Neonatal alloimmune thrombocytopenia due to a new platelet-specific alloantibody

Abstract

An infant with severe neonatal alloimmune thrombocytopenia is described in whom an antibody directed at a new platelet-specific alloantigen, Ca (HPA-6b), is implicated. The new alloantigen is of low frequency in the population and was localized to platelet glycoprotein (GP) IIIa. Immunoprecipitation studies using murine monoclonal antibodies specific for the GP complex IIb-IIIa and GPIIIa alone (AP2 and AP3) suggest that the location of the Ca epitope on GPIIIa may be near the binding site for AP3. Neonatal alloimmune thrombocytopenia associated with Ca is likely to be as severe as that seen in cases due to incompatibilities for the HPA-1 (PIA) and HPA-4 (Pen) platelet alloantigen systems, because each is located on GPIIIa, a densely represented molecule on the platelet surface.

Maternal DRB1*1501, DQA1*0102, DQB1*0602 haplotype in fetomaternal alloimmunization against human platelet alloantigen HPA‐6b (GPIIIa‐G1n489)

“…Both these DR antigens associate with the DQA1*0102 allele, which thus may be the major susceptibility allele for AIN against NA1. Interestingly, the mother E of this study had twins of whom one suffered from NAIT and the other from AIN due to NA1 antibodies (8).…”

“…The biallelic amino acid residue Arg/Gln 489 of GPIIIa is the basis for HPA-6 (Tu/Ca) polymorphism (5). which has recently been recognized to associate with fetomaternal alloimmunization (6)(7)(8). The Gln 459 residue associates with the HPA-6b alloantigenic epitope.…”

The Arg633His substitution responsible for the private platelet antigen Groa unravelled by SSCP analysis and direct sequencing

“…The GP IIIa (b 3 ) subunit of the glycoprotein (GP) IIb/IIIa complex (Ginsberg et al, 1988;Phillips et al, 1991) (also known as the integrin a IIb b 3 ) (Hynes, 1987), which functions as a fibrinogen receptor on platelets, carries the majority of these alloantigen determinants, i.e. those belonging to the HPA-1, -4, -6W, -7W, -8W systems (van der Schoot et al, 1986;Rosa & McEver, 1989;McFarland et al, 1993;Kuijpers et al, 1993;Kroll et al, 1990). The recently described private platelet antigen Gro a also resides on GP IIIa (Simsek et al, 1994b).…”

Alloimmunization against ly, a Low-Frequency Antigen on Platelet Glycoprotein Ib/IX as a Cause of Severe Neonatal Alloimmune Thrombocytopenic Purpura

“…This corresponds to a common strategy in red blood cell serology. In the meantime, other 'low-frequency' platelet alloantigens against epitopes on the platelet GP Ilb/llIa complex have been found in conjunction with the clinical condition of NAIT: Va" [14], Tu" [15], which is serologically indistinguishable from Ca [16], Mo [17], Gro [18], Max" [19] and La" [20]. These antigens reflect a high degree of genetic po- lymorphism of the GP IIb/IIIa complex.…”