The non-vitamin K antagonist oral anticoagulants and heparin-induced prolongation of the activated coagulation time.

Background And Aims: Unfractionated-heparin (UFH) is the first-choice parenteral anticoagulant during invasive percutaneous procedures and its effect is monitored by the activated coagulation time (ACT). The effects of the non-vitamin K antagonist oral anticoagulants (NOACs) on the ACT and on ACT prolongation by UFH were not clearly established. We assessed the ACT prolongation induced by different UFH concentrations in blood samples of patients taking the four types of currently marketed NOACs and in patients not taking anticoagulants.

Methods And Results: We measured the ACT in patients on dabigatran 110 mg (n = 8), rivaroxaban (n = 10), apixaban (n = 9) and edoxaban (n = 10) at supposed peak plasma concentrations, before and after in vitro addition of 3 UFH concentrations, corresponding to doses of 2000, 5000 and 10,000 IU. Seven non-anticoagulated patients served as controls. Patients in the 5 groups did not differ significantly for age, body weight and glomerular filtration rate. Baseline ACTs (s, mean ± SD) were 192 ± 27, 124 ± 14, 132 ± 14, 151 ± 30 and 134 ± 7 in dabigatran 110, rivaroxaban, apixaban, edoxaban and controls, respectively (P < 0.05 for dabigatran vs the other NOACs). We found a linear prolongation of the ACT with the in vitro UFH addition (P < 0.001), but prolongation was similar between the NOACs and controls.

Conclusions: Dabigatran induces a moderate, significant ACT prolongation. None of the NOACs affects the UFH-induced ACT prolongation in the commonly used UFH range. The dose of UFH currently recommended to achieve the target ACT should thus be used irrespective of whether patients are taking NOACs or not.