Mantha Simon, Tallman Martin S, Soff Gerald A
Memorial Sloan Kettering Cancer Center, New York, USA.
Curr Opin Hematol. 2016 Mar;23(2):121-6. doi: 10.1097/MOH.0000000000000221.
Acute promyelocytic leukemia (APL) is associated with a complex coagulopathy. In spite of substantial recent improvements in treatment regimens, hemorrhagic death remains the main cause of induction failure. In this review, we delineate recent understanding of the pathophysiology and management of the hemorrhagic diathesis of APL.
Laboratory and clinical data suggest that the malignant leukocytes mediate the hemorrhagic diathesis associated with APL through multiple mechanisms which lead to a combination of consumptive coagulopathy and primary hyperfibrinolysis. Exposure of tissue factor and Annexin II by the leukemic blasts is the main determinants of these processes. Promyelocyte-derived microparticles have recently been implicated in the coagulopathy as well. Total white cell count and platelet count have emerged as good general predictors of hemorrhagic death, along with the different routine hemostatic parameters. Prompt treatment with all-trans retinoic acid, with or without arsenic trioxide, is the most important step in preventing bleeding complications. Repletion of coagulation factors and platelets with blood products remains the mainstay of supportive treatment, whereas the role of recombinant soluble thrombomodulin is currently being investigated.
The coagulopathy of APL is multifactorial, with both disseminated intravascular coagulation and primary hyperfibrinolysis mediated largely by the malignant leukocytes.
急性早幼粒细胞白血病（APL）与复杂的凝血病相关。尽管近期治疗方案有了显著改进，但出血性死亡仍是诱导治疗失败的主要原因。在本综述中，我们阐述了对APL出血素质病理生理学和管理的最新认识。
实验室和临床数据表明，恶性白细胞通过多种机制介导与APL相关的出血素质，这些机制导致消耗性凝血病和原发性纤溶亢进的联合。白血病原始细胞暴露组织因子和膜联蛋白II是这些过程的主要决定因素。早幼粒细胞衍生的微粒最近也与凝血病有关。白细胞总数和血小板计数以及不同的常规止血参数已成为出血性死亡的良好总体预测指标。全反式维甲酸的及时治疗，无论是否联合三氧化二砷，是预防出血并发症的最重要步骤。用血液制品补充凝血因子和血小板仍然是支持治疗的主要手段，而重组可溶性血栓调节蛋白的作用目前正在研究中。
APL的凝血病是多因素的，弥散性血管内凝血和原发性纤溶亢进主要由恶性白细胞介导。
