Haemostasis & Thrombosis
HAEMOSTASIS and THROMBOSIS
Restriction Fragment Length Polymorphism (RFLP)
Genetic polymorphisms associated with venous and arterial thrombosis
Thrombosis is a multifactorial disorder, with acquired or congenital risk factors. There are many genetic abnormalities
causing an increased risk of thrombophilia, and the presence of more than one abnormality gives rise to further
increase in thrombotic risk. Haemostasis is a balance between the procoagulant factors and anticoagulant proteins.
The first genetic thrombotic disorders described were the deficiencies of natural procoagulant, such as antithrombin,
protein C and protein S, but these abnormalities are rare and are caused by many different mutations. More recently,
relatively common individual polymorphisms in the population have been described in procoagulant factors, such as
factor V and prothrombin that cause an increased risk of venous thrombosis. Analyzing the haemostatic system, other
polymorphisms have come to light, such as genetic polymorphisms associated with thrombosis and arteriovascular
disease were found in many procoagulant proteins, including factor V, prothrombin, fibrinogen, Factor VII, Factor XI
and factor XIII. Moreover, polymorphisms of platelet glycoproteins, fibrinolytic proteins, and enzymes in the metabolic
pathway of transulfuration leading to high levels of homocysteine have been described in association with thrombotic
vascular disease. In general, the risk factors that promote venous thrombosis are abnormalities via anticoagulant,
while polymorphisms of procoagulant proteins and metabolic pathway of transulfuration are mainly associated with
arterial disease. So it is useful to examine the association between polymorphisms recently discovered studied by the
recent literature, for the evaluation of thromboembolic risk. According with the literature, we note the lack of
attention for the polymorphisms linked to enzymes involved in homocysteine metabolism such as A1298C MTHFR,
MTRR A66G, CBSA114V, I278T CBS and CBS 844ins68. These polymorphisms have been studied in several diseases,
but not correlated with the risk of thrombosis. Few studies have evaluated the possible interaction between these new
polymorphisms and those already widely studied (FV Leiden, FII, MTHFR C677T) not clarifying a possible increased in
thrombotic risk.