Noninvasive prenatal HPA-1 typing in HPA-1a negative pregnancies selected in the Polish PREVFNAIT screening program.

Abstract

BACKGROUND:

Anti-HPA-1a alloantibodies in HPA-1a negative mothers can lead to fetal/neonatal alloimmune thrombocytopenia (FNAIT). Noninvasive prenatal testing (NIPT) of HPA-1a determines fetuses at risk and the course of maternal antenatal treatment.

STUDY DESIGN AND METHODS:

The aim was to develop and validate HPA-1a NIPT by real-time polymerase chain reaction (PCR) or next-generation sequencing (NGS) for a high-throughput screening setting. DNA from 328 plasma samples of 299 HPA-1a negative pregnant women was examined for HPA-1a by real-time PCR and in two cases also by NGS (Ion Torrent). The results were compared with neonatal HPA-1a genotyping in 281 cases.

RESULTS:

HPA-1a NIPT was negative in 44 of 51 HPA-1a negative fetuses, inconclusive in five, and false positive in two. In 228 of 229 HPA-1a positive fetuses, the NIPT results were positive (mean threshold cycle 36.0 ± 1.7) and inconclusive in one. In 22 cases with HPA-1a positive fetuses analyzed twice, the sensitivity of HPA-1a detection was significantly higher at 28 weeks compared with 16 to 20 weeks. NGS efficiently detected the ITGB3 coding HPA-1a/b (1% and 5% fetal HPA-1a reads).

CONCLUSION:

Real-time PCR is reliable to predict the fetal HPA-1a positive genotype in a screening study, but false-positive results are reported in 4%, with unnecessary prenatal treatment if anti-HPA-1a is detected.

• Authors: Agnieszka Orzińska, Katarzyna Guz, Małgorzata Uhrynowska, Marzena Dębska, Michal Mikula, Jerzy Ostrowski, Maria Therese Ahlen, Anne Husebekk, Ewa Brojer
• Journal: Transfusion (Transfusion) Vol. 58 Issue 11 Pg. 2705-2711 (11 2018) ISSN: 1537-2995 [Electronic] United States
• PMID: 30260485 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 AABB.

Chemical References

• Antigens, Human Platelet
• ITGB3 protein, human
• Integrin beta3
• Isoantibodies

Topics

• Adult
• Antigens, Human Platelet (genetics)
• Female
• Genotype
• Humans
• Infant, Newborn
• Integrin beta3
• Isoantibodies (immunology)
• Pregnancy
• Prenatal Diagnosis
• Real-Time Polymerase Chain Reaction
• Thrombocytopenia, Neonatal Alloimmune (genetics, immunology)