Study of thrombin generation in three populations of patients on oral anticoagulants: Bleeding with reversion, haemorrhagic accidents without reversion or haemorrhagic accident

Abstract

Bleeding under oral anticoagulant is a frequent reason for consultation in the emergency department. The aim of our study was to compare thrombin generation (TG) parameters in 3 populations under oral anticoagulant: severe bleeding patients who received procoagulant factors, patients with non-severe bleeding without reversion and anticoagulated patients without bleeding events. We conducted a prospective, single-center study of TG in patients under oral anticoagulant (VKA, Direct Oral Anticoagulants (DOACs): rivaroxaban, dabigatran, apixaban). The study was performed on platelet-poor plasma collected on arrival (V1) before reversal therapy, then 30 min (V2), 6 h (V3) and 24 h (V4) after reversal. A total of 307 patients were included in this study with 98 severe bleeding reversed, 95 patients with clinical relevant bleeding but non-reversed and 108 patients without bleeding. For V1, VKA patients with reversed bleeding had a significant decrease in the main TG parameters compared to patients without bleeding ( P = 0.017). Moreover at V1, the main parameters of TG were significantly decreased for VKA compared to DOACs ( P < 0.001) and between anti-IIa compared to anti-Xa ( P < 0.001). At visits V2, V3 and V4, reversal therapy restored a normocoagulable state for VKA patients with a significant increase in key TG parameters between V1 and V2-V3-V4 ( P < 0.001). For DOACs reversed by PCC or PCCactivated, a significant hypercoagulability state was demonstrated on the TG whereas a normal coagulation and no hypercoagulable state was found for those under dabigatran reversed by the idarucizumab. Patients on VKA regained a comparable coagulation state as healthy subjects after reversal therapy, whereas patients treated with DOACs and reversed with PCC or PCCa induced a hypercoagulable state. Probably, this hypercoagulable state could be minimized by reducing the doses of PCC or PCCa, or be circumvented by the use of specific antidotes.