Thrombophilia refers to the predisposition to form blood clots, caused by an underlying hypercoagulation state attributable to inherited or acquired disorders of blood coagulation or fibrinolysis.
The G20210A mutation in the prothrombin gene (FII) has been associated with an increased risk of thrombosis. Furthermore, it is well documented that another missense mutation, the G1691A mutation in the gene that encodes for the coagulation Factor V (known as FV Leiden or FVL) is also associated with an increased risk of thrombophilia and venous thrombosis.
Since the discovery of these variants, other conditions predisposing patients with thromboembolic disorders have been described. These prothrombotic risk factors primarily include qualitative or quantitative defects of endogenous coagulation factor inhibitors, increased concentration or function of coagulation proteins, defects in the fibrinolytic system, impaired platelet function, and hyperhomocysteinemia.
Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common genetic cause of elevated plasma homocysteine levels. Certain variants in the MTHFR gene can lead to an enzyme that is not fully active and, consequently, to elevated homocysteine levels. The best-characterized MTHFR gene polymorphisms are C677T and A1298C.
Other hereditary factors most studied in the predisposition to thrombophilia include plasminogen activator inhibitor-1 (PAI-1) and the p.Val35Leu variant of factor XIII (FXIII), historically referred to as Val34Leu.
INTENDED USE
Genvinset® Thrombo panel is a semi-automated kit for the in vitro qualitative detection of the G20210A variant (NCBI dbSNP rs1799963; NM_000506.5:c.*97G>A) in the prothrombin (FII) gene (OMIM: 176930), the G1691A variant (NCBI dbSNP rs6025; NM_000130.5:c.1601G>A) in the factor V (FV) gene (OMIM: 612309), the A1298C (NCBI dbSNP rs1801131; NM_001330358.2:c.1409A>C), and C677T (NCBI dbSNP rs1801133; NM_001330358.2:c.788C>T) variants in the Methylene tetrahydrofolate reductase (MTHFR) gene (OMIM: 607093), the -675 PAI-1 4G/5G variant (NCBI dbSNP rs1799762; NM_000602.5:c.-820G[(4_5)]) at the promoter region of the Plasminogen activator inhibitor 1 (SERPINE1) gene (OMIM: 173360) and the rs5985 variant (NCBI dbSNP rs5985; NM_000129.4:c.103G>T) at the coagulation factor XIII A chain (F13A1) gene (OMIM: 134570), associated with thrombophilia risk, in genomic DNA extracted from whole blood using Real-Time PCR technology with specific TaqMan® probes.
The patient referred by the corresponding health specialist (cardiologist, internist, reproductive clinician), and taking into account the compatibility of the symptoms presented; abnormal clots that may cause long-term or life-threatening health problems, most often in the legs and lungs, women suffering idiopathic recurrent pregnancy loss (RPL), and/or his family history (for example, a direct ascendant having had episodes of thrombosis) may be subject to the determination of the variants assessed by this kit. The results of this test should not be the only ones on which the therapeutic decision is based and should be used as an aid in the diagnosis together with results of other markers of the disease.
The intended user of the kit is technical personnel trained to carry out the protocol and the interpretation of results described in the instruction for use.
WORKFLOW
RESULTS
Homozygous wild-type FV and heterozygous FII sample:
Heterozygous 1298A/C and homozygous wild-type 677C/C sample:
Heterozygous FXIII and homozygous wild-type PAI-1 sample:
Limitations
- Mutations or polymorphisms at annealing primer/probe sites are possible and may result in the lack of allele definition. Other technologies could be necessary to resolve the genotyping.
- Data and result interpretation should be revised by qualified personnel.
- This product is an auxiliary tool for the diagnosis of patients with suspected thrombophilia. Use these results in conjunction with clinical data and results of other tests performed on the patient.
