Discussion

Isolated thrombocytopenia in our Saudi neonate was not initially suspected as NAITP, as there was no history of a previously affected sibling. Other etiologies of thrombocytopenia, including DIC, infection, maternal ITP, consumption hemangioma and drug intake were excluded. Diagnosis of NAIT was virtually confirmed by positive indirect PIFT and spontaneous recovery of the thrombocytopenia. However, identification of the specific platelet alloantigen linked to thrombocytopenia in this infant was confirmed by PCR. This was necessary for counselling the family regarding future pregnancies. It was also relevant for the management of future pregnancies, with or without the need for intrauterine treatment or cesarean delivery. Maternal platelets can be collected in advance for later transfusion to the newborn if NAIT is anticipated. Further genotyping becomes essential in those cases where PIFT or other serological tests are negative.

In our patient's family, the father was heterozygous for HPA-2b, whereas the mother was homozygous for HPA-2a allele. This means that there is a 50% chance of having HPA-2b-positive babies in future pregnancies. This may explain the previous three unaffected children, who were probably homozygous for HPA-2a. It is also remotely possible that the two abortions might well have been due to NAIT, as a result of the heterozygous state of the fetus. However, further pregnancies would be carefully monitored for possible recurrence of the same problem. Among the different platelet alloantigens recently classified by Von dem Borne, 8 the most frequently implicated in Caucasians are HPA-1A (PIA1), accounting for 78%, and HPA-5b (Br), accounting for 19% of cases of NAIT. Thus, HPA-2 (Ko), HPA-3 (Bak) and HPA-4 (Pen) account for only the remaining 3%. 9 The contribution made by various HPA to NAIT appears to be racially determined; the Japanese, for example, have a higher incidence of anti-HPA-4-related NAIT. 7 Anti-HPA-1 is the most commonly reported cause of NAIT. HPA-2 (Ko) system is a rare cause of NAIT. Since the discovery of this system in 1960, only a few cases have been reported. One rare case of prolonged neonatal alloimmune megakaryocytopenia was attributed to anti-HPA-2b. Molecular studies have shown that the two allelic forms of HPA-2 (ie, 2a and 2b) are polymorphic at a single amino acid at position 145 from the N-terminal elastase-sensitive fragment of glycoprotein lb chain. 10 To our knowledge, this is the first reported case of NAIT due to anti-HPA-2b in Saudi Arabia. The HPA system responsible for the majority of NAIT in the Kingdom is not yet known. In our recent study on healthy Saudis, HPA distribution revealed a pattern peculiar to this population that was different from Western and Oriental populations. 11 The distribution of the different HPA alleles in Saudis was as follows: HPA-1a 80%, HPA-1b 20%, HPA-2a 80.5%, HPA-2b 19.5%, HPA-3a 88%, HPA-3b 12%, HPA-4a 97%, HPA-4b 3%, HPA-5a 84.5%, and HPA-5b 15.5%. The estimated risk (ER) of NAIT in pregnancies can be predicted from the probability that an antigen-negative mother becomes pregnant with an antigen-positive baby. ER for NAIT= aa×(ab+ bb)+ bb×(ab+ aa), where a and b are codominant alleles of each HPA type. The ER for NAIT associated with anti-HPA antibodies is: HPA-1a= 0%,