Lecture 7: Thrombosis Flashcards
What are the deep veins of the leg?
Illiac, femoral, popliteal and tibial
What are the superficial veins of the leg?
Greater and lesser saphenous veins
What are the three components of virchows triad?
Circulatory stasis, hyper-coagulable state and endothelial injury
What are the symptoms of a DVT?
Can be asymptomatic
Unilateral calf swelling, heat, pain, redness, hardness
What could be the differential diagnoses of a DVT?
Cellulitis, Bakers cyst, muscular pain
What is shown by doppler ultrasound in presence of DVT?
Shows velocity and direction of blood flow
In DVT the veins will be non-compressible by U/S probe
What do D-dimers indicate?
Activation of the clotting cascade
What can be used to assess the likelihood of having a DVT?
Wells risk score and D-dimer test
What is the initial treatment for a DVT?
Therapeutic anti-coagulation using sub-cut LMW heparin
Dosing according to patients weight
If the patient has renal impairment (creatinine clearance less than 30ml/min) then anti-coagulant with IV unfractionated heparin instead
What is the subsequent treatment for a DVT?
Load with oral warfarin for 3-5 days, stop LMW weight once INR>2.0 for 2 days
1st DVT = 6 months warfarin
2nd DVT/PE = lifelong warfarin
Maintain INR between 2-3
What are the symptoms of a PE?
Microemboli - asymptomatic
Classic symptoms:
- Pleuritic pain
- Dyspnoea
- Haemoptysis
Massive: syncope, death
Also:
- Tachycardia
- Tachypnoeic
- Hypotensive
What can be used to investigate a possible PE?
CTPA
V/Q scan (limitation: underlying lung disease)
ECG (sinus tachycardia, AF, right heart strain)
CXR (usually normal)
How would you treat a massive PE?
Thrombolysis and IV heparin
How would you treat a standard PE?
LMW heparin injections, warfarin for 6 months
Consider DOAC as alternative
What is a thrombophillia screen?
Done in younger patients with VTE
Inherited: prothrombin gene variant, anti-thrombin deficiency, protein C deficiency, protein S deficiency
Acquired: anti-phospholipid syndrome
Which drugs are anti-coagulants?
Warfarin
Heparin (LMW or unfractionated)
DOACS (dabigatran - thrombin inhibitor; rivaroxaban - factor Xa inhibitor)
Anti-platelet drugs
Anti-fibrinolytic
What is warfarin?
Vitamin K antagonist - prevents gamma-carboxylation of factors II, VII, IX and X
Prolongs the extrinsic pathway (PT time)
Monitored by INR
What is the target INR for DVT, PE and AF?
2.5
What is the target INR for VTE or metal heart valves?
3.5
What are the half lives of the clotting factors associated with warfarin - II, VII, IX, X
VII - 6 hours
IX - 24 hours
X - 40 hours
II - 60 hours
How long can it take warfarin to reach therapeutic levels?
> 3 days
What drug can also inhibit protein C and protein S?
Warfarin
How would you prescribe warfarin?
Load patient with LMW heparin (10mg, 10mg, 5mg) - bc of fall is protein C and protein S
Patients have different sensitivity to warfarin
LMW continued until the INR is >2 for 2 days
Which clinical states have an INR target of 2.5?
DVT, PE, AF, recurrent DVT off warfarin, thrombophilia, cardiomyopathy
Which clinical states have an INR target of 3.0?
Recurrent DVT while on warfarin, mechanical heart valves, anti-phospholipid syndrome
Which drug is metabolised by CYTP450?
Warfarin
Inhibitors of this enzyme potentiate warfarin and vv
What are the side effects of warfarin?
Teratogenic (use LMW heparin in pregnancy)
Significant haemorrhage risk (1%)
Minor bleeding (20%)
Skin necrosis
Alopecia
How can you reverse warfarin?
Give vitamin K 2-10mg IV/PO depending on INR level
If life threatening bleed can give activated prothrombin complex (octaplex) containing FII, VII, IX and X
Can also give FFP
What is heparin?
A mucopolysaccharide that potentiates anti-thrombin 3
Irreversibly inactivates factors IIa (thrombin) and Xa
How is unfractionated heparin given?
IV infusion
5000U bolus and ~1000U/hour infusion
Monitored by APTT with target range of 1.5-2.5x normal
Safe in renal failure
How is LMW heparin given?
SC injection
Prescribed acc to patients weight
Not usually monitored but patient have to have creatinine clearance of over 30ml/min
What drug can be partially reversed with protamine sulphate?
Unfractionated heparin
Which drug is used for thromboprophylaxis for hospital in-patients?
LMW heparin
What are NOACs?
Alternative to warfarin
Oral
Dont require monitoring
Dabigatran and rivaroxaban
Irreversible
What is dabigatran?
Direct thrombin inhibitor
Used for VTE prophylaxis, treatment of DVT and PE, stroke prevention in AF
110mg bd or 150mg bd
What is rivaroxaban?
Direct factor Xa inhibitor
Used for VTE prophylaxis, treatment of DVTs and Yes, stroke prevention in AF
15mg bd for 3 weeks, then 20mg od (or 15mg od if CrCl is 15-50ml/min)
Which drug is a COX inhibitor?
Aspirin
What is clopidogrel?
ADP receptor inhibitor (anti-platelet drug)
How does dipyridamole work?
Inhibits phosphodiesterase
How does prostacyclin work?
Stimulates adenylate cyclase
What are abciximab, eptifibatide and tirofiban?
Glycoprotein2b3a inhibitors
Name two fibrinolytic agents
tPA and streptokinase
Used to lyse fresh thrombi (arterial) by converting plasminogen to plasmin
Acute MI, thrombotic stroke, major PE, iliofemoral thrombosis
Aim to use within 6 hours
