FETAL BLEEDING IN NEONATAL ALLOIMMUNE THROMBOCYTOPENIA MEDIATED BY ANTI-PL(AL) IS NOT ASSOCIATED WITH INHIBITION OF FIBRINOGEN BINDING TO PLATELET GPIIB IIIA/

Antibody directed against the platelet-specific alloantigen, Pl(A1), i s the most frequently reported cause of two syndromes, post-transfusio n purpura (PTP), and neonatal alloimmune thrombocytopenia (NAIT). Nume rous reports have indicated that anti-Pl(A1) also has the ability to b lock certain responses of platelets to stimulation, including fibrinog en binding, platelet aggregation, and serotonin release. Because the P l(A1) epitope is located on platelet membrane glycoprotein (GP) IIb/II Ia that also contains the fibrinogen receptor, these effects may be me diated by antibody binding at or near the fibrinogen receptor site. Th is study examines the capacity of anti-Pl(A1) from patients with PTP a nd from mothers of infants affected by the NAIT to block the binding o f radio-labeled fibrinogen to washed human platelets stimulated by ADP and epinephrine. In sis of the seven PTP patients, there was inhibiti on of fibrinogen binding, ranging from 28% to 84% inhibition. In contr ast, all anti-Pl(A1) sera from nine mothers of infants with NAIT, incl uding four with intracranial hemorrhage, failed to inhibit fibrinogen binding, Despite the generally higher anti-Pl(A1) titers of the PTP se ra, the ability to inhibit fibrinogen binding did not appear attributa ble to antibody titers. These results suggest that interference with f ibrinogen binding to platelets by maternal anti-Pl(A1) does not underl ie the increased risk of bleeding in NAIT, whereas inhibitory activity directed against fibrinogen binding appears to be a characteristic fe ature of the sera from PTP patients.