HAEMATOLOGY - THROMBOPHILIA

Question 1

What is the most common inherited thrombophilia in those of Caucasian descent?

Answer 1

Factor V leiden

Question 2

How do protein S and C prevent excessive coagulation

Answer 2

Excess thrombin binds to thrombomodulin so it can’t be part of coagulation princess
Protein S and protein C bind to those thrombin-thrombomodulin complex
Protein S binding to the complex activates the proteolytic site of protein C = cleaves and inactivates active factor 5 and factor 8
This slows down coagulation

The factor 5 degradation product binds to this complex also and further inhibits the ability to cleave factor 5 and 8

Question 3

What is factor 5 Leiden?

Answer 3

Factor V Leiden results from a mutation in clotting factor V that causes activated clotting factor V (factor Va) to be resistant to inactivation by activated protein C, and thereby leads to an increase in thrombin generation.
It increases the risk of VTE fivefold throughout life

Question 4

What causes factor 5 Leiden?

Answer 4

A single point mutation in the factor 5 gene
Autosomal dominant disease
Homozygotes have a high risk of venous thromboembolism

Question 5

How is fcator 5 Leiden diagnosed?

Answer 5

Suspect in those with recurrent venous thromboembolism or has a strong FHx or a young age VTE
PTT shortened or normal
DNA testing for factor 5 Leiden mutation

Question 6

How is fcator 5 Leiden disease treated?

Answer 6

Anticoagulation medication when thrombosis occurs
No role for prophylaxis unless high risk surgery or pregnant

Question 7

What is antiphospholipid syndrome?

Answer 7

An acquired prothrombotic disorder where antiphospholipid antibodies attack phospholipids in cell membrane or the proteins bound to phospholipids. This causes a hypercoagulable state
It’s an autoimmune disease

Question 8

Whats the most common phospholipid antibody?

Answer 8

Anti-beta2-glycoprotein 1
Another common one is anti-cardiolipin

Question 9

What happens in reduced Antithrombin activity?

Answer 9

Increased thrombin generation and activity = predisposes to thrombosis
Increases risk of VTE by 10 fold

Question 10

What happens when there are protein C and S deficiencies?

Answer 10

They cause an increase of thrombin generation and predisposition to thrombosis
Increase risk of VTW at least fivefold

Question 11

What are symptoms of antiphospholipid syndrome?

Answer 11

Complications in pregnancy e.g. recurrent miscarriages
Live do reticularis
VTE

Question 12

Who does antiphospholipid syndrome typically affect?

Answer 12

Women 20-50

Question 13

What blood results does antiphospholipid cause?

Answer 13

Thrombocytopenia
rise in APTT

Antibodies: anticardiolipin, lupus anticoagulant, anti-beta-2-glycoprotein

Question 14

What cause antiphospholipid syndrome?

Answer 14

May be primary or secondary (if secondary most likely caused by SLE)

Question 15

Whats the prevalence of factor V leiden?

Answer 15

5% uk population

Question 16

What is factor V leiden AKA?

Answer 16

Activated protein C resistance

Question 17

Outline the pathophysiology of factor V leiden?

Answer 17

Activated factor V is resistance to cleavage by protein C due to misshapen cleavage site - factor Va is inactivated 10x more slowly than usual

Question 18

What causes protein C or protein S deficiencies?

Answer 18

Can be genetic
Can be acquired e.g. liver dysfunction, warfarin use or nephrotic syndrome

Question 19

Outline the pathophysiology of antithrombin III defieicny?

Answer 19

Type 1 - genetic mutation makes Antithrombin deficient
Type 2 - genetic mutation makes defective antithrombin

Antithrombin III binds exces thrombin and factor X from secondary haemostasis

Question 20

What causes antithrombin III deficiency?

Answer 20

Typically acquired from impaired production e.g, liver disease OR protein losses e.g. DIC or nephrotic sydnrome