T7-L6: Thrombosis

Question 1

What are the risk factors for VTE?

Answer 1

• Oestrogen only pill
• Surgery
• Malignancy
• Pregnancy and Post-partum
• Thrombophillia
• Sedentary
• Major Trauma
• Hormone replacement therapy
• Obesity
• First degree relative with VTE
• One or more significant medical comorbilities
• Personal history of VTE
• Dehydration
• age over 60- years
• Critical care admission

Question 2

What pharmacological prophylaxis can we use for VTE?

Answer 2

• Low dose of LMWH compared to treatment
• DOCAs such as Rivoroxaban, Apixaban and Dabigatran
• Fontaparinux (synthetic pentasaccarude) - is not derived from porcine products

Question 3

What exclusion tests can we use to exclude VTE?

Answer 3

• D-Dimer Test
• Wells Score
  Use these together in an agreed algorithm
• Ultrasound
• CT of chest in PE
• VQ-Scan

Question 4

How do DOCAs work?

Answer 4

• Rivaroxan and Apixaban act as FcXa inhibitors. They do this without having to be bound to antithrombin.
• Dabigatran - Direct inhibitor of thrombi

Question 5

What is the advantage of DOCAs over Wafarin?

Answer 5

The dose of DOCAs are more predictable than Warfarin. The dose is uniform in most patients and there is no need for routine monitoring. There are some cases where an alteration is needed e.g. renal disease or in the elderly.

We also do not need a run in period with heparin like warfarin which takes 5 days to take effect.

Question 6

What is the role of LMWH in there treatment of VTE?

Answer 6

It can be used as a run-in before Warfarin. We tend to use warfarin in patients with severe renal impairment and would therefore start them on LMWH. This is as DOCAs are secreted through the kidneys. It can also be used in suspicion of VTE where tests have not been done yet.

Question 7

How do we manage VTE?

Answer 7

• In a first episode create with Warfarin or DOCA for 3-6 months
• If a reversible risk is identified the drug can be discontinued. If we cannot identify a reversible risk, the drug is continued indefinitely.
• In recurrent VTE on therapeutic anticoagulation consider thrombophilia or issue with adherence, change in dose due to changes in weight for example.

Question 8

Define thrombophillia.

Answer 8

Thrombophilia’s are familial or acquired disorders of the haemostatic mechanism which are likely to predispose to thrombosis.

Patients spontaneously develop VTE:

• Spontaneously when young
• Of disproportionate severity
• At an early age

Question 9

Give examples of heritable thrombophillias.

Answer 9

• Protein S deficiency
• Protein C deficiency
• Antithrombin deficiency
• Factor V Leiden
• Antithrombin deficiency

Less common defiicneies include:

• Dysfibrinogenamia
• Prothrombin 20210A

Question 10

What is Antiphospholipid syndrome?

Answer 10

An autoimmune disorder in which patients develop antibodies against negatively charged phopsholipids. These phospholipids are important in the complexes that form during the coagulation cascade. These autoantibodies disrupt these complexes and tip the body into a coagulative state.

It tends to present with recurrent venous/arterial thrombosis and miscarriages.

Question 11

What are clinical feature of thrombophilla?

Answer 11

• DVT
• PE
• Superficial thrombophlebitis - thrombi forming in superficial veins often associated with inflammation
• Thrombosis of cerebral, axillary, portal, mesenteric veins - these vessels are less commonly affected in the healthy
• Arterial thrombosis - feature of APLS not the heritable disorders
• Coumarin induced skin necrosis (particularly protein C deficiency)
  Obstetric complications : foetal wastage (in APLS)

Question 12

What is Factor V Leiden?

Answer 12

A point mutation in the gene that codes for the factor V procoagulant protein. This is at the point protein C cleaves factor V. It makes FcV procoagulant protein hang around for longer, as protein C cannot cleave it. It is protein C resistance. Patients have sufficient levels of protein C but it just cannot do its job.

- Homozygotes: 30-50 fold OR for venous thrombosis
- Interacts with other risk factors for VTE - such as pregnancy, obesity, oestrogen pill etc.
- Risk of recurrent VTE not increased - it is therefore not used to make decisions about long term anticoagulation

Question 13

What is Prothrombin 20210A?

Answer 13

• Point mutation in 3’ untranslated region of prothrombin gene
  
  • Associated with increased prothrombin levels
  • 3 fold increase in venous thrombosis
    Occurs in 1-2% healthy UK population

Question 14

What are confounding factors in thrombophillia testing?

Answer 14

• Pregnancy
• Liver failure
• COCP/Oestrogen use
• Major major illness e.g. sepsis
• Anticoagulation use
• Acute phase of thrombosis

Question 15

What is the role of Protein S and Protein C?

Answer 15

Protein C breaks down activated FcV and FcVIII. Protein S is a cofactor for Protein C.

Protein C deficiency, found in 0.3% of the population leads to a 10% risk of venous thrombosis. Protein S deficiency found in 0.3% of the population, leads to a 10% risk fo venous thrombosis.