Predictive Value of Thrombus Attenuation on Thin-Slice Non-Contrast CT for Persistent Occlusion after Intravenous Thrombolysis

Niesten, Joris M.; Schaaf, Irene C. van der; Graaf, Y. van der; Kappelle, L. Jaap; Biessels, Geert-Jan; Horsch, Alexander D.; Dankbaar, Jan Willem; Luitse, Merel J A; Seeters, Tom van; Smit, Ewoud J.; Mali, Willem P.Th.M.; Velthuis, Birgitta K.

doi:10.1159/000357420

Cited by 40 publications

(34 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it is only effective in less than half of the patients that receive rt-PA. 2,3 The mechanisms underlying this so called "rt-PA-resistance" are not completely understood but previous reports indicated that RBC-dominant thrombi respond better to rt-PA than platelet-dominant thrombi. [18][19][20][21][22][23][24][25][26] Our histological findings provide new molecular insights on the composition of RBC-rich and platelet-rich thrombus material. It seems plausible that rt-PA, which promotes the degradation of fibrin, can have a direct and efficient thrombolytic effect on the RBC-rich areas in which thin fibrin is the main extracellular scaffold.…”

Section: Discussionmentioning

confidence: 79%

Structural analysis of ischemic stroke thrombi: histological indications for therapy resistance

et al. 2019

View full text Add to dashboard Cite

Ischemic stroke is caused by a thromboembolic occlusion of cerebral arteries. Treatment is focused on fast and efficient removal of the occluding thrombus, either via intravenous thrombolysis or via endovascular thrombectomy. Recanalization, however, is not always successful and factors contributing to failure are not completely understood. Although the occluding thrombus is the primary target of acute treatment, little is known about its internal organization and composition. The aim of this study, therefore, was to better understand the internal organization of ischemic stroke thrombi on a molecular and cellular level. A total of 188 thrombi were collected from endovascularly treated ischemic stroke patients and analyzed histologically for fibrin, red blood cells, von Willebrand factor , platelets, leukocytes and DNA, using bright field and fluorescence microscopy. Our results show that stroke thrombi are composed of two main types of areas: red blood cell-rich areas and platelet-rich areas. Red blood cell-rich areas have limited complexity as they consist of red blood cells that are entangled in a meshwork of thin fibrin. In contrast, platelet-rich areas are characterized by dense fibrin structures aligned with von Willebrand factor and abundant amounts of leukocytes and DNA that accumulate around and in these platelet-rich areas. These findings are important to better understand why platelet-rich thrombi are resistant to thrombolysis and difficult to retrieve via thrombectomy and can guide further improvements of acute ischemic stroke therapy.

show abstract

Section: Discussionmentioning

confidence: 79%

Structural analysis of ischemic stroke thrombi: histological indications for therapy resistance

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Nevertheless, the inverse correlation of VWF presence with red blood cell content in the thrombus is particularly interesting because radiological imaging on admission was shown to predict thrombus red cell content. 6,44 Determining thrombus composition from radiological signs may help identify patients who could benefit from specific thrombolytic approaches such as the use of ADAMTS13.…”

