Individual variability in von willebrand factor fragility in response to shear stress : A possible clue for predicting bleeding risk.
Individual variability in von willebrand factor fragility in response to shear stress : A possible clue for predicting bleeding risk.
复制标题
血管性血友病因子响应剪切应力的脆性的个体差异：预测出血风险的可能线索。
DOI：
10.1097/mat.0000000000001623
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发表时间：
2022
期刊：
影响因子：
4.2
通讯作者：
Sakatsume K
中科院分区：
文献类型：
--
作者：
Ishikawa K;Sugimoto S;Oda M;Fujii M;Toshimitsu K;Sawada K;Shimokawa M;Saito M;Kawasaki K;Ishii R;Taniguchi K;Sato T.;Yoshimura Kiyoshi;Sakatsume K
获得性血管性血友病综合征（AVWS）的特征是血管性血友病因子（VWF）大多聚体减少，最近被认为是植入左心室辅助装置（LVAD）患者出血的主要机制。AVWS的血液学严重程度因患者而异，即使植入了相同的器械。我们研究了血液学严重程度的这种多样性是否是由于VWF脆性的个体差异，根据对增量剪切应力的反应。全血样品在20，000 - 40，000 s-1剪切速率（剪切应力指数）下剪切，使用定制的剪切应力源，该剪切应力源可以产生与LVAD产生的剪切应力相容的剪切应力。使用VWF大多聚体指数评价VWF大多聚体降解的程度。观察到VWF大多聚体指数与LVAD相容的剪切应力大小之间存在显著的负相关性：在20，000、25，000、30，000、35，000和40，000 s-1剪切速率下，VWF大多聚体指数分别为68.5±18.3、48.0±13.9、33.9±12.1、23.7±7.9和18.7%±8.7%，P< 0.0001。此外，实验VWF大多聚体指数值与植入LVAD患者的值（中位数; 28.9%）一致。最后，与剪切力对应的VWF大多聚体指数的降低显示出个体差异。我们证明，联合使用一种新型的高剪切应力加载装置和定量评价VWF大多聚体可以预测LVAD植入前出血的风险。
Acquired von Willebrand syndrome (AVWS), characterized by reduced von Willebrand factor (VWF) large multimers, has recently been implicated as the principal mechanism underlying bleeding in patients implanted with left ventricular assist devices (LVADs). Hematological severity of AVWS varies among patients, even if an identical device is implanted. We investigated whether this diversity in hematological severity is due to individual variability in VWF fragility, according to responses to incremental shear stress. Whole-blood samples were sheared at 20,000–40,000 s–1 shear rate, an index of shear stress, using a custom-made shear stressor that could generate shear stress compatible with that produced by an LVAD. The degree of VWF large multimers degradation was evaluated using the VWF large multimer index. A significant inverse correlation was observed between the VWF large multimer index and LVAD-compatible magnitudes of shear stress: the VWF large multimer indices were 68.5±18.3, 48.0±13.9, 33.9±12.1, 23.7±7.9, and 18.7%±8.7% at 20,000, 25,000, 30,000, 35,000, and 40,000 s–1 of shear rates, respectively (P< 0.0001). Furthermore, experimental VWF large multimer index values were compatible with those derived from patients with implanted LVADs (median; 28.9%). Finally, reduction in the VWF large multimer index corresponding to shear stress showed individual variation. We demonstrated that the combined use of a novel high shear stress loading device and quantitative evaluation of VWF large multimers may predict risk of bleeding before LVAD implantation.