A thrombus or blood clot is a solid mass, made up of a network of fibrin, platelets and other blood components. Blood clots can form through various pathways, for example as a result of exposed ...tissue factor from vascular injury, as a result of low flow/stasis, or in very high shear flow conditions. Embolization of cardiac or vascular originating blood clots, causing an occlusion of the neurovasculature, is the major cause of stroke and accounts for 85% of all stroke. With mechanical thrombectomy emerging as the new standard of care in the treatment of acute ischemic stroke (AIS), the need to generate a better understanding of the biomechanical properties and material behaviour of thrombus material has never been greater, as it could have many potential benefits for the analysis and performance of these treatment devices. Defining the material properties of a thrombus has obvious implications for the development of these treatment devices. However, to-date this definition has not been adequately established. While some experimentation has been performed, model development has been extremely limited. This paper reviews the previous literature on mechanical testing of thrombus material. It also explores the use of various constitutive and computational models to model thrombus formation and material behaviour.
About 20% of patients with acute ischemic stroke due to large-artery occlusion do not achieve recanalization with mechanical thrombectomy. We aimed to determine whether the speed of retrieval of the ...stent retriever influences the efficacy in removing different clot types.
Sixty mechanical thrombectomies were performed using an in vitro pulsatile cerebrovascular circulation model with controlled pressure and flow rate. Experiments were dichotomized into fast and slow retrieval using a wedging technique, in which the stent retriever and distal catheter are retrieved together. We used 3 different clot types: erythrocyte-rich, fibrin-rich, and friable clots. Primary end points were complete (TICI 3) and successful (TICI 2b-3) recanalizations. Secondary measures were distal and new territory embolizations.
Fast retrieval was more frequently associated with complete (RR = 1.83; 95% CI, 1.12-2.99) and successful recanalization (RR = 1.50; 95% CI, 1.03-2.19) than slow retrieval, without a difference in distal embolization (RR = 0.75; 95% CI, 0.29-1.90). There were no emboli in a new territory. The advantage of fast retrieval over slow retrieval differed according to the clot composition, with a stronger effect with fibrin-rich clots with regard to complete (RR = 4.00; 95% CI, 1.11-14.35;
int
.04) and successful (
int
.10) recanalization.
In our experimental model, a fast removal improved recanalization rates of mechanical thrombectomy, especially in the case of fibrin-rich clots. An in vivo confirmation is warranted to see whether our findings can have an impact in clinical practice.
•We investigated the effect of full and partial reperfusion on MMP-9 expression.•Partial reperfusion reduced %HLV and oedema but less pronounced than full reperfusion.•MMP-9 expression increased in ...the lesioned anterior and posterior temporal cortex.•Both partial and full reperfusion reduced the regional MMP expression significantly.•This study shows MMP-9 brain levels reduce relative to the extent of reperfusion.
We investigated the effect of full and partial mechanical reperfusion on MMP-9 expression in rat brain following middle cerebral artery occlusion, mimicking mechanical thrombectomy. Using percentage hemispheric lesion volume and oedema as measures, partial reperfusion reduced extent of brain damage caused by MCA occlusion, but the protective effect was less pronounced than with complete reperfusion. Using ELISA quantification in fresh frozen tissue, confirmed by immunofluorescence in perfusion fixed tissue, increased MMP-9 expression was observed in infarcted tissue. MMP-9 was increased in lesioned tissue of the anterior and posterior temporal cortex and underlying striatal tissue, but also the normal appearing frontal cortex. No significant increase in MMP-9 in the hippocampus was observed, nor in the unlesioned contralateral hemisphere. Both partial reperfusion and full reperfusion reduced the regional MMP expression significantly. The highest levels of MMP-9 were observed in lesioned brain regions in the non-reperfused group. MMP-9 expression was evident in microvessels and in neuronal cell bodies of affected tissue. This study shows that MMP-9 brain levels are reduced relative to the extent of reperfusion. These observations suggest targeting early increases in MMP-9 expression as a possible neuroprotective therapeutic strategy and highlight the rat MCA occlusion model as an ideal model in which to study candidate therapeutics.
Malgré l’amélioration constante des techniques de thrombectomie, 20 à 30 % des patients ne sont pas recanalisés. Les raisons peuvent être variées, telles que la composition du thrombus et la ...technique de thrombectomie en elle-même. Nous avons émis l’hypothèse que la vitesse de retrait du stent/cathéter pouvait influence l’efficacité à retirer certains types de thrombus. L’objectif était de déterminer s’il existait une relation entre la vitesse de retrait et l’efficacité à retirer les thrombus.
