Transcript (FEIBA) for the Rapid Reversal of Major Bleeding in Patients with

Factor Eight Inhibitor Bypassing Activity
(FEIBA) for the Rapid Reversal of Major
Bleeding in Patients with Warfarin Induced
Coagulopathy: A Pilot Study
David Barounis, MD1
Catherine Knight, MD2
Ben-Paul Umunna, MD2
Mary Hormese, PharmD, BCPS2
Elise Lovell, MD2
1Stanford
University, Stanford, CA; 2Advocate Christ Medical Center, Oak Lawn, IL
No financial disclosures
or
conflict of interest
Background
• Fresh frozen plasma (FFP) + vitamin K to reverse
major bleeding due to warfarin associated
coagulopathy
• FFP shortcomings
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▫
▫
▫
▫
incomplete reversal
time delay for ABO compatibility, thawing
large volume
time to transfuse
risk of TRALI
• Prothrombin complex concentrates (PCC)
recommended since 2012
FEIBA
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•
•
•
•
Plasma derived
4 coagulation factors (II, VII, IX, X)
FDA approved in hemophilia
Small volume
No blood typing/thawing
Clinical Experience with FEIBA
• Retrospective comparison of 72 pts receiving FEIBA
to 69 patients receiving FFP
• Median time to reversal of INR < 1.4 was 2 hours in
FEIBA group, 25 hours in FFP group
• 7% TAE, 22% mortality in FEIBA group
Wojcik C, Schymik ML, Cure EG. Activated prothrombin complex concentrate
factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarininduced coagulopathy. Int J Emerg Med 2009;2:217-225.
Study Purpose
• To evaluate the efficacy and safety of FEIBA and
IV vitamin K for the reversal of warfarinassociated coagulopathy in patients with major
hemorrhage
Hypothesis
• The use of FEIBA and IV vitamin K will result in
the rapid reversal of warfarin associated
coagulopathy in patients with major bleeding
• Adverse event rate will be low
Methods - Study Setting
• Tertiary care suburban community teaching
hospital
• 100,000 ED visits per year
• 700 inpatient beds
Methods - Study Design
• Ongoing prospective, observational study
• ED patients on warfarin presenting with major
bleeding
• INR ≥ 5.0  1000U of FEIBA
• INR < 5.0  500U of FEIBA IV
• 10mg IV vitamin K
• Repeat INR 30 minutes, 4 and 24 hours
Inclusion Criteria
• Age > 18
• Present to the ED with major hemorrhage while
on warfarin
▫ life or limb threatening bleed or
▫ bleed in critical location (intracranial, ophthalmic,
intraspinal) or
▫ 2 gram fall in hemoglobin
• Initial INR >1.5
Exclusion Criteria
•
•
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Coagulopathy not due to warfarin
On warfarin, but INR ≤ 1.5
No major hemorrhage
Received additional reversal agents prior to/in
ED (FFP, aFactor VII, PCCs, vitamin K
PO/SQ/IM)
Methods of Measurement
• All eligible patients identified by M/W/F review
of FEIBA dispensed to ED
Outcome Measures
• Primary Outcome: Time to INR ≤ 1.5
• Secondary outcomes:
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▫
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Thrombotic adverse events, allergic reaction
FEIBA dose required to reverse
Units of PRBCs transfused
Mortality
Statistical Analysis
• Reporting of descriptive measures (means,
medians, IQRs, as appropriate)
Results
• Between 2/8/2013 and 8/30/2013, 44 ED patients
received FEIBA
• 9 did not meet inclusion criteria
▫ 6 not major bleed
▫ 3 INR ≤ 1.5
• 14 patients excluded
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▫
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▫
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6 FFP or alternate route vitamin K
4 died before consent obtained
1 no POA
1 withdrew consent
2 ethical issue to approach for consent
Results
• 21 patients enrolled
▫ 11 CNS bleed, 8 GI bleed, 1 Hematuria, 1 Pulmonary
hemorrhage
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•
•
•
Mean initial INR was 5.5
16/21 patients admitted to ICU for at least 1 day
Achieved INR ≤ 1.5 in all patients
Mean time to INR ≤ 1.5 was 127 minutes
▫ 1 patient’s repeat INR was drawn ~12 hrs after FEIBA
▫ if this patient excluded, mean time to INR ≤ 1.5 was 98
minutes
Results
• Four (19%) patients died (none with TAE)
▫ 2 GI bleed
▫ 2 CNS bleed
• Four thrombotic adverse events (TAE) in 3
(14%) patients
▫ 2 ischemic CVAs
▫ 2 extremity DVTs
Results: Mortality
Age
Diagnosis
Cause of death
Hospital Day
78 yo male
CNS bleed
herniation/withdr 2
awal of care
41 yo male
GI bleed
GI bleed/arrest
12
76 yo male
GI bleed
GI bleed/arrest
18
88 yo female
CNS bleed
withdrawal of care 8
Results: TAE
Diagnosis
History
TAE
Hospital Day
GI bleed
DVT
DVT on US; not
definitively acute
vs chronic
3
CNS bleed
severe arterial dz,
multiple arterial
clots, afib, valve
ischemic CVA +
arm DVT
7
15
CNS bleed
titanium aortic
valve, afib
embolic ischemic
CVA
18
TAE: Background
• Kcentra: 9% TAE vs. 5.5% TAE in FFP group (ns)
• Wojcik: 1.4% TAE in FFP group
• MEDENOX trial: 15% rate of DVT in patients
admitted without SQ enoxaparin
• FEIBA in hemophilia: TAE rate of 4 per 100,000
infusions
Limitations
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•
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Single center
Observational study design
Disease oriented primary outcome
4 patients died before consent obtained (impacts
mortality rate)
• Contribution of FEIBA to thrombotic adverse
events uncertain
Conclusions
• FEIBA and IV vitamin K result in rapid reversal
of warfarin-induced coagulopathy in patients
with major bleeding
• Thrombotic adverse event rate was 14%
23
What about Kcentra?
• FDA approved April 30, 2013
• PCC given along with Vitamin K
▫ Factors II, VII, IX, X, with proteins C and S,
antithrombin III
▫ Includes heparin
• Dosing based on INR, body weight
• No repeat dosing
• Known risks
Cost of FEIBA vs FFP
• Feiba: $1.48 per unit
▫ Hospital cost: $740 for 500 units, $1480 for 1000
units
▫ Patient cost: $3,496 and $5,920
• FFP: $65 -70 per unit, start with 10 cc/kg, 200
cc in unit of FFP, so 100 kg pt needs 5 units FFP
= $350
4 Patients with 3 TAEs
• Leg DVT, 2 ischemic CVAs, and arm DVT. One pt
with both arm DVT and CVA.
• Pt with leg DVT admitted with GI Bleed, had h/o
DVT. US hospital day 3 with DVT which could not
be definitively called acute versus chronic.
• Pt with arm DVT and CVA admitted with acute on
chronic subdural hematoma, h/o severe arterial
disease/multiple peripheral arterial clots, also
mitral valve replacement, afib
• Pt with other CVA (thought to be embolic) admitted
with SAH, had h/o titanium aortic valve and afib.
Clinical Experience with FEIBA
• FEIBA usage summarized in 16 patients at
community hospital
• 87% of patients survived to discharge
• No signs or symptoms of TAE
Stewart WS, Pettit H. Experiences with an activated 4-factor prothrombin
complex concentrate (FEIBA) for reversal of warfarin-related bleeding.
AJEM 2013; 31:1251-1254.