Type 2N von Willebrand disease (VWD) is characterized by impaired factor VIII (FVIII) binding to von Willebrand factor (VWF). Type 2N VWD patients generally exhibit mild bleeding tendency, but some exhibit a more severe hemorrhagic pattern. An assay for assessing hemostatic potential and predict clinical severity could significantly improve clinical management in these patients. We examined the relationship between bleeding score (BS) and the potential for thrombus formation in whole blood from type 2N VWD patients with various BS using rotational thromboelastometry (ROTEM) and microchip flow-chamber system (T-TAS®). Collagen-coated PL-chips, or thromboplastin- and collagen-coated AR-chips, were utilized in the T-TAS to assess platelet thrombus formation at high shear flow, or fibrin-rich platelet thrombus formation at low shear flow, respectively. Neither ROTEM nor the T-TAS using PL-chips reflected the BS. The AR-chip parameters in the T-TAS, however, were highly sensitive to different BS levels among these patients, despite similar FVIII/VWF-related measurements including FVIII/VWF binding. Additionally, the results with AR-chip assay were restored to normal after infusions of FVIII/VWF concentrates in the most severe patients. The data indicate that T-TAS using AR-chips may be a useful assay for predicting clinical severity and assessing therapeutic efficiency in type 2N VWD patients.

中文翻译：

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使用基于微芯片的流腔系统评估2N型von Willebrand病患者的临床严重程度。

2N型von Willebrand病（VWD）的特征在于受损的VIII因子（FVIII）与von Willebrand因子（VWF）的结合。2N型VWD患者通常表现出轻度出血趋势，但有些患者表现出更严重的出血模式。评估止血潜力并预测临床严重性的测定方法可以显着改善这些患者的临床管理。我们使用旋转血栓弹力测定法（ROTEM）和微芯片流腔系统（T-TAS®）检查了出血评分（BS）与2N型VWD伴有各种BS的全血中血栓形成潜力之间的关系。在T-TAS中分别使用胶原蛋白包被的PL芯片，或凝血酶原和胶原蛋白的AR芯片来分别评估高剪切流量下血小板血栓的形成或低剪切流量下富含血纤蛋白的血小板血栓的形成。使用PL芯片的ROTEM或T-TAS都没有反映BS。然而，尽管包括FVIII / VWF结合在内的FVIII / VWF相关测量相似，但T-TAS中的AR芯片参数对这些患者中不同的BS水平高度敏感。此外，在最严重的患者中输注FVIII / VWF浓缩液后，AR芯片测定的结果恢复到正常。数据表明，使用AR芯片的T-TAS可能是预测2N型VWD患者临床严重程度和评估疗效的有用方法。在最严重的患者中，输注FVIII / VWF浓缩液后，AR芯片分析的结果恢复到正常。数据表明，使用AR芯片的T-TAS可能是预测2N型VWD患者临床严重程度和评估疗效的有用方法。在最严重的患者中，输注FVIII / VWF浓缩液后，AR芯片分析的结果恢复到正常。数据表明，使用AR芯片的T-TAS可能是预测2N型VWD患者临床严重程度和评估疗效的有用方法。