Thrombophilia

Each year, venous thombosis occurs in about 1 in 1000 people in developed countries and many of those patients die from a pulmonary embolus, the most frequent complication of thromboses. In Germany for example five times as many people die from the consequences of a thrombosis as from a motor vehicle accident. This does not have to be the case: thrombosis prophylaxis using drugs, for example, can reduce the occurrence of thrombosis and emboli in risk situations. For this purpose, however, efficient preliminary diagnosis of thrombophilia is necessary in order to identify patients at risk.
The term “thrombosis” is used to designate the occlusion of a blood vessel by a blood clot which develops due to disruptions during blood clotting. Various risk factors may be responsible for these disruptions which are collectively referred to by the term “thrombophilia”. Along with external risk factors, such as confinement to bed, for example, genetic predispositions in particular also lead to an increased risk of thrombosis. In general, clotting factors are affected by these genetic changes. Thus a mutation can, for example, cause inactivation of a clotting factor or cause the concentration of the clotting factor to increase. However, changes in other genes can also lead to an increased risk of thrombosis.
About 60% of all venous thrombosis occurs in connection with hereditary thrombophilia. Thus, hereditary risk factors play a crucial role in the development of thrombosis. Since it is important to know all risk-factors to assess the individual risk of thrombosis, it is essential to determine genetic risk factors.

Factor V Leiden Mutation
The Factor V Leiden mutation is the most frequent and most important change in the human genome associated with thrombophilia. The cleavage site for activated protein C is destroyed by a point mutation at position 1691 in the factor V gene. This causes the activated factor V to be inactivated much more slowly and therefore blood clotting is stimulated over a longer period of time. The heterozygous Factor V Leiden mutation causes a five- to tenfold increased risk of thrombosis. In the homozygous disease, the risk of thrombosis is increased 100 times.

Faktor II Mutation (Prothrombin Muation)
The second most frequent mutation is the prothrombin G20210A mutation. This point mutation involves the noncoding regulatory area of the Factor II gene (prothrombin). It is assumed that the change leads to increased protein synthesis by increasing translational efficiency. In heterozygous carriers, the mutation is associated with a threefold increase in thrombosis risk.

Methylentetrahydrofolat Reductase (MTHFR)
Homocysteine affects the arterial and venous vascular system in various ways. For example, it has a cytotoxic effect on the cells of blood vessels. Along with an increased risk of thrombosis, particularly in connection with additional thrombosis-related mutations, this can lead to clinical pictures such as atherosclerosis, strokes or myocardial infarcts. An increase in the homocysteine level has therefore been known for a long time to be a risk factor for cerebral and cardiovascular as well as venous thromboses.
Along with acquired causes such as, for example, vitamin B12 deficiency, mutations within the methylenetetrahydrofolate reductase (MTHFR) gene also lead to an increase in the homocysteine level. The best described change within the MTHFR gene is a point mutation at position 677. This genetic change leads to a thermolabile protein which is limited in its catalytic effect. This in turn leads to a loss of activity of up to 60%. An additional change at position 1298 likewise leads to a reduced enzymatic effect, which however is not as pronounced as with the previously mentioned mutation. Compound heterozygous carries also develop reduced MTHFR activity.

By the Way…
Determination of the hereditary risk factors should be done when, among other things, thrombosis appears in childhood or if the thromboses are particularly severe. In addition, determination is indicated when thromboses occur frequently in the family. Approximately 10-30% of thrombosis patients with a Factor V Leiden mutation also have the prothrombin mutation. Persons with multiple gene defects have a significantly increased risk of thrombosis as compared to persons with only one or no genetic change. Testing for the presence of the two MTHFR mutations can aid in the assessment of cardiovascular risk. In addition, determining the parameters in combination with additional thrombosis-related changes allows for the assessment of the individual thrombosis risk.

Products for Your Diagnostics of Thrombophilia
Our test systems for the diagnostics of thrombophilia detect clinical relevant genetic risk factors - fast and reliable.

It is your choice: two different technologies provide your individual result.

The test systems ThromboType^®, ThromboType^®plus and GenoType MTHFR are based on the reliable DNA•STRIP Technology – The test systems FluoroType^® Factor V, FluoroType^® Factor II and FluoroType^® MTHFR C677T rely on an innovative fluorescence-based technology .
The following table demonstrate the output range of the different test systems:  

To the products

FluoroType^® Factor V

FluoroType^® Factor II

FluoroType^® MTHFR C677T

GenoType CVD

ThromboType^®plus

ThromboType^®

GenoType MTHFR