rivaroxaban and ferric-chloride

It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect.. Ten-week-old C57Bl/6 mice (n = 338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1 to 4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1 to 3 days received single-dose aspirin. Thereafter, we induced FeCl. We observed a ~ 40% higher volume of carotid thrombus after dabigatran cessation at 1 to 3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through thrombin or arachidonic acid, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤ 3 days) cessation of NOAC therapy, compared with longer-term (≥ 5 days) cessation, tended to be associated with relatively high stroke severity.. We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. ANN NEUROL 2021;89:444-458.

Topics: Aged; Aged, 80 and over; Animals; Antithrombins; Arachidonic Acid; Aspirin; Carotid Artery Thrombosis; Cerebral Infarction; Chlorides; Computed Tomography Angiography; Dabigatran; Deprescriptions; Factor Xa Inhibitors; Female; Ferric Compounds; Humans; Ischemic Stroke; Magnetic Resonance Angiography; Male; Mean Platelet Volume; Mice; Noxae; Pilot Projects; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Pyrazoles; Pyridones; Rivaroxaban; Severity of Illness Index; Substance Withdrawal Syndrome; Thrombin; Thrombophilia; X-Ray Microtomography