Neonatal alloimmune thrombocytopenia in the Irish population: a discrepancy between observed and expected cases. (Original Article).

Aims: To estimate the rate of detection of neonatal alloimmune thrombocytopenia (NAITP) in the Irish population, to investigate clinical presentation and outcome in affected infants, and to determine the extent, if any, to which this condition is underdiagnosed at present.

Methods: Cases were collected in a retrospective fashion from a review of platelet serology laboratory records from January 1992 to December 2000. Clinical data were obtained from hospital records. Testing for maternal antiplatelet antibody was by one or more of the following: the platelet suspension immunofluorescence test, a commercial antigen capture enzyme linked immunosorbent assay (GTI-PakPlus[R]), and the monoclonal antibody immobilisation of platelet antigens assay. Platelet antigen typing was by the polymerase chain reaction technique with sequence specific primers.

Results: Twenty seven serologically verified cases of NAITP were identified in 18 families. Maternal antibody to human platelet antigen 1 a accounted for 25 of the 27 confirmed cases. Twenty one of 26 infants were born with severe thrombocytopenia. Nineteen of 27 infants had bleeding manifestations at birth. Petechiae and bruising were most commonly observed (n = 17). There were no documented cases of intracranial haemorrhage in this group but systematic cranial ultrasound was not performed.

Conclusions: Screening studies in predominantly white populations have estimated the incidence of NAITP to be between 1 in 1000 and 1 in 2000 live births. With 50 000 births each year in Ireland, these results give a clinical detection rate for NAITP of just 1 case in 16 500 live births, strongly suggesting that NAITP is currently underdiagnosed. Antenatal screening to detect women at risk of having babies with NAITP is now scientifically feasible and should be considered.

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Neonatal alloimmune thrombocytopenia (NAITP) is the platelet equivalent of haemolytic disease of the newborn (HDN), and is the most common cause of severe neonatal thrombocytopenia in otherwise well term infants. (1) NAITP is the result of maternal alloimmunisation to antigens on fetal platelets. The resultant transplacental passage of maternal IgG antibodies causes accelerated destruction of fetal/neonatal platelets, with resultant thrombocytopenia and bleeding manifestations. Maternal alloimmunisation to human platelet antigen Ia (HPA-la) in a mother homozygous for the alternative allele, HLA-lb, accounts for most (85-90%) cases of NAITP in white individuals, followed at a much lower frequency by anti-HPA 5b. (2)

HPAs are polymorphic platelet surface glycoproteins. There are five well characterised biallelic platelet alloantigen systems, in addition to several low frequency or private antigens. HPA systems are named alphabetically, with the high incidence allele first (a) and the lower incidence allele second (b). The molecular basis of platelet glycoprotein polymorphisms is a single nucleotide substitution in the DNA coding for the relevant glycoprotein. (3)

Platelet antigen typing or screening for platelet specific alloantibodies is not part of routine antenatal care. Therefore, NAITP is usually diagnosed only after the birth of a first clinically affected infant. Symptoms range from asymptomatic thrombocytopenia to intracranial haemorrhage (ICH). The latter can result in death of the fetus/neonate or residual brain damage. (2 4 5) Unlike HDN, NAITP affects first …