results over time in a single laboratory, but also renders between-laboratory comparisons difficult.These issues highlight the need for standardized tests.The DOACs have half-lives of ≈12 hours.Consequently, circulating drug levels and their subsequent effects on the aPTT and PT depend on when the blood sample was collected relative to the timing of the last drug dose.Even when measured soon after drug intake, a prolonged aPTT in patients taking dabigatran or an elevated PT in those on rivaroxaban, apixaban, or edoxaban gives no information about how much drug is in the circulation, and a normal test result does not exclude the presence of drug.Therefore, more accurate tests are needed.Such tests are currently available in research facilities and include the diluted thrombin time and ecarin clot time or ecarin chromogenic assay for dabigatran, as well as chromogenic anti-factor Xa assays for rivaroxaban, apixaban, and edoxaban. 5Unfortunately, these tests are not widely available, and even if available, the turnaround time is often too slow to be useful.This needs to change.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.025 | 0.061 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.001 | 0.004 |
| Scholarly communication | 0.005 | 0.010 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.008 | 0.013 |
| Insufficient payload (model declined to judge) | 0.014 | 0.006 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".