Genotyping of Human Platelet Alloantigens : Non-invasive Prenatal Diagnosis

Neonatal thrombocytopenia isoimmunization maternal-fetal is related to maternal immunization against fetal platelet antigens with paternal origin not present in the mother. It is considered the equivalent of hemolytic disease of the newborn. The incidence of this disease is about 1 in 800-1000 births. The most severe forms associated petechiae, purpura or cephalhematoma at birth with a major risk of cerebral hemorrhages (20% to 25% of cases) can cause the death of the child (15%) or severe neurological troubles (15-30%) Biologic diagnosis requires the detection of anti-platelet antibodies with maternal determination of platelet phenotypes and genotypes of the two parents.

The objective of this work is to develop specific molecular tools to fetal platelet genotyping from maternal blood. We are particularly interested to antigens HPA-1, HPA-5 , HPA-3 and HPA-4. We evaluate the sensitivity and specificity of this test by comparing these results with those obtained from an invasive sampling of amniotic fluid.

This is a prospective study to assess the technical and diagnostic performance of a new molecular method noninvasive prenatal diagnosis of platelet genotyping.

Study Overview

• Status: Withdrawn
• Conditions: Neonatal Thrombocytopenia Isoimmunization Maternal-fetal
• Intervention / Treatment: Biological: Extra blood draw samples; Biological: extra amniotic fluid samples

Detailed Description

Neonatal thrombocytopenia isoimmunization maternal-fetal is related to maternal immunization against fetal platelet antigens with paternal origin not present in the mother. It is considered the equivalent of hemolytic disease of the newborn. The incidence of this disease is about 1 in 800-1000 births. The most severe forms associated petechiae, purpura or cephalhematoma at birth with a major risk of cerebral hemorrhages (20% to 25% of cases) can cause the death of the child (15%) or severe neurological troubles (15-30%) Biologic diagnosis requires the detection of anti-platelet antibodies with maternal determination of platelet phenotypes and genotypes of the two parents. When it is diagnosed, genetic counseling to the couple for a future pregnancy is necessary because the risk of recurrence is important and severity increases with the number of pregnancies. The risk depends on the nature of paternal antigens, homozygous or heterozygous. In case of heterozygosity, prenatal diagnosis is based on fetal platelet genotyping by an invasive procedure (amniocentesis or chorionic villus sampling) associated with a risk of fetal loss. The alloantibodies responsible for fetal damage are directed against platelet alloantigens: this is HPA system (human platelet alloantigen). 24 alloantigens have been described and 12 of them have a biallelic polymorphism (a: the most frequent allele and b the rare allele) divided into 6 groups (HPA-1, 2, 3, 4, 5, and 15). The genotype-phenotype correlations were performed for 22 of the 24 alloantigens and show that the antigenic polymorphism results from the presence of a SNP (single nucleotide polymorphism-).

In 1997, Lo et al showed the presence of 3-6% of fetal DNA in maternal blood. This discovery led to the development of methods of non-invasive prenatal diagnosis: 1/ the determination of fetal Rhesus 2/ fetal sex by real-time quantitative PCR.

The objective of this work is to develop specific molecular tools to fetal platelet genotyping from maternal blood. We are particularly interested to antigens HPA-1, HPA-5 , HPA-3 and HPA-4. We evaluate the sensitivity and specificity of this test by comparing these results with those obtained from an invasive sampling of amniotic fluid.

This is a prospective study to assess the technical and diagnostic performance of a new molecular method noninvasive prenatal diagnosis of platelet genotyping.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13005
    • Assistance Publique Hopitaux de Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients with known risk of platelet alloimmunization
• patients for whom suspicion of fetal cerebral hemorrhage has been advanced on ultrasound or fetal MRI signs

Exclusion Criteria:

• Twin pregnancy or triple

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pregnant women	Biological: Extra blood draw samples; NEVER STARTED; Biological: extra amniotic fluid samples; NEVER STARTED

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
number of Fetomaternal platelet incompatibilities detected	30 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: Urielle DESALBRES, Assistance Publique Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2023
• Primary Completion (Actual): July 27, 2023
• Study Completion (Actual): July 27, 2023

Study Registration Dates

• First Submitted: September 9, 2016
• First Submitted That Met QC Criteria: September 9, 2016
• First Posted (Estimated): September 14, 2016

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Infant, Newborn, Diseases; Blood Platelet Disorders; Thrombocytopenia; Thrombocytopenia, Neonatal Alloimmune
• Other Study ID Numbers: 2012-55 (CCRRC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No