Thrombotic disorders Flashcards
Complete the diagram
What is Virchow’s triad and what is it a risk for?
Deep vein thrombosis
Name 8 thrombotic risk factors
◦Post-operative, especially orthopaedic
◦Hospitalisation
◦Cancer
◦Pregnancy
◦Oral contraceptive pill
◦Long-haul flights
◦Obesity
◦i.v. drug abuse
What condition does this show?
Deep vein thrombosis
What are the symptoms of a DVT?
Can be no symptoms at all – clinically silent
Unilateral calf swelling/ heat/ pain/ redness/ hardness
What are the differential diagnoses for DVT?
Cellulitis, Baker’s cyst, muscular pain
What is the investigation of choice for a DVT and why?
Doppler ultrasound
Veins are non-compressible by U/S probe
How can you assess the likelihood of having a DVT?
The Wells risk score and doing a D-dimer test
Low Wells score and negative D-dimer test have a high negative predictive value (>99% NPV)
If high Wells score or positive D-dimer then proceed to U/S scan to confirm DVT
What is a d-dimer test?
D-dimers indicate activation of the clotting cascade
What 3 veins are classed as an above-knee DVT
Iliac, femoral or popliteal veins
What is the initial treatment for DVT?
Therapeutic anti-coagulation using sub-cut LMW heparin (such as tinzaparin or enoxaparin)
Dose of LMW heparin according to patient’s weight
No monitoring required (but can use anti-Xa assay)
When would you use IV unfractionated heparin?
Ensure adequate EGFR > 30ml/min
Otherwise use iv unfractionated heparin (APTR 2.0)
What drug do you load the DVT patient with after 3-5 days?
Oral warfarin
When do you stop initial heparin after a DVT?
Stop LMW heparin once INR > 2.0 for 2 days
How long are patients anticoagulated for after a DVT?
1st DVT: anticoagulated for 6 months
2nd DVT/PE: lifelong anticoagulation
In what range should the INR be maintained in post-DVT patients?
Maintain INR between 2.0-3.0 (target 2.5)
Monitor INR every 3 weeks
What type of pulmonary emobolism is asymptomatic?
Micro-emboli
What are the symptoms of a pulmonary embolism?
What signs would you fin on examination?
pleuritic pain
dyspnoea
haemoptysis
What are the symptoms of a massive PE?
syncope, death
What does this show?
Pulmonary embolism
What investigations would you do for a pulmonary embolism?
CTPA scan (CT pulmonary angiogram)
V/Q Scan (ventilation/perfusion radio-isotope scan)
ECG
CXR
What type of scan is this and what does it show?
CTPA scan (CT pulmonary angiogram)
Saddle embolus: pre & post-thrombolysis
What indicates a PE on a V/Q scan?
Underperfusion - V/Q mismatch
What type of scan is this and what does it show?
V/Q Scan (ventilation/perfusion radio-isotope scan)
PE
What is the main limitation of V/Q scans?
Underlying lung disease
What will an ECG show in a PE?
Sinus tachycardia
Atrial fibrillation
Right heart strain (RBBB)
Classic: SI, QIII, TIII (rare)
What will a chest x-ray of a PE patient look like?
Usually normal
Linear atelectasis
Small effusions
What is a leading cause of ‘preventable death’ in the Western world?
PE
What signs of shock will patients with a massive PE have?
hypotension, acute dyspnoea, collapse, syncope
What is the treatment for a massive PE?
Thrombolysis with tPA (Alteplase)
Tissue plasminogen activator (fibrinolytic)
IV unfractionated heparin
Monitor with APTR
What is the risk associated with tissue plasminogen activator?
2-6% risk of serious bleeding
What is the treatment for a standard PE?
LMW heparin injections – e.g. tinzaparin
Warfarin (target INR 2.5) for 6 months
Consider underlying causes
For treatment of standard PE, which anticoagulant is best for patients with cancer?
