FETAL BLEEDING IN NEONATAL ALLOIMMUNE THROMBOCYTOPENIA MEDIATED BY ANTI-PL(AL) IS NOT ASSOCIATED WITH INHIBITION OF FIBRINOGEN BINDING TO PLATELET GPIIB IIIA/
Wv. Beadling et al., FETAL BLEEDING IN NEONATAL ALLOIMMUNE THROMBOCYTOPENIA MEDIATED BY ANTI-PL(AL) IS NOT ASSOCIATED WITH INHIBITION OF FIBRINOGEN BINDING TO PLATELET GPIIB IIIA/, American journal of clinical pathology, 103(5), 1995, pp. 636-641
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.