Simultaneous Occurrence of Neonatal Alloimmune Thrombocytopenia and Neutropenia Associated with Multiple Maternal Antibodies

Background: Neonatal alloimmune thrombocytopenia (NAIT) results from feto-maternal platelet antigen incompatibility leading to the production of maternal antibodies and destruction of fetal platelets during pregnancy. Similarly neonatal alloimmune neutropenia (NAN) is caused by maternal alloimmunization to incompatible fetal neutrophil antigens followed by transplacental transfer of the maternal anti-neutrophil antibody causing fetal or neonatal neutropenia. Although there are many reports in the literature describing these rare disorders, the simultaneous occurrence of NAIT and NAN has not been systematically evaluated. In this study we report a case of NAIT associated with NAN.

Material and Methods: A healthy 46-year-old primiparous woman gave birth to triplets in the 30.9^th gestational week, by C-section, after a fertility treatment using an egg donation banking. The first neonate, a 1,600g female newborn with a first/fifth minute Apgar score of 8/9, healthy at physical examination, showed severe thrombocytopenia (platelet count = 30x10⁹/L) and a neutrophil count of 1.6X10⁹/L at birth. The second neonate, a 1,275g male newborn had a first/fifth minute Apgar score of 7/7, was healthy at physical examination and showed thrombocytopenia (platelet count = 82x10⁹/L) and neutropenia (neutrophil count = 0.66x10⁹/L). Intracranial bleeding, perinatal infections, genetic and hematologic disorders were ruled out and the neonates showed a spontaneously normalization of the platelets and neutrophils counts. Unfortunately, blood sample from the third neonate, a 1,525g female newborn with first/fifth minute Apgar score of 9/9, was not available. Mother and neonates were genotyped for platelets antigens (HPA-1-11,-15) and neutrophil antigens (HNA-1,-3). HPA genotyping was performed by PCR-SSP, PCR-RFPL and xMAP technology (IDHPA^XT, Progenika-Grifols, Spain). HNA genotyping was performed by PCR-SSP and PCR-RFPL. Platelets antibodies were investigated in maternal serum by platelet enzyme-linked immunosorbent assay (PaK12G, Immucor GTI Diagnostic Inc, USA); neutrophil antibodies were investigated by granulocyte agglutination test (GAT) using a panel of donors previously genotyped for HNA-1,-3 systems, while anti-HLA antibodies were investigated by ELISA (LAT Mixed, One Lambda Inc., USA and PaK12G, Immucor GTI Diagnostic Inc, USA).

Results: Genotyping studies revealed mismatches for HPA-1,-5 and HNA-1,-3 systems between mother and neonates (Table1). Serologic antibody screening tests showed presence of anti-HPA-5b, anti-HNA-3b and anti-HLA in maternal serum.

Conclusion: We described the occurrence of NAIT associated with NAN in preterm neonates with important thrombocytopenia and neutropenia due a multiple maternal sensitization to incompatible fetal antigens. As these syndromes pose a risk to the neonate’s life, the early and correct diagnosis is very important in order to apply appropriate treatment to the neonates and allow an effective prenatal therapy for future pregnancies.