Antibody response to platelet Lap(a) causing Fetal and neonatal alloimmune thrombocytopenia (FNAIT)

Status:

Ready to upload

Record number:

1654

Adverse Occurrence type:

Passive alloimmune thrombocytopenia

MPHO Type:

Platelets

Estimated frequency:

Rare

Time to detection:

Immediate

Alerting signals, symptoms, evidence of occurrence:

This newborn developed hematoma and petechiae directly after birth. An initial full blood count showed a platelet (PLT) count of 2 x 10(9)/L (reference interval, 140 x 10(9) -360 x 10(9)/L). The patient received a PLT transfusion with poor increment and required further transfusions for the next 2 weeks to maintain a PLT count of higher than 50 x 10(9)/L.

Demonstration of imputability or root cause:

The cross-match test between maternal serum and paternal PLTs was clearly positive for GPIIb/IIIa and HLA Class I. Immunoprecipitation analysis was performed with biotin-labeled paternal PLTs, maternal serum precipitated predominantly PLT GPIIb. Molecular genetic analysis was carried out, including nucleotide sequencing, and demonstrated a mutation on paternal and infant sequences. Allele specific constructs were then transfected into human derived HEK cells which could then be shown to react with the alloantibody by flow cytometry.

Imputability grade:

3 Definite/Certain/Proven

Groups audience:

Clinical complications

Keywords:

FNAIT (fetal and neonatal alloimmune thrombocytopenia)

References:

Alloantibody against new platelet alloantigen (Lapa) on glycoprotein IIb is responsible for a case of fetal and neonatal alloimmune thrombocytopenia

Suggest new keywords:

Fetal and neonatal alloimmune thrombocytopenia, FNAIT, cross-match, GPIIb/IIIa, HLA Class I, genotyping, sequencing, transfection, monoclonal antibodies, serology, immunochemistry, nucleotide sequencing, biotin, platelets, flow cytometry

Reference attachment:

Antibody to Lap(a), Wihadmadyatami, 2015.pdf

Suggest references:

Wihadmadyatami,H., Heidinger, K., Roder, L., Werth, S., Giptner, A., Hackstein, H., Knorr, M., Bein, G., Sachs,U.J. and Santoso, S. (2015). Alloantibody against new platelet alloantigen (Lapa) on glycoprotein IIb is responsible for a case of fetal and neonatal alloimmune thrombocytopenia. Transfusion doi:10.1111/trf.13238.

Expert comments for publication:

Rare human PLT antigens (HPA) residing on PLT GPIIb/IIIa in the pathomechanism of FNAIT and the importance of performing serologic cross-matches between maternal serum are demonstrated. Better serologic assays are needed to detect platelet reactive antibodies.