Inherited thrombophilias

Question 1

List the thrombophilias in order of frequency in the population

Answer 1

Hyperhomocysteinaemia
Factor V leiden
Prothrombin gene mutation
Antithrombin III, protein C and S deficiency

Also antiphospholipid Ab (unknown frequency)

Question 2

What is the mechanism of Activated protein C resistance AKA factor V leiden

Answer 2

Normally protein C acts as an anticoagulant by neutralising (cleaving) activated Factor V. In this case Factor V has a point mutation so cannot be cleaved (Factor V leiden)

Question 3

What is the increased risk with APC resistance?

Answer 3

Hetero- 8x increase
Hetero and oestrogen - 35x increase but absolute risk still only 3% over 10 years on OCP
Homo- 100 x increase

AD inheritance

Question 4

Is APC resistance associated with stroke or IHD?

Answer 4

NO

Question 5

PT gene mutation inheritance

Answer 5

AD

Question 6

RR thrombosis with prothrombin gene mutation

Answer 6

4 x increase

Question 7

High homocysteine levels increase risk of what?

Answer 7

Atherothrombosis
Venous thrombosis
Coronary artery disease

Question 8

Mild increase in homocysteine is often to do with what?

Answer 8

Deficiency in B12, pyridoxine, folic acid, hypothyroidism, smoking, methotrexate, CKD

Risk associated with high factor VIII, alone not a risk factor

Question 9

Explain lupus anticoagulant, antiphospholipid antibodies, anticardiolipin.

Answer 9

Antiphospholipid Ab are detected by two assays, lupus anticoagulant and anticardiolipin Ab assays

Question 10

What can you not check in the acute phase?

Answer 10

Antithrombin def, protein C and S

CAN check antiphospholipid Ab, factor V leiden, PT gene mutation

Question 11

`What can you not check on warfarin?

Answer 11

Protein C or S
Lupus anticoagulant can be false positive.

Cannot check lupus anticoagulant on heparin

Question 12

What are the high risk thrombophilias?

Answer 12

Protein C and S deficiency
Antithrombin 3 deficiency

up to 20 x inrease risk

Also homozygous factor 5 leiden