Genvinset® PAI-1 / FXIII multiplex

Thrombophilia refers to the predisposition to form blood clots, caused by an underlying state of hypercoagulability, attributable to disorders of blood coagulation or fibrinolysis that can be hereditary or acquired. Thrombophilia is associated with the risk of deep vein thrombosis (DVT) and/or venous thromboembolism (VTE).

PAI-1 is one of the most important components of the fibrinolytic system, responsible for approximately 60% of the inhibitory activity against plasminogen activators. Recent studies have investigated the 4G/5G polymorphism located in the promoter region of the gene coding for PAI-1, SERPINE1, as a mechanism that regulates both the plasma levels and activity of PAI-1. The 4G allele could bind to the transcription activator, enhancing mRNA transcription and increasing PAI-1 levels, leading to a reduced fibrinolytic state and, consequently, a higher risk of venous thromboembolism.

On the other hand, factor XIII is a transglutaminase that plays an essential role in stabilizing the fibrin clot through cross-linking of fibrin fibers. The Val34Leu mutation, located in the A subunit of FXIII, causes a change in the protein structure that alters its coagulation activity. Unlike other mutations associated with thrombophilia, the Val34Leu mutation has been linked to a protective effect against thrombosis due to its ability to accelerate FXIII activation and promote the formation of a more resilient fibrin clot that is less prone to promoting thrombosis.

INTENDED USE

Genvinset^® PAI-1/FXIII multiplex kit is a semi-automated kit for the in vitro qualitative detection of both the 4G/5G deletion (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 (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), and taking into account the compatibility of the symptoms presented; abnormal clots that may cause longterm or life-threatening health problems, most often in the legs and lungs, and/or his family history (for example, a direct ascendant having had episodes of thrombosis) may be subject to the determination of the mutation in the SERPINE1 gene. 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

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.