Transcript Medical Issues in the Trauma Patient

Care of the
Anti-coagulated
Trauma Patient
Julie Mayglothling, MD, FACEP
Emergencies in Medicine
March 8th, 2012
Dabigatran, Apixaban,
Rivaroxaban- Oh My!
Emerging Anticoagulants and
Their Impact on Trauma
Julie Mayglothling, MD, FACEP
Emergencies in Medicine
March 8th, 2012
Objectives
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Discuss evaluation and management of injured
patients on anti-coagulant medications
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Antiplatelet, coumadin, newer anticoagulants
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Review reversal agents used in anti-coagulated
trauma patients
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Discuss potential reversal of new agents
Anti-coagulants
The Breakdown…
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Anticoagulant
Anti-platelet
 Coumadin
 Dabigatran, Rivaroxaban
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Severity of Illness
Acute hemorrhage/hemodynamically unstable
 Intracranial Hemorrhage
 Mildly injured/Asymptomatic
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Age
Anti-platelet Agents
46 year old, on daily ASA, hit in
the head with a 2x4
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Antiplatelet agents
5 studies reviewed (3 of 5 show increased risk)
 Ages > 50, > 60, no age limit
 Significant mechanism (fall?)
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Associated with morbidity, possibly mortality
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Especially in age > 50
Major Trauma
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>1.2 million patients
>36,000 warfarin users
4% in 2006
12.8% in patients > 65
Major Trauma
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Warfarin use associated with double mortality (9.3%)
Both in all patients and patients > 65
 All patients and all injury patterns
 Most pronounced for TBI patients < 65
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Warfarin
6 of 8 studies found increased risk of morbidity and
mortality with warfarin
 Especially in elderly patients (regardless of ISS)
 Level of INR associated with mortality
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Coumadin in Minor Head Trauma
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5 Retrospective studies
65-144 patients in each
 2 studies support clinical exam
 2 studies state scan regardless of normal neuro exam
 1 study uses INR cut-off 2.37
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Age certainly a factor
Unclear for patients < 50
What about a normal head CT?
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81 years old
Fall with no LOC
INR 2.8
Initial CT with no
ICH
 Dispo?
To observe, or not to observe…
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European guidelines
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Negative head CT  24 hours observation followed
by a 2nd head CT (Vos. Eur J Neurol. 2002)
Menditto (Ann Emerg Med 2012)
97 patients with neg head CT (To Obs)
 5 patients (6%) with delayed bleed
 Increased risk with INR > 3
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Reversal of Anti-Coagulation
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Anti-platelet agents
Platelets
 Desmopressin (ddAVP) (0.3 mcg/kg)
 Recombinant activated factor VIIa (big gun…)
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Thromboelastography (TEG)
fibrinolysis
Activated clotting time
Reversal of Anti-Coagulation
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Warfarin
Vitamin K
 Fresh Frozen Plasma
 Cryoprecipitate
 Prothrombin complex concentrate
 Activated Factor VIIa
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Reversal of Anti-Coagulation
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Vitamin K
Cofactor II, VII, IX, X
 10 mg IV (no IM or SQ)
 Full effect 12-24 hours
 Repeated doses as needed
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Fresh Frozen Plasma
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Delayed time to reversal
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Risks of Volume overload
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Thawing and cross-matching
10-15 mL/kg = 700 mL = 3 units FFP
TRALI
ABO incompatibilities
Prothrombin Complex Concentrate
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Concentrate of Factors II, VII, IX, X, Prot C&S
Factor IX is the workhorse (dosing)
 pooled human plasma from healthy donors
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Half Life:
Factor VII: 2-4 hrs
 Factor IX: 24 hrs
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Complication rate < 1%
Availability in US
Activated Factor VIIa
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Never been formally studied for reversal of
warfarin in TBI
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Non-anticoag pts!
Half life ~ 2.5 hours
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Add Vitamin K and
FFP or PCC
•
Role and dose debatable
Dabigatran (Pradaxa)
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Direct thrombin inhibitor (DTI)
Better than coumadin
Works better!
 Decreased risk of bleeding
 No monitoring
 One dose fits all
 No dietary interactions
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No P450
What’s important to know?
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Peak effect 2-3 hours
80% excreted (unchanged) in urine
Normal renal function
½ life 13 hours
 Any renal dysfunction has longer duration
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Measurement (aPTT, TT, ECT)
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Prolonged ACT IN rTEG
Factor Xa Inhibitors
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Rivaroxaban
Direct competitive inhibitor
 ROCKET study
 Similar efficacy and decreased bleeding than coumadin
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Apixaban
Direct competitive inhibitor
 Aristotle trial
 Decreased stroke, decreased bleeding
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Sites of Action of New
Anticoagulant Agents
Figure 1: Site of action of new anticoagulant drugs. From Brighton T. Experimental and clinical pharmacology: new oral
anticoagulant drugs – mechanisms of action. Aust Prescr. 2010;33:38-41. Reprinted with permission from Australian
Prescriber.
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Proposed Reversal Agents
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Dialysis
Package insert
 Logistics???
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Activated charcoal (within 2-3 hours)
Vitamin K
FFP
PCC
Factor VIIa
Sites of Action of New
Anticoagulant Agents
Figure 1: Site of action of new anticoagulant drugs. From Brighton T. Experimental and clinical pharmacology: new oral
anticoagulant drugs – mechanisms of action. Aust Prescr. 2010;33:38-41. Reprinted with permission from Australian
Prescriber.
28
The Only Study!!!
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Cofact (4 factor PCC)
12 healthy volunteers, Crossover study
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Totally reversed Rivaroxaban
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Dabigatran or Rivaroxaban
Prolongation of PT reversed
No effect of Dabigatran
Increased aPTT NOT reversed
 No effect on ecarin CT and TT
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Recommendations for Reversal
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Intracranial hemorrhage or life-threatening
traumatic hemorrhage
Anti-platelet therapy
Platelet transfusion (10 pack)
 Possibly ddAVP (0.3 mcg/kg)
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Warfarin
Vitamin K 10 mg IV + FFP 15 mL/kg
 Use of PCC may increase in the future
 rFVIIa role is debatable
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Reversal of the new guys…
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Dialysis
80% of dabigatran is renally excreted
 66% of rivaroxaban
 25% of apixaban
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Conclusions
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Patients on oral anti-coagulant therapy have
increased morbidity and mortality after trauma
Reversal strategies for anti-platelet and warfarin
are fairly well established
New DTI’s and Factor Xa inhibitors pose a
unique challenge
Dialysis (not always feasible)
 PCC (possible but poor data)
 Factor VIIa (unclear)
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Thank You