Schoeman R M, Rana K, Danes N, Lehmann M, Di Paola J A, Fogelson A L, Leiderman K, Neeves K B
Chemical and Biological Engineering Department, Colorado School of Mines, Golden, CO.
Applied Mathematics and Statistics Department, Colorado School of Mines, Golden, CO.
Cell Mol Bioeng. 2017 Feb;10(1):3-15. doi: 10.1007/s12195-016-0469-0. Epub 2016 Oct 24.
Hemostasis is the process of sealing a vascular injury with a thrombus to arrest bleeding. The type of thrombus that forms depends on the nature of the injury and hemodynamics. There are many models of intravascular thrombus formation whereby blood is exposed to prothrombotic molecules on a solid substrate. However, there are few models of extravascular thrombus formation whereby blood escapes into the extravascular space through a hole in the vessel wall. Here, we describe a microfluidic model of hemostasis that includes vascular, vessel wall, and extravascular compartments. Type I collagen and tissue factor, which support platelet adhesion and initiate coagulation, respectively, were adsorbed to the wall of the injury channel and act synergistically to yield a stable thrombus that stops blood loss into the extravascular compartment in ~7.5 min. Inhibiting factor VIII to mimic hemophilia A results in an unstable thrombus that was unable to close the injury. Treatment with a P2Y12 antagonist to reduce platelet activation prolonged the closure time two-fold compared to controls. Taken together, these data demonstrate a hemostatic model that is sensitive to both coagulation and platelet function and can be used to study coagulopathies and platelet dysfunction that result in excessive blood loss.
止血是通过血栓封闭血管损伤以阻止出血的过程。形成的血栓类型取决于损伤的性质和血流动力学。有许多血管内血栓形成模型，其中血液暴露于固体基质上的促血栓形成分子。然而，血管外血栓形成模型很少，即血液通过血管壁上的孔逸出到血管外空间。在此，我们描述了一种止血微流控模型，其包括血管、血管壁和血管外隔室。分别支持血小板粘附和启动凝血的I型胶原蛋白和组织因子被吸附到损伤通道壁上，并协同作用产生稳定的血栓，在约7.5分钟内阻止血液流失到血管外隔室。抑制因子VIII以模拟A型血友病会导致血栓不稳定，无法封闭损伤。与对照组相比，用P2Y12拮抗剂治疗以减少血小板活化使封闭时间延长了两倍。综上所述，这些数据证明了一种对凝血和血小板功能均敏感的止血模型，并可用于研究导致过度失血的凝血病和血小板功能障碍。
