Department of Anesthesiology and Intensive Care, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Br J Anaesth. 2013 Dec;111(6):1013-23. doi: 10.1093/bja/aet229. Epub 2013 Jun 20.
Blood flow patterns are important modifiers of platelet interactions with plasma coagulation factors. However, it is not feasible to evaluate rheological effects of haemodilution on coagulation using conventional coagulation testing.
We evaluated thrombus formation with a microchip-based flow-chamber system using whole blood from 12 healthy volunteers (with/without 40% dilution with saline), and 15 cardiac patients [before/after cardiopulmonary bypass (CPB)] in parallel with thromboelastometry. The in vitro additions of von Willebrand factor (vWF, 1.5 U ml(-1)), prothrombin complex concentrate (PCC, 0.3 U ml(-1)), fibrinogen (2 g litre(-1)), or combined PCC (0.3 U ml(-1)) and fibrinogen (1 g litre(-1)) were examined. Recalcified whole-blood samples were perfused over the microchip coated with collagen and tissue thromboplastin at flow rates of 10 and 3 µl min(-1).
Dilution of whole blood led to delayed onset of thrombus formation (Ton), and thrombus growth (T80). Changes relative to baseline values were more extensive at 10 µl min(-1) (≥85% prolongation for Ton and T80) than at 3 µl min(-1) (≥40% prolongation for Ton and T80). Adding vWF accelerated thrombus formation only at 10 µl min(-1), while PCC increased thrombin generation in the thrombus at both flow rates. Fibrinogen increased mural thrombus formation at 3 µl min(-1). Decreased clot strength after dilution was restored by fibrinogen, but not by vWF or PCC on thromboelastometry. Additive effects of fibrinogen and PCC in post-CPB blood were demonstrated by both flow chamber and thromboelastometry.
Blood flow affects thrombus formation after haemodilution and subsequent haemostatic component interventions, with differential effects at low and high flow.
血流模式是血小板与血浆凝血因子相互作用的重要调节剂。然而，使用常规凝血检测评估血液稀释对凝血的流变学影响是不可行的。
我们使用微芯片流动室系统评估了 12 名健康志愿者（用生理盐水稀释 40%与未稀释）和 15 名心脏患者（体外循环前后）的全血血栓形成，同时进行血栓弹性描记术。体外添加血管性血友病因子（vWF，1.5 U ml(-1)）、凝血酶原复合物浓缩物（PCC，0.3 U ml(-1)）、纤维蛋白原（2 g 升(-1)）或联合 PCC（0.3 U ml(-1)）和纤维蛋白原（1 g 升(-1)）进行了检测。再钙化的全血样本以 10 和 3 µl min(-1)的流速在涂有胶原蛋白和组织凝血活酶的微芯片上灌注。
全血稀释导致血栓形成起始时间（Ton）和血栓生长（T80）延迟。与基线值相比，10 µl min(-1)的变化更为广泛（Ton 和 T80 延长≥85%），而 3 µl min(-1)的变化则较为局限（Ton 和 T80 延长≥40%）。vWF 仅在 10 µl min(-1)时加速血栓形成，而 PCC 则在两种流速下均增加血栓中的凝血酶生成。纤维蛋白原增加了 3 µl min(-1)时的壁血栓形成。在血栓弹性描记术上，稀释后凝血强度的降低可通过纤维蛋白原恢复，但不能通过 vWF 或 PCC 恢复。纤维蛋白原和 PCC 在体外循环后血液中的相加效应在流动室和血栓弹性描记术上都得到了证明。
血液稀释后血流会影响血栓形成，随后对止血成分的干预也会产生影响，在低流速和高流速下会产生不同的影响。
