Thrombophilia
What is Thrombophilia?
Each year, venous thrombosis 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 more people die from the consequences of thrombosis than in a traffic accident. This does not have to be the case; for example, the occurrence of thromboses and embolisms in risk situations can be reduced through thrombosis prophylaxis with medication. However, this requires efficient thrombophilia diagnostics in advance to identify patients at risk.
Thrombosis is the occlusion of a blood vessel by a blood clot that occurs due to disorders during blood clotting. Various risk factors can be responsible for these disorders, which are summarized under the umbrella term thrombophilia. In addition to external risk factors, such as bedriddenness, genetic predispositions in particular also lead to an increased risk of thrombosis. The clotting factors are usually affected by these genetic changes. For example, a mutation can influence the inactivation of a clotting factor or cause its concentration to increase. However, changes in other genes can also lead to an increased risk of thrombosis.
About 60% of all venous thromboses occur in association with hereditary thrombophilia. Thus, hereditary risk factors have a decisive influence on the development of thromboses. Since it is important to include all risks when assessing the individual risk of thrombosis, the determination of genetic risk factors is indispensable.
Especially persons with a combination of several hereditary risk factors have a significantly increased risk of thrombosis compared to persons with only one or no genetic modification. Therefore, an examination the most frequent risk factors should be carried out for the individual risk assessment in thrombosis patients.
Factor V Leiden Mutation
The factor V Leiden mutation is the most frequent and most important thrombophilia-associated change in the human genome. A point mutation at position 1691 in the factor V gene destroys the cleavage site for activated protein C. This leads to the activated factor V being inactivated much more slowly, thus stimulating blood clotting over a longer period. In heterozygous factor V Leiden mutations, there is a 5- to 10-fold increased risk of thrombosis. In the homozygous case, the risk of thrombosis is even increased 100-fold.
Factor II mutation (prothrombin mutation)
The second most common hereditary mutation is the factor II or prothrombin G20210A mutation. This point mutation is in the non-coding regulatory region of the factor II gene (prothrombin). It is suspected that the mutation leads to increased protein synthesis by increasing translational efficiency. In heterozygous carriers, the mutation is associated with a 3-fold increase in the risk of thrombosis.
The combination of Factor V and Factor II mutation means that serious thrombosis can occur at a young age or the risk of recurrent thrombosis is also significantly increased.
Methylentetrahydrofolat Reductase (MTHFR)
Homocysteine influences the arterial and venous vascular system in many ways. For example, it acts as a cytotoxin for the cells of the blood vessels. In addition to an increased risk of thrombosis, this can lead to clinical pictures such as atherosclerosis, strokes or heart attacks, especially in conjunction with other thrombosis-associated mutations. An increase in homocysteine levels has therefore long been known as a risk factor for cerebral- and cardiovascular as well as venous thromboses.
In addition to acquired causes, such as vitamin B12 deficiency, mutations within the methylenetetrahydrofolate reductase (MTHFR) gene also lead to an increase in homocysteine levels. The best described change within the MTHFR gene is a point mutation at position 677. This genetic change leads to a thermolabile protein that is limited in its catalytic effect. This in turn leads to a loss of activity that can be up to 60%. A further change at position 1298 also leads to a reduced enzymatic effect, although this is not as pronounced as with the mutation described previously. Compound heterozygosity also leads to lower MTHFR activity.
Plasminogen activator inhibitor type 1 (PAI-1)
An increase in plasminogen activator inhibitor type 1 (PAI-1) levels is also considered a risk factor for venous and arterial thrombosis. PAI-1 is responsible for inhibiting two proteins that play an important role in the re-dissolution of a thrombus. Consequently, an increased PAI-1 level leads to a stronger inhibition of the proteins and thus to a slower breakdown of the blood clot.
Two polymorphisms in the PAI-1 gene are associated with increased PAI-1 levels. Either 4 or 5 guanine nucleotides can be present at position -675 due to insertion or deletion. The presence of the 4G allele leads to an increased risk of venous thrombosis, mainly in the presence of other thrombosis-relevant mutations. In addition, an increased risk of heart attacks and early miscarriages has also been found for this genotype. Furthermore, A-844G, another polymorphism in the PAI-1 gene, is also relevant. In the presence of the AA genotype, the risk of venous thrombosis is increased in Factor V Leiden carriers.