Les thrombectomies étaient réalisés sur un modèle in vitro pulsatile de circulation cérébrale intracrânienne, avec un contrôle de la pression et du flux. Les expériences ont été dichotomisées en « vitesse rapide » et « vitesse lente » de retrait du couple stent-cathéter. Dans ces groupes, nous avons distribués de manière égale, trois types de caillots analogues (riches en erythrocytes, riches en fibrine et caillots hybrides particulièrement friables).
Soixante thrombectomies ont été réalisées et filmées. Les vitesses de retrait moyennes étaient de 2,4s (1–8s) dans le groupe « rapide » contre 27,3s (15–37s) dans le groupe « lent ». Une recanalization complète et quasi-complète était plus fréquemment atteinte avec un retrait « rapide » : 73,3 % vs 40,0 % (p=0,009) et 80,0 % vs 53,3 % (p=0,02), respectivement. L’efficacité du retrait rapide était plus importante sur les thrombus riche en fibrine (p=0,02). Des fragmentations sont survenues uniquement avec les caillots hybrides friables. Il n’y avait pas de différence de fréquence, ni de nombre d’emboles distaux entre les deux groupes de retrait (p=0,54).
Les résultats sur modèle in vitro montrent une meilleure efficacité d’une vitesse de retrait rapide, notamment lorsque les thrombus sont riches en fibrine. La rapidité du retrait n’influençait pas la fragmentation du thrombus.
An excess of mixed-handedness in schizophrenia has been reported. However, it is not established whether this excess is manifest in non-schizophrenic psychoses, nor whether the underlying etiology is ...genetic or environmental. We investigated these issues in a group of patients with schizophrenia (
n=94), affective psychosis (
n=63), other psychosis (
n=26); their respective first-degree relatives (total
n=183) and a control group (
n=85). A narrow definition of mixed-handedness was used corresponding to groups 5 and 6 as defined by the Annett Handedness Questionnaire.
We found an excess of mixed-handedness in the schizophrenic group compared with controls (OR=5.2, 1.4–18.6,
p<0.006). There was no difference between the other psychotic groups and controls. There was a trend for an excess of mixed-handedness in the first-degree relatives (
n=99) of schizophrenic patients (
p=0.055), but not in the relatives of affective or other psychotic patients. There was a striking linear trend in the proportion of mixed-handedness between controls, the relatives and the schizophrenic patients (χ
2=7.0,
p=0.008). There was no association between mixed-handedness and a history of pregnancy or birth complications in the schizophrenic group. There was some evidence for impaired sociability in the mixed-handed schizophrenic patients.
Our results indicate that the excess of mixed-handedness in schizophrenia may have a genetic basis.
There remains disagreement over whether increased risk of schizotypal personality disorder (SPD) is confined to the relatives of patients with a diagnosis of schizophrenia or whether it is a more ...general characteristic of the relatives of all psychotic patients. To examine the relationship between schizotypal dimensions in relatives and psychopathological syndromes in patients with functional psychoses, factor analysis was carried out on (1) ratings from Present State Examination (PSE) interviews with 172 consecutively admitted patients with psychosis (52% of them with schizophrenia), and (2) ratings on items from three schizotypal scales concerning 263 of their nonpsychotic first degree relatives. The factors derived from the patients' PSE interviews were correlated with the schizotypal factors and the nine DSM-IV criteria for SPD concerning the relatives and subjected to a canonical correlation analysis. In this study, no differences were observed concerning the distribution of schizotypal factors or DSM-IV schizotypal features in the relatives of patients with different psychotic diagnoses. However, a syndrome characterized by delusions, hallucinations, and thought interference (positive symptoms) in patients was correlated with high scores on the three schizotypy scales and with positive and negative schizotypal features in relatives.
Limited data exist on clot composition and detailed characteristics of arterial thrombi associated with large vessel occlusion in acute ischemic stroke. Advances in endovascular thrombectomy and ...related imaging modalities have created a unique opportunity to analyze thrombi removed from cerebral arteries. Insights into thrombus composition, etiology, physical properties and neurovascular interactions may lead to future advancements in acute ischemic stroke treatment and improved clinical outcomes. Advances in imaging techniques may enhance clot characterization and inform therapeutic decision-making prior to treatment and reveal stroke etiology to guide secondary prevention. Current imaging techniques can provide some information about thrombi, but there remains much to evaluate about relationships that may exist among thrombus composition, occlusion characteristics and treatment outcomes. Improved pathophysiological characterization of clot types, their properties and how these properties change over time, together with clinical correlates from ongoing studies, may facilitate revascularization with thrombolysis and thrombectomy. Interdisciplinary approaches covering clinical, engineering and scientific aspects of thrombus research will be key to advancing the understanding of thrombi and improving acute ischemic stroke therapy. This consensus statement integrates recent research on clots and thrombi retrieved from cerebral arteries and provides a rationale for further analyses, including current opportunities and limitations.
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