Institute for Prevention of Cardiovascular Diseases, LMU (Ludwig-Maximilians University Munich), Munich, Germany.
Medizinische Klinik und Poliklinik I, Klinikum rechts der Isar, Medizinische Fakultät, Technische Universität München, Munich, Germany.
Thromb Haemost. 2019 Aug;119(8):1212-1221. doi: 10.1055/s-0039-1687877. Epub 2019 May 14.
Bruton's tyrosine kinase (Btk) is essential for B cell differentiation and proliferation, but also platelets express Btk. Patients with X-linked agammaglobulinemia due to hereditary Btk deficiency do not show bleeding, but a mild bleeding tendency is observed in high dose therapy of B-cell malignancies with ibrutinib and novel second-generation irreversible Btk inhibitors (acalabrutinib and ONO/GS-4059). This review discusses recent studies that may explain this apparent paradox and gives mechanistic insights that suggest a unique potential of low dose irreversible Btk inhibitors as atherothrombosis-focused antiplatelet drugs.
布鲁顿酪氨酸激酶（Btk）对于 B 细胞的分化和增殖是必需的，但血小板也表达 Btk。由于遗传性 Btk 缺乏导致的 X 连锁无丙种球蛋白血症患者不会出现出血，但在接受伊布替尼和新型第二代不可逆 Btk 抑制剂（阿卡替尼和 ONO/GS-4059）治疗 B 细胞恶性肿瘤的高剂量治疗时，会观察到轻微的出血倾向。这篇综述讨论了最近的研究，这些研究可能解释了这一明显的悖论，并提供了机制上的见解，表明低剂量不可逆 Btk 抑制剂作为动脉血栓形成为重点的抗血小板药物具有独特的潜力。
