Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Thromb Haemost. 2013 Apr;109(4):676-83. doi: 10.1160/TH12-07-0522. Epub 2013 Feb 7.
Data on the in vivo function of platelets induced by the thrombopoietin receptor agonist eltrombopag are scarce. To assess a possible influence of eltrombopag we compared platelet function of eltrombopag-treated immune thrombocytopenia (ITP) patients (group 1; n=10) after treatment response to that from control ITP patients (group 2; n=12). We further analysed platelet function at baseline and after one, three, and four weeks of eltrombopag treatment and estimated daily changes of platelet function during the eltrombopag-induced platelet rise. The formation of platelet-monocyte aggregates (PMA), P-selectin expression [MFI], and platelet adhesion under high shear conditions (surface coverage, SC) in vivo and after in vitro addition of agonists (ADP, TRAP-6, Collagen) were similar between both groups after response to eltrombopag treatment. Only TRAP-6 induced a lower SC in the eltrombopag group (p=0.03). All platelet function parameters except for Collagen-induced P-selectin expression changed significantly during treatment with eltrombopag. PMA, naïve and after addition of ADP or TRAP-6 increased with increasing platelet counts. P-selectin expression decreased, when measured without and upon addition of ADP, increased in the presence of TRAP-6, and remained unchanged after addition of Collagen. SC increased during the eltrombopag-induced platelet rise. All significant changes of platelet function correlated to changes in platelet counts. Two patients developed venous thromboses during eltrombopag treatment, but no association with any distinct single platelet function parameter or combinations thereof was identifiable. Thus, eltrombopag-induced platelets function similar to those from control ITP patients without discernible increased hyper-reactivity.
关于促血小板生成素受体激动剂艾曲泊帕诱导的血小板体内功能的数据很少。为了评估艾曲泊帕可能的影响，我们比较了治疗反应后的艾曲泊帕治疗免疫性血小板减少症（ITP）患者（组 1；n=10）和对照组 ITP 患者（组 2；n=12）的血小板功能。我们还分析了艾曲泊帕治疗前、治疗后 1、3 和 4 周的血小板功能，并估计了艾曲泊帕诱导血小板升高期间血小板功能的每日变化。在体内和体外加入激动剂（ADP、TRAP-6、胶原）后，血小板-单核细胞聚集体（PMA）的形成、P-选择素表达[MFI]和高剪切条件下的血小板黏附（表面覆盖率，SC）在两组之间在对艾曲泊帕治疗有反应后相似。只有 TRAP-6 在艾曲泊帕组诱导的 SC 较低（p=0.03）。除胶原诱导的 P-选择素表达外，所有血小板功能参数在艾曲泊帕治疗期间均发生显著变化。PMA、未加和加 ADP 或 TRAP-6 时的 PMA随着血小板计数的增加而增加。当不加 ADP 测量时，P-选择素表达减少，加 TRAP-6 时增加，加胶原时不变。在艾曲泊帕诱导的血小板升高期间，SC 增加。血小板功能的所有显著变化均与血小板计数的变化相关。两名患者在艾曲泊帕治疗期间发生静脉血栓形成，但未发现与任何明显的单个血小板功能参数或其组合有关。因此，艾曲泊帕诱导的血小板功能与对照组 ITP 患者的血小板功能相似，没有明显的高反应性增加。
