IMMUNOREACTIONS INVOLVING PLATELETS. V. POST-TRANSFUSION PURPURA DUE TO A COMPLEMENT-FIXING ANTIBODY AGAINST A GENETICALLY CONTROLLED PLATELET ANTIGEN. A PROPOSED MECHANISM FOR THROMBOCYTOPENIA AND ITS RELEVANCE IN “AUTOIMMUNITY”*

Abstract

A distinct immunologic entity was differentiated from the syndrome of idiopathic thrombocytopenic purpura (ITP) by the finding that sera from 2 patients who developed severe purpura one week after blood transfusion contained an antibody which destroyed the sensitized individual''s own platelets. The mechanism of thrombocytopenia suggested by clinical and experimental observations is that transfused foreign platelet antigen survives in vivo longer than the period of antibody induction, and that antibody, complexed with foreign antigen, is adsorbed by autologous platelets. Platelets with adsorbed antigen-antibody complexes are rendered more susceptible to sequestration. Experimental in vivo infusions of antibody permitted estimating the amounts of antibody and complement (C) adsorbed per platelet when thrombocytopenia developed. Chemical and physical characteristics of the antigen and antigen-antibody complex responsible for the disease, as well as the antigenic properties of the antigen help explain the frequency of occurrence and duration of post-transfusion purpura. Exchange transfusion was found to be effective therapy for the disease. Similarities found between the immunoreactions of post-transfusion and drug purpura permit interpreting the pathogenesis of ITP (and other disorders thought to be "autoimmune") in terms of sensitization by foreign antigens. Fixation of C was found to be a more sensitive test for antibody than platelet agglutination, inhibition of clot retraction, immunofluorescent, and antihuman globulin consumption techniques. By means of quantitative C'' fixation reactions and geneologic studies, the antigen content of 3 platelet phenotypes was differentiated, there being a clear cut proportionality between gene dose and quantity of antigen per cell. The antigen, labelled P1A1, is controlled by a gene capable of expressing itself in a single or double dose. Phenotypes could be translated directly into genotypes P1A1 P1A1, P1A1 P1 and P1 P1 which have a frequency in the general population of 75%, 23% and 2%, respectively. Suggestions for a uniform notation of platelet antigen systems were made. The method of phenotyping used appears to be applicable to other types of cells.