HPA-1 Genotyping

 HPA-1 gene encodes the glycoprotein IIIa found in the cell membrane of platelets.  This glycoprotein harbors the PLA1/A2 alloantigens expressed on platelets and is a principal receptor for platelet aggregation.  This PLA glycoprotein therefore occupies a pivotal role in thrombosis.  A simple polymorphism within the HPA-1 gene alters the biochemical and immunological properties of the PLA polypeptide and has also been linked to an increased incidence of thrombosis leading to coronary artery disease.  Knowing patient genotype can lead to lifestyle and behavior modifications that will minimize risk.  In addition, mothers mismatched with their fetus for the PLA antigen can develop antibodies that will induce fetal thrombocytopenia with its associated risks for fetal bleeding complications during delivery.

Reasons for ReferraL:

• To determine the potential cause of unexplained thrombosis in children or adults.
• Patients undergoing surgery especially the potentially high-risk class of women taking estrogen supplements.
• To investigate a family history of thrombosis for patients with other indicators of cardiovascular disease.
• Evaluation of individuals before initiation of oral contraceptives.
• To genotype a fetus for HPA-1 carried by a mother known to have antibodies against the antigen which could lead to fetal thrombocytopenia and associated complications during delivery.

• May be combined with testing for Prothrombin, MTHFR, & Factor V in a Thrombosis Risk Panel.

Testing Methodology:

Genotyping for the HPA-1 gene is accomplished using PCR of the specific region of the gene responsible for the different alleles. In situations involving prenatal genotyping for HPA-1,  it is recommended that parents be tested along with fetal DNA to screen for possible family anomalies that might lead to erroneous interpretation of fetal genotyping results.

Specimen Requirements:

For prenatal genotyping, 2-5 cc of amniotic fluid, or a 25cm² flask of amniocytes in culture.  Buccal swabs (2-4) taken from the mother and father, air dried, and enclosed in labeled paper envelopes is adequate for parental genotyping.  For patients being tested due to thrombosis, buccal swabs collected and packaged as above are acceptable.  Alternatively, 5-7 mL of blood collected in purple top (EDTA) or yellow top (ACD) anticoagulant is acceptable as a source of DNA.