Genotyping of Human Platelet Alloantigens : Non-invasive Prenatal Diagnosis
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.
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.
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