van Genderen P J, van Vliet H H, Prins F J, van de Moesdijk D, van Strik R, Zijlstra F J, Budde U, Michiels J J
Department of Hematology, University Hospital Dijkzigt, Rotterdam, The Netherlands.
Ann Hematol. 1997 Nov-Dec;75(5-6):215-20. doi: 10.1007/s002770050345.
Patients with essential thrombocythemia (ET), who frequently have bleeding complications, may manifest an excessive prolongation of the bleeding time (BT) after ingestion of aspirin (ASA). The reason for this excessive prolongation of the BT is unknown, but it is attributed to qualitative platelet defects. Since patients with ET may also have acquired abnormalities of plasma and platelet von Willebrand factor (vWF), we questioned whether the excessive prolongation of the BT by ASA was related to changes in either plasma or platelet vWF. To that end, we studied BT and plasma and platelet vWF in ten ET patients, ten patients with reactive thrombocytosis (RT), and ten normal individuals, both before and after administration of 500 mg ASA for 7 days. In a second study, the effect of DDAVP infusion on plasma vWF in relation to the BT was studied in ten normal individuals and ten ET patients after treatment with 100 mg ASA for 3 days. In the first study, treatment with ASA resulted in a significant prolongation of the BT in normal subjects, RT patients, and ET patients. However, in five ET patients an excessive (> 2 SD) prolongation of the BT by ASA was observed. Although ASA induced no direct changes in either plasma or platelet vWF levels in either normal subjects, RT patients, or ET patients, all five ET patients who showed an excessive prolongation of the BT by ASA had significantly decreased levels of large vWF multimers in plasma. In the second study, infusion with DDAVP resulted in a significant increase in plasma large vWF multimers, paralleled by a normalization of (excessively) prolonged BT. Our data suggest that in ET inhibition of platelet function by ASA in the presence of concurrently decreased levels of large vWF multimers in plasma may have provoked the excessive BT prolongation.
真性红细胞增多症（ET）患者经常出现出血并发症，在摄入阿司匹林（ASA）后可能表现出出血时间（BT）过度延长。BT过度延长的原因尚不清楚，但归因于血小板质量缺陷。由于ET患者也可能存在血浆和血小板血管性血友病因子（vWF）的后天异常，我们质疑ASA导致的BT过度延长是否与血浆或血小板vWF的变化有关。为此，我们研究了10例ET患者、10例反应性血小板增多症（RT）患者和10名正常个体在服用500mg ASA 7天前后的BT以及血浆和血小板vWF。在第二项研究中，在10名正常个体和10例ET患者用100mg ASA治疗3天后，研究了去氨加压素输注对与BT相关的血浆vWF的影响。在第一项研究中，ASA治疗导致正常受试者、RT患者和ET患者的BT显著延长。然而，在5例ET患者中观察到ASA导致BT过度（>2SD）延长。尽管ASA在正常受试者、RT患者或ET患者中均未引起血浆或血小板vWF水平的直接变化，但所有5例显示ASA导致BT过度延长的ET患者血浆中大分子vWF多聚体水平均显著降低。在第二项研究中，输注去氨加压素导致血浆大分子vWF多聚体显著增加，同时（过度）延长的BT恢复正常。我们的数据表明，在ET患者中，在血浆中大分子vWF多聚体水平同时降低的情况下，ASA对血小板功能的抑制可能引发了BT的过度延长。
