Casonato Alessandra, Galletta Eva, Galvanin Federico, Daidone Viviana
Department of Medicine University of Padua Medical School First Chair of Internal Medicine Padua Italy.
EJHaem. 2021 May 5;2(3):340-348. doi: 10.1002/jha2.196. eCollection 2021 Aug.
Type Vicenza von Willebrand disease (VWD) features a von Willebrand factor (VWF) with a very short half-life, and is classified as a form of type 1 VWD. To test the appropriateness of type Vicenza VWD classification, the main features of 17 patients from eight unrelated families were analysed. They had low VWF antigen levels and function (always below 20 U/dl); ristocetin-induced platelet aggregation sometimes normal, sometimes reduced/absent (even in the same patient); normal platelet VWF levels; an increased VWF propeptide to VWF antigen ratio (8.74 ± 1.65 vs. normal 1.04 ± 0.28) and a reduced VWF half-life. Plasma VWF multimer levels were homogeneously reduced, and unusually large VWF multimers were sometimes present. Recombinant p.R1205H VWF showed a normal synthesis, release, function, and multimer pattern, with no ultra-large VWF multimers. The mathematical model by Galvanin et al. was used to explore the kinetic changes in VWF after DDAVP. It showed that the release, but especially the proteolysis ( 1.0 ± 2.5 vs. normal 4.5 ± 6.4) and elimination ( 1.0 ± 5.2 vs. normal 1.1 ± 6.8) of type Vicenza VWF were significantly higher than normal. The increased elimination is consistent with the short half-life, while the increased proteolysis was unexpected. As a shorter survival of VWF is wholly responsible for the type Vicenza VWD phenotype (VWF synthesis, structure and function are normal), it might be better to classify it as a type 2 VWD (rather than type 1) to emphasise the greater interaction with clearance receptors as a new VWF functional defect.
威尼托型血管性血友病（VWD）的特点是血管性血友病因子（VWF）半衰期极短，被归类为1型VWD的一种形式。为了检验威尼托型VWD分类的合理性，分析了来自8个无亲缘关系家庭的17例患者的主要特征。他们的VWF抗原水平和功能较低（始终低于20 U/dl）；瑞斯托霉素诱导的血小板聚集有时正常，有时降低/缺失（甚至在同一患者中）；血小板VWF水平正常；VWF前肽与VWF抗原的比值增加（8.74±1.65，而正常为1.04±0.28），VWF半衰期缩短。血浆VWF多聚体水平均一性降低，有时存在异常大的VWF多聚体。重组p.R1205H VWF显示出正常的合成、释放、功能和多聚体模式，没有超大VWF多聚体。使用Galvanin等人的数学模型来探索去氨加压素（DDAVP）后VWF的动力学变化。结果显示，威尼托型VWF的释放，尤其是蛋白水解（1.0±2.5，而正常为4.5±6.4）和清除（1.0±5.2，而正常为1.1±6.8）显著高于正常水平。清除增加与半衰期缩短一致，而蛋白水解增加则出乎意料。由于VWF较短的存活时间完全导致了威尼托型VWD表型（VWF的合成、结构和功能正常），将其归类为2型VWD（而非1型）可能更好，以强调作为一种新的VWF功能缺陷，其与清除受体的相互作用更强。
