title: The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening.
abstract: 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 x 10(9)/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.
authors.affiliation: Division of Transfusion Medicine, University of Cambridge, Cambridge, UK. lorna.williamson@nbs.nhs.uk
authors.forename: L M
authors.initials: LM
authors.lastname: Williamson
authors.forename: G
authors.initials: G
authors.lastname: Hackett
authors.forename: J
authors.initials: J
authors.lastname: Rennie
authors.forename: C R
authors.initials: CR
authors.lastname: Palmer
authors.forename: C
authors.initials: C
authors.lastname: Maciver
authors.forename: R
authors.initials: R
authors.lastname: Hadfield
authors.forename: D
authors.initials: D
authors.lastname: Hughes
authors.forename: S
authors.initials: S
authors.lastname: Jobson
authors.forename: W H
authors.initials: WH
authors.lastname: Ouwehand
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology; D000328:Adult; D016824:Antigens, Human Platelet / Q000235:genetics / Q000276:immunology*; D002543:Cerebral Hemorrhage / Q000151:congenital / Q000000981:diagnostic imaging / Q000196:embryology / Q000209:etiology; D004739:England / Q000453:epidemiology; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005313:Fetal Death / Q000209:etiology; D005315:Fetal Diseases / Q000000981:diagnostic imaging / Q000209:etiology; D006684:HLA-DR Antigens / Q000235:genetics; D059826:HLA-DRB3 Chains; D006801:Humans; D006849:Hydrocephalus / Q000209:etiology; D007112:Immunity, Maternally-Acquired; D007114:Immunization; D007231:Infant, Newborn; D039661:Integrin beta3; D007518:Isoantibodies / Q000097:blood; D010298:Parity; D010976:Platelet Count; D011237:Predictive Value of Tests; D011247:Pregnancy; D011256:Pregnancy Outcome; D011263:Pregnancy Trimester, Third; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D012307:Risk Factors; D013921:Thrombocytopenia / Q000151:congenital / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D016216:Ultrasonography, Prenatal
chemical_list: D016824:Antigens, Human Platelet; D006684:HLA-DR Antigens; D059826:HLA-DRB3 Chains; C061248:ITGB3 protein, human; D039661:Integrin beta3; D007518:Isoantibodies