PL A1/A2 POLYMORPHISM DETECTION

The Coagulation and Molecular Immunodiagnostics Laboratory of ITxM Diagnostics is pleased to offer a genetic assay for the detection of PL A1/A2 Polymorphism.

BACKGROUND

Platelet membrane glycoprotein IIb/IIIa plays a major role and functions as a receptor for fibrinogen and von Willebrand factor during platelet aggregation.  Recent studies have suggested that the PLA2 polymorphism of the glycoprotein IIIa constituent of the platelet integrin receptor may be a risk factor for myocardial infarction.  Approximately 25% of people with Northern European ancestry have either the PLA1/A2 or PLA2/A2 genotype.  Of patients admitted to a coronary care unit, the prevalence of the A2 allele was twice what it was in a control group admitted to the hospital with no history of vascular disease.

Additionally the PLA1/A2 polymorphism has been associated with neonatal alloimmune thrombocytopenic purpura (NAITP).  NAITP occurs when the mother is PLA2/A2 and therefore generated antibodies against the blood of the PLA1/A2 infant.  If this polymorphism is detected prior to delivery, a cesarean section may be performed to reduce the risk to the infant.

METHODS

Lymphocytes are processed to extract DNA.  Third Wave Technologies’ Invader assay is used to genotype the target DNA.  Briefly, two specific oligonucleotide probes and controls hybridize in tandem to a specific region of the gene encoding the mutation site.  Cleavase III enzyme cleaves at a specific invasive structure generated within the probe oligonucleotides creating products.  These sequential cleavage reactions produce 1-10 million fluorescein labeled products per target sequence hour.  This results in the accumulation of a signal molecule only when the specific target DNA or control sequence is present.  A fluorescent multiwell plate reader is used to quantitate signal amplification for interpretation of genotype.  Homozygosity for PL A2 (A2/A2) is associated with increased arterial thrombotic risk.

CLINICAL SIGNIFICANCE

Platelet membrane glycoprotein IIb/IIIa, a receptor for fibrinogen and von Willebrand’s factor plays a major role in platelet function.  The functional consequences of the PLA1/A2 polymorphism are not fully understood at present.  An association of the PLA2 allele with increased platelet aggregability in vitro has been described and several studies have linked this genetic marker to cardiovascular disease.  Although the overall cardiovascular risk in the general population is weak, higher risk has been identified in younger patients and in restenosis subsets with stents.

In general screening for arterial thrombosis is best accomplished by evaluating for the traditional cardiovascular markers, such as diabetes mellitus, smoking, hypertension and hypertriglyceridemia.  The use of the PL A1/A2 polymorphism assay may be of value in the following situations: 

Ø       Children and young individuals with arterial thrombosis.

Ø       Any individual with arterial disease in the absence of atypical cardiovascular risk factors.

Ø       Patients with past medical history of restenosis and stent failure

Ø       Prediction of fetal risk of neonatal alloimmune thrombocytopenia. 

SPECIMEN REQUIREMENTS

In order to assure the accuracy of our test results, the PL A1/A2 polymorphism assay must be performed on whole blood.

1.      Blood must be collected in one (1) yellow  top tube (ACD).   DO NOT centrifuge the specimen and DO NOT separate plasma.

2.      Ship sample at room temperature.

3.      Specimen must be received within 72 hours of collection.

4.       We request that a completed Genetic Consent Form accompany the specimen.

TEST INFORMATION

The PL A1/A2 Polymorphism testing fee is $180.25.

TEST CODE:  5621   CPT CODES:  83891  83892x2  83896x2  83903x2  83912

This test was developed and its performance characteristics determined by ITxM Diagnostics.  It has not been cleared or approved by the U.S. Food and Drug Administration.  This test is used for clinical purposes and should not be regarded as investigational or for research use.  This laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as qualified to perform high complexity clinical testing.

FOR FURTHER INFORMATION CONTACT 412-209-7270  OR  1-800-967-9672

REFERENCES 

1. Feng, D.L., Lindpaintner, K., Larson, M.G. et. al., Increased platelet aggregability associated with platelet GPIIIa PlA2 Polymorphism.  Arterioscler. Thromb. Vasc. Biol. 1142-1147, April, 1999.
2. Gardemann, A., Humme, J., Stricker, J., et.al. Association of the platelet glycoprotein IIIa PlA1/A2 Gene polymyorphism to coronary artery disease but not to myocardial infarction in low risk patients.  Thromb. Haemost 80: 214-7, 1998.
3. Walter, D.H., Schachinger, V., Eisner,M. et al., Platelet glycoprotein IIIa polymorphisms and risk of coronary stent thrombosis.  The Lancet 350: 1217-1219, 1997.