2: Inherited and Acquired Thrombophilias

Question 1

What is a thrombophilia

Answer 1

Inherited or acquired genetic disorder that leads to recurrent DVTs or PEs

Question 2

What are 5 inherited thrombophillias

Answer 2

• Factor V Leiden
• Prothrombin mutation
• Protein C deficiency
• Protein S deficiency
• Antithrombin 3 mutation
• Hyperhomocystinaemia

Question 3

What is the most common inherited thrombophilia

Answer 3

Factor V Leiden

Question 4

What is the second most common inherited thrombophilia

Answer 4

Prothrombin gene mutation

Question 5

Name 3 aquired thrombophillias

Answer 5

COCP
SLE
HRT

Question 6

how do thrombophillias usually present

Answer 6

Recurrent VTE

Question 7

what may arterial involvement cause

Answer 7

• Stroke
• MI
• Miscarriage

Question 8

what is the inheritance pattern of all thombophillias, except hyper homocystinaemia

Answer 8

Autosomal Dominant

Question 9

what is the most common inherited thrombophilia

Answer 9

Factor V Leiden

Question 10

explain pathophysiology of factor V Leiden

Answer 10

Protein C normally inhibits F5. In F5 Leiden, there is mutation meaning protein C can’t bind and inhibit F5. Therefore F5 stimulates pro-thrombin

Question 11

what is prothrombin gene mutation

Answer 11

Increase prothrombin levels

Question 12

what factor does Protein C inhibit

Answer 12

F5

Question 13

what factor does protein S inhibit

Answer 13

F8

Question 14

what does protein C and S deficiency cause

Answer 14

Increase activation coagulation cascade

Question 15

what also may occur in protein C and S deficiency

Answer 15

Skin necrosis - especially if on warfarin

Question 16

what will homozygous deficiency for either protein C or S cause

Answer 16

Neonatal purpura fulminans

Question 17

what is the role of anti-thrombin

Answer 17

Co-factor for heparin

Question 18

if homozygous anti-thrombin deficiency what happens

Answer 18

Individual is incompatible with life

Question 19

what is the role of hyperhomocystinaemia

Answer 19

increase F5 and F7

Question 20

what does hyperhomocystinaemia lead to

Answer 20

increase viscosity of blood

Question 21

what is the inheritance pattern of hyperhomocystinaemia

Answer 21

autosomal recessive

Question 22

what does antiphospholipid syndrome increase risk of

Answer 22

arterial and venous thrombosis

Question 23

how may antiphospholipid syndrome present

Answer 23

• History recurrent arterial and venous thrombosis
• Recurrent miscarriages
• Livedo reticularis
• Pre-Eclampsia

Question 24

what is key in history with thrombophilia

Answer 24

FH

Question 25

what is a key investigation for thrombophilias

Answer 25

Coagulation studies

Question 26

how will anti-phospholipid syndrome present in coagulation studies

Answer 26

Raised APTT

Question 27

what is APTT

Answer 27

Partial thromboplastin time

Question 28

what does APTT test

Answer 28

Intrinsic pathway

Question 29

what 4 factors comprise the intrinsic pathway

Answer 29

F12
F11
F9
F8

Question 30

how does factor V Leiden present on coagulation studies

Answer 30

Increased PT

Question 31

what is PT

Answer 31

prothrombin time

Question 32

what does PT test

Answer 32

extrinsic pathway

Question 33

what are the factors in the extrinsic pathway

Answer 33

F5
F7
F10
Prothrombin
Fibrinogen

Question 34

who should be tested for thrombophilia

Answer 34

• MI or stroke under 50 years
• unprovoked VTE under 40 years
• Recurrent VTE
• > 3 miscarriages

Question 35

how are thrombophilias managed

Answer 35

lifelong warfarin: aiming for INR 2-3

Question 36

what is problem with warfarin in protein C and S deficiency

Answer 36

can promote skin necrosis

Question 37

which thrombophilia has the highest risk of VTE

Answer 37

antithrombin 3 deficiency (10-20)