Venous thrombosis

thrombosis

1. Venous Thrombosis

2. 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.

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

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

12. Venous Thrombosis 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

13. Venous Thrombosis

14. Venous Thrombosis In heterozygous individuals, FVL increases the risk factor of 1 st 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 1 st episode, but together they act and increase risk of recurrence 2-3 fold.

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

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