Key result
Bleeding in AF patients on DOACs is linked to ~3-fold higher plasma levels than trough controls.
Why the study?
Patients with AF on long-term DOACs may have higher bleeding risk due to elevated anti-Xa or anti-IIa levels, but no postmarketing study had evaluated DOAC plasma levels at the time of bleeding.
Are DOAC plasma levels higher in patients with atrial fibrillation at the time of a bleeding event compared to patients tolerating DOACs without bleeding?
Observational (n=104)
No
Are DOAC plasma levels higher in patients with atrial fibrillation at the time of a bleeding event compared to patients tolerating DOACs without bleeding?
p-value: p=<0.001
DOAC plasma levels are significantly elevated in atrial fibrillation patients presenting with bleeding complications compared to those tolerating therapy without bleeding.
Elevated DOAC levels associated with bleeding in AF; hypothesis-generating for monitoring, should not yet change practice.
Patients with atrial fibrillation (AF) on long-term direct oral anticoagulants (DOACs) may be at higher risk of bleeding because of higher anti-Xa or anti-IIa levels. However, there is no postmarketing study investigating these DOAC plasma levels at the time of bleeding. The aim of this study was to evaluate DOAC levels at the time of a bleeding emergency. We analyzed 5440 patients examined at our Emergency Department in from April 1, 2019, to September 30, 2019. During this period, we prospective identified 105 consecutive patients with bleeding while on long-term antithrombotic therapy; 49 patients had AF on DOACs. We compared DOAC levels in patients who bled against a control sample of 55 patients who tolerated long-term high dose DOAC therapy without any emergency. Samples of these patients were tested with drug-specific anti-Xa chromogenic analysis (rivaroxaban and apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). Dabigatran-treated patients who bled had significantly higher anti-IIa levels when compared with trough (261.4 ± 163.7 vs. 85.4 ± 57.2 ng/mL, P < 0.001) and peak samples of controls (261.4 ± 163.7 vs. 138.8 ± 78.7 ng/mL, P < 0.05). Similarly, there were significantly higher anti-Xa levels in rivaroxaban-treated and apixaban-treated patients with bleeding compared with trough control samples (rivaroxaban: 245.9 ± 150.2 vs. 52.5 ± 36.4 ng/mL, P <0.001 and apixaban: 311.8 ± 142.5 vs. 119.9 ± 81.7 ng/mL, P < 0.001), as well as in apixaban-treated patients when compared with peak control samples (311.8 ± 142.5 vs. 210.9 ± 88.7 ng/mL, P < 0.05). Finally, rivaroxaban anti-Xa levels in patients who bled tended to be higher compared with peak control samples (245.9 ± 150.2 vs. 177.6 ± 38.6 ng/mL, P = 0.13). This observational study showed a significant difference in anti-IIa and anti-Xa plasma levels in patients with AF with bleeding complications compared with those who tolerated long-term high-dose DOAC therapy without bleeding complications.
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Škorňová et al. (2021) conducted an observational in Atrial fibrillation (n=104). Direct oral anticoagulants (dabigatran, rivaroxaban, apixaban) vs. Patients tolerating long-term high dose DOAC therapy without emergency was evaluated on DOAC plasma levels (anti-IIa and anti-Xa) (p=<0.001). Patients with atrial fibrillation on DOACs presenting with bleeding had significantly higher anti-IIa and anti-Xa levels compared to trough controls (e.g., dabigatran 261.4 vs 85.4 ng/mL; P<0.001).
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