thrombosis Flashcards
how does a disorder of thrombosis usually present?
- pulmonary embolism
- deep vein thrombosis
what are the symptoms of pulmonary embolism?
- Tachycardia
- Hypoxia
- Shortness of breath
- Chest pain
- Haemoptysis
- Sudden death
what is the presentation of deep vein thrombosis
- Painful leg
- Swelling
- Red
- Warm
- May embolise to lungs causing pulmonary embolism
- Post-thrombotic syndrome
what factors contribute to thrombosis?
- blood (dominant in venous thrombosis)
- vessel wall (dominant in arterial thrombosis)
- blood flow (dominant in arterial and venous thrombosis)
how does vessel wall affect thrombosis?
- Many proteins active in coagulation are expressed on surface of endothelial cells and their expression altered in inflammation
how does blood flow affect thrombosis?
- Reduced flow (stasis) increases risk of thrombosis
- Surgery, pregnancy, long haul travel
what do the 3 contributory factors to thrombosis make up?
virchow’s triad
what is venous thrombosis called?
thrombophilia
how does thrombophilia present?
- Thrombosis at young age
- ‘spontaneous thrombosis’- no clear risk factor
- Multiple thromboses
- Thrombosis whilst anticoagulated
what can tip the balance towards venous thrombosis?
the decrease in fibrinolytic factors (decrease breakdown clots)
increase coagulant factors & platelets
what are the main proteins involved in anticoagulation?
antithrombin
protein c
protein s
- antithrombin inactivates thrombin (F2a) and F10a
- Protein C and Protein S inactivate F5a and F8a
what is the treatment of venous thrombosis?
- Prevention (Thromboprophylaxis)
- Assess and prevent risks
- Prophylactic anticoagulant therapy
- Reduce risk recurrence/ extension
- Lower procoagulant factors
- Warfarin, DOACs
- Increase anticoagulant activity
- Heparin
- Lower procoagulant factors
when does anticoagulant therapy have therapeutic effect?
- Venous thrombosis
- Initial treatment to minimise clot extension/ embolism (<3months)
- Long term treatment to reduce risk of recurrence
- Atrial fibrillation
- To reduce risk of embolic stroke
- Mechanical prosthetic heart valve
when can anticoagulant therapy have preventative effects?
(thromboprophylaxis)
Following surgery, during hospital admission, during pregnancy
what are the different types of heparin?
- Long chains- unfractionated (UFH)- intravenous administration, short half life
- Low molecular weight (LMWH)- subcutaneous administration
what are the actions of unfractionated heparin?
- Enhancement of antithrombin
- Inactivation of throbin (Hep binds AT + thrombin)
- Inactivation of FXa (hep binds AT only)
- (Inactivation of FIXa, FXIa, FXIIa)
- Increases APTT
what are the actions of low molecular weight heparin?
- Contain pentasaccharide sequence for binding AT
- Predictable dose response in most cases so does not require monitoring -measure anti-Xa as doesn’t change APTT
- Action predominantly against factor Xa with some antithrombin effect
what is an examples of a vitamin K antagonist?
warfarin
how does warfarin work?
competes with Vit K reduction from epoxide to hydroquinone
reduces the production of functional coagulation factors
induces an anticoagulated state slowly
reversible
what is the difficulty of VKA?
narrow therapeutic index and requires monitoring
how can VKA be reversed?
- Reversed slowly by vit K administration- takes several hours
- Reversed rapidly by infusion of coagulation factors
- POCC (prothrombin complex concentrate- contains factors II, VII, IX and XI)
- FFP (fresh frozen plasma)
what are the side effects of VKAs?
- Bleeding
- Skin necrosis
- Severe protein C deficiency- 2-3 days after starting warfarin
- Thrombosis predominantly in adipose tissue
- Purple syndrome
- Disrupted atheromatous plaques bleed
- Cholesterol emboli lodge in extremities
- Embryopathy
- Chondrodysplasia punctata
- Early fusion of epiphyses
- Warfarin teratogenic in 1st trimester
- Chondrodysplasia punctata
what can cause resistance to warfarin?
- Lack of patient compliance
- Measure warfarin levels
- Proteins induce by vit k absence (PIVKA)
- Diet, increased vit K intake
- Increased metabolism Cyt P450 (CYP2C9)
- Reduced binding (VKORC1)
what are some examples of direct oral anticoagulants (DOACS)?
rivaroxaban
apixaban
dabigatran
where do DOACs act on the coagulation pathway?
what is the difference between warfarin and DOACs?
what therapeutic treatment is used in venous thrombosis?
- Initial treatment to minimise clot extension/ emoblisation (<3month)
- DOAC or LMWH for first few days followed by DOAC or warfarin (not started immediately as takes time to work and avoid skin necrosis)
- Long term treatment to reduce risk of recurrence
- DOAC or warfarin
what therapeutic treatment is used in atrial fibrillation?
- To reduce risk of embolic stroke
- DOAC or warfarin
what therapeutic treatment can be used for mechanical prosthetic heart valve?
- Warfarin (DOACS not effective and should be avoided)
when can an anticoagulant preventative be used and what type of drug is more appropriate?
- Lower doses used
- Following surgery
- LMWH or DOAC
- During hospital admission
- DOAC not effective for use as medical thromboprophylaxis
- LMWH used
- During pregnancy
- LMWH
- DOACs not safe in pregnancy – cross placenta
