Ibrutinib inhibits collagen-mediated but not ADP-mediated platelet aggregation
Ibrutinib inhibits collagen-mediated but not ADP-mediated platelet aggregation
复制标题
DOI：
10.1038/leu.2014.247
复制
发表时间：
2015-04-01
期刊：
影响因子：
11.4
通讯作者：
Tam, C. S.
中科院分区：
文献类型：
--
作者：
Kamel, S.;Horton, L.;Tam, C. S.
BTK（布鲁顿酪氨酸激酶）抑制剂伊布替尼与出血风险增加相关。先前的一项研究报告了当将伊鲁替尼离体添加到患者样本中时，胶原蛋白和二磷酸腺苷（ADP）依赖性血小板反应的缺陷。鉴于BTK在糖蛋白VI信号传导中的中心作用，预期胶原蛋白缺陷，而ADP缺陷缺乏机制解释。为了确定BTK血小板阻滞的现实后果，我们在23例接受伊鲁替尼治疗的患者中进行了光透射聚集测定。所有患者的胶原介导的血小板聚集减少，抑制程度与临床出血或瘀伤的发生之间存在显著相关性（P = 0.044）。这种胶原蛋白缺陷在停药后是可逆的。与之前的离体报告相反，我们在接受标准剂量的伊曲替尼的受试者中未发现体内ADP缺陷。这些结果确立了血小板光透射聚集测定法可作为一种至少定性测定接受伊曲替尼治疗患者血小板损伤严重程度的方法。
The BTK (Bruton's tyrosine kinase) inhibitor ibrutinib is associated with an increased risk of bleeding. A previous study reported defects in collagen-and adenosine diphosphate (ADP)-dependent platelet responses when ibrutinib was added ex vivo to patient samples. Whereas the collagen defect is expected given the central role of BTK in glycoprotein VI signaling, the ADP defect lacks a mechanistic explanation. In order to determine the real-life consequences of BTK platelet blockade, we performed light transmission aggregometry in 23 patients receiving ibrutinib treatment. All patients had reductions in collagen-mediated platelet aggregation, with a significant association between the degree of inhibition and the occurrence of clinical bleeding or bruising (P = 0.044). This collagen defect was reversible on drug cessation. In contrast to the previous ex vivo report, we found no in vivo ADP defects in subjects receiving standard doses of ibrutinib. These results establish platelet light transmission aggregometry as a method for gauging, at least qualitatively, the severity of platelet impairment in patients receiving ibrutinib treatment.