LMW heparin is better if underlying cancer
What is the alternative treatment for a standard PE?
Consider a DOAC as an alternative
- Dabigatran po (direct thrombin inhibitor)
- Rivaroxaban po (direct Xa inhibitor)
When would you consider a thrombophilia screen?
Consider in young patients with spontaneous DVT
What are the inherited and acquired causes that a thrombophilia screening looks for?
Inherited causes:
Factor V Leiden (5% of people)
Deficiency of natural anticoagulants:
- Anti-thrombin deficiency
- Protein C deficiency
- Protein S deficiency
Acquired causes:
Anti-phospholipid syndrome
- Test for lupus anticoagulant (DRVVT) and anticardiolipin Abs
Draw the coagulation cascade
What are the 5 types of anti-thrombotics?
Warfarin
Heparin
◦Unfractionated heparin
◦Low molecular weight heparin
Newer agents
◦Dabigatran – oral direct thrombin (factor IIa) inhibitor
◦Rivaroxaban, Apixaban – oral direct factor Xa inhibitors
Anti-platelet drugs
Fibrinolytic agents (thrombolytics)
How does warfarin work?
Vitamin K antagonist
Prevents γ-carboxylation of factors II, VII, IX, X
Required for functional maturation of these factors
What affect does warfarin have on the prothrombin time and why?
Prolongs the extrinsic pathway (prothrombin time)
Monitored by the international normalised ratio (INR)
What is the target INR for warfarin patients?
Target INR usually 2.5 for DVT/PE and AF
Target 3.5 for recurrent VTE or metal heart valves
How long can warfarin take to reach theraputic levels?
>3 days
What 2 natural anti-coagulants does warfarin also inhibit?
◦Protein C
◦Protein S
What drug interactions occur with warfarin due to cytochrome P450?
Inhibitors
Inducers
Enzyme inhibitors potentiate warfarin:
Enzyme inducers inhibit warfarin:
What are the affects of alcohol on warfarin?
◦Binge drinking tends to potentiate warfarin
◦Chronic alcoholism tends to inhibit warfarin
What 4 things is warfarin control affected by?
◦Binding to albumin
◦Absorption of vitamin K from GI tract
◦Synthesis of vitamin K factor by liver
◦Hereditary resistance
Which anticoagulant is teratogenic?
Warfarin
What drug should be used in pregnancy instead of warfarin?
LMW heparin
What are the 4 side-effects of warfarin?
Significant haemorrhage risk
- Intra-cranial bleeds up to 1% per year
- Increased risk in elderly and with higher INR target
Minor bleeding up to 20% per year
Skin necrosis
Alopecia
How would you treat a life-threateing warfarin bleed?
Give activated prothrombin complex (e.g., Octaplex or Beriplex) which contains vitamin K dependent factors II, VII, IX and X
Dose is 25-50 units per kg depending on INR level (usual dose 1500-3000 units Octaplex)
Give vitamin K 2-10mg iv/po depending on INR level
Patient can become refractory to re-loading with warfarin
Fresh frozen plasma (FFP) can also be used but this is not optimised for warfarin reversal
What is heparin and how does it work?
Mucopolysaccharide that works by potentiating anti-thrombin
Irreversibly inactivates factor IIa (thrombin) and factor Xa
How is heparin administered?
Administered parenterally (injected)
What are the 2 formations of heparin and how are they administered?
◦Unfractionated heparin given by i.v. infusion
◦Low molecular weight heparin given as s.c. injections
Is heparin safe in pregnancy?
Yes
What type of heparin is more commonly used?
LMW heparin is very convenient due to once daily s.c. injections
Unfractionated heparin not often used due to inconvenience of administration
How is unfractionated heparin monitored and what is the target?
Monitored by APTT ratio (APTR) with target of 2.0 x normal
What anticoagulant is safe in renal failure and why?
