Thrombophilia

Question 1

What are the two main classes of thrombophilia

Answer 1

Inherited

Acquired

Question 2

What is thrombophilia

Answer 2

A coagulopathy that predisposes to thrombosis - usually VTE - DVT/PE

Question 3

What are some risk factors for arterial thrombosis

Answer 3

Smoking
HTN
DM
Hyperlipidaemia

Question 4

What are some risk factors for venous thromboembolism

Answer 4

Surgery 
Trauma
Immobility 
Pregnancy or COCP, HRT
Age 
Obesity 
Varicose veins
Other conditions - heart failure, malignancy, IBD, nephrotic syndrome, paroxysmal nocturnal haemoglobinuria

Question 5

What must you give for thrombophilia in pregnancy

Answer 5

Anticoagulant and thromboprophylaxis - prophylactic heparin in some and aspirin if antiphospholipid syndrome

Question 6

What is the most common inherited thrombophilia

Answer 6

Activated protein C (APC) resistance/factor V Leiden

Question 7

What percentage of the population has APC?

Answer 7

5%

Question 8

What genetic change causes APC?

Answer 8

Single point mutation in factor V, so this clotting factor is not broken down by activated protein C

Question 9

How much is the risk of thrombosis increased if heterozygous for the mutation?

Answer 9

5 fold

Question 10

How much is the risk of thrombosis increased if homozygous for the mutation

Answer 10

50 fold

Question 11

Describe prothrombin gene mutation

Answer 11

Causes high prothrombin levels and increased thrombosis due to down regulation of fibrinolysis, by thrombin activated fibrinolysis inhibitor

Question 12

Describe protein C and S deficiency

Answer 12

These vitamin K dependent factors act together to cleave and neutralize factors 5 and 8 .
Heterozygotes deficient for either protein risk thrombosis. Skin necrosis can occur especially on warfarin
Homozygotes deficient for either protein causes neonatal purpura fulminans which is fatal if untreated

Question 13

Describe antithrombin deficiency

Answer 13

Antithrombin is a co-factor of heparin and inhibits thrombin
Less common but more serious - increases VTE more than protein C and S deficiency if heterozygous and if homozygous then incompatible with life

Question 14

List the inherited thrombophilias

Answer 14

APC resistance/factor V Leiden
Prothrombin gene mutation
Protein C and S deficiency
Antithrombin deficiency

Question 15

List the causes of acquired thrombophilia

Answer 15

Antiphospholipid syndrome
OCP/HRT
Any cause of polycythaemia or thrombocytosis

Question 16

Describe antiphospholipid syndrome

Answer 16

Serum antiphospholipid antibodies predispose to venous and arterial thrombosis, thrombocytopenia and recurrent foetal loss
Mostly primary disease but can be seen in SLE

Question 17

Which tests for thrombophilia would you order

Answer 17

FBC
Film
Clotting - PT, thrombin time, APTT, fibrinogen
APC resistance test - if positive do DNA analysis for factor V mutation
Prothrombin gene mutation PCR
Lupus anticoagulant
Anticardiolipin antibodies
Assays for antithrombin, protein C and S deficiency

Question 18

When should tests for thrombophilia be done?

Answer 18

When patient is well, not pregnant and off anticoagulation for 1 month

Question 19

Who should you test for thrombophilia

Answer 19

Recurrent foetal loss >3
Arterial thrombosis or MI <50yo
Unprovoked VTE <40 and no RF
Unusual site - mesenteric or portal vein thrombosis

Question 20

How are thrombophilias treated

Answer 20

Anticoagulate acute thrombosis
If recurrent consider life long anticoagulation
If thrombosis happens when on treatment, increase treatment intensity - increase target INR 3-4
In antithrombin deficiency, high doses of heparin may be needed, Liase with a haematologist
In protein C and S deficiency, monitor treatment closely as skin necrosis may occur with warfarin