By the Way…
A determination of the hereditary risk factors should be carried out, among other things, if thromboses already occur at a young age or if they are particularly severe. Furthermore, a determination makes sense if thromboses occur frequently in the family. In particular, people with several defects have a significantly increased risk of thrombosis compared to people with only one or no genetic change. Testing for the presence of the two MTHFR mutations can support the assessment of cardiovascular risk. Furthermore, the determination of the parameters in combination with other thrombosis-associated changes enables 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® VER 2.0, ThromboType®plus VER 3.0 and GenoType MTHFR VER 3.0 are based on the reliable DNA•STRIP Technology – The test systems FluoroType® Factor V VER 1.0, FluoroType® Factor II VER 1.0 and FluoroType® MTHFR C677T VER 1.0 rely on an innovative fluorescence-based technology.
Product range
Your fluorescence-based test system for the reliable detection of the Factor V Leiden mutation.
Your benefits with FluoroType® Factor V VER 1.0
- No limitation: Genetic detection can also be done under anticoagulation treatment and thus at any point in time.
- Reliable Result: The test-specific evaluation software guaranteed objective and valid result interpretation.
- User-friendly: Due to its very low pipetting effort the test system can easily be integrated into every routine laboratory.
- Cost-effective: No costly equipment is needed to perform the test, therefore making it appealing to laboratories of all size.
At a glance
Molecular genetic fluorescence-based test system for the analysis of the Factor V Leiden mutation.
Starting material:
EDTA/Citrate blood
DNA Isolation:
GXT Blood Extraction Kit VER 2.0 (with GenoXtract®)
Instrument for Amplification and Detection:
FluoroCycler® 12
FluoroCycler® XT
Technology:
Downloads:
Your fluorescence-based test system for the reliable detection of the Factor II mutation (prothrombin G20210A mutation).
Your benefits with FluoroType® Factor II VER 1.0
- No limitation: Genetic detection can also be done under anticoagulation treatment and thus at any point in time.
- Reliable Result: The test specific evaluation software guaranteed objective and valid result interpretation.
- Innovative: FluoroType® Factor II is based on an innovative fluorescence-based technology – this enables rapid and reliable results.
- User-friendly: Due to its very low pipetting effort the test system can easily be integrated into every routine laboratory.
At a glance
Molecular genetic fluorescence-based test system for the analysis of the Factor II mutation (prothrombin G20210A mutation)
Starting material:
EDTA/Citrate blood
DNA Isolation:
GXT Blood Extraction Kit VER 2.0 (with GenoXtract®)
Instrument for Amplification and Detection:
FluoroCycler® 12
FluoroCycler® XT
Technology:
Downloads:
Your fluorescence-based test system for the reliable detection of the C677T mutation in the MTHFR gene.
Your benefits with FluoroType® MTHFR C677T VER 1.0
- Reliable Result: The test specific evaluation software guaranteed objective and valid result interpretation.
- User-friendly: Due to its very low pipetting effort the test system can easily be integrated into every routine laboratory.
- Cost-effective: No costly equipment is needed to perform the test, therefore making it appealing to laboratories of all size.
- Maximum of Automation: The combination of fully automated nucleic extraction and subsequent amplification with fluorescence-based detection saves time-consuming hands on time.
At a glance
Molecular genetic fluorescence-based test system for the analysis of the C677T mutation in the MTHFR gene
Starting material:
EDTA/Citrate blood
DNA Isolation:
GXT Blood Extraction Kit VER 2.0 (with GenoXtract®)
Instrument for Amplification and Detection:
FluoroCycler® 12
FluoroCycler® XT
Technology:
Downloads:
Your molecular genetic test system for the reliable detection of eight thrombophilia-associated mutations
It is estimated that 2 of 1,000 people worldwide are affected by thrombophilia. The individual risk of disease depends on different factors. Genetically caused blood-clotting disorders play a major role. The Factor V Leiden mutation is the most common thrombophilia-associated mutation. A point mutation within the Factor V gene causes an amino acid exchange of arginine versus glutamine. The mutation eliminates the activated protein C (APC) cleavage site, thus the result is an increased stimulation of blood coagulation. The second most frequent mutation is the prothrombin G20210A mutation. This point mutation involves the noncoding regulatory area of the Factor II gene and leads to an increased prothrombin concentration in plasma.
Most patients who suffer from thrombophilia do have more than one genetic predisposition. A combination of genetic defects leads to an increased risk for thrombosis, thus a combined analysis of thrombophilia-associated parameters is reasonable. Mutations within the Factor V gene as Factor V Cambridge, Factor V Hong Kong and Factor V Liverpool are rare but still relevant for thrombophilia and should not be disregarded. The identification of these parameters in combination with further thrombophilia-associated mutations as MTHFR C677T, MTHFR A1298C and PAI -675 4G/5G permits a reliable estimation of the individual risk for thrombosis.
GenoType CVD VER 1.0 enables the detection of these eight different thrombophilia-associated mutations for broad and reliable thrombophilia diagnostics.
