Bleeding in patients taking target specific oral anticoagulants (TSOAC)

A review was recently published in the American Journal of Emergency Medicine.

Key points:

Effects on coagulation assays:

Readily available coag tests cannot precisely determine the intensity of anticoagulation. However, knowing the effects of the TSOACs on thest tests does help in assessing, qualititatively, “drug on board.”

Dabigatran

The PT has low sensitivity to the activity of dabigatran, and therapeutic plasma concentrations of dabigatran frequently reflect none to only modest elevations in the PT, and therefore, its use is not recommended… Dabigatran increases the aPTT in a curvilinear fashio. This test is rapidly available at most facilities and may be useful as a qualitative assessment of dabigatran's effects… Some clinical experts and guidelines have suggested that, in a patient who is taking dabigatran and experiences bleeding, if the aPTT is normal, then dabigatran is not likely to be present in significant amounts and contributing to the bleeding event [25]. However, a recent investigation demonstrated that depending on the aPTT reagent used, 15% to 35% of patients with a normal aPTT have plasma dabigatran concentrations greater than 100 ng/mL, well within the expected range of trough plasma concentrations on the standard 150 mg twice a day dose. As such, clinicians should use caution when interpreting aPTT results…

At the time of this publication, when faced with a dabigatran patient who is bleeding, the aPTT is the most readily available test; however, a normal test result cannot exclude expected plasma concentrations at standard dosing, although it does rule out supratherapeutic concentrations.

Rivaroxaban

At the time of this publication, when faced with a rivaroxaban patient who is bleeding, the PT is still the most available and useful assay to use; a prolonged PT simply represents that some drug is still present.

Apixaban

Less information is available for apixaban and its effect on a variety of coagulation assays. As a direct Xa inhibitor, apixaban's effect on various laboratory assays is similar to those of rivaroxaban. Prothrombin time is likely the most sensitive and widely available test to detect apixaban activity in plasma, but this test is limited by the high variability..

Attempted reversal in the severely bleeding patient:


Acknowledging the controversy and lack of high level evidence, the following tentative recommendations are made:

For dabigatran:

1. Consider activated charcoal if within 2-3 h of an overdose 2. Dialysis 3. Consider aPCC (Feiba VH 20-40 U/kg) 4. Or 4-PCC (25-50 IU/kg) a5. Or factor VIIa (20 U/kg) may repeat every 2 h

For rivaroxaban:

1. Consider activated charcoal if within 2-3 h of an overdose 2. Consider 4-PCC (25-50 IU/kg) over aPCC (Feiba VH 20-40 U/kg) a3. Or factor VIIa (20 U/kg) may repeat every 2 h

For apixaban:

1. Consider activated charcoal if within 2-3 h of an overdose 2. Consider 4-PCC (25-50 IU/kg) over aPCC (Feiba VH 20-40 U/kg) 3. Or factor VIIa (20 U/kg) may repeat every 2 h