Thrombotic disorders Flashcards
what is deep vein thrombosis
blood clot in deep veins (iliac, femoral, popliteal, tibial)
can become an embolism
what are thrombotic risk factors
Post-operative, especially orthopaedic Hospitalisation Cancer Pregnancy OCP Long-haul flights Obesity IV drug abuse
how do DVT’s present
Can be no symptoms at all – clinically silent
Unilateral calf swelling/ heat/ pain/ redness/ hardness
Differential diagnosis: cellulitis, Baker’s cyst, muscular pain
what can DVT be mistaken for
Differential diagnosis: cellulitis, Baker’s cyst, muscular pain
Potentially fatal if missed
what is a doppler ultrasound
Ultrasound transducer produces a real-time two dimensional image of soft tissue structure
Colour duplex shows velocity and direction of blood flow
how is a doppler ultrasound used for diagnose DVT
Veins are non-compressible by U/S probe
Investigation of choice
Colour duplex shows velocity and direction of blood flow
what used to diagnose DVT
Venogram done in past
how can a D-dimer test be used to diagnose DVT
D-dimers indicate activation of the clotting cascade
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 U/S scan to confirm DVT
What can a D dimer test be used for
Likelihood of having a DVT can be assessed using the Wells risk score and doing a D-dimer test
what is an above knee DVT
iliac, femoral or popliteal veins
How is an above knee DVT treated
Therapeutic anti-coagulation using sub-cut LMW heparin (such as tinzaparin or enoxaparin)
Dose of LMW heparin according to weight
No monitoring required (but can use anti-Xa assay)
Ensure adequate EGFR > 30ml/min
Otherwise use iv unfractionated heparin (APTR 2.0)
how can a patient be switched to oral warfarin (if heparin ineffective)
Load patient with oral warfarin for 3-5 days
Stop LMW heparin once INR > 2.0 for 2 days
Maintain INR between 2.0-3.0 (target 2.5)
Monitor INR every 3 weeks
what is a PE
Pulmonary embolism
what are symptoms of micro-emboli
asymptomatic
what are the classical symptoms of PE
pleuritic pain
dyspnoea
haemoptysis
What are the symptoms of massive PE
syncope, death
What are other symptoms of PE
Observed or expected, tachycardia, tachypnoea, hypotension
what should you do for 1st and 2nd DVT
1st DVT: anticoagulants for 6 months
2nd DVT/PE: lifelong anticoagulation
what is a CTPA scan
CTPA scan (CT pulmonary angiogram) used to investigate DVT
What is a V/Q scan
ventilation/perfusion radio-isotope scan used to diagnose PE
Limitation: underlying lung disease
Many scans are – hence rarely done
what do V/Q scans indicate
Underperfusion ~ V/Q mismatch
how can an ECG be used to diagnose PE
Sinus tachycardia
Atrial fibrillation
Right heart strain (RBBB)
Classic: SI, QIII, TIII (rare)
How can a CXR be used to diagnose PE
Usually normal
Linear atelectasis
Small effusions
What are the outcomes of PE
5% mortality rate despite treatment
4% develop pulmonary hypertension
Cause of death in 10-30% of in-patient post-mortems
Up to 60% have micro-emboli at post-mortem
how is massive PE treated
Mx: thrombolysis with tPA (Alteplase) Tissue plasminogen activator (fibrinolytic) 2-6% risk of serious bleeding iv unfractionated heparin Monitor with APTR
what can massive PE lead to
Signs of shock
hypotension, acute dyspnoea, collapse, syncope
how is standard PE treated
LMW heparin injections – e.g. tinzaparin
Warfarin (target INR 2.5) for 6 months
Consider underlying causes
what is LMW heparin used for specifically
is better if underlying cancer IVC filters (inferior vena cava filter) for treating PE
How can DOAC be used to treat PE
Consider a DOAC as an alternative Dabigatran po (direct thrombin inhibitor) Rivaroxaban po (direct Xa inhibitor)
What is a thrombophilia screen
Consider in young patients with spontaneous VTE
what are inherited causes of thrombophilia
Factor V Leiden (5% of people) Deficiency of natural anticoagulants: Anti-thrombin deficiency Protein C deficiency Protein S deficiency
what are acquired causes of thrombophilia
Anti-phospholipid syndrome
Test for lupus anticoagulant (DRVVT) and anticardiolipin Abs
what are anti thrombotics
Warfarin Heparin (Unfractionated heparin LMW heparin) Newer agents Dabigatran – oral direct thrombin (factor IIa) inhibitor Rivaroxaban, Apixaban – oral direct factor Xa inhibitors Anti-platelet drugs Fibrinolytic agents (thrombolytics)
What is warfarin
Vitamin K antagonist
Prevents γ-carboxylation of factors II, VII, IX, X
Required for functional maturation of these factors
what does warfarin do
Prolongs the extrinsic pathway (prothrombin time)
Monitored by the international normalised ratio (INR)Target INR usually 2.5 for DVT/PE and AF
Target 3.5 for recurrent VTE or metal heart valves
