Blood Journal
Leading the way in experimental and clinical research in hematology

Autoimmune thrombocytopenic purpura

  1. S Karpatkin

Abstract

Adult autoimmune throbocytopenic purpura (ATP) is a platelet disorder that develops in certain individuals with a genetic as well as sex (female) predisposition following an environment event (?viral). This results in the production of an IgG antiplatelet antibody capable of reacting with the host's platelets, as well as crossing the placenta. This leads to the rapid clearance and destruction of opsonized platelets by the reticuloendothelial system, particularly the spleen, by greater than tenfold the normal rate. Bound platelet IgG correlates with disease severity, whereas serum antiplatelet IgG does not. It has not been rigorously established whether bound platelet IgG is directed against a platelet antigen or represents an immune complex bound to the platelet Fc receptor. Nevertheless, several lines of evidence suggest that antiplatelet IgG binds directly to a platelet antigen(s). Megakaryocyte number, volume, and mass are increased commensurate with increased platelet turnover. Platelets of increased size, megathrombocytes, are noted on peripheral smear or via platelet volume distribution analysis. Megathrombocyte number is proporationate to megakarocyte number and to platelet turnover. Megathrombocyte diameter is inversely proportional to platelet survival. Antiplatelet antibody is also associated with qualitative platelet functional defects, which are indistinguishable from those noted with thrombopathia (i.e., apparent platelet release defect). Antibody-induced functional defects are probably more common than quantitative thrombocytopenic defects and may represent a significant portion of those women with the “easy bruising” syndrome and normal platelet count. Adults who develop ATP generally develop the chronic variety, which remains permanently with the patient. Treatment should be directed towards maintaining the patient free of purpura, not restoring the platelet count to normal. This can generally be accomplished with a platelet count of < 40,000/cu mm with patients having this disorder. Approximately 50% of patients respond to steroids by a significant elevation of platelet count and improvement of purpura. However, cessation of therapy results in eventual relapse if the disease is of the chronic variety. Splenectomy is successful in approximately 65–75% of patients, resulting in a restoration of the platelet count to normal or safe levels by removing a major source of platelet destruction as well as antibody production; platelet survival improves. At least 50% of patients “in remission” following steroids or splenectomy generally have a compensated thrombocytolytic state in which increased platelet production keeps up with increased platelet destruction. Antiplatelet IgG can often be found in the serum of these patients. Patients refractory to steroids and/or splenectomy present with a serious therapeutic problem. Immunosuppressive therapy is effective in approximately one-third of refractory patients, but often relapses occur, requiring maintenance therapy with potentially mutagenic drugs...