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

Abstract

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 FeCl 3 -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.

Determinants of Emergency Medical Services Utilization Among Acute Ischemic Stroke Patients in Hubei Province in China

“…1 Recombinant tissue-type plasminogen activator, when given to patients with appropriate acute ischemic stroke (AIS) soon after symptom onset, can reduce the risk of severe disability and mortality. 2 Unfortunately, <5% of AIS patients received intravenous recombinant tissue-type plasminogen activator in China 3 mainly because the best treatment window for thrombolysis is often missed. 4 Utilization of emergency medical services (EMS) can increase the likelihood of appropriate therapy with recombinant tissue-type plasminogen activator.…”

Blood clot contraction differentially modulates internal and external fibrinolysis

“…Less porous fibrin clots lyse more slowly than clots composed of loose fibers, which has been attributed to a reduction in fibers per volume [9,32,65,66]. Taken together, our findings may help to explain how older clots that are more likely to have undergone intravital contraction become less amenable to exogenous thrombolytics [67].…”

ADAMTS13-mediated thrombolysis of t-PA–resistant occlusions in ischemic stroke in mice

“…Moreover, aging of a thrombus is also known to affect its stability and susceptibility to thrombolysis. 28,29 We therefore assessed the thrombolytic potential of ADAMTS13 in a more clinically realistic time window. One hour after inducing large t-PA-resistant MCA occlusions in C57BL/6J mice, rhA-DAMTS13 (3500 U/kg) was IV injected.…”