Thrombosis Flashcards
two types of thombotic events
arterial
- coronary, cerebral, peripheral
venous
- DVT/PE
Differences between arterial + venous systems
arterial
- much thicker, have to withstand higher pressures
venous
- thinner, lower pressure, have valves
what causes an arterial thrombosis
atherosclerosis
how is an arterial thrombosis formed
damage to the epithelium – platelets adhesion + aggregation – coagulation – may completely occlude the vessel or can embolise
platelet rich thrombus
treatment of arterial thrombus
aspirin / clopidogrel
modify risk factors for atherosclerosis
what is activated in a venous thrombosis
coagulation cascade i.e. fibrin clot
platelets not activated
what dysfunction leads to venous thrombosis
dysfunction in VIRCHOW’S TRIAD
- stasis
- vessel wall damage
- hypercoagulability
treatment of venous thrombosis
heparin/warfarin/ other new oral anticoagulants
which type of thrombus is platelet rich
arterial
which type of thrombus is fibrin rich
venous
signs of DVT
limb feels HOT, SWOLLEN, TENDER
pitting oedema
signs of PE
pleuritic chest pain
hypoxia
cardiovascular collapse
right heart strain
risk factors for venous thromboembolism
Age obesity pregnancy previous DVT/PE trauma/surgery oestrogen therapy thrombophilia paralysis
why is pregnancy a risk factor for venous thromboembolism
clotting factors raise to about 3 times normal level to prepare for child birth
why does hypercoagulability increase risk of venous thromboembolism
all associated with the release of tissue factor, raised VWF and factor 8
what is thrombophilia
familial or acquired disorders of the haemostatic mechanism which are likely to predispose to thrombosis
mechanism for thrombophilia
decreased anti-coagulant activity
potential reasons for decreased anti-coagulant activity in thrombophilia
low levels of antithrombin III
low levels of protein C and S
role of protein C and S
switch off factor V, VIII, X
most common cause for decreased anti-coagulant activity
Factor V leiden
- varient in factor V gene- makes it more difficult for protein C and S to switch off factor V
what are hereditary thrombophilias
group of genetic defects in which affected individuals have increased tendency to develop premature, unusual and recurrent thrombosis
examples of hereditary thrombophilias
factor V leiden prothrombin 20210 mutation anti-thrombin deficiency protein C deficiency protein S deficiency
when should hereditary thrombophilia screening be considered
venous thrombosis <45 years old recurrent venous thrombosis unusual venous thrombosis family history of venous thrombosis family history of thrombophilia
management of hereditary thrombophilia
advice on avoiding risk
short term prophylaxis
- to prevent thrombic events during periods of known risk e.g. long haul flight
short term anticoagulation
- to treat thrombotic events
long term anticoagulation
- if recurrent thrombotic events
what is a risk of long term anticoagulation
serious haemorrhage
what is the most important tool in assessing risk of recurrent thrombosis
clinical history
- history of previous thrombosis
- spontaneous thrombosis
- family history
example of an acquired thrombophilia
antiphospholipid syndrome
which has a higher risk of thrombosis - anti-phospholipid or hereditary thrombophilia
anti-phospholipid syndrome
features of antiphospholipid syndrome
young women recurrent thromboses - DVT, PE recurrent fetal loss mild thrombocytopenia other autoimmune conditions
antibodies seen in antiphospholipid syndrome
anti-cardiolipin
lupus anticoagulant
effects of antibodies in antiphospholipid syndrome
conformation change in beta2 glycoprotein 1
- activation of primary + secondary haemostasis + vessel wall abnormalities
treatment of anti-phospholipid
aspirin + warfarin
- both given as there is activation of primary and secondary haemostasis systems – risk of arterial + venous thrombosis
how does atherosclerosis occur
- damage to endothelium
- recruitment of foamy macrophage rich in cholesterol
- forms plaques rich in cholesterol
- calcifies – hardens arteries
how do stable atherosclerotic plaques present
intermittent symptoms on exertion
e.g. angina (coronary artery)
claudication (leg artery)
what happens when an unstable plaque ruptures
plaque ruptures – platelets are recruited + cause acute thrombosis
sudden onset of symptoms
e.g. central crushing chest pain, SOB in MI
arterial thrombosis risk factors
hypertension
smoking
high cholesterol
diabetes
what chemicals released by platelets enhance platelet recruitment to the site
ADP
thromboxane A2
How does clopidogrel work
ADP receptor antagonist
how does aspirin work
inhibits COX1 – this is necessary to produce thromboxane A2
side effects of aspirin
- bleeding
2. blocks prostaglandin production – GI ulceration/bronchospasm
DVT prophylaxis
TED stockings
physio
early mobilisation
heparin/warfarin
how does dipyridamole work
phosphodiesterase inhibitor- decreases production of cAMP
tamoxifen
increases DVT risk
