van Dijk Wobke E M, Poolen Geke C, Huisman Albert, Koene Harry R, Fijnheer Rob, Thielen Noortje, van Bladel Esther R, van Galen Karin P M, Schutgens Roger E G, Urbanus Rolf T
Center for Benign Hematology, Thrombosis and Hemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
J Thromb Haemost. 2023 Apr;21(4):1020-1031. doi: 10.1016/j.jtha.2022.11.039. Epub 2022 Dec 22.
Thrombopoietin receptor agonists are frequently used in treating immune thrombocytopenia (ITP) owing to high response rates and good tolerability. ITP is associated with an increased risk of thrombosis. Whether treatment with eltrombopag further increases this risk is controversial. The mechanisms behind the thrombotic risk in ITP are unclear.
To assess platelet function and hypercoagulability in patients with ITP and the effect of eltrombopag thereon.
This prospective multicenter study assessed adult primary patients with ITP who were starting eltrombopag treatment. Platelet (re)activity and hypercoagulability were measured in whole blood or plasma before start and after 2 to 3 weeks of eltrombopag treatment and compared with those of controls. Change over time was assessed by mixed-effects models, and the results were corrected for multiple testing.
We included 16 patients and 33 controls. At baseline, patients with ITP exhibited lower expression of glycoprotein VI, more activated platelets, and lower reactivity toward agonists compared with controls. β-Thromboglobulin levels reduced and thrombin generation peak height increased compared with those of controls. In line with this finding, patients with ITP showed high factor VIII (median, 217%; IQR, 174%-272%) and von Willebrand factor levels (median, 167%; IQR, 109%-198%). Eltrombopag treatment increased thrombin generation potential: lag time decreased and peak height and endogeneous thrombin potential increased. The latter changes were not significant after correction for multiple testing.
Patients with ITP in this study were in a hypercoagulable state, with preactivated platelets, increased thrombin generation potential, and increased levels of factor VIII and von Willebrand factor. Eltrombopag treatment further increased plasma thrombin generation potential but no other hemostatic parameters.
由于反应率高且耐受性良好，血小板生成素受体激动剂常用于治疗免疫性血小板减少症（ITP）。ITP与血栓形成风险增加有关。艾曲泊帕治疗是否会进一步增加这种风险存在争议。ITP血栓形成风险背后的机制尚不清楚。
评估ITP患者的血小板功能和高凝状态以及艾曲泊帕对其的影响。
这项前瞻性多中心研究评估了开始接受艾曲泊帕治疗的成年原发性ITP患者。在开始治疗前以及艾曲泊帕治疗2至3周后，在全血或血浆中测量血小板（再）活性和高凝状态，并与对照组进行比较。通过混合效应模型评估随时间的变化，并对结果进行多重检验校正。
我们纳入了16例患者和33例对照。在基线时，与对照组相比，ITP患者糖蛋白VI表达较低，血小板活化程度更高，对激动剂的反应性更低。与对照组相比，β-血小板球蛋白水平降低，凝血酶生成峰值升高。与此发现一致，ITP患者的因子VIII（中位数，217%；四分位间距，174% - 272%）和血管性血友病因子水平较高（中位数，167%；四分位间距，109% - 198%）。艾曲泊帕治疗增加了凝血酶生成潜力：延迟时间缩短，峰值高度和内源性凝血酶潜力增加。在进行多重检验校正后，后两者的变化不显著。
本研究中的ITP患者处于高凝状态，血小板预激活，凝血酶生成潜力增加，因子VIII和血管性血友病因子水平升高。艾曲泊帕治疗进一步增加了血浆凝血酶生成潜力，但未改变其他止血参数。
