Normal prothrombin times in the presence of therapeutic levels of apixaban – in‐vivo experience from King's College Hospital

Influence of apixaban on commonly used coagulation assays: results from the Belgian national External Quality Assessment Scheme

“…Among aPTT reagents, there was no appreciable difference in sensitivity at the concentrations tested. Our results confirm and extend previous reports that PT and aPTT reagents are much less sensitive to apixaban than to rivaroxaban, another direct FXa inhibitor with a similar molecular weight, and endorse the recommendations made by the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis and the British Committee for Standards in Haematology stipulating that laboratories should be aware of the sensitivity of their own reagent/instrument combination to each of the DOAC . The different effects of apixaban and rivaroxaban on the PT and aPTT could be explained by their respective rates of FXa inhibition .…”

“…Antithrombin activity measurement, on the other hand, proved to be similarly affected by apixaban as by rivaroxaban. Indeed, as mentioned in earlier publications [7,12,16,18,21], the FXa-based antithrombin activity assays significantly overestimated the antithrombin level of the apixaban-spiked samples. The factitious elevation of antithrombin activity was approximately 8%, 15% and 33% at 41, 94 and 225 ng/mL apixaban, respectively.…”

“…Both PT and aPTT were barely affected by apixaban indicating that patients may have normal coagulation times despite therapeutic concentrations of apixaban and thus making these tests unsuitable for indicating the presence or absence of apixaban [2,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Hence, a normal PT or aPTT result does not exclude a concentration higher than 30 or 50 ng/mL being the thresholds proposed for antidote administration [23].…”

Prothrombin times in the presence of edoxaban – in‐vivo experience from King's College hospital

“…When these standards were published, 3 DOACs were available for clinicians to prescribe in the UK; apixaban, rivaroxaban and dabigatran. Since then, edoxaban has become available following NICE approval for the acute treatment of venous thromboembolism (VTE) and secondary prevention of VTE and stroke prophylaxis in non-valvular AF (National Institute for Health and Care Excellence, 2015a; National Institute for Health and Care Excellence, 2015b).In the past, we have shared our experience of the impact of rivaroxaban and apixaban on the prothrombin time (PT) reagent used at our Denmark Hill laboratory site (Patel et al, 2013(Patel et al, , 2015, and how the sensitivity of this reagent has influenced the bleeding guidelines we have in place in our Trust. With the recent availability of edoxaban, we sought to understand edoxaban's impact on the prothrombin time reagents used locally.…”

“…In the past, we have shared our experience of the impact of rivaroxaban and apixaban on the prothrombin time (PT) reagent used at our Denmark Hill laboratory site (Patel et al, 2013(Patel et al, , 2015, and how the sensitivity of this reagent has influenced the bleeding guidelines we have in place in our Trust. With the recent availability of edoxaban, we sought to understand edoxaban's impact on the prothrombin time reagents used locally.…”