Kim, Jiwon Jang, Hee Jeong Schellingerhout, Dawid Lee, Su-Kyoung Kim, Ha Kim, Young Dae Lee, Kyung-Yul Choi, Hye-Yeon Cho, Han-Jin Jang, Seong-Soo Jeon, Sangmin Kwon, Ick Chan Kim, Kwangmeyung Ryu, Wi-Sun Nahrendorf, Matthias Choi, Seungbum Kim, Dong-Eog 2024-01-19T15:30:34Z 2024-01-19T15:30:34Z 2021-09-02 2021-03 0364-5134 https://pubs.kist.re.kr/handle/201004/117373 Objective 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. Methods 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 FeCl3-mediated carotid thrombosis in 130 mice, after which we performed micro computed tomography 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 cessation-related cerebral infarction in a large acute stroke cohort. Results We observed a similar to 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. Interpretation We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. ANN NEUROL 2020 English WILEY DIRECT THROMBIN INHIBITOR ORAL ANTICOAGULANT-THERAPY ATRIAL-FIBRILLATION THROMBOEMBOLIC EVENTS RANDOMIZED EVALUATION COMPUTED-TOMOGRAPHY IN-VIVO COAGULATION WARFARIN ETEXILATE Short-Term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State Article 10.1002/ana.25964 1 ANNALS OF NEUROLOGY, v.89, no.3, pp.444 - 458 ANNALS OF NEUROLOGY 89 3 444 458 scie scopus 000603306400001 2-s2.0-85098228915 Clinical Neurology Neurosciences Neurosciences & Neurology Article DIRECT THROMBIN INHIBITOR ORAL ANTICOAGULANT-THERAPY ATRIAL-FIBRILLATION THROMBOEMBOLIC EVENTS RANDOMIZED EVALUATION COMPUTED-TOMOGRAPHY IN-VIVO COAGULATION WARFARIN ETEXILATE