Glycoprotein IIIa

Clinical Usage

  • To identify individuals with genetic predisposition to thrombosis 
  • To screen individuals with family history of CVD to determine underlying cause
  • To identify individuals most likely to benefit form GPIIb/IIIa inhibitor therapy
  • To assess patients that have or are undergoing stent placement

Background Information

Glycoprotein IIb/IIIa (GpIIb/IIIa) complex is an integrin aggregation receptor on platelets. This receptor is activated when the platelet is stimulated by ADP, epinephrine, collagen, or thrombin. GpIIb/IIIa is essential to blood coagulation since the activated receptor has the ability to bind fibrinogen (as well as von Willibrand factor, fibronectin and vitronectin), which is required for fibrinogen-dependent platelet-platelet interaction (aggregation) and hemostasis.

Two allelic polymorphisms, the A1 and the A2 polymorphisms (C to T substitution at base 196 of the mRNA in exon 2; commonly called A1 and A2) have been described. The A2 is associated with premature (<55y of age) myocardial infarction, unstable angina and re-occlusion. In addition, the A2 allele is associated with coronary stent thrombosis.

Gene Information

The human Glycoprotein IIIa gene is ITGB3 (Integrin alpha-V/beta-3) and is located on chromosome 17 (17q21.32). The following three genotypes of the Glycoprotein IIIa are possible:
(A1/A1) – Normal
(A1/A2) – Heterozygous: slightly increased risk for thrombosis
(A2/A2) – Homozygous: markedly increased risk for thrombosis

Population Information

The frequency of the A1/A1; A1/A2; and A2/A2 are 64%; 34%; and 2%, respectively in the Caucasian population.

Test Method

The test was developed using CLSI guidelines.  Control DNA samples of known genotype are tested together with each patient sample to monitor the performance of the test.  Genomic DNA is extracted from the submitted specimen and analyzed by Polymerase chain reaction (PCR) followed by restriction digest

Specimen

Collection

Whole blood in a purple top (EDTA) tube 

Rejection Criteria

• Blood specimen:
–  It is collected in a heparin-containing tube because heparin can inhibit the PCR reaction.
–  It leaked in the shipping container.
–  The name on the tube does not match the name on the paperwork.
–  It is older than 10 days.

Interpretation

Homozygous wild-type (A1/A1): Normal

Heterozygous (A1/A2): May be associated with slightly increased risk of thrombosis

Homozygous mutant (A2/A2): May be associated with markedly increased risk of thrombosis

This genotype result is but one factor affecting thrombosis risk, and other genetic and clinical factors should also be considered.  Multiple thrombosis risk factors are usually additive. Additional risk factors for development of thrombosis include:  older age, surgery, obesity, prolonged travel, immobility, hospitalization, oral contraceptive use, hormonal replacement therapy, pregnancy, and malignancy.

CPT code

81400

Test Limitations

Other genetic variants of the Glycoprotein IIIa gene are not detected in this assay and may influence the risk of thrombosis. Other genetic and non-genetic factors may also influence the balance of proper thrombosis.  The detection of genetic variants does not replace the need for appropriate clinical monitoring by the health care provider.  These tests were developed and the performance characteristics were determined by MDL.  This test has not been cleared or approved by the US Food and Drug Administration.

References

1. Zotz, RB, et al., (1998) Polymorphism of platelet membrane glycoprotein IIIa; Human platelet antigen 1b (HPA-1b/P1A2) is an inherited risk factor for premature 
myocardial infarction in coronary artery disease. Throm Haemost. 79:731-5.
2. Weiss, EJ, et al., (1996) The platelet glycoprotein IIIa polymorphism P1A2 : an 
inherited platelet risk factor for coronary thrombotic events. N. Engl. J.. Med. 
334:1090-4.
3. PRISM Study Group; > 30 contributors from several different countries. (1998) A 
comparison of Asprin plus Tirofiban with Asprin plus heparin for unstable angina. N. Engl. J. Med. 338:1498-1505.
4. Ibid. (1998) Inhibition of the platelet glycoprotein IIb/IIIa receptor with Tirofiban in unstable angina and non-Q-wave myocardial infarction. N. Engl. J. Med. 338:1488
5. Glueck, C.J. M.J. Kupferminc, R.N. Fontaine, P. Wang, B.B. Weksler and A. Eldor.(2001) Genetic hypofibrinolysis in complicated pregnancies. Obstet. and Gynecol. 
97:44-8.
For more information go to National Center for Biotechnology Information (NCBI).