Venous thrombosis

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Transcript of Venous thrombosis

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.

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.

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.

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

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

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

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

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.

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

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

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

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.

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.

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.

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

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