Clonal hematopoietic mutations linked to platelet traits and the risk of thrombosis or bleeding

Alicia Veninga, Ilaria De Simone, Johan W. M. Heemskerk, Hugo Ten Cate, Paola E. J. van der Meijden*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

18 Citations (Web of Science)
9 Downloads (Pure)

Abstract

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 JAK2. 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.

Original languageEnglish
Pages (from-to)2020-2031
Number of pages12
JournalHaematologica-the Hematology Journal
Volume105
Issue number8
DOIs
Publication statusPublished - 1 Aug 2020

Keywords

  • WISKOTT-ALDRICH SYNDROME
  • ACUTE MYELOID-LEUKEMIA
  • MYELOPROLIFERATIVE NEOPLASMS
  • ACCELERATES ATHEROSCLEROSIS
  • MEGAKARYOCYTE DEVELOPMENT
  • MYELODYSPLASTIC SYNDROMES
  • DEFICIENCY
  • MEGAKARYOPOIESIS
  • GENE
  • PROTEIN

Cite this