Foetal-neonatal alloimmune thrombocytopenia due to anti-HPA-2b antibodies present in the serum of a mother initially mistyped as HPA-1a negative.

Abstract

Thrombocytopenia is one of the commonest haematological problems observed in neonates, with a prevalence of 1 to 5% in all neonates but reaching 20 to 30% among neonates admitted to intensive care units1. The timing of onset, together with the accompanying clinical data, are useful for predicting its underlying cause. Foetal-neonatal alloimmune thrombocytopenia (FNAIT) arises from the destruction of foetal platelets induced by maternal alloantibodies directed against specific platelet antigens. The degree of thrombocytopenia is variable, but can be extremely severe and may result in major bleeding, particularly intracranial haemorrhage. Relevant criteria for the clinical diagnosis of FNAIT include unexplained thrombocytopenia in the first day of life, particularly if it is severe (<50×109/L), in term infants and without any apparent cause. The diagnosis is confirmed if maternal sensitisation against specific platelet antigens is found. Human platelet antigens (HPA) result from polymorphisms in the genes encoding the major platelet membrane glycoproteins (GP). More than 20 platelet-specific alloantigens have been defined, of which 12 are grouped in six biallelic systems2. Antibodies against HPA-1a antigen are implicated in about 80% of cases of FNAIT and those against HPA-5b in nearly 15%. Other specificities are infrequently identified3. The identification of anti-HPA antibodies in the maternal serum requires the combination of several techniques, such as immunofluorescence tests, enzyme-linked immunosorbent assay (ELISA) or monoclonal antibody immobilisation platelet antigens (MAIPA). Laboratory investigations include HPA genotyping to establish the existence of foeto-maternal incompatibilities. Finally, a cross-match against paternal platelets should be performed to ensure the detection of antibodies against low frequency antigens. It is important to proceed with all investigations in order to confirm the diagnosis of FNAIT because, if verified, the mother must be counselled on the high risk of recurrence in subsequent pregnancies. Furthermore, when FNAIT has been diagnosed in a previous sibling, the administration of antenatal treatment can reduce the risk of thrombocytopenia and haemorrhagic complications in the foetus4. We present a case of FNAIT in which alloimmunisation against the HPA-2b antigen was identified. Reaching an accurate diagnosis in this case was hampered by initial misleading results, which highlights the need to combine suitable techniques during the investigation of suspected cases of FNAIT.