Mereweather Laura J, Harwood Daniel, Ahnström Josefin, van Batenburg-Sherwood Joseph, Salles-Crawley Isabelle I, Crawley James T B
Centre for Haematology, Department of Immunology and Inflammation, Hammersmith Hospital Campus, Imperial College London, London, UK.
Department of Bioengineering, White City Campus, Imperial College London, London, UK.
Sci Adv. 2025 Feb 7;11(6):eadr5250. doi: 10.1126/sciadv.adr5250. Epub 2025 Feb 5.
Deep vein thrombosis is a major cause of morbidity and mortality worldwide. However, because of the absence of overt blood vessel damage, how venous thrombosis is actually initiated remains unclear. Using endothelialized fluidic devices, we show that aberrant flow patterns that may occur in venous valve pockets of individuals with common stasis-related risk factors can cause the formation of von Willebrand factor-platelet tangles that are resistant to ADAMTS13 removal. These von Willebrand factor-bound platelets specifically recruit neutrophils in a manner that is dependent on platelet-activated αβ, neutrophil SLC44A2, and endothelial P-selectin. The interaction of SLC44A2 with activated αβ promotes formation of prothrombotic neutrophil extracellular traps. These data provide molecular and cellular insights into the proclivity for venous thrombosis to develop in venous valve pockets and suggest an alternative strategy to protect against the initiation of venous thrombosis.
深静脉血栓形成是全球发病和死亡的主要原因。然而，由于没有明显的血管损伤，静脉血栓形成实际上是如何启动的仍不清楚。使用内皮化流体装置，我们发现，在具有常见的与血流淤滞相关风险因素的个体的静脉瓣膜袋中可能出现的异常血流模式，可导致形成对ADAMTS13清除具有抗性的血管性血友病因子-血小板缠结。这些与血管性血友病因子结合的血小板以依赖于血小板活化的αβ、中性粒细胞SLC44A2和内皮P-选择素的方式特异性募集中性粒细胞。SLC44A2与活化的αβ的相互作用促进促血栓形成的中性粒细胞胞外陷阱的形成。这些数据为静脉瓣膜袋中静脉血栓形成的倾向提供了分子和细胞层面的见解，并提出了一种预防静脉血栓形成起始的替代策略。
