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Short-Term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State

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dc.contributor.author김영대-
dc.contributor.author이경열-
dc.date.accessioned2021-10-21T00:07:15Z-
dc.date.available2021-10-21T00:07:15Z-
dc.date.issued2021-03-
dc.identifier.issn0364-5134-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/185385-
dc.description.abstractObjective: 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 ~ 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.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherWiley-Liss-
dc.relation.isPartOfANNALS OF NEUROLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleShort-Term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Neurology (신경과학교실)-
dc.contributor.googleauthorJiwon Kim-
dc.contributor.googleauthorHee Jeong Jang-
dc.contributor.googleauthorDawid Schellingerhout-
dc.contributor.googleauthorSu-Kyoung Lee-
dc.contributor.googleauthorHa Kim-
dc.contributor.googleauthorYoung Dae Kim-
dc.contributor.googleauthorKyung-Yul Lee-
dc.contributor.googleauthorHye-Yeon Choi-
dc.contributor.googleauthorHan-Jin Cho-
dc.contributor.googleauthorSeong-Soo Jang-
dc.contributor.googleauthorSangmin Jeon-
dc.contributor.googleauthorIck Chan Kwon-
dc.contributor.googleauthorKwangmeyung Kim-
dc.contributor.googleauthorWi-Sun Ryu-
dc.contributor.googleauthorMatthias Nahrendorf-
dc.contributor.googleauthorSeungbum Choi-
dc.contributor.googleauthorDong-Eog Kim-
dc.identifier.doi10.1002/ana.25964-
dc.contributor.localIdA00702-
dc.contributor.localIdA02648-
dc.relation.journalcodeJ00166-
dc.identifier.eissn1531-8249-
dc.identifier.pmid33219556-
dc.identifier.urlhttps://onlinelibrary.wiley.com/doi/10.1002/ana.25964-
dc.subject.keywordAged-
dc.subject.keywordAged, 80 and over-
dc.subject.keywordAnimals-
dc.subject.keywordAntithrombins / adverse effects*-
dc.subject.keywordAntithrombins / pharmacology-
dc.subject.keywordArachidonic Acid / blood-
dc.subject.keywordAspirin / pharmacology-
dc.subject.keywordCarotid Artery Thrombosis / chemically induced-
dc.subject.keywordCarotid Artery Thrombosis / diagnostic imaging*-
dc.subject.keywordCarotid Artery Thrombosis / prevention & control-
dc.subject.keywordCerebral Infarction / diagnostic imaging-
dc.subject.keywordCerebral Infarction / etiology-
dc.subject.keywordCerebral Infarction / physiopathology-
dc.subject.keywordCerebral Infarction / prevention & control-
dc.subject.keywordChlorides / toxicity-
dc.subject.keywordComputed Tomography Angiography-
dc.subject.keywordDabigatran / adverse effects*-
dc.subject.keywordDabigatran / pharmacology-
dc.subject.keywordDeprescriptions*-
dc.subject.keywordFactor Xa Inhibitors / adverse effects-
dc.subject.keywordFemale-
dc.subject.keywordFerric Compounds / toxicity-
dc.subject.keywordHumans-
dc.subject.keywordIschemic Stroke / diagnostic imaging-
dc.subject.keywordIschemic Stroke / etiology-
dc.subject.keywordIschemic Stroke / physiopathology-
dc.subject.keywordIschemic Stroke / prevention & control-
dc.subject.keywordMagnetic Resonance Angiography-
dc.subject.keywordMale-
dc.subject.keywordMean Platelet Volume-
dc.subject.keywordMice-
dc.subject.keywordNoxae / toxicity-
dc.subject.keywordPilot Projects-
dc.subject.keywordPlatelet Aggregation / drug effects*-
dc.subject.keywordPlatelet Aggregation Inhibitors / pharmacology-
dc.subject.keywordPlatelet Count-
dc.subject.keywordPyrazoles / adverse effects-
dc.subject.keywordPyridones / adverse effects-
dc.subject.keywordRivaroxaban / adverse effects-
dc.subject.keywordSeverity of Illness Index-
dc.subject.keywordSubstance Withdrawal Syndrome / blood*-
dc.subject.keywordSubstance Withdrawal Syndrome / etiology-
dc.subject.keywordSubstance Withdrawal Syndrome / prevention & control-
dc.subject.keywordThrombin / metabolism-
dc.subject.keywordThrombophilia / blood*-
dc.subject.keywordThrombophilia / etiology-
dc.subject.keywordThrombophilia / prevention & control-
dc.subject.keywordX-Ray Microtomography-
dc.contributor.alternativeNameKim, Young Dae-
dc.contributor.affiliatedAuthor김영대-
dc.contributor.affiliatedAuthor이경열-
dc.citation.volume89-
dc.citation.number3-
dc.citation.startPage444-
dc.citation.endPage458-
dc.identifier.bibliographicCitationANNALS OF NEUROLOGY, Vol.89(3) : 444-458, 2021-03-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers

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