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Cited by 66Platelet Disorders and TreatmentsMyeloproliferative Neoplasms: Diagnosis and TreatmentBlood Coagulation and Thrombosis Mechanisms

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Novel mechanisms of platelet clearance and thrombopoietin regulation

Open access
Grozovsky, Renata, Giannini, Silvia, Falet, Hervé, Hoffmeister, Karin M.·2015·Current Opinion in Hematology
DOI 10.1097/moh.0000000000000170PMC PMC5326579
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Abstract

PURPOSE OF REVIEW: The human body produces and removes 10 platelets daily to maintain a normal steady-state platelet count. Platelet production must be tightly regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Multifaceted and complex mechanisms control platelet removal and production in physiological and pathological conditions. This review will focus on different mechanisms of platelet clearance, with focus on the biological significance of platelet glycans. RECENT FINDINGS: The Ashwell-Morrell receptor (AMR) recognizes senescent, desialylated platelets under steady state conditions. Desialylated platelets and the AMR are the physiological ligand-receptor pair regulating hepatic thrombopoietin (TPO) mRNA production, resolving the longstanding mystery of steady state TPO regulation. The AMR-mediated removal of desialylated platelets regulates TPO synthesis in the liver by recruiting JAK2 and STAT3 to increase thrombopoiesis. SUMMARY: Inhibition of TPO production downstream of the hepatic AMR-JAK2 signaling cascade could additionally contribute to the thrombocytopenia associated with JAK1/2 treatment, which is clinically used in myeloproliferative neoplasms.

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Metadata

Authors
Grozovsky, R., Giannini, S., Falet, H., & Hoffmeister, K. M.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Hoffmeister, Karin M.
ORCID
Venue
Current Opinion in Hematology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2015-09
Volume
22
Issue
5
Pages
445-451
ISSN
1065-6251 (ISSN-L)
DOI
10.1097/moh.0000000000000170
PMC
PMC5326579
OpenAlex
W2404121852
Cited by
66
References
6
Citations by year
2026: 2 · 2025: 5 · 2024: 4 · 2023: 10 · 2022: 13 · 2021: 11 · 2020: 9 · 2019: 7 · 2018: 2 · 2017: 3
FWCI
0.25
Type
journal article
Language
en
Open access
Locations
  • Current Opinion in Hematology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Heart, Lung, and Blood Institute (HL089224, R01HL126743, HL107146, P01HL107146, R01HL089224)
Topics
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
  • Health Sciences › Medicine › Hematology › Myeloproliferative Neoplasms: Diagnosis and Treatment
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
platelet clearance, JAK2 signaling, STAT3, megakaryopoiesis, thrombocytopenia, JAK1/2 inhibitor, myeloproliferative neoplasms
MeSH terms
Blood Platelets, Humans, Liver, Platelet Count, RNA, Messenger, Thrombocytopenia, Thrombopoietin, Signal Transduction, Cellular Senescence, Thrombopoiesis, STAT3 Transcription Factor, Janus Kinase 2

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