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Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2280-2287
The Natural History of Fetomaternal Alloimmunization to the
Platelet-Specific Antigen HPA-1a (PlA1, Zwa) as
Determined by Antenatal Screening
Lorna M. Williamson,
Gerald Hackett,
Janet Rennie,
Christopher R. Palmer,
Caroline Maciver,
Ruth Hadfield,
Darren Hughes,
Shirley Jobson, and
Willem H. Ouwehand
From the Division of Transfusion Medicine, University of Cambridge,
Cambridge, UK; the National Blood Service, East Anglia and Birmingham
Centres, UK; the Departments of Obstetrics and Paediatrics,
Addenbrooke's Hospital, Cambridge, UK; Centre for Applied Medical
Statistics, Department of Community Medicine, University of Cambridge,
Cambridge, UK; and the National Institute for Biological Standards and
Controls, Potters Bar, UK.
Immunization against the human platelet antigen (HPA)-1 alloantigen
is the most common cause of severe fetal and neonatal thrombocytopenia.
Fetal therapy has substantial risks and its indications need better
definition. Of 24,417 consecutive pregnant women, 618 (2.5%) were
HPA-1a negative of whom 385 entered an observational study. All were
HLA-DRB3*0101 genotyped and screened for anti-HPA-1a. Their partners
and neonates were HPA-1 genotyped and the latter were assessed by cord
blood platelet counts and cerebral ultrasound scans. Anti-HPA-1a was
detected in 46 of 387 pregnancies (12.0%; 95% CI 8.7%-15.2%). All
but one were HLA-DRB3*0101 positive (odds ratio 140; 95% CI 19-1035;
P< .00001). One baby died in utero, and of 26 HPA-1a-positive babies born to women with persistent antenatal
antibodies, 9 were severely thrombocytopenic (8 with a count <10 × 109/L, 1 with a large porencephalic cyst), 10 were mildly
thrombocytopenic, whereas 7 had normal platelet counts. Severe
thrombocytopenia was significantly associated with a third trimester
anti-HPA-1a titer  1:32 (P = .004), but was not observed
in babies of women with either transient or postnatal-only antibodies.
HPA-1a alloimmunization complicates 1 in 350 unselected pregnancies,
resulting in severe thrombocytopenia in 1:1,200. HPA-1a and
HLA-DRB3*0101 typing combined with anti-HPA-1a titration allows
selection of the majority of pregnancies at risk of severe
thrombocytopenia.
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