Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine...

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Care of the Care of the Anti-coagulated Anti-coagulated Trauma Patient Trauma Patient Julie Mayglothling, MD, FACEP Julie Mayglothling, MD, FACEP Emergencies in Medicine Emergencies in Medicine March 8 March 8 th th , 2012 , 2012

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Transcript of Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine...

Page 1: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Care of the Care of the Anti-coagulated Anti-coagulated Trauma PatientTrauma Patient

Julie Mayglothling, MD, FACEPJulie Mayglothling, MD, FACEPEmergencies in MedicineEmergencies in Medicine

March 8March 8thth, 2012, 2012

Page 2: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Dabigatran, Dabigatran, Apixaban, Apixaban,

Rivaroxaban- Oh My!Rivaroxaban- Oh My!Emerging Anticoagulants and Emerging Anticoagulants and

Their Impact on TraumaTheir Impact on Trauma

Julie Mayglothling, MD, FACEPJulie Mayglothling, MD, FACEPEmergencies in MedicineEmergencies in Medicine

March 8March 8thth, 2012, 2012

Page 3: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Objectives

Discuss evaluation and management of injured patients on anti-coagulant medications

Antiplatelet, coumadin, newer anticoagulants

Review reversal agents used in anti-coagulated trauma patients

Discuss potential reversal of new agents

Page 4: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Anti-coagulants

Page 5: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

The Breakdown…

Anticoagulant Anti-platelet Coumadin Dabigatran, Rivaroxaban

Severity of Illness Acute hemorrhage/hemodynamically

unstable Intracranial Hemorrhage Mildly injured/Asymptomatic

Age

Page 6: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Anti-platelet Agents

Page 7: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

46 year old, on daily ASA, 46 year old, on daily ASA, hit in the head with a 2x4hit in the head with a 2x4

Page 8: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Antiplatelet agents 5 studies reviewed (3 of 5 show increased risk) Ages > 50, > 60, no age limit Significant mechanism (fall?)

Associated with morbidity, possibly mortality Especially in age > 50

Page 9: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Major Trauma

>1.2 million patients >36,000 warfarin users 4% in 2006 12.8% in patients > 65

Page 10: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Major Trauma

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

Page 11: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

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

Page 12: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Coumadin in Minor Head Trauma

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

Age certainly a factor Unclear for patients < 50

Page 13: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

What about a normal What about a normal head CT?head CT?

81 years old81 years old Fall with no LOCFall with no LOC INR 2.8INR 2.8 Initial CT with Initial CT with

no ICHno ICH

Dispo?Dispo?

Page 14: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

To observe, or not to To observe, or not to observe…observe…

European guidelinesEuropean guidelines Negative head CT Negative head CT 24 hours 24 hours

observation followed by a 2observation followed by a 2ndnd head CT head CT (Vos. (Vos. Eur J Neurol.Eur J Neurol. 2002) 2002)

Menditto (Menditto (Ann Emerg Med 2012)Ann Emerg Med 2012) 97 patients with neg head CT (To Obs)97 patients with neg head CT (To Obs) 5 patients (6%) with delayed bleed5 patients (6%) with delayed bleed Increased risk with INR > 3Increased risk with INR > 3

Page 15: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Reversal of Anti-Coagulation

Anti-platelet agents Platelets Desmopressin (ddAVP) (0.3 mcg/kg) Recombinant activated factor VIIa (big

gun…)

Page 16: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Thromboelastography Thromboelastography (TEG)(TEG)

fibrinolysis

Activated clotting time

Page 17: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Reversal of Anti-Coagulation

Warfarin Vitamin K Fresh Frozen Plasma Cryoprecipitate Prothrombin complex concentrate Activated Factor VIIa

Page 18: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Reversal of Anti-Coagulation

Vitamin K Cofactor II, VII, IX, X 10 mg IV (no IM or SQ) Full effect 12-24 hours Repeated doses as needed

