Thrombophilia Flashcards
What are the two main classes of thrombophilia
Inherited
Acquired
What is thrombophilia
A coagulopathy that predisposes to thrombosis - usually VTE - DVT/PE
What are some risk factors for arterial thrombosis
Smoking
HTN
DM
Hyperlipidaemia
What are some risk factors for venous thromboembolism
Surgery Trauma Immobility Pregnancy or COCP, HRT Age Obesity Varicose veins Other conditions - heart failure, malignancy, IBD, nephrotic syndrome, paroxysmal nocturnal haemoglobinuria
What must you give for thrombophilia in pregnancy
Anticoagulant and thromboprophylaxis - prophylactic heparin in some and aspirin if antiphospholipid syndrome
What is the most common inherited thrombophilia
Activated protein C (APC) resistance/factor V Leiden
What percentage of the population has APC?
5%
What genetic change causes APC?
Single point mutation in factor V, so this clotting factor is not broken down by activated protein C
How much is the risk of thrombosis increased if heterozygous for the mutation?
5 fold
How much is the risk of thrombosis increased if homozygous for the mutation
50 fold
Describe prothrombin gene mutation
Causes high prothrombin levels and increased thrombosis due to down regulation of fibrinolysis, by thrombin activated fibrinolysis inhibitor
Describe protein C and S deficiency
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
Describe antithrombin deficiency
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
List the inherited thrombophilias
APC resistance/factor V Leiden
Prothrombin gene mutation
Protein C and S deficiency
Antithrombin deficiency
List the causes of acquired thrombophilia
Antiphospholipid syndrome
OCP/HRT
Any cause of polycythaemia or thrombocytosis
Describe antiphospholipid syndrome
Serum antiphospholipid antibodies predispose to venous and arterial thrombosis, thrombocytopenia and recurrent foetal loss
Mostly primary disease but can be seen in SLE
Which tests for thrombophilia would you order
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
When should tests for thrombophilia be done?
When patient is well, not pregnant and off anticoagulation for 1 month
Who should you test for thrombophilia
Recurrent foetal loss >3
Arterial thrombosis or MI <50yo
Unprovoked VTE <40 and no RF
Unusual site - mesenteric or portal vein thrombosis
How are thrombophilias treated
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
