Riddell Anne, Vinayagam Saravanan, Gomez Keith, Laffan Mike, McKinnon Tom
Katharine Dormandy Haemophilia Centre and Thrombosis Unit Royal Free London NHS Foundation Trust London UK.
Department of Haematology Imperial College of Science Technology and Medicine London UK.
Res Pract Thromb Haemost. 2018 Dec 7;3(1):126-135. doi: 10.1002/rth2.12166. eCollection 2019 Jan.
Von Willebrand disease (VWD) results from quantitative or qualitative deficiency of von Willebrand factor (VWF) and is treated using VWF-containing concentrates. Several studies have compared the function of various VWF containing concentrates however this has not been performed using shear based assays.
To compare the platelet-capture potential of 10 commercially available, plasma-derived VWF concentrates under shear conditions.
VWF containing concentrates were assessed for VWF:Ag, VWF:CB, VWF:RCo, factor VIII:C ADAMTS13 content, VWF multimeric profile and glycan content using lectin binding assays. Free-thiol content of each concentrate was investigated using MPB binding assays. An in vitro flow assay was used to determine the ability of each concentrate to mediate platelet capture to collagen.
VWF multimeric analysis revealed reduction of high molecular weight (HMW) forms in four of the concentrates (Alphante, Octanate and Haemoctin, and 8Y). The high MW multimer distribution of the remaining six concentrates (Optivate, Wilate, Fandhi, Wilfactin, Haemate P, and Voncento) was similar to the plasma control. Lectin analysis demonstrated that 8Y had increased amount of T-antigen. Although platelet capture after 5 minutes perfusion was similar for all concentrates; Alphante, Octanate, and Haemoctin, demonstrated the lowest levels of platelet capture after 60 seconds of perfusion. Free-thiol content and ADAMTS13 levels varied widely between the concentrates but was not correlated with function.
Alphanate, Octanate, and Haemoctin, lacked HMW multimers and had the lowest initial platelet capture levels suggesting that the presence of VWF HMW multimers are required for initial platelet deposition.
血管性血友病(VWD)是由血管性血友病因子(VWF)的数量或质量缺陷引起的,使用含VWF的浓缩物进行治疗。多项研究比较了各种含VWF浓缩物的功能,但尚未使用基于剪切力的检测方法进行。
比较10种市售血浆源性VWF浓缩物在剪切条件下的血小板捕获潜力。
使用凝集素结合试验评估含VWF浓缩物的VWF:Ag、VWF:CB、VWF:RCo、因子VIII:C、ADAMTS13含量、VWF多聚体谱和聚糖含量。使用MPB结合试验研究每种浓缩物的游离巯基含量。采用体外流动试验测定每种浓缩物介导血小板捕获胶原蛋白的能力。
VWF多聚体分析显示,四种浓缩物(Alphante、Octanate和Haemoctin以及8Y)中高分子量(HMW)形式减少。其余六种浓缩物(Optivate、Wilate、Fandhi、Wilfactin、Haemate P和Voncento)的高MW多聚体分布与血浆对照相似。凝集素分析表明,8Y的T抗原量增加。尽管所有浓缩物在灌注5分钟后的血小板捕获情况相似;但Alphante、Octanate和Haemoctin在灌注60秒后的血小板捕获水平最低。浓缩物之间的游离巯基含量和ADAMTS13水平差异很大,但与功能无关。
Alphanate、Octanate和Haemoctin缺乏HMW多聚体,且初始血小板捕获水平最低,这表明VWF HMW多聚体的存在是初始血小板沉积所必需的。