Noninvasive prenatal diagnosis by cell-free DNA screening for fetomaternal HPA-1a platelet incompatibility.

Abstract

BACKGROUND:

The development of new noninvasive approaches for the diagnosis of human platelet antigen (HPA)-1 fetomaternal incompatibility has become of great interest. These approaches allow determination of whether the fetus is incompatible or not with the mother and a decision on antenatal therapy to avoid fetal or neonatal alloimmune thrombocytopenia (FNAIT). The objective of this work was to perform rapid, noninvasive prenatal test for HPA-1ab fetal antigen detection after the detection of an HPA-1-homozygous mother by using plasma cell-free DNA (cfDNA).

STUDY DESIGN AND METHODS:

The HPA-1 genotypes of 142 pregnant women and 17 nonpregnant controls were retrospectively determined by high-resolution melting (HRM) polymerase chain reaction (PCR). Coamplification at lower denaturation temperature (COLD) HRM PCR was performed to determine the fetal genotype analyzing cfDNA from all HPA-1bb pregnant women.

RESULTS:

After the HRM analysis, the following genotypes were identified: HPA-1aa (71.13%), HPA-1bb (2.8%), and HPA-1ab (26.06%). Four HPA-1bb-homozygous pregnant women were carrying an incompatible fetus. Plasma samples from these mothers were analyzed by HRM COLD-PCR. Homozygous HPA-1bb pregnant women carrying an HPA-1ab-heterozygous fetus did not group with either the HPA-1ab or the HPA-1bb controls. Thus, COLD-PCR analysis allows the detection of HPA-1ab-heterozygous fetuses carried by homozygous mothers during first weeks of pregnancy.

CONCLUSION:

The fetal genotype from HPA-1bb-homozygous women was detected by a noninvasive prenatal test as soon as 12 weeks of gestation.

• Authors: Marta Ferro, Hada C Macher, Gema Fornés, Jesús Martín-Sánchez, Pilar Jimenez-Arriscado, Patrocinio Molinero, José A Pérez-Simón, Juan M Guerrero, Amalia Rubio
• Journal: Transfusion (Transfusion) Vol. 58 Issue 10 Pg. 2272-2279 (10 2018) ISSN: 1537-2995 [Electronic] United States
• PMID: 30222855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 AABB.

Chemical References

• Antigens, Human Platelet
• Cell-Free Nucleic Acids
• ITGB3 protein, human
• Integrin beta3
• human platelet antigen 1b

Topics

• Adolescent
• Adult
• Antigens, Human Platelet (blood, immunology)
• Case-Control Studies
• Cell-Free Nucleic Acids (analysis)
• Female
• Genotype
• Histocompatibility, Maternal-Fetal (genetics)
• Homozygote
• Humans
• Integrin beta3
• Mass Screening (methods)
• Polymerase Chain Reaction (methods)
• Pregnancy
• Prenatal Diagnosis (methods)
• Thrombocytopenia, Neonatal Alloimmune (diagnosis, prevention & control)
• Young Adult