Brass L F, Diamond S L
Departments of Medicine and Systems Pharmacology, University of Pennsylvania, Philadelphia, PA, USA.
Institute for Medicine and Engineering, Department of Chemical Engineering, Philadelphia, PA, USA.
J Thromb Haemost. 2016 May;14(5):906-17. doi: 10.1111/jth.13280. Epub 2016 Mar 30.
The biophysics of blood flow can dictate the function of molecules and cells in the vasculature with consequent effects on hemostasis, thrombosis, embolism, and fibrinolysis. Flow and transport dynamics are distinct for (i) hemostasis vs. thrombosis and (ii) venous vs. arterial episodes. Intraclot transport changes dramatically the moment hemostasis is achieved or the moment a thrombus becomes fully occlusive. With platelet concentrations that are 50- to 200-fold greater than platelet-rich plasma, clots formed under flow have a different composition and structure compared with blood clotted statically in a tube. The platelet-rich, core/shell architecture is a prominent feature of self-limiting hemostatic clots formed under flow. Importantly, a critical threshold concentration of surface tissue factor is required for fibrin generation under flow. Once initiated by wall-derived tissue factor, thrombin generation and its spatial propagation within a clot can be modulated by γ'-fibrinogen incorporated into fibrin, engageability of activated factor (FIXa)/activated FVIIIa tenase within the clot, platelet-derived polyphosphate, transclot permeation, and reduction of porosity via platelet retraction. Fibrin imparts tremendous strength to a thrombus to resist embolism up to wall shear stresses of 2400 dyne cm(-2) . Extreme flows, as found in severe vessel stenosis or in mechanical assist devices, can cause von Willebrand factor self-association into massive fibers along with shear-induced platelet activation. Pathological von Willebrand factor fibers are A Disintegrin And Metalloprotease with ThromboSpondin-1 domain 13 resistant but are a substrate for fibrin generation due to FXIIa capture. Recently, microfluidic technologies have enhanced the ability to interrogate blood in the context of stenotic flows, acquired von Willebrand disease, hemophilia, traumatic bleeding, and drug action.
血流生物物理学可决定血管系统中分子和细胞的功能，进而影响止血、血栓形成、栓塞和纤维蛋白溶解。血流和运输动力学在以下方面有所不同：（i）止血与血栓形成；（ii）静脉事件与动脉事件。在止血实现或血栓完全阻塞的瞬间，凝块内的运输会发生显著变化。与在管中静态凝结的血液相比，在流动条件下形成的凝块中血小板浓度比富含血小板血浆高50至200倍，其组成和结构也有所不同。富含血小板的核心/壳结构是在流动条件下形成的自限性止血凝块的一个显著特征。重要的是，在流动条件下生成纤维蛋白需要表面组织因子达到临界阈值浓度。一旦由血管壁衍生的组织因子启动，凝块中凝血酶的生成及其空间传播可通过掺入纤维蛋白的γ'-纤维蛋白原、凝块内活化因子（FIXa）/活化FVIIIa 凝血酶原酶的可结合性、血小板衍生的多磷酸盐、凝块通透以及通过血小板收缩减少孔隙率来调节。纤维蛋白赋予血栓巨大的强度，使其在高达2400达因/平方厘米的壁面剪应力下抵抗栓塞。在严重血管狭窄或机械辅助装置中发现的极端血流，可导致血管性血友病因子自聚合成大量纤维，并伴随剪切诱导的血小板活化。病理性血管性血友病因子纤维对具有血小板反应蛋白-1结构域的去整合素和金属蛋白酶13具有抗性，但由于FXIIa的捕获，它们是纤维蛋白生成的底物。最近，微流控技术增强了在狭窄血流、获得性血管性血友病、血友病、创伤性出血和药物作用等背景下研究血液的能力。
