title: Measurement of endogenous and exogenous alpha-granular platelet proteins in patients with immune and nonimmune thrombocytopenia.
abstract: Idiopathic thrombocytopenic purpura (ITP) is caused by antiplatelet antibodies and is characterized by increased platelet destruction and elevated levels of IgG (platelet-associated IgG, PAIgG). Nonimmune thrombocytopenic patients also have elevated levels of PAIgG. In this study we investigated two possible biological explanations for the increased levels of PAIgG in these patients. The first hypothesis suggests that a thrombocytopenic stress causes increased thrombocytopoiesis with increased numbers and content of the platelet alpha granules. The second hypothesis is that for uncertain reasons (immunological or cytokine) there is increased absorption of plasma proteins by either megakaryocytes or by the platelets themselves. To address this issue, we compared the level of megakaryocyte synthesized alpha granular proteins [platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG)] to plasma-absorbed alpha granular proteins (albumin, IgG and fibrinogen) in patients with immune (n = 39) and nonimmune (n = 60) thrombocytopenias. Plasma-absorbed alpha-granular proteins were elevated in both immune and nonimmune thrombocytopenia with no increase in megakaryocyte synthesized alpha-granular proteins. These plasma-derived protein elevations were not attributable to elevated mean platelet volumes or elevated plasma concentrations of the respective protein. We hypothesize that the increased IgG in these platelets is not the result of production of larger platelets, but reflects a selective increase in the endocytosis of plasma-absorbed alpha-granular proteins at the megakaryocyte and/or platelet level.
authors.affiliation: Department of Pathology, Faculty of Health Sciences, McMaster University Division, Hamilton, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Hughes
authors.forename: C P
authors.initials: CP
authors.lastname: Hayward
authors.forename: P
authors.initials: P
authors.lastname: Horsewood
authors.forename: T E
authors.initials: TE
authors.lastname: Warkentin
authors.forename: J G
authors.initials: JG
authors.lastname: Kelton
mesh_terms: D000418:Albumins / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood*
chemical_list: D000418:Albumins; D007074:Immunoglobulin G; D005340:Fibrinogen