what are the pharmaco-dynamics of warfarin
Warfarin can take > 3 days to achieve therapeutic levels
Warfarin also inhibits the natural anti-coagulants:
Protein C
Protein S
how does warfarin interact with cytochrome P450
Enzyme inhibitors potentiate warfarin:
Enzyme inducers inhibit warfarin:
how does warfarin interact with alcohol
Binge drinking tends to potentiate warfarin
Chronic alcoholism tends to inhibit warfarin
what is warfarin control also affected by
Binding to albumin
Absorption of vitamin K from GI tract
Synthesis of vitamin K factor by liver
Hereditary resistance
what are warfarin side effects
Teratogenic – therefore use LMW heparin in pregnancy
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
what reverses warfarin
If life-threatening bleed, give activated prothrombin complex (e.g., Octaplex or Beriplex) which contains vitamin K dependent factors II, VII, IX and X
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 the dose for activated prothrombin complex during life threatening bleed
Dose is 25-50 units per kg depending on INR level (usual dose 1500-3000 units Octaplex)
what is heparin
Mucopolysaccharide that works by potentiating anti-thrombin
what does heparin do
Irreversibly inactivates factor IIa (thrombin) and factor Xa Administered parenterally (injected)
what are the types of heparin
Two formulations of heparin:
Unfractionated heparin given by i.v. infusion
Low molecular weight heparin given as s.c. injections
is heparin safe in pregnancy
Safe in pregnancy
what is unfractionated heparin used for
Given i.v. with 5000U bolus and ~1000U/hour infusion
Monitored by APTT ratio (APTR) with target of 2.0 x normal
Safe in renal failure as unfractionated heparin is metabolised by the liver and not renally excreted
If bleeding, protamine sulphate can be partially reverse heparin
why is unfractionated heparin not often used
Not often used due to inconvenience of administration
what is a rare complication of heparin
Heparin-induced thrombocytopenia (or HIT)
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 used for
LMW heparin include: Tinzaparin (Innohep) Enoxaparin (Clexane) Dalteparin (Fragmin) Used for thromboprophylaxis for hospital in-patients: Tinzaparin Enoxaparin
how is LMW heparin used
Very convenient due to once daily s.c. injections
Prescribed according to patient’s weight
Patient must have creatinine clearance of over 30ml/minute
Not usually monitored (but can use the anti-Xa assay to monitor)
what are direct oral anti-coagulants
Developed as oral alternatives to warfarin
No monitoring required, flat dosing, good safety profile
what are DOACs used for
Developed as oral alternatives to warfarin
No monitoring required, flat dosing, good safety profile
what are the two types of DOACs
direct thrombin (IIa) inhibitor, e.g. dabigatran – direct factor Xa inhibitor, e.g. rivaroxaban, apixaban
when shouldn’t DOACs be used
Trials show clinical non-inferiority of DOACs when compared to warfarin and LMW heparin for VTE and AF
Should not be used for cardiac valves as inferior to warfarin
what is rivaroxaban
a direct factor Xa inhibitor
Causes irreversible anti-coagulation
what are indications of rivaroxaban
Indications:
VTE prophylaxis
Used for treatment of DVTs and PEs
Stroke prevention in atrial fibrillation
what are the doses of rivaroxaban
Dosing is 15mg bd for 3 weeks, then 20mg od
or 15mg od if CrCl is 15-50ml/min
Apixaban is alternative anti-Xa drug dosed bd
Less affected by renal function (safe above 15ml/min)
what is dabigatran
a direct thrombin inhibitor
what are indications of dabigatran
VTE prophylaxis
Used for treatment of DVTs and PEs
Stroke prevention in atrial fibrillation
what are the doses of dabigatran
Treatment dose is 150mg bd
Prophylactic dose is 110mg bd
Confirm creatinine clearance > 30ml/min
Can be reversed by Praxbind (Idarucizumab)
what are the types of anti platelet drugs
Aspirin – cyclo-oxygenase inhibitor
Clopidogrel – ADP receptor blocker
Dipyridamole – inhibits phosphodiesterase
Prostacyclin – stimulates adenylate cyclase
Glycoprotein IIb/IIIa inhibitors
what are Glycoprotein IIb/IIIa inhibitors used in
Used in angioplasty procedures
what are thrombolytic agents used for
used to lyse fresh thrombi (usually arterial) by converting plasminogen to plasmin
what are fibrinolytic agents
tPA, Alteplase
Also streptokinase and urokinase
how are fibrinolytics used
Administered systemically in acute MI, recent thrombotic stroke, major PE, or massive iliofemoral thrombosis
Standardized dosage regimens, aim to use within 6 hours
what are the risks of fibrinolytics
Beware of contra-indications to thrombolysis
Risk-benefit ratio = haemorrhage/thrombotic risk balance
