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Test Name:
Glycoprotein IIIa (A1 vs. A2)

• SBMF No:
  45187
• Performance Lab Name:
  Molecular Diagnostics Laboratories
• Test Mnemonic:
  GLYCO IIIA
• ABN:
  Required – Not FDA-Approved
• CPT Code:
  83890; 83892; 83896; 83903; 83912
• LOINC Code:
  19146-0
• Ref Lab Test No:
  GP-3
• Also Known As:
  A1 vs. A2 Polymorphism
• Spec Type:
  Whole blood
• Spec Container:
  Lavender top (EDTA) tube
• Alt Spec Type:
  Whole blood
• Alt Spec Container:
  Pale yellow top (ACD) or light blue top (3.2% buffered sodium citrate) tube
• Pref Vol:
  4.0 mL
• Min Vol:
  2.0 mL
• Fasting:
  No
• Patient Prep:
  Informed consent is recommended for genetic testing
  Consent forms are available online
• Spec Collect:
  Routine venipuncture
  Collect two (2) tubes for leukopenic patients
• Spec Process:
  Do not centrifuge
  Do not remove plasma from cells
• Spec Store Transport:
  May be stored up to 2 weeks refrigerated until shipped
  Ship sample at room temperature
• Spec Stability:
  2 weeks refrigerated (2-8°C)
• Use:
  Determination of Glycoprotein IIIa genotype
• Clinical Significance:
  Glycoprotein IIIa is part of a receptor, the glycoprotein IIb/IIIa receptor, on the surface of platelets.

  This complex binds fibrinogen and von Willibrand factor and it is essential for platelet aggregation and hemostasis. Two allelic polymorphisms, the P1A1 and the P1A2 polymorphisms (C to T substitution at base 196 of the mRNA in exon 2) have been described. The P1A2 is associated with premature (<55y of age) myocardial infarction, unstable angina and re-occlusion after PCTR. In addition, the P1A2 allele is associated with coronary stent thrombosis, adds ratio, 5.26.

  The use of stents in occlusive coronary vascular disease has increased dramatically in the past 3 years. Anti platelet therapy with glycoprotein IIb/IIIa inhibitors may be useful in preventing stent re-stenosis and stent thrombosis. although care must be taken that bleeding complications are avoided. Currently, only intravenous inhibitors are available; oral inhibitors are in phase II-III trials in humans.

  The genotype frequencies for this polymorphism are: P1A1/P1A1, 64%; P1A1/P1A2, 34%; and P1A2/P1A2, 2.4%.

  Reference:
  "Glycoprotein IIIA (A1 vs A2)", Molecular Diagnostics Laboratories (www.mdl-labs.com), Web. 8 Apr. 2010.

• Reference Range:
  By report

  Interpretive Data:
  (A1/A1): Normal: Generally no increased risk for thrombosis.

  (A1/A2): Heterozygous: Slightly increased risk for thrombosis especially in combination with other thrombotic risk factors.

  (A2/A2): Homozygous: markedly increased risk for thrombosis.

  DNA from individual's blood was analyzed for Glycoprotein IIb/IIIa (PLA1 & PLA2) mutation (a cytosine to thymine substitution at position 196) resulting in a proline substitution for leucine at amino acid 66 using Invader DNA assay from Third Wave Technologies. Glycoprotein IIb/IIIa complex (GP) is a platelet membrane receptor for fibrinogen, initiating platelet aggregation and subsequent thrombus formation. GP contains two polymorphic alloantigenic determinant sites (P1A1 & P1A2, commonly referred to as A1 and A2). In patients homozygous for the PLA2 allele a strong association between A2 allele and acute coronary syndromes with a 5-fold increased risk of stent thrombosis has been noted. Some, but not all, studies have found an association of the PLA1/PLA2 genotype with thrombosis. The frequency for A1/A1: A1/A2: A2/A2 alleles are 64%: 34%: 2% respectively in the Caucasian population. In rare instances individuals may have more than one thrombotic risk factor, leading to a more increased but unquantifiable risk.

  Recommendations:
  Genetic counseling is recommended for both heterozygotes and homozygotes. In patients with this mutation, clinicians may recommend treatment with specific inhibitors of fibrinogen/GP receptor interactions.

  * The performance characteristics of this test have been developed by TWT.
  ** This test should not be used as the sole diagnostic or therapeutic criterion. Negative results do not rule out the possibility that thrombosis is caused by other genetic or non-genetic defects. Given the limitations of the current technology of this type, there is a 1 in 1000 possibility that an error may occur. the test is approximately 99.9% accurate for detection of the specific mutation.

• Day Run:
  Varies
• Test Type:
  GENETIC