Regulating billions of blood platelets: glycans and beyond

Abstract

The human body produces and removes 1011 platelets daily to maintain a normal steady state platelet count. Platelet production must be regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Multifaceted and complex mechanisms control platelet production and removal in physiological and pathological conditions. This review will focus on different mechanisms of platelet senescence and clearance with specific emphasis on the role of posttranslational modifications. It will also briefly address platelet transfusion and the role of glycans in the clearance of stored platelets.

Contribution of Human Thrombospondin-1 to the Pathogenesis of Gram-Positive Bacteria

“…They therefore come into contact with platelets, which are the most abundant cells after red blood cells, with a concentration ranging from 150 to 400 × 10 9 platelets/L in healthy humans [83, 84]. The classical physiological function of platelets is the immediate binding to the exposed subendothelium of damaged blood vessels, aggregation, and thrombus formation to prevent excessive bleeding [85, 86].…”

An incomplete trafficking defect to the cell-surface leads to paradoxical thrombocytosis for human and murine MPL P106L

“…1,2 Hereditary thrombocytosis (HT) and essential thrombocythemia (ET) are 2 forms of chronic thrombocytosis associated with genetic alterations targeting this axis. 3,4 Both HT and ET can be the consequence of germ line or sporadic activating mutations in JAK2 and MPL.…”

Platelet production: new players in the field

“…However, modern approaches have facilitated haplo BMT, including T-cell-depleted "megadose" CD34 1 allografting, granulocyte colony-stimulating factor-primed T-cell-replete allografting with intensive pharmacologic GVHD prophylaxis, and T-cell-replete allografting with PTCy-based GVHD prophylaxis. 3 Over the last couple of years, a growing body of literature has emerged from multiple groups in the United States and Europe indicating that haplo BMT using PTCy results in outcomes on par with those using HLAmatched donors. [4][5][6] A recent comparison of BMT outcomes for acute myeloid leukemia showed equivalent survival but less acute and chronic GVHD for haplos with PTCy compared with MUD allografts.…”

“…Postnatal platelet production is centered on the bone marrow, where mature megakaryocytes (MKs) move to sinusoids and extend long processes (proplatelets) that shed platelets into the bloodstream, 2 where they can circulate for several days. The regulation of platelet production, or thrombopoiesis, has recently been reviewed in Blood, 3 and although recent findings have added new complexities, the process as it proceeds under normal circumstances can still be depicted in a fairly simple manner.…”