Heightened activation of embryonic megakaryocytes causes aneurysms in the developing brain of mice lacking podoplanin.

During early embryonic development in mammals, including humans and mice, megakaryocytes (Mks) first originate from primitive hematopoiesis in the yolk sac. These embryonic Mks (eMks) circulate in the vasculature with unclear function. Herein, we report that podoplanin (PDPN), the ligand of C-type lectin-like receptor (CLEC-2) on Mks/platelets, is temporarily expressed in neural tissue during midgestation in mice. Loss of PDPN or CLEC-2 resulted in aneurysms and spontaneous hemorrhage, specifically in the lower diencephalon during midgestation. Surprisingly, more eMks/platelets had enhanced granule release and localized to the lower diencephalon in mutant mouse embryos than in wild-type littermates before hemorrhage. We found that PDPN counteracted the collagen-1-induced secretion of angiopoietin-1 from fetal Mks, which coincided with enhanced TIE-2 activation in aneurysm-like sprouts of PDPN-deficient embryos. Blocking platelet activation prevented the PDPN-deficient embryo from developing vascular defects. Our data reveal a new role for PDPN in regulating eMk function during midgestation.

A comparison of surgical pulmonary embolectomy and catheter-directed lysis for life-threatening pulmonary emboli.

OBJECTIVES: Patients with life-threatening pulmonary emboli (PE) have traditionally been treated with anticoagulation alone, yet emerging data suggest that more aggressive therapy may improve short-term outcomes. The purpose of this study was to compare postoperative outcomes between catheter-directed thrombolysis (CDL) and surgical pulmonary embolectomy (SPE) in the treatment of life-threatening PE. METHODS: A retrospective single-centre observational study was conducted for patients who underwent SPE or CDL at a single US academic centre. Preprocedural and postprocedural echocardiographic data were collected. Unadjusted regression models were constructed to assess the significance of the between-group postoperative differences. RESULTS: A total of 126 patients suffered a life-threatening PE during the study period [60 SPE (47.6%), 66 CDL 52.4%]. Ten (24.4%) SPE patients and 10 (15.2%) CDL patients had massive PEs marked by preprocedural hypotension. Six (10.0%) SPE patients and 4 (6.0%) CDL patients suffered a preprocedure cardiac arrest (P = 0.41). In-hospital mortality rate was 3.3% (2) for SPE, and 3.0% (2) for CDL (P = 0.99). SPE patients were more likely to require prolonged ventilation (15.0% vs 1.5%, P = 0.01). No significant differences were found in other major complications. At baseline echocardiography, 76.9% of SPE patients and 56.9% of CDL patients had moderate or severe right ventricular (RV) dysfunction. Both treatment groups showed marked and durable improvement in echocardiographic markers of RV function from baseline at midterm follow-up. CONCLUSIONS: Both SPE and CDL can be applied to well-selected high-risk patients with low rates of morbidity and mortality. Further research is necessary to delineate which patients would benefit most from either SPE or CDL following a life-threatening PE.