2: Inherited and Acquired Thrombophilias Flashcards
What is a thrombophilia
Inherited or acquired genetic disorder that leads to recurrent DVTs or PEs
What are 5 inherited thrombophillias
- Factor V Leiden
- Prothrombin mutation
- Protein C deficiency
- Protein S deficiency
- Antithrombin 3 mutation
- Hyperhomocystinaemia
What is the most common inherited thrombophilia
Factor V Leiden
What is the second most common inherited thrombophilia
Prothrombin gene mutation
Name 3 aquired thrombophillias
COCP
SLE
HRT
how do thrombophillias usually present
Recurrent VTE
what may arterial involvement cause
- Stroke
- MI
- Miscarriage
what is the inheritance pattern of all thombophillias, except hyper homocystinaemia
Autosomal Dominant
what is the most common inherited thrombophilia
Factor V Leiden
explain pathophysiology of factor V Leiden
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
what is prothrombin gene mutation
Increase prothrombin levels
what factor does Protein C inhibit
F5
what factor does protein S inhibit
F8
what does protein C and S deficiency cause
Increase activation coagulation cascade
what also may occur in protein C and S deficiency
Skin necrosis - especially if on warfarin
what will homozygous deficiency for either protein C or S cause
Neonatal purpura fulminans
what is the role of anti-thrombin
Co-factor for heparin
if homozygous anti-thrombin deficiency what happens
Individual is incompatible with life
what is the role of hyperhomocystinaemia
increase F5 and F7
what does hyperhomocystinaemia lead to
increase viscosity of blood
what is the inheritance pattern of hyperhomocystinaemia
autosomal recessive
what does antiphospholipid syndrome increase risk of
arterial and venous thrombosis
how may antiphospholipid syndrome present
- History recurrent arterial and venous thrombosis
- Recurrent miscarriages
- Livedo reticularis
- Pre-Eclampsia
what is key in history with thrombophilia
FH
what is a key investigation for thrombophilias
Coagulation studies
how will anti-phospholipid syndrome present in coagulation studies
Raised APTT
what is APTT
Partial thromboplastin time
what does APTT test
Intrinsic pathway
what 4 factors comprise the intrinsic pathway
F12
F11
F9
F8
how does factor V Leiden present on coagulation studies
Increased PT
what is PT
prothrombin time
what does PT test
extrinsic pathway
what are the factors in the extrinsic pathway
F5 F7 F10 Prothrombin Fibrinogen
who should be tested for thrombophilia
- MI or stroke under 50 years
- unprovoked VTE under 40 years
- Recurrent VTE
- > 3 miscarriages
how are thrombophilias managed
lifelong warfarin: aiming for INR 2-3
what is problem with warfarin in protein C and S deficiency
can promote skin necrosis
which thrombophilia has the highest risk of VTE
antithrombin 3 deficiency (10-20)
