Thrombosis & Genetic Disorders

Thrombosis, Thrombophilia and Factor V Leiden

The definition of thrombosis is the formation of a blood clot, a thrombus, in the cardiovascular system. Depending on where it occurs, it can be differentiated between a venous thrombosis (blood clot in the veins) or an arterial thrombosis (a blood clot in the arteries).

A thrombus can partially or completely block the blood stream. It might also dislodge and follow the blood flow to other locations in the cardiovascular system. The vascular occlusion (blood vessel blocking) which might result from this is called 'thromboembolism'. Venous thrombosis usually occurs in the deep veins of the legs or the pelvis (Deep Vein Thrombosis, DVT). The incidence rate in the western industrialised nations ranges between one and five out of 1000 persons per year. All in all, venous thrombosis shows the second highest incidence rate of all acute cardiovascular diseases after myocardial infarction (heart attacks)

The definition of thrombophilia is the tendency towards developing a thrombus. The contrary phenomenon, the tendency towards extensive bleeding is called haemophilia. Clinical characteristics of thrombophilia include: thrombosis at an age of less than 45 years, relapsing thrombosis, a positive family history and non-typical localisation of thrombus such as in the cerebral veins, (veins in the brain) mesenteric veins (veins in the abdomen), spleen, portal vein (between bowel and liver), liver and kidney.

But what actually causes thrombophilia?

Thrombophilia is a multifactorial disorder, which means that it can be caused by several different factors, which might potentiate dramatically under certain circumstances. These factors can be divided into genetic and acquired (i.e. non-genetic) risk factors.

Acquired factors, the non-genetic risk factors comprise, among others: age (most important factor), overweight, smoking, lack of exercise, use of contraceptives containing oestrogen, pregnancy, immobilisation caused by illness or after operations, heart failure, malignant diseases and Lupus anticoagulant.

Genetic factors, genetic disposition for thrombophilia means that some coagulation factors are modified by gene mutations. Genetic risk factors have an influence on the probability of the disease, the age at which the disease occurs and on the severity of the disease.

Factor V Leiden is the most common cause for genetic thrombophilia. It is called Factor V Leiden as it was first described by a study-group in the town of Leiden, in the Netherlands.

The activation of blood coagulation is not affected by the presence of Factor V Leiden. Instead the inactivation of coagulation is altered by this mutation and normal inactivation is impaired. This impairment of normal inactivation in coagulation can result in thrombosis.

With an occurrence of about five per cent in the population, Factor V Leiden is the most frequent genetic risk factor for thrombosis. However, there are major regional differences: in the North of Europe, the mutation occurs much more frequently than in the South. Within the Japanese and Chinese populations, as well as amongst the native inhabitants of Australia and Africa, the defect is not present.

The relative risk of thrombosis increases by five to ten-fold in heterozygote individuals (where the gene mutation is inherited from one parent) where as the relative risk of thrombosis is increased by 50 to 100 fold in homozygous individuals (mutation inherited from both parents).

Other genetic causes of thrombophilia include the much less abundant Factor V Cambridge and Prothrombin G20210A. This mutation was first described in 1996.


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