Thrombophilia and clotting disorders

Question 1

What are the inherited causes of thrombophilia?

Answer 1

Factor V Leiden (most common, resistance to protein C)
Prothrombin gene mutation (Second most common)
Antithrombin III deficiency,
Protein C deficiency,
Protein S deficiency.

Question 2

What are acquired causes of thrombophilia?

Answer 2

Antiphospholipid syndrome,
Combined oral contraception pills,
Malignancy,
Nephrotic syndrome
PNH,
Obesity,
Surgery,
Smoking,
Long haul flights (>4h)

Question 3

Describe features of Factor V Leiden

Answer 3

Autosomal dominant - Protein C when bound to Protein S and thrombin-thrombomodulin, breaks down factor 5 and 8, thus reducing coagulation. Factor V leiden is factor V resistent to protein C.
This can cause DVT, PR, strokes

Question 4

What is antiphospholipid syndrome?

Answer 4

It is when there are antiphospholipid antibodies. Examples include lupus anticoagulant, cardiolipin antibodies or beta-2 glycoprotein-1 antibodies.
These disrupt the annexin V sheild, exposing phospholipid and triggering thrombosis. Can be priamry or occur secondary to other conditions eg, SLE

Question 5

What are the features of antiphospholipid syndrome?

Answer 5

Venous and arterial thrombosis,
Recurrent miscarriages,
Livido reticularis,
Pre-eclampsia and pulmonary hypertension

Question 6

What are the investigations for antiphospholipid syndrome?

Answer 6

Antibodies: Anticardiolipin, anti-beta2 glycoprotein 1 and lupus anticoagulant.
Thrombocytopenia.
Prolonged APTT (paridozical)

Question 7

what is the management of antiphospholipid syndrome?

Answer 7

Primary thromboprophylaxis - low dose aspirin.
Secondary thrombocytopenia - Initial VTE/arterial thrombus then lifelong warfarin with INR 2-3. If recurrent or had thrombus while on warfarin then increase INR to 3-4 and consider low dose aspirin

Question 8

What is the management of antiphospholipid syndrome in pregnancy?

Answer 8

Low dose aspirin as soon as pregnancy confirmed.
Low molecular weight heparin once fetal heart beat is heard and stopped at 34 weeks

Question 9

What are the investigations for thrombophilia?

Answer 9

FBC,
Blood film,
APTT,
Fibrinogen,
PT,
D-dimer,
serum albumin, cholesterol and triglycerides (to investigate nephrotic syndrome as a cause),

Question 10

What are the mechanisms of action of DOACs?

Answer 10

Dabigitran is a direct thrombin inhibitor,
Apixaban, rivaroxiban and edoxiban - Factor Xa inhibitors.

Question 11

What are the reversal agents for doacs?

Answer 11

Dabigitran - Idarucizumab
Rivaroxaban and apixiban - Andexanet