Know Your Patient's Risk of Thrombosis
As
a health care professional, you know that thrombophilia can be a
hereditary disease. Genetic variations in the genes encoding MTHFR,
Factor II and Factor V can lead to clotting disorders.
Identifying early whether your patient has these genetic variants can help you:
- Decide whether to recommend more frequent coagulation screening.
- Make anticoagulant therapy decisions.
- Prescribe prevention strategies to reduce cardiovascular risk factors.
Know Before You Prescribe
Iverson's Thrombophilia Panel screens for any combination of MTHFR, Factor II and Factor V that you select.
MTHFR
Genetic
mutations are the most common inherited risk factor for elevated
homocysteine levels. MTHFR is an enzyme that helps the body metabolize
homocysteine. It does this by converting folic acid to its activated
form: methyl folic acid (5-methyl-tetrahydrofolate). This conversion
activates folic acid and allows it to be used to help metabolize
homocysteine to the amino acid methionine. Without MTHFR, folic acid
cannot be converted to its activated, methylated form and, therefore,
homocysteine cannot be metabolized to methionine. When genetic
mutations create an MTHFR problem, homocysteine levels may rise and
start to cause atherosclerosis, oxidative stress, and clotting
disorders.
Factor II Prothrombin
Prothrombin
is a coagulation factor that is needed for the normal clotting of
blood. It is the precursor to thrombin, which converts fibrogen into
strands of fibrin.
The factor II mutation is a common genetic defect for inherited thrombosis, and is present in 1-3% of the general population.1 This mutation can lead to hypercoagulability and also may contribute to infertility.
Factor V Leiden
Factor
V Leiden is a variant of human factor V that causes hypercoagulability.
The mutation creates a condition in which the coagulation factor cannot
be destroyed. Inefficient inactivation of Factor V then facilitates
overproduction of thrombin, leading to an excess of fibrin generation
and increased clotting.
Factor V Leiden is the most common inherited form of thrombophilia, affecting 3-8% of the Caucasian population in the US and Europe as reported by the National Institutes of Health (NIH).2 It is less common in other populations.
Testing is Fast and Simple
With
our easy-to-use test kit, you simply take a sample and send it to our
laboratory. In just days, you'll have a definitive report that will
help you make the very best decisions to help your patients avoid
hereditary clotting disorders.
Understanding the Genetics
MTHFR: The
most common MTHFR variant is C677T. It causes the production of a
thermolabile enzyme and decreased recycling of folate required for
homocysteine metabolism. The presence of a second mutation in the MTHFR
gene, A1298C, in conjunction with C677T has been associated with
decreased enzyme activity and hyperhomocysteinemia. The C677T
variant is extremely common: 43% of the population is heterozygous and
approximately 12% are homozygous for the variant.3,4
C677T homozygosity is associated with a three-fold risk of premature
cardiovascular disease, including pulmonary embolism, stroke, coronary
artery disease and myocardial infarction in adults. It also
may play a role in the risk of high blood pressure in pregnancy
(pre-eclampsia). The frequency of the A1298C variant is reported to be
as high as 30% in the general Caucasian population. A1298C in
conjunction with C677T is associated with decreased MTHFR activity and
hyperhomocysteinemia.5 Additionally,
research suggests the A1298C and C677T variants lead to low levels of
folate, and for pregnant women with brain and neural tube (spinal cord)
defects in their children.6
Factor II: The
second most common genetic risk factor for thrombophilia is the
prothrombin G20210A mutation also called the Factor II mutation.
G20210A indicates a guanine-to-adenine base substitution at position
20210 near the gene that codes for Factor II and results in an
overproduction of prothrombin, which can cause thrombophilia.
Factor V: The
Factor V Leiden (FVL) variant results from a guanine for adenine
substitution at base 1691 (G1691A) in the gene that codes for Factor V.
The G1691A translates into a single amino acid substitution, which
makes the Leiden variant resistant to cleavage by APC. FVL persists in
the plasma about 10 times longer, which can promote a hypercoagulable
state (thrombophilia).References
1. Salomon O, Steinberg DM, Ziyelin A, Gitel S, Dardik R, Rosenberg N, Berliner S, Inbal A, Many A, Lubetsky
A, et al. Single and combined prothrombic factors in patients with
idiopathic venous thrombolism: prevalence and risk assessment.
Arterioscler Throm Vasc Biol [Internet]. 1999 [cited 2008 Oct
21];19:511-518. Available from:
http://atvb.ahajournals.org/cgi/content/full/19/3/511
2. Genome.gov: Learning about Factor V Leiden Thrombophilia. National Human Genome Research Institute: National Institutes of Health [Internet]. [cited 2008 Nov 10]. Available from: http://www.genome.gov/15015167
3.
Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease:
evidence on causality from meta-analysis. BMJ [Internet]. 2002 [cited
2008 July 22];325:1202-1206. Available from: http://bmj.com/cgi/content/full/325/7374/1202
4. Botto LD, Yang Q. 5,10-methylenetetrahydrofolate reductase gene variants and congenital anomalies: a huge review. Am J Epidemiol. 2000;151(9):862-877.
5. Markan S, Meenakshi S, Sehrawat BS, Kumari S, Jain S, Khullar M. MTHFR 6777 CT/MTHFR 1298 CC genotypes are associated with increased frisk of hypertension in Indians. Mol Cell Biochem [Internet]. 2007 [cited 2008 Nov 10];302:125-131. Available from: http://www.springerlink.com/content/trx5864m28851177/full test.pdf?page=1
6. Sunder-Plassmann G, Födinger M. Genetic determinants of homocysteine level. Kidney International. 2003;63 suppl 84:S141-S144.
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