Figure 7

Monitoring in vitro reversal of VKA- and rivaroxaban anticoagulation with TGA-AUC. VKA plasma (INR 3.6, George King Biomedical Inc) and rivaroxaban-anticoagulated plasma spiked with increasing PCC dose (4-factor PCC, Cofact, Sanquin) was subjected to TGA (4 μM phospholipids and 5 pM TF as described [32,68]. TGA-AUC is expressed as % of not anticoagulated normal plasma without PCC. Correlation between PCC and TGA-AUC is more or less linear for VKA while less steeper and decaying for rivaroxaban. For apixaban and dabigatran, similar decaying curves were observed [32]. A decaying curve results in PCC incapable in restoring TGA-AUC to normal at high to extreme NOAC levels. This figure also shows that the suggested PCC dose for treatment of rivaroxaban-associated bleeds of 50 IU per kg body weight (±1.25 IU/ml) [12] is able to fully normalize the TGA-AUC at 200 μg/L rivaroxaban and to achieve almost complete TGA-AUC normalization at 500 μg/L.