Comparison of aspiration thrombectomy to other endovascular therapies for proximal upper extremity deep venous thrombosis.

OBJECTIVE: Catheter-directed thrombolysis (CDT) provides an effective method for clearing deep venous thrombosis (DVT). Unfortunately, CDT is associated with hemorrhagic complications. This study evaluated the technical success of the various endovascular therapies including a new mechanical aspiration thrombectomy (AT) device for the treatment of acute upper extremity DVT (UEDVT). METHODS: This single-center retrospective review included patients with acute symptomatic proximal UEDVT secondary to venous thoracic outlet syndrome. Undergoing endovascular therapy from December 2013 to June 2019. Patients were treated with a variety of methods including CDT, ultrasound-assisted thrombolysis (USAT), rheolytic thrombectomy, and AT. We evaluated outcomes for patients undergoing AT compared with nonaspiration thrombectomy (NAT) techniques. The primary outcome was technical success, defined as resolution of more than 70% of the thrombus. The secondary end point was the ability to complete the therapy in a single session. RESULTS: There were 22 patients who had endovascular management of their symptomatic proximal UEDVT. All 22 patients (100%) were successfully treated with more than a 70% thrombus resolution. Ten patients underwent AT, of which 50% (5/10) had single session therapies. Twelve patients underwent NAT (three had CDT or USAT alone; three had USAT with rheolytic thrombectomy; and six had CDT followed by rheolytic thrombectomy), with single session therapy occurring in only 8.3% of the NAT group (1/12). The average total dose of thrombolytics was 12.6 ± 9.65 mg in the AT group compared with 19.0 ± 5.78 mg in the NAT group (mean difference, -6.4; 95% confidence interval, -1.1 to 13.9). All but one of the patients in the AT group went on to have successful first rib resections. All NAT patients had successful first rib resections. A venogram was not performed at the time of decompression. All patients except one underwent resection via the infraclavicular approach, with rib removal posterior to the brachial plexus, a median of 8.0 (interquartile range, 6.0-12.0) days after DVT therapy. CONCLUSIONS: In this study, a technical success rate of 100% was achieved for acute symptomatic proximal UEDVT therapies. AT technology allows for higher rates of treatment in a single session, thereby minimizing a patient's risks of bleeding complications. More research is needed to further define the role of this new technology in the treatment paradigm of UEDVT management.

Endothelial ephrinB2 is controlled by microenvironmental determinants and associates context-dependently with CD31.

OBJECTIVE: The EphB ligand ephrinB2 has been identified as a critical determinant of arterial endothelial differentiation and as a positive regulator of invading endothelial cells during angiogenesis. This study was aimed at identifying determinants of endothelial cell ephrinB2 expression. METHODS AND RESULTS: Arteriovenous asymmetrical endothelial cell ephrinB2 expression in vivo is lost on transfer into culture with aortic endothelial cells becoming partially ephrinB2-negative and saphenous vein endothelial cells becoming partially ephrinB2-positive. Contact with smooth muscle cells and angiogenic stimulation by vascular endothelial growth factor lead to an increased endothelial cell ephrinB2 expression. Quiescent, smooth muscle-contacting endothelial cells express ephrinB2 uniformly on their luminal surface. In contrast, monolayer endothelial cells translocate ephrinB2 to interendothelial cell junctions, which is strongly enhanced by EphB4-Fc-mediated receptor body activation. Junctional ephrinB2 colocalizes and coimmunoprecipitates with CD31. CONCLUSIONS: This study identifies distinct regulatory mechanisms of endothelial ephrinB2 expression and cellular distribution in quiescent and activated endothelial cells. The data demonstrate that endothelial cell ephrinB2 expression is controlled by microenvironmental determinants rather than being an intrinsic endothelial cell differentiation marker.

Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells.

Contact-dependent interactions between endothelial cells (ECs), as well as between ECs and mural cells, play a key role in the formation of a regular vascular system and the assembly of the vessel wall. Recent studies have identified ephrinB2 and EphB4 as markers and makers of arteriovenous differentiation during vascular development. On the basis of these findings, we hypothesized that Ephephrin interactions in the vascular system mediate distinct propulsive and repulsive effector functions that provide guidance signals for the proper spatial organization of the developing vasculature. Utilizing a set of specialized endothelial differentiation and angiogenesis assays, the present study was aimed at studying vascular morphogenic functions of endothelial EphB4 and ephrinB2 activation. EphrinB2-Fc acts anti-adhesively and induces detachment of ECs, as demonstrated by (1) inhibition of adhesion to ephrinB2-Fc-coated culture dishes, (2) detachment of ECs grown as differentiated 3D spheroids, and (3) endothelial denudation of explanted fragments of umbilical vein. Conversely, soluble ephrinB2-Fc inhibits lateral cell migration, vascular endothelial growth factor (VEGF) gradient-driven chemotaxis, capillary-like network formation and sprouting angiogenesis. In turn, soluble EphB4-Fc is pro-adhesive and stimulates EC migration and sprouting angiogenesis. EphrinB2-mediated repulsive signals are transduced by EphB4, as demonstrated by EphrinB2-Fc inhibition of sprouting angiogenesis of constitutively EphB4-overexpressing ECs. Confrontation experiments of EphB4-overexpressing ECs with ECs overexpressing full-length or truncated ephrinB2 that lacks the cytoplasmic catalytic domain demonstrated that forward EphB4 signaling with EphB4 tyrosine phosphorylation restricts intermingling of cells and supports cellular segregation. Taken together, these data identify distinct propulsive and repulsive effector functions of endothelial ephrinB2 and EphB4 that mediate spatial positional signals during angiogenesis and vessel assembly.