Your benefits with GenoType CVD VER 1.0
- User-friendly: The test system is based on the user-friendly DNA•STRIP technology. A ready-to-use amplification mix is already included and also the Taq polymerase is provided in the kit. This saves time and money enabling an optimal integration in your daily routine.
- Individual automation: DNA isolation and detection can be performed automatically. Batch or individual automation can be performed, thus gaining maximum flexibility.
- Simple evaluation: using an evaluation template, the test result can be read rapidly and clearly.
At a glance
Molecular genetic assay to detect following thrombophilia associated mutations:
- Factor V Leiden
- Cambridge
- Hong Kong
- Liverpool
- Prothrombin G20210A
- MTHFR C677T
- MTHFR A1298C
- PAI -675 4G/5G
Starting material:
EDTA/Citrate blood
DNA Isolation:
GXT Blood Extraction Kit VER 2.0 (with GenoXtract®)
Technology:
Downloads:
Your test system for the definitive detection of Factor V Leiden and prothrombin G20210A mutations as well as two mutations within the MTHFR gene.
Our ThromboType®plus VER 3.0 test system allows you to simultaneously and definitively detect several clinically relevant thrombosis-related mutations and thus an effective diagnosis of thrombophilia.
Your benefits with ThromboType® plus VER 3.0
- Definite result: If the test is not processed under optimal conditions, this will be indicated by an internal control.
- More information: The combined determination of these four thrombosis-related mutations allows for effective diagnosis of thrombophilia.
- No limitation: Genetic detection can also be done under anticoagulation treatment and thus at any point in time.
At a glance
Molecular genetic assay for analysis of the Factor V Leiden, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C mutations
Starting material:
EDTA/Citrate blood
DNA Isolation:
GENO•CARD VER 1.0 or
GXT Blood Extraction Kit VER 2.0 (with GenoXtract®)
Technology:
Downloads:
Your test system for the definitive detection of Factor V Leiden and Prothrombin G20210A mutations.
Our ThromboType® VER 2.0 test system allows you to detect the two most common thrombophilia associated mutations simultaneously.
Your benefits with ThromboType® VER 2.0
- Definite result: The combined determination of the two most frequent thrombosis-related mutations allow for effective diagnosis of thrombophilia.
- No limitation: Genetic detection can also be done under anticoagulation treatment and thus at any point in time.
- Efficient processing: Since ThromboType® VER 2.0 can be combined with other parameters from the GenoType product line, joint processing of several human genetic parameters is possible. This allows effective integration into your routines.
At a glance
Molecular genetic assay for analysis of the Factor V Leiden and Prothrombin G20210A mutations
Starting material:
EDTA/Citrate blood
DNA Isolation:
GENO•CARD VER 1.0 or
GXT Blood Extraction Kit VER 1.0 (with GenoXtract®)
Technology:
Downloads:
Your test system for the definitive detection of two mutations within the MTHFR gene.
With our GenoType MTHFR test system, you can rapidly and easily detect the C677T and A1298G mutations within the MTHFR gene together.
Your benefits with GenoType MTHFR VER 3.0
- Definite result: If the test is not processed under optimal conditions, this will be indicated by an internal control.
- Simple evaluation: Using an evaluation template, the test result can be interpreted rapidly and clearly.
- Efficient processing: Since GenoType MTHFR VER 3.0 can be combined with other parameters from the GenoType product line, joint processing of several human genetic parameters is possible. This allows effective integration into your routines.
At a glance
Molecular genetic assay for analysis of the MTHFR gene mutations C677T and A1298C
Starting material:
EDTA/Citrate blood
DNA Isolation:
GENO•CARD VER 1.0 or
GXT Blood Extraction Kit VER 1.0 (with GenoXtract®)
Technology:
Downloads:
Your test system for the reliable detection of the -675 4G/5G and A-844G polymorphisms within the PAI-1 gene.
Your benefits with GenoType PAI-1 VER 2.0
- No limitation: the PAI-1 level in the blood is influenced by different factors, such as glucose or also insulin. Therefore, biochemical methods only allow the documentation of an actual state. A permanently elevated PAI-1 level, on the other hand, is only recognized to a limited extent. An examination of the genetic basis is therefore sensible and advisable.
- Reliable result: if the test is not processed under optimal conditions, this will be indicated by an internal control.
- Simple evaluation: using an evaluation template, the test result can be read rapidly and clearly.
Starting material:
EDTA blood/Citrate blood
DNA Isolation:
GENO•CARD VER 1.0 or
GXT Blood Extraction Kit VER 2.0 (with GenoXtract®)
Technology:
DNA•STRIP technology
Downloads:
Please contact your local representative for availability in your country.
Not for sale in the USA.
Legal Manufacturer is Hain Lifescience GmbH – A Bruker Company
