Department of Hematology, Zealand University Hospital, Roskilde, Denmark.
Clinic of Vascular and Endovascular Surgery, Düsseldorf, Germany; and.
Blood. 2021 Apr 22;137(16):2152-2160. doi: 10.1182/blood.2020008109.
Thrombotic, vascular, and bleeding complications are the most common causes of morbidity and mortality in the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). In these disorders, circulating red cells, leukocytes, and platelets, as well as some vascular endothelial cells, each have abnormalities that are cell-intrinsic to the MPN driver mutations they harbor (eg, JAK2 V617F). When these cells are activated in the MPNs, their interactions with each other create a highly proadhesive and prothrombotic milieu in the circulation that predisposes patients with MPN to venous, arterial, and microvascular thrombosis and occlusive disease. Bleeding problems in the MPNs are caused by the MPN blood cell-initiated development of acquired von Willebrand disease. The inflammatory state created by MPN stem cells in their microenvironment extends systemically to amplify the clinical thrombotic tendency and, at the same time, preferentially promote further MPN stem cell clonal expansion, thereby generating a vicious cycle that favors a prothrombotic state in these diseases.
血栓形成、血管和出血并发症是费城染色体阴性骨髓增殖性肿瘤（MPN）中发病率和死亡率的最常见原因。在这些疾病中，循环中的红细胞、白细胞和血小板，以及一些血管内皮细胞，都存在与其所携带的 MPN 驱动突变（如 JAK2 V617F）内在相关的异常。当这些细胞在 MPN 中被激活时，它们彼此之间的相互作用在循环中产生了一种高度黏附和促血栓形成的环境，使 MPN 患者易患静脉、动脉和微血管血栓形成和闭塞性疾病。MPN 中的出血问题是由 MPN 血细胞引发的获得性血管性血友病发展而来的。MPN 干细胞在其微环境中产生的炎症状态会系统性地放大临床血栓形成倾向，同时优先促进进一步的 MPN 干细胞克隆扩增，从而产生一个有利于这些疾病中促血栓形成状态的恶性循环。
