Transcript Factor VIIa - Emergency Medicine Education

What a Bloody Mess!
A/Professor Kent Robinson
Senior Staff Specialist, Liverpool &
Campbelltown Hospitals.
www.emergencyeducation.net
Objectives
Aspirin and Clopidogrel
Warfarin
NOAC’s (Newer Oral Anticoagulants) –
Dabigatran and Rivoroxaban, Apixaban
Summary - Aspirin and
Clopidogrel.
Platelets, DDAVP
Minimal data on effectiveness currently
Summary - Dabigatran
Consider dialysis
Tranexamic Acid
PCC’s
Factor VIIa
FEIBA
Summary - Rivoroxaban
Tranexamic Acid
Prothrombinex (Most effective)
Factor VIIa
Summary - Warfarin
Vitamin K slow to reverse INR
FFP slow to reverse effect of INR
PCC results in rapid reversal of INR
Case 1
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60 year old male
High Speed MVA
Severe lower back pain
HR = 110, BP 90/60, RR 16, GCS 15
IHD, Stents 8 months ago
Aspirin and Clopidogrel
Aspirin
• Irreversible acetylation of platelets
• Rapid elimination – out of system in 45 minutes
• Most centers recommend platelet transfusion (1
unit of pooled platelets)
• dDAVP – vasopressin analogue (0.3mcg/kg or 20
mcg in 50 mL NS over 15-30 minutes) – increases
levels of Factor VIII and vWF
Aspirin
• Some centers recommend the use of
tranexamic acid (based on reduced bleeding in
cardiothoracic literature)
• PATCH Study – RCT looking at the effect of
platelet transfusion on patients with ICH on
aspirin. (Results yet to be published)
Clopidogrel (Plavix)
Binds ADP receptor preventing platelet aggregation
(irreversible effect)
Stays in the serum for approximately 8 hours
following a dose.
Most centers recommend platelet transfusion (2
units of pooled platelets) and the use of dDAVP.
Factor VIIa – Aspirin and Clopidogrel
• Single study
• Reversal of effect in healthy volunteers
• Dosage 10-20 mcg/kg
• Consider in life threatening bleeding following
discussion with hematology.
Case 2
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71 year old female
Abdominal Pain and Malaena
AF, Cerebrovascular Disease
Dabigatran (Pradaxa)
• HR 120, BP 70/-, GCS 13
Dabigatran (Pradaxa)
Direct thrombin inhibitor
Fixed dosing
? Reliable plasma levels
Minimal interactions
? No monitoring
Dabigatran
• Rapid onset of action (2-4 hours)
• Predominantly renal excretion
• Indications
– Prevention of VTE in orthopaedic patients
– Prevention of stroke in patients with non-valvular
AF
Dabigatran
• Dosage is 150 mg BD
• Statistically has lower rates of major bleeding
when compared to warfarin.
• Rates of ICH – relative risk reduction of 50%
compared to warfarin
• Slight increase in rates of myocardial infarction
(RR 1.35) – not clinically or statistically significant.
Dabigatran
Check TT or APPT – normal levels exclude the
presence of significant levels of dabigatran
Short duration of effect (12 hours)
At Liverpool ask for a dabigatran level and they
will do a HEMOCLOT thrombin inhibitor test
Rivoroxaban (Xarelto)
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Direct inhibitors of Factor Xa
Half life 5-13 hours
Excreted via renal and hepatic pathways
Rivoroxaban dosage is 20 mg daily
Indications;
– Post-op DVT prophylaxis in orthopaedic patients
– Prevention of stroke in non-valvular AF
– Treatment of DVT and PE
Rivoroxaban
• Normal PT/ INR levels suggests that levels of
rivoroxaban are low
• For a test of rivoroxaban or apixaban, ask for
an anti-Xa assay.
Reversibility of NOAC’s
Main concern of NOAC’s is their lack of
reversibility.
Reversibility of NOAC’s
• Haemodialysis is particularly effective in
dabigatran toxicity as the drug is poorly protein
bound.
• A single dialysis procedure will reduce plasma
levels by 50%
• Consider in patients with severe life threatening
haemorrhage or severe renal impairment.
NOAC’s & PCC’s
• Prothrombinex is a 3-factor concentrate
(Factors II, IX and X)
• Prothrombinex has greater efficacy against
rivoroxaban, with less evidence for use in
dabigatran.
NOAC’s and rFVIIa
• Minor activity as a reversal agent, and should
be only used when other therapies have
failed.
• Dose required for efficacy (100-8000 mcg/kg)
is greatly in excess of the usual therapeutic
dosing (30-120 mcg/kg)
• Cost is approximately $1 per mcg
Dabigatran and FEIBA
• FEIBA is a humanized monoclonal antibody
fragment (Fab) with a 350 fold increase in
binding to dabigatran compared to dabigatran
binding to native thrombin.
• FEIBA dosage 25-100 IU/kg
• Cost is approximately $40 000 per dose!
Case 3
75 year old female
Collapse while gardening
GCS E2V2M4 = 8/15
Warfarin for AF
Reversal of Coagulopathy
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Discontinuation of Warfarin
Vitamin K
FFP
PCC
Factor VIIa
Warfarin Discontinuation
• Warfarin half life is 36-42 hours
• Prolonged time for reversal by discontinuation
of warfarin alone.
Vitamin K
• Give in parenteral form for life threatening
bleeding.
• Anaphylactoid reaction occurs with oral &
parenteral dosing.
• Slow to reduce INR levels to normal range
(usually 2-6 hours, but up to 24 hours)
FFP
Average dose to maintain haemostasis is 20 ml/kg
Risk of volume overload
Slow to reverse anticoagulation – median 30 hours
Prothrombin Complex Conjugates - PCC
Pooled Plasma Products
Factor II, IX, X
Rapid reversal – INR normal at 30/60 in 93% patients
Haemostatic efficacy good – 98%
25-50 IU/kg intravenously
Recombinant Factor VIIa
• Reduction in haematoma growth6
• No reduction in mortality.
• No improvement in functional outcome.
Summary - Aspirin and
Clopidogrel.
Platelets, DDAVP
Minimal data on effectiveness currently
Summary – Dabigatran.
Consider dialysis
Tranexamic Acid
PCC’s
Factor VIIa
FEIBA
Summary - Rivoroxaban
Tranexamic Acid
Prothrombinex (Most effective)
Factor VIIa
Summary - Warfarin
Vitamin K slow to reverse INR
FFP slow to reverse effect of INR
PCC results in rapid reversal of INR
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