Isoimmune Neonatal Thrombocytopenic Purpura. Clinical and Therapeutic Considerations.

SYMPTOMATI C thrombocytopenia occurring in the neonatal period is a potentially serious disorder resulting in death in approximately 14 per cent of reported cases.1'2 Some affected infants are born of mothers who have, or have had, idiopathic thrombocytopenic purpura (ITP) In these cases it is assumed that a thrombocytopenic factor is transmitted to the fetus across the placenta, but the nature of this humoral factor (possibly anti-body) is still obscure. In about 20 per cent of the reported cases of neonatal thrombocytopenia, there is no history of maternal hematologic disease. In such instances an immune etiologic mechanism involving maternal-fetal incompatibility of platelet antigens, analogous to incompatibility of erythrocyte antigens in erythroblastosis fetalis, has been suspected.4 However, reliable and reproducible technics for demonstrating antibodies against platelet antigens have not been generally available, and in many instances it has been impossible to establish an immune basis for neonatal thrombocytopenia in infants born of normal mothers. Recently, sensitive technics based on complement fixation have been developed for detecting and characterizing anti-platelet isoantibodies.57 Definite isoantibodies against specific platelet antigens have been demonstrated in sera of hematologically normal mothers who had given birth to thrombo-cytopenic infants.6 In all cases these antibodies were active against specific antigens present on the platelets of both the infant and the father but absent from the mother's platelets. None of these isoantibodies could be detected with certainty by the agglutination procedures which have been used in previous studies of neonatal thrombocytopenia. This report describes the clinical course of neonatal thrombocytopenic purpura in nine infants from six families in which serologic findings indicated an isoimmune etiology. Correlation of hematologic and serologic findings and results of experimental therapy provide a basis for diagnosis and evaluating treatment of this disorder more effectively. MATERIALS AND METHODS Measurement of Antibodies The complement fixation technics used to measure isoantibodies against platelet anti-gens have been described in detail in previous reports.'7 Accuracy and sensitivity of the ISOIMMUNE NEONATAL THROMBOCYTOPENIC PURPURA 155 methods are due primarily to the use of a quantitative, rather than qualitative, comple-nn ent assay and to the careful selection of appropriate cell and serum concentrations to assure optimal ratios for maximum complement fixation. Antibodies against three different well-characterized platelet antigen systems have been found in mothers sensitized during pregnancy. Antibodies against these same antigens have also been found in individuals sensitized by transfusion (table 1).7 All of the platelet antigens identified by these anti-bodies …