Factor V Leiden

(Activated Protein C Resistance)

<Presentations>

<Index>

 

 

Definition

-  Autosomal dominant genetic mutation of factor V leading to hypercoagulable state

 

Features

-  Activated Factor Va catalyses prothrombin to thrombin --> coagualtion

-  Single point mutation of gene R506Q

-  More slowly degraded by activated Protein C (aPC)

-  Homozygous (1%) or heterozygous: incomplete dominance

-  Most common inherited thombophillic disease in Caucasians

-  5% population, 12-20% Caucasians

-  Normal factor V serum levels

-  Worse phenotype if combined w factor V def (rare)

-  Suspect in any Caucasian w thrombotic event <50yrs

 

Associated S/S

-  Thrombophillia

-  Almost exclusively venous

-  Less events than def of antithrombin III or protein C or S

-  DVT

-   50-60% of events

-   Found in up to 30% of DVTs

-  SVT

-  PE

-  Unusual sites: cerebral, mesenteric, central retinal vein

-  Increased risk miscarriage & still birth

-   ? increased risk of preeclampsia

-  Events often ass w trigger: pregnancy, trauma, OCP, smoking..

-  Risk factors for events: age, obesity, lack of exercise

 

Ix

-  Coags

-  APTT + aPC: increased = aPC resistance

-  Initial test of choice unless pt has Lupus anticoagulant or on Heparin

-  If increased requires PCR to Dx

-  Sometimes skipped: straight to PCR

-  PT: +/- increased

-  +/- INR: +/- decreased

-  Mixing test: normalises

-  Factor V activity & Ag

-  PCR: R506Q mutation

 

Mx

-  As per complications: DVT, PE, SVT..

-  If events +/- prophylaxis w Warfarin

-  Peri-operative prophylaxis: Enoxaparin

-  Mx of risk factors

-  Contraception, HRT +/-

-  Smoking cessation

-  Weight loss

-  Exercise

-  Screening of family members: controversial