Measurement of endogenous and exogenous alpha-granular platelet proteins in patients with immune and nonimmune thrombocytopenia

Idiopathic thrombocytopenic purpura (ITP) is caused by antiplatelet antibod ies and is characterized by increased platelet destruction and elevated lev els of IgG (platelet-associated IgG, PAIgG). Nonimmune thrombocytopenic pat ients also have elevated levels of PAIgG. In this study we investigated two possible biological explanations for the increased levels of PAIgG in thes e patients. The first hypothesis suggests that a thrombocytopenic stress ca uses increased thrombocytopotesis with increased numbers and content of the platelet alpha granules. The second hypothesis is that for uncertain reaso ns (immunological or cytokine) there is increased absorption of plasma prot eins by either megakaryocytes or by the platelets themselves. To address th is issue, we compared the level of megakaryocyte synthesized alpha granular proteins [platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG)] to p lasma-absorbed alpha granular proteins (albumin, IgG and fibrinogen) in pat ients with immune (n=39) and nonimmune (n=60) thrombocptopenias. Plasma-abs orbed alpha-granular proteins were elevated in both immune and nonimmune th rombocytopenia with no increase in megakaryocyte synthesized alphagranular proteins. These plasma-derived protein elevations were not attributable to elevated mean platelet volumes or elevated plasma concentrations of the res pective protein. We hypothesize that the increased IgG in these platelets i s not the result of production of larger platelets, but reflects a selectiv e increase in the endocytosis of plasma-absorbed alpha-granular proteins at the megakaryocyte and/or platelet level.