A venous thrombosis occurs when a blood clot (thrombus) forms inside a vein. Certain genetic factors like mutations in Factor V and prothrombin genes can increase the risk of thrombosis by making the blood more likely to clot. Environmental factors like taking oral contraceptives also increase risk. Deep vein thrombosis (DVT) in the legs is a common type of thrombosis that can dislodge and become a potentially fatal pulmonary embolism. Testing for Factor V and prothrombin mutations is recommended for those with a history of unusual or recurrent thrombosis, especially at a young age or while taking oral contraceptives.

2.  A venous thrombosis is a blood clot (thrombus)
that forms within a vein. Thrombosis is a term for a
blood clot occurring inside a blood vessel.
It is one of the examples of gene-gene interaction
predisposing to disease.
It is found in hypercoagulability state, where venous
or arterial clots form inappropriate and cause life
threatening complications.
These predisposing genetic factor along with
environmental influence increases the risk of the
disease.

3. One such disorder is idiopathic cerebral vein thrombosis.
It is the clot formed in the venous system of brain.
Mortality
untreated: 50%
treated: nonseptic cause 10%
septic cause 30%
Outcome
77% no sequelae
20% develop thrombosis intra or extracerebrally
It is uncommon but life threatening disease.
Mimic many benign condition.

4. There are 3 common factors that lead to abnormal
coagulation of clotting system, which in turn increases
the risk of cerebral vein thrombosis. They are 2 genetic
factor and 1 environmental factor.
1. common missense mutation in a clotting factor,
factor v,
2. common variant in 3’untranslated region of gene for
clotting factor, prothrombin,
3. using oral contraceptives.

5. 1. Mutant allele of factor v ( factor v Leiden FVL)
 arginine replaced by glutamine at position 506
 Allele frequency 2.5% in white people
 Cleavage site for the degradation of factor v is
affected by this alteration, thus making more
stable protein and exert effective procoagulant
 5% of whites who are heterozygous carriers of FVL
have 7 times higher risk of cerebral vein
thrombosis than the general population
 Whereas homozygous have 80 times higher risk

6. 2. Mutation in prothrombin gene
 G replaced by A at position 20210 in 3’
untranslated region of gene
 This change leads to increased level of prothrombin
mRNA, which result in increased translation and
elevated protein level
 2.4% of white people are heterozygotes and they
have 3 fold to 6 fold increased risk of CVT

7. 3. Oral contraceptives
 Independent of FVL and prothrombin, oral
contraceptive that contain synthetic estrogen increases
the risk of thrombosis 14 fold to 22 fold
 Being heterozygous for FVL and using oral
contraceptives cause only a modest increase in risk
factor
 Whereas, being heterozygous for prothrombin with
the usage of oral contraceptives has a relatively higher
risk from 30 to 150 fold

8. Placental artery thrombosis
 FVL and prothrombin allele along with heat-
sensitive methylene tetrahydrofolate reductase allele
lead to this serious predisposing risk factor
 Having at least one complication result in 5 fold
increased risk factor
 Result in placental dysfunction

9.  A classical venous thrombosis is deep vein
thrombosis (DVT), which can break off (embolize),
and become a life-threatening pulmonary
embolism (PE). The disease process venous
thromboembolism (abbreviated as VTE or DVT/PE)
can refer to DVT and/or PE.
 The lower extremity DVT is more common than
idiopathic CVT or placental artery thrombosis.
 The mortality rate due to pulmonary embolus is
upto 10%.
 Environmental factor increase the risk of DVT.

10. These pulmonary emboli removed at autopsy look like casts
of the deep veins of the leg where they originated

11. This patient underwent a thrombectomy. The
thrombus has been laid over the approximate location
in the leg veins where it developed.

12. DVT usually originates in the lower extremity venous
level ,starting at the calf vein level and progressing
proximally to involve popliteal ,femoral ,or iliac
system. .80 -90 % pulmonary emboli originates here .
More than 100 years ago, Virchow described a triad of
factors of
venous stasis,
endothelial damage, and
hypercoagulable state

14. In heterozygous individuals, FVL increases the risk
factor of 1st episode of DVT 7 fold, whereas in
homozygous 80 fold.
Heterozygotes using oral contraceptives have 30 fold
increased risk factor.
Heterozygotes for prothrombin 2 fold to 3 fold.
Double heterozygotes for FVL and prothrombin 20
folds more than that of general population.
Heterozygosity for either FVL or prothrombin has
only less effect on recurrence risk of DVT after 1st
episode, but together they act and increase risk of
recurrence 2-3 fold.

15. The primary objectives of the treatment of DVT are
to
prevent pulmonary embolism,
reduce morbidity, and
prevent or minimize the risk of developing the
postphlebitic syndrome.
 Medications used to treat this condition include
anticoagulants such as heparin, fondaparinux and
more recently dabigatran has shown promise. Vitamin
K antagonists such as warfarin are also commonly
used.

16. FVL and prothrombin allele carriers have an
increased risk for thrombotic events than that of non
carriers.
If oral contraceptives are used, then the risk factor is
increased even more.

17. Consensus recommendations for testing for factor v
Leiden or prothrombin 20210G>A:
•Any venous thrombosis in an individual younger than
50 years
•Venous thrombosis in unusual sites (such as hepatic,
mesenteric, and cerebral veins)
•Recurrent venous thrombosis
•Venous thrombosis in pregnant woman or woman
taking oral contraceptives
•Relatives of individuals with venous thrombosis
younger than 50 years
•Myocardial infarction in female smokers younger than
50 years

18. This consensus recommendation do not include
screening all young women contemplating starting
oral contraceptives in the absence of personal or family
history of thrombosis.