Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN...
Transcript of Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN...
2.26.14 Patricia Leung SUNY Downstate
ANTICOAGULATION REVERSAL IN THE HEMORRHAGING
PATIENT
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WE 302496 58 year old male PMH: HTN, squamous cell carcinoma, Afib on Coumadin, gout PSH: LRRT ’88 Medications: Prednisone, Cyclosporine, Lasix, Atenolol,
Minoxidil, Nexium, Coumadin 6 qHS NKDA
CASE PRESENTATION
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1/27 PM CC: worsening SOB x 1 week; subjective fever x 1 day Also with complaints of right flank pain of acute onset but
denied any recent trauma Vital signs: T 99.8 BP 155/82 HR 65 Physical exam: tenderness to palpation of the right flank; no
external findings Labs: INR of 2.6; WBC 6.7, Hct 35.3; Cr 1.48 Admitted to transplant service
CASE PRESENTATION
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HOD#1 Labs: INR 3.2; Coumadin order was suspended He received another dose of Coumadin both that night and the
following morning CT C/A/P obtained
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HOD#2 Small area of ecchymosis overlying the area of reported right
flank pain Serial Hct 32.831.528.7 and INR was 4.9. 2 FFP and Vitamin K x 1 dose given Repeat INR 3.4; another FFP was given
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HOD#3 Area of ecchymosis had expanded with accompanied
worsening right flank pain Labs: INR 3 and Hct 27.6 2 u FFP given in preparation for the OR OR: Evacuation of approximately 700 cc retroperitoneal
hematoma Post-op Hct 23.6; 2 u FFP, 1u pRBC given
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HOD#4 Labs: Hct 21.6 2 u pRBC given with post-transfusion Hct 26.3 HOD#5 CT C/A/P obtained
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HOD#6 Hct 21.9 and 2 u pRBC were transfused with response to 25.3 HOD#7 Hct 25.6; hemodynamically stable OR: Evacuation of approximately 800 cc hematoma with
washout and packing with plan for return next day HOD #8 Re-exploration with hemostasis Post-op Hct stable Daily physical therapy Discharged home HOD#11
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Coagulation cascade Indications for use Agents of reversal Treatment/Guidelines for reversal The decision to continue anticoagulation
OVERVIEW
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COAGULATION CASCADE
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intrinsic extrinsic
common pathway Antithrombin III
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ANTICOAGULANTS
Lovenox Fragmin Innohep
Coumadin
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v
HEPARIN
Antithrombin III
FONDAPARINUX LOVENOX
DABIGATRAN ARGATROBAN
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DVT prophylaxis DVT/PE CVA prophylaxis Afib NSTEMI STEMI
INDICATIONS FOR USE
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ATRIA STUDY 2009
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Agent Cost
Vitamin K $10
Protamine Sulfate $147
Fresh Frozen Plasma (FFP) $178
Prothrombin complex concentrate (PCC