Unfractionated heparin is safe in renal failure as it is metabolised by the liver and not renally excreted
How is a unfractionated heparin bleed treated?
If bleeding, protamine sulphate can be partially reverse heparin
What is heparin-induced thrombocytopenia and how is it diagnosed?
Heparin-induced thrombocytopenia (or HIT) is a rare complication of heparin:
◦Suspect if platelet count falls on heparin
◦This is paradoxically a prothrombotic condition that can cause VTE
◦Diagnosis by doing a HIT screen and discontinuation of heparin
What is LMW heparin prescribed according to?
Prescribed according to patient’s weight
How is thromboprophylaxis for hospital in-patients treated?
LMW heparin
3,500U or 4,500U Tinzaparin
20 or 40mg Enoxaparin
When does the dosing of rivaroxaban change from 15mg bd to 20mg od?
After 3 weeks
Patients must have a creatinine clearance rate of what to use LMW heparin?
over 30ml/minute
Does LMW heparin need monitoring?
No
Name 3 formulas of LMW heparin
- Tinzaparin (Innohep) 175U/kg
- Enoxaparin (Clexane) 1.5mg/kg
- Dalteparin (Fragmin)
What is the minimum creatinine clearance for dabigatran?
> 30ml/min
Why were direct oral anti-coagulants (DOACs) developed?
Developed as oral alternatives to warfarin
What does DOACs stand for?
Direct oral anti-coagulants, DOACs
What are the benefits of DOACs?
No monitoring required, flat dosing, good safety profile
Trials show clinical non-inferiority of DOACs when compared to warfarin and LMW heparin for VTE and AF
When should DOACs not be used?
Should not be used for cardiac valves as inferior to warfarin
What are the 2 classes of DOACs?
– direct thrombin (IIa) inhibitor, e.g. dabigatran
– direct factor Xa inhibitor, e.g. rivaroxaban, apixaban
What is rivaroxaban and how does it work?
Rivaroxaban is a direct factor Xa inhibitor
Causes irreversible anti-coagulation
What are the 3 indications for rivaroxaban?
◦VTE prophylaxis
◦Used for treatment of DVTs and PEs
◦Stroke prevention in atrial fibrillation
What are the 5 antiplatelet drugs?
Aspirin – cyclo-oxygenase inhibitor
Clopidogrel – ADP receptor blocker
Dipyridamole – inhibits phosphodiesterase
Prostacyclin – stimulates adenylate cyclase
Glycoprotein IIb/IIIa inhibitors
When would the dose of rivaroxaban remain at 15mg od?
In patients with creatinine clearance of◦15-50ml/min
What is apixaban and when is it used?
Apixaban is alternative anti-Xa drug dosed bd
Less affected by renal function (safe above 15ml/min)
What is dabigatran?
Dabigatran is a direct thrombin inhibitor
What are the 3 contraindications for Dabigatran?
◦VTE prophylaxis
◦Used for treatment of DVTs and PEs
◦Stroke prevention in atrial fibrillation
What is the treatment and prophylactic dose of dabigatran?
◦Treatment dose is 150mg bd
◦Prophylactic dose is 110mg bd
How is dabigatran reversed?
Can be reversed by Praxbind (Idarucizumab)
What are fibrinolytic agents?
Thrombolytic agents used to lyse fresh thrombi (usually arterial) by converting plasminogen to plasmin
Which anti-platelet drug is used in angioplasty?
Glycoprotein IIb/IIIa inhibitors
Name 3 fibrinolytic agents
Tissue Plasminogen Activator (tPA, Alteplase)
Also streptokinase and urokinase
When are fibrinolytic agents used?
Administered systemically in acute MI, recent thrombotic stroke, major PE, or massive iliofemoral thrombosis
What is the risk of fibrinolytic agents?
Beware of contra-indications to thrombolysis
Risk-benefit ratio = haemorrhage/thrombotic risk balance
