Lecture 13: Thrombotic disorders Flashcards
Virchow’s triad?
Vascular injury
- trauma, surgery
- prior thrombosis, atherosclerosis
Stasis
- Immbolity - post-op, debility, coma
- pressure - catheter, tumour
- Increased viscosity
Hypercoagulability
- increased procoagulants
- decrease in inhibitors
- (impaired fibrinolysis - rare)
DVT and PE?
Deep vein thrombosis - clot in one of the deep veins of the legs (mostly proximal ones are dangerous as can lead to PE- above the knee), abdomen or rarely the arms. Cause obstructed backflow to the heart. 1 per 1000 per year increasing with age.
Pulmonary embolism - clot travels up vena cava through RHS of heart and into the pulmonary arteries. Can block the pulmonary trunk but more commonly spreads out and blocks smaller arteries in the lungs. 1 in 2000 with 5-10% fatal
Diagnosis of DVT and PE?
DVT:
- Leg swelling
- leg pain
- Oedema
PE:
- SOB
- chest pain
- tachycardia and tachypnoea
Clinically this can be very hard and so we use a scale to give a risk score of a DVT or PE and then if it is borderline we do a D-dimer test to assess risk further. If their initial score was very high then we go straight to a diagnostic test - Ultrasound for DVT and CT for PE
D dimer test?
Looks at the breakdown products of fibrin and in Auckland it is positive in 98% of DVT and PE cases. This means that the negative result (NPV - negative predictive value) can close to rule out a DVT or PE
BUT
A postitive result (PPV - positive predictive value) is bad and can be from a number of things like surgery, inflammation, cancer, a big bruise…
Thrombophilia?
The tendency to develop thrombosis (virchow’s hypercoagulability) and can be aquired or inherited but usually apply the term to hereditary cases.
Manifested as venous thromboembolism (VTE)
VTE causes?
- ≈30-40% Spontaneous
- about 50% of these will have hereditary factor which increases risk: thrombophilia
- Remainder is provoked events
- surgery or trauma
- immobility (absolute risk 1/4656 flights >4hours)
- malignancy
- Other aquired things
Types of inherited thrombophilia?
Abnormal inhibitor function:
- Resistance to activated protein C (Factor V Leiden)
Deficiency of inhibitors:
- Antithrombin, protein C, protein S deficiency
- Rare; antithrombin deficiency is high risk for future thrombosis
Increased factor levels:
- Prothrobin gene mutation 20210A - levels of factor II are higher than normal
- elevated factor VIII
Factor V Lieden?
- point mutation in factor V gene meaning protein C doesn’t bind as easy to Va = heterzygotes have 3-7x risk of thrombosis with homosygotes 50-100x
Relative risk is increased but the absolute risk for DVT is still relatively low. However, if you are heterzygous for F. V-Leiden and go on the oral contraceptive you RR is 35 and AR 0.3
Treatment of PE and DVT with anticoagulants?
Unfractionated heparin has immediate effect and interacts with antithrombin inactivating Xa and IIa (thrombin)
Low molecular weight heparin is what we use more of these days and is smaller glycosaminoglycan chains. Given subcutaneously at 1mg/kg 2td
Warfarin (supressing VitK dep II, VII, IX and X) is given as long term treatment. Needs monitoring and has many drug interactions. Takes 5-7 days to work. Reversal is through VitK for 12-24 hours or with prothrombinX for immediate reversal.
Direct acting oral anticoagulants?
DOACs
- oral direct inhibitors of activated clotting factors
- T1/2 = 9-14h
- Rivaroxaban (Xa) and dabigatran (thrombin/IIa) are both the same as warfarin for treatment of VTE
- Probably superior to warfarin for anticoagulation in AF and as stroke prevention with similar rates of bleeding
- no monitoring needed - fixed does
- less intracranial haemorrhages
Differences between Dabigatran and Rivaroxaban? Reversal?
Dabigatran:
- extremely sensitive to TCT
- APTT prolonged at therapeutic levels (1+1 prologed)
- PR prolonged if very high
- Reversed using idarucizumab - an AB that binds v tightly
Rivaroxaban:
- PR prolonged to some extent APTT less so
- antidote not yet available in NZ so if desperate we us prothrombinX
