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.
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.
Authors: L M Calvi; G B Adams; K W Weibrecht; J M Weber; D P Olson; M C Knight; R P Martin; E Schipani; P Divieti; F R Bringhurst; L A Milner; H M Kronenberg; D T Scadden Journal: Nature Date: 2003-10-23 Impact factor: 49.962
Authors: Zhi-Jian Liu; Karin M Hoffmeister; Zhongbo Hu; Donald E Mager; Sihem Ait-Oudhia; Marlyse A Debrincat; Irina Pleines; Emma C Josefsson; Benjamin T Kile; Joseph Italiano; Haley Ramsey; Renata Grozovsky; Peter Veng-Pedersen; Chaitanya Chavda; Martha Sola-Visner Journal: Blood Date: 2014-03-05 Impact factor: 22.113
Authors: A Balduini; I Pallotta; A Malara; P Lova; A Pecci; G Viarengo; C L Balduini; M Torti Journal: J Thromb Haemost Date: 2008-08-22 Impact factor: 5.824
Authors: Viktoria Rumjantseva; Prabhjit K Grewal; Hans H Wandall; Emma C Josefsson; Anne Louise Sørensen; Göran Larson; Jamey D Marth; John H Hartwig; Karin M Hoffmeister Journal: Nat Med Date: 2009-09-27 Impact factor: 53.440
Authors: Marzieh Ezzaty Mirhashemi; Ravi V Shah; Robert R Kitchen; Jian Rong; Aferdita Spahillari; Alexander R Pico; Olga Vitseva; Daniel Levy; Danielle Demarco; Sajani Shah; Mark D Iafrati; Martin G Larson; Kahraman Tanriverdi; Jane E Freedman Journal: Arterioscler Thromb Vasc Biol Date: 2020-12-10 Impact factor: 8.311
Authors: Jonathan I Silverberg; Eric L Simpson; Jacob P Thyssen; Melinda Gooderham; Gary Chan; Claire Feeney; Pinaki Biswas; Hernan Valdez; Marco DiBonaventura; Chudy Nduaka; Ricardo Rojo Journal: JAMA Dermatol Date: 2020-08-01 Impact factor: 10.282