Per-Pass Analysis of Thrombus Composition in Patients With Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

Background and Purpose- Mechanical thrombectomy may involve multiple attempts to retrieve the occluding thrombus. This study examined the composition of thrombus fragments retrieved with each pass of a device during the thrombectomy procedure. Second, the per-pass composition was compared with procedural and clinical data including angiographic outcome and stroke etiology. Methods- Thrombi were retrieved from 60 patients with acute ischemic stroke, where thrombus fragments retrieved in each pass were segregated as individual samples and maintained throughout the histological analysis as independent samples. All samples were stained with hematoxylin and eosin and Martius Scarlet Blue. The relative composition of red blood cells, fibrin, and white blood cells in thrombus fragments from each pass was quantified. Results- Over the 60 cases, thrombus material was retrieved in 106 of 138 passes. The number of passes required to complete the cases ranged from 1 to 6 passes. The analysis of thrombus fragments retrieved in each pass provided a greater insight into the thrombectomy procedure progression than the overall thrombus composition; the red blood cell content of thrombus fragments retrieved in passes 1 and 2 was significantly higher than that retrieved in passes 3 to 6. The removal of thrombus material in a total of 1, 2, or 3 passes was associated with the highest percentage of final modified Thrombolysis in Cerebral Infarction score of 2c-3. There was no association between modified Thrombolysis in Cerebral Infarction score and per-pass thrombus composition. Conclusions- The differentiation achieved through the per-pass analysis of acute ischemic stroke thrombi provides a greater insight into the thrombectomy procedure progression than the combined per-case thrombus analysis. Insights gained may be a useful consideration in determining the treatment strategy as a case evolves and may be useful for the development of new devices to increase rates of 1-pass recanalization.

Novel methodology to replicate clot analogs with diverse composition in acute ischemic stroke.

BACKGROUND: Translational research on clot composition may be advanced by the use of clot analogs for the preclinical evaluation of mechanical thrombectomy devices. This work describes a novel set of clot analogs to represent a diverse range of fibrin and red blood cell (RBC) compositions for use in acute ischemic stroke (AIS) occlusion models. METHOD: Fresh whole blood obtained from ovine species was used to create seven different clot analog types. Five replicates were formed for each clot type. Varying amounts of whole blood constituents were mixed with thrombotic factors to create clots of varying compositions. Following histological processing, five sections from each clot were stained with H&E and Martius Scarlet Blue. Fibrin, RBC and white blood cell compositions were quantified. RESULTS: Histological examination demonstrated that the clot types had a distinct RBC and fibrin composition. No significant difference in composition was shown between replicates (p>0.05), indicating that the method of clot formation was reproducible. Percentage fibrin composition of the clot types was 1%, 8%, 31%, 38%, 64%, 79%, and 100%. A significant difference in fibrin and RBC composition between clot types was observed (p<0.05). CONCLUSIONS: Seven different clot types were developed to replicate common AIS thrombi. These clot analogs may be beneficial for the preclinical evaluation of endovascular therapies, and may be applied to interventional technique training.

Interleukin 10, produced in abundance by human newborn T cells, may be the regulator of increased tolerance associated with cord blood stem cell transplantation.

The use of human umbilical cord blood as an alternative source of stem cells to bone marrow for the reconstitution of the immune system is associated with less frequent and less severe incidence of graft-versus-host disease (GVHD). This study focuses on aspects of cord blood T-cell biology that may contribute to a perceived increased tolerance associated with the neonatal immune response. A skewing of the T-helper (Th)1/Th2 phenotype of cord blood T cells towards a Th2 response has frequently been cited as a possible cause. In this study, primary and repeated stimulation via the T-cell receptor (TCR) complex induced a Th0-type cytokine response, with both adult and cord blood-derived naïve T cells producing interferon gamma (IFN-gamma), interleukin 4 (IL-4) and IL-5. IL-10 was induced in cord blood T-cell cultures during primary stimulation, while adult T cells began to secrete IL-10 only after repeated stimulation. The presence of the antigen-presenting cell (APC)-derived cytokine IL-1beta inhibited IL-10 production by cord blood cells. The effects of IL-12 and IL-4 on T-cell cytokine responses were also examined. In addition to their differential Th1/Th2 skewing effects on cord and adult T cells, both cytokines augmented IL-10 production in both T-cell populations. These findings demonstrate that cord blood T cells may secrete large amounts of the anti-inflammatory cytokine IL-10 and that the presence of IL-1beta or Th1/Th2 skewing cytokines can regulate its production. This data provides support for the recognized tolerant nature of the newborn immune response that may contribute to the reduced incidence of GVHD associated with cord blood transplantation.