Page 19: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Fresh Frozen Plasma

Delayed time to reversal Thawing and cross-matching

Risks of Volume overload 10-15 mL/kg = 700 mL = 3 units FFP

TRALI ABO incompatibilities

Page 20: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Prothrombin Complex Concentrate

Concentrate of Factors II, VII, IX, X, Prot C&S Factor IX is the workhorse (dosing) pooled human plasma from healthy donors

Half Life: Factor VII: 2-4 hrs Factor IX: 24 hrs

Complication rate < 1% Availability in US

Page 21: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Activated Factor VIIa

Never been formally studied for reversal of warfarin in TBI Non-anticoag pts!

Half life ~ 2.5 hours Add Vitamin K and

FFP or PCC

• Role and dose debatable

Page 22: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Dabigatran (Pradaxa)

Direct thrombin inhibitor (DTI) Better than coumadin

Works better! Decreased risk of bleeding No monitoring One dose fits all No dietary interactions

No P450

Page 23: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.
Page 24: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

What’s important to What’s important to know?know?

Peak effect 2-3 hoursPeak effect 2-3 hours 80% excreted (unchanged) in urine80% excreted (unchanged) in urine Normal renal function Normal renal function

½ life 13 hours½ life 13 hours Any renal dysfunction has longer Any renal dysfunction has longer

durationduration

Measurement (aPTT, TT, ECT)Measurement (aPTT, TT, ECT) Prolonged ACT IN rTEGProlonged ACT IN rTEG

Page 25: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Factor Xa Inhibitors

Rivaroxaban Direct competitive inhibitor ROCKET study Similar efficacy and decreased bleeding

than coumadin ApixabanApixaban

Direct competitive inhibitorDirect competitive inhibitor Aristotle trialAristotle trial Decreased stroke, decreased bleedingDecreased stroke, decreased bleeding

Page 26: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

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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.

Sites of Action of New Sites of Action of New Anticoagulant AgentsAnticoagulant Agents

Page 27: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Proposed Reversal Proposed Reversal AgentsAgents

DialysisDialysis Package insertPackage insert Logistics???Logistics???

Activated charcoal (within 2-3 Activated charcoal (within 2-3 hours)hours)

Vitamin KVitamin K FFPFFP PCCPCC Factor VIIaFactor VIIa

Page 28: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

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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.

Sites of Action of New Sites of Action of New Anticoagulant AgentsAnticoagulant Agents

Page 29: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

The Only Study!!!The Only Study!!!

Cofact (4 factor PCC)Cofact (4 factor PCC) 12 healthy volunteers, Crossover 12 healthy volunteers, Crossover

studystudy Dabigatran or RivaroxabanDabigatran or Rivaroxaban

Totally reversed RivaroxabanTotally reversed Rivaroxaban Prolongation of PT reversedProlongation of PT reversed

No effect of DabigatranNo effect of Dabigatran Increased aPTT NOT reversedIncreased aPTT NOT reversed No effect on ecarin CT and TTNo effect on ecarin CT and TT

Page 30: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Recommendations for Reversal

Intracranial hemorrhage or life-threatening traumatic hemorrhage

Anti-platelet therapy Platelet transfusion (10 pack) Possibly ddAVP (0.3 mcg/kg)

Warfarin Vitamin K 10 mg IV + FFP 15 mL/kg Use of PCC may increase in the future rFVIIa role is debatable

Page 31: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Reversal of the new Reversal of the new guys…guys…

DialysisDialysis 80% of dabigatran is renally excreted 80% of dabigatran is renally excreted 66% of rivaroxaban 66% of rivaroxaban 25% of apixaban25% of apixaban

Page 32: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Conclusions

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)

Page 33: Care of the Anti-coagulated Trauma Patient Julie Mayglothling, MD, FACEP Emergencies in Medicine March 8 th, 2012.

Thank YouThank You


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