Studies on platelets. IX. Observations on the properties and mechanism of action of a potent platelet agglutinin detected in the serum of a patient with idiopathic thrombocytopenic purpura, with a note on the pathogenesis of the disease.

Abstract 1. A case of chronic idiopathic thrombocytopenic purpura (I.T.P.) exhibited a circulating platelet agglutination of high titer. This could be demonstrated not only through its ability to clump various platelet preparations at extremely high titers, but also to interfere with the functional activity of normal platelets. The agglutinin could be absorbed upon packed platelets and, when eluted from them, its agglutinating activity remained intact. Platelets obtained from the patient were found to be “coated” by an agent capable of reacting with anti-human globulin rabbit serum. Complement played no role in the reaction of agglutinin and platelets. Various properties of the agglutinin were established and this was also characterized and purified by electrophoretic technics. The agglutinin was found to be in the β2 globulin area and to represent 9.33 per cent of the entire serum protein. All indications pointed to the characterization of the agglutinin as a platelet iso- (and auto-) antibody, although this could not be definitely proven. 2. Platelets injected into the circulation of the patient disappeared very promptly. When the patient’s plasma was injected into normal recipients, a series of effects followed: (a) striking degenerative changes of the bone marrow megakaryocytes with lack of formation of platelets; (b) an extreme degree of platelet reduction with the development of hemorrhagic phenomena; (c) detectable platelet agglutinin in the recipient’s serum persisting for twelve to fourteen days. The recipient platelets were also found to be coated with a substance capable of reacting with antihuman globulin rabbit serum (positive Coombs test). 3. Various procedures including the administration of cortisone and splenectomy failed to modify the thrombocytopenic response of normal recipients to the patient’s plasma, although appreciable individual variations in thrombocytopenic response were observed. Repeated venesections, however, resulted in a definite reduction in the concentration of platelet agglutinin. The titer of agglutinin in the patient remained unmodified after splenectomy. 4. Splenectomy was followed by a complete arrest of the bleeding manifestations and a temporary rise in the platelet count, which soon fell to a relatively low level, although somewhat higher than that prior to splenectomy. Prothrombin utilization during clotting and capillary fragility slowly returned to normal. On the other hand, the appearance of the platelets in the peripheral blood and of the bone marrow megakaryocytes remained unmodified, and the bleeding time remained prolonged. 5. The response of splenectomized recipients to the patient’s plasma was of the same immediate intensity, but of much shorter duration than that of normal recipients. Since, furthermore, splenectomy induced a moderate rise in the patient’s platelet count, but failed to reduce the concentration of the serum platelet agglutinin, it is postulated that, in this particular case, the thrombocytopenia was probably due to the direct injury of circulating platelets and of the bone marrow megakaryocytes by the circulating agglutinin, thus resulting not only in increased destruction but in reduced formation and release of platelets. Some of our experimental results in animals also indicate the possibility of removal of “sensitized” injured platelets by the intact spleen.