Section: Discussionmentioning

confidence: 99%

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

Denorme

Langhauser²,

Desender

et al. 2016

Blood

147

172

View full text Add to dashboard Cite

Key Points• ADAMTS13 dissolves t-PAresistant cerebral occlusions in a mouse model of stroke.• The thrombolytic activity of ADAMTS13 could become useful for more efficient and safer thrombolytic treatment of acute ischemic stroke.Rapid vascular recanalization forms the basis for successful treatment of cerebral ischemia. Currently, tissue plasminogen activator (t-PA) is the only approved thrombolytic drug for ischemic stroke. However, t-PA does not always result in efficient thrombus dissolution and subsequent blood vessel recanalization. To better understand thrombus composition, we analyzed thrombi retrieved from ischemic stroke patients and found a distinct presence of von Willebrand factor (VWF) in various samples. Thrombi contained on average 20.3% 6 10.1% VWF, and this was inversely correlated with thrombus red blood cell content. We hypothesized that ADAMTS13 can exert a thrombolytic effect in VWF-containing thrombi in the setting of stroke. To test this, we generated occlusive VWF-rich thrombi in the middle cerebral artery (MCA) of mice. Infusion of t-PA did not dissolve these MCA occlusions. Interestingly, administration of ADAMTS13 5 minutes after occlusion dose-dependently dissolved these t-PA-resistant thrombi resulting in fast restoration of MCA patency and consequently reduced cerebral infarct sizes (P < .005). Delayed ADAMTS13 administration 60 minutes after occlusion was still effective but to a lesser extent (P < .05). These data show for the first time a potent thrombolytic activity of ADAMTS13 in the setting of stroke, which might become useful in treatment of acute ischemic stroke.

show abstract

“…They therefore had suspected stroke and an indication for IV-rtPA. Moreover, the detection of ischemia on CT perfusion is not 100%; small infarcts and infarcts outside the scan range can be missed [27]. Since this is true for the entire study population, it should not have influenced the analyses.…”

Section: Discussionmentioning

confidence: 99%

Wake-Up Stroke versus Stroke with Known Onset Time: Clinical and Multimodality CT Imaging Characteristics

et al. 2018

Self Cite

View full text Add to dashboard Cite

Background: Current guidelines for the treatment of acute ischemic stroke are mainly based on the time between symptom onset and initiation of treatment. This time is unknown in patients with wake-up stroke (WUS). We investigated clinical and multimodality CT imaging characteristics on admission in patients with WUS and in patients with a stroke with a known onset time. Methods: All patients were selected from a large prospective cohort study (Dutch acute stroke study). WUS patients last seen well > 4.5 and ≤4.5 h were separately compared to patients with a known onset time ≤4.5 h. In addition, WUS patients with a proximal occlusion of the anterior circulation last seen well > 6 and ≤6 h were separately compared to patients with a known onset time ≤6 h and a proximal occlusion. National Institute of Health Stroke Score, age, gender, history of atrial fibrillation, non-contrast CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS), CT-perfusion abnormalities, proximal occlusions, and collateral filling on CT angiography were compared between groups using the Mann-Whitney U test and Fisher’s exact test. Results: WUS occurred in 149/1,393 (10.7%) patients. Admission clinical and imaging characteristics of WUS patients last seen well > 4.5 h (n = 81) were not different from WUS patients last seen well ≤4.5 h (n = 68). Although WUS patients last seen well > 4.5 h had a significantly lower NCCT ASPECTS than patients with a known time of stroke symptom onset of ≤4.5 h (n = 1,026), 85.2% had an NCCT ASPECTS > 7 and 75% had a combination of favorable ASPECTS > 7 and good collateral filling. There were no statistically significant differences between the admission clinical and imaging characteristics of WUS patients with proximal occlusions last seen well > 6 h (n = 23), last seen well ≤6 h (n = 40), and patients with a known time to stroke symptom onset ≤6 h (n = 399). Of all WUS patients with proximal occlusions last seen well > 6 h, only 4.3% had severe ischemia (ASPECTS < 5), 13 (56.5%) had ASPECTS > 7 and good collateral filling. Conclusions: There are only minor differences between clinical and imaging characteristics of WUS patients and patients who arrive in the hospital within the time criteria for intravenous or endovascular treatment. Therefore, CT imaging may help to identify WUS patients who would benefit from treatment and rule out those patients with severe ischemia and poor collaterals.

show abstract

Predictive Value of Thrombus Attenuation on Thin-Slice Non-Contrast CT for Persistent Occlusion after Intravenous Thrombolysis

Cited by 40 publications

References 38 publications

Structural analysis of ischemic stroke thrombi: histological indications for therapy resistance

Structural analysis of ischemic stroke thrombi: histological indications for therapy resistance

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

Wake-Up Stroke versus Stroke with Known Onset Time: Clinical and Multimodality CT Imaging Characteristics

Contact Info

Product

Resources

About