BRAF 抑制剂的出血并发症
G Gurumurthy1, J Kropidlowska2, L Reynolds3
1The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust, Kings Lynn, UK.
概括
BRAF 抑制剂可以改善黑色素瘤的结果,但可以导致出血,包括罕见的致命事件. 管理包括风险评估,患者咨询和针对出血并发症的量身定制干预措施.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 血管生物学 血管生物学
背景情况:
- BRAF抑制剂是BRAF变体黑色素瘤的关键治疗方法.
- 已报告与BRAF抑制剂相关的临床显著出血事件.
- 该机制涉及到内皮中矛盾的MAPK激活,导致微血管泄漏和潜在的血凝活性降低.
研究的目的:
- 审查与BRAF抑制剂相关的出血的发生率和机制.
- 为经历出血事件的患者概述管理策略.
- 讨论继续治疗,停止治疗和重新开始治疗的考虑因素.
主要方法:
- 在BRAF抑制剂试验中报告的出血事件的文献综述.
- 对BRAF抑制剂诱导出血的建议机制的分析.
- 综合当前的管理原则和证据缺口.
主要成果:
- 出血是BRAF抑制剂的不常见但异质的副作用,罕见的等级≥3事件和致命的内出血.
- 矛盾的是,BRAF抑制剂可能会激活内皮中的MAPK信号,破坏结节的稳定,并导致微血管泄漏.
- BRAF 抑制剂也可能降低组织因子依赖的血凝活性.
结论:
- 管理需要基线出血风险评估,包括中枢神经系统疾病和抗血栓使用.
- 低度出血可以通过局部静血和持续治疗来管理,而主要/内出血需要暂停和多学科输入.
- 重复治疗的证据有限;在轻微事件后恢复可能是可能的剂量修改,但重大出血通常需要停止治疗.
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