Short-term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State
- Short-term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State
- 권익찬; 김광명; 전상민; 김지원; 장희정; Dawid Schellingerhout; 이수경; 김하; 김용대; 이경열; 최혜연; 조한진; 장성수; Wi-Sun Ryu; Mattias Nahrendorf; 최승범; 김동억
- Issue Date
- Annals of neurology
- VOL 89, NO 3-458
It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if shortterm (13？days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect.
Tenweekold C57Bl/6 mice (n=338) received one of the following oral treatments: phosphatebuffered saline (PBS), dabigatran for 7？days with or without 14 day cessation, and aspirin in either a single dose or daily for 7？days. Some of the animals that ceased dabigatran for 13？days received singledose aspirin. Thereafter, we induced FeCl3mediated carotid thrombosis in 130 mice, after which we performed microCT thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessationrelated cerebral infarction in a large acute stroke cohort.
We observed a higher volume of carotid thrombus after dabigatran cessation at 13？days than after vehicle treatment and showed that this effect could be prevented by singledose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2？days after drug cessation, an effect mediated through arachidonic acid or thrombin, which effect was significantly attenuated by singledose aspirin pretreatment. In patients, shortterm (≤3 day) cessation of NOAC therapy, compared with longerterm (≥5 days) cessation, tended to be associated with relatively high stroke severity.
We provide the first preclinical evidence that a rebound prothrombotic state follows shortterm cessation of dabigatran therapy.
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