Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht.
Thrombosis Expertise Center, Heart and Vascular Center, Maastricht University Medical Center, Maastricht.
Haematologica. 2020 Aug;105(8):2020-2031. doi: 10.3324/haematol.2019.235994. Epub 2020 Jun 18.
Platelets are key elements in thrombosis, particularly in atherosclerosis-associated arterial thrombosis (atherothrombosis), and hemostasis. Megakaryocytes in the bone marrow, differentiated from hematopoietic stem cells are generally considered as a uniform source of platelets. However, recent insights into the causes of malignancies, including essential thrombocytosis, indicate that not only inherited but also somatic mutations in hematopoietic cells are linked to quantitative or qualitative platelet abnormalities. In particular cases, these form the basis of thrombo-hemorrhagic complications regularly observed in patient groups. This has led to the concept of clonal hematopoiesis of indeterminate potential (CHIP), defined as somatic mutations caused by clonal expansion of mutant hematopoietic cells without evident disease. This concept also provides clues regarding the importance of platelet function in relation to cardiovascular disease. In this summative review, we present an overview of genes associated with clonal hematopoiesis and altered platelet production and/or functionality, like mutations in We consider how reported CHIP genes can influence the risk of cardiovascular disease, by exploring the consequences for platelet function related to (athero)thrombosis, or the risk of bleeding. More insight into the functional consequences of the CHIP mutations may favor personalized risk assessment, not only with regard to malignancies but also in relation to thrombotic vascular disease.
血小板是血栓形成的关键因素，特别是在动脉粥样硬化相关的动脉血栓形成（动脉血栓形成）和止血中。骨髓中的巨核细胞由造血干细胞分化而来，通常被认为是血小板的统一来源。然而，最近对包括原发性血小板增多症在内的恶性肿瘤病因的深入了解表明，不仅是遗传性的，而且造血细胞的体细胞突变也与血小板数量或质量异常有关。在某些情况下，这些是经常在患者群体中观察到的血栓-出血并发症的基础。这导致了不确定潜能的克隆性造血（CHIP）的概念，定义为突变造血细胞克隆性扩增而没有明显疾病的体细胞突变。这一概念还为血小板功能与心血管疾病之间的关系的重要性提供了线索。在这篇综述中，我们概述了与克隆性造血和改变的血小板生成和/或功能相关的基因，如基因突变。我们考虑了报告的 CHIP 基因如何通过探索与（动脉）血栓形成相关的血小板功能或出血风险来影响心血管疾病的风险。对 CHIP 突变的功能后果的更多了解可能有利于个性化风险评估，不仅与恶性肿瘤有关，而且与血栓性血管疾病有关。
