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Time-Dependent Thrombus Resolution After Tissue-Type Plasminogen Activator in Patients With Stroke and Mice

 Young Dae Kim  ;  Hyo Suk Nam  ;  Seo Hyun Kim  ;  Eung Yeop Kim  ;  Dongbeom Song  ;  Il Kwon  ;  Seung-Hee Yang  ;  Kijeong Lee  ;  Joonsang Yoo  ;  Hye Sun Lee  ;  Ji Hoe Heo 
 STROKE, Vol.46(7) : 1877-1882, 2015 
Journal Title
Issue Date
Aged ; Animals ; Female ; Follow-Up Studies ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Prospective Studies ; Retrospective Studies ; Species Specificity ; Stroke/diagnosis* ; Stroke/drug therapy* ; Thrombolytic Therapy/trends* ; Thrombosis/diagnosis* ; Thrombosis/drug therapy* ; Time Factors ; Tissue Plasminogen Activator/administration & dosage* ; Treatment Outcome
3D image ; ferric chloride ; stroke ; thrombolytic therapy ; thrombosis
BACKGROUND AND PURPOSE: We investigated the relationship between the degree of thrombus resolution and the time from stroke onset or thrombus formation to intravenous tissue-type plasminogen activator (tPA) treatment. METHODS: In patients with stroke, we measured thrombus volume on thin-section noncontrast brain computed tomographic scans taken at baseline and 1 hour after tPA administration. We determined the association between the time from symptom onset to tPA treatment and the degree of thrombus resolution. In a C57/BL6 mouse model of FeCl3-induced carotid artery thrombosis, we investigated the effect of tPA administered at different time intervals after thrombus formation, using Doppler-based blood flow measurement. RESULTS: Of 249 patients enrolled, 171 showed thrombus on baseline computed tomography. Thrombus was resolved by ≥50% in 43 patients (25.1%, good volume reduction) and by <50% in 94 patients (55.0%, moderate volume reduction) 1 hour after tPA treatment. In 34 patients (19.9%, nonvolume reduction; either no change or thrombus volume increased), overall thrombus volume increased. The probability of thrombus resolution decreased as the time interval from symptom onset to treatment increased. On multivariate analysis, good volume reduction was independently related with shorter time intervals from symptom onset to tPA treatment (odds ratio, 0.986 per minute saved; 95% confidence interval, 0.974-0.999). In the mouse model, as the interval between thrombus formation and tPA treatment increased, the initiation of recanalization was delayed (P=0.006) and the frequency of final recanalization decreased (P for trends=0.006). CONCLUSIONS: Early administration of tPA after stroke onset is associated with better thrombus resolution.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Il(권일) ORCID logo https://orcid.org/0000-0001-9449-5646
Kim, Young Dae(김영대) ORCID logo https://orcid.org/0000-0001-5750-2616
Nam, Hyo Suk(남효석) ORCID logo https://orcid.org/0000-0002-4415-3995
Song, Dong Beom(송동범)
Yoo, Joon Sang(유준상)
Lee, Ki Jeong(이기정)
Lee, Hye Sun(이혜선) ORCID logo https://orcid.org/0000-0001-6328-6948
Heo, Ji Hoe(허지회) ORCID logo https://orcid.org/0000-0001-9898-3321
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