» Articles » PMID: 26154508

Novel Mechanisms of Platelet Clearance and Thrombopoietin Regulation

Overview
Specialty Hematology
Date 2015 Jul 9
PMID 26154508
Citations 33
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Plasma concentration of thrombopoietin in dogs with immune thrombocytopenia.

Brooks M, Brooks J, Catalfamo J, Zhu Y, Goggs R, Babasyan S J Vet Intern Med. 2024; 38(5):2507-2517.

PMID: 39143652 PMC: 11423463. DOI: 10.1111/jvim.17152.


Determinants of Variable Total Platelet Count in Healthy Plateletpheresis Donor.

Prakash S, Sahu A, Mishra D, Datta N, Mukherjee S Indian J Hematol Blood Transfus. 2024; 40(3):448-453.

PMID: 39011268 PMC: 11246351. DOI: 10.1007/s12288-023-01721-7.


Predicting Abrocitinib Efficacy at Week 12 Based on Clinical Response at Week 4: A Post Hoc Analysis of Four Randomized Studies in Moderate-to-Severe Atopic Dermatitis.

Armstrong A, F Alexis A, Blauvelt A, Silverberg J, Feeney C, Levenberg M Dermatol Ther (Heidelb). 2024; 14(7):1849-1861.

PMID: 38896380 PMC: 11264490. DOI: 10.1007/s13555-024-01183-3.


Viruses and thrombocytopenia.

Rasizadeh R, Ebrahimi F, Kermanshahi A, Daei Sorkhabi A, Sarkesh A, Nahand J Heliyon. 2024; 10(6):e27844.

PMID: 38524607 PMC: 10957440. DOI: 10.1016/j.heliyon.2024.e27844.


Evaluation of the Effect of Induced Endotoxemia on ROTEM S and Platelet Parameters in Beagle Dogs Anaesthetized with Sevoflurane.

Kutter A, Joerger F, Riond B, Steblaj B Animals (Basel). 2023; 13(19).

PMID: 37835603 PMC: 10572017. DOI: 10.3390/ani13192997.


References
1.
Levine R, Gilliland D . Myeloproliferative disorders. Blood. 2008; 112(6):2190-8. PMC: 2962533. DOI: 10.1182/blood-2008-03-077966. View

2.
LaFave L, Levine R . JAK2 the future: therapeutic strategies for JAK-dependent malignancies. Trends Pharmacol Sci. 2012; 33(11):574-82. DOI: 10.1016/j.tips.2012.08.005. View

3.
Wolber E, Ganschow R, Burdelski M, Jelkmann W . Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood. Hepatology. 1999; 29(6):1739-42. DOI: 10.1002/hep.510290627. View

4.
Liu Z, Hoffmeister K, Hu Z, Mager D, Ait-Oudhia S, Debrincat M . Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. Blood. 2014; 123(22):3381-9. PMC: 4041172. DOI: 10.1182/blood-2013-06-508200. View

5.
Rumjantseva V, Grewal P, Wandall H, Josefsson E, Sorensen A, Larson G . Dual roles for hepatic lectin receptors in the clearance of chilled platelets. Nat Med. 2009; 15(11):1273-80. PMC: 4428152. DOI: 10.1038/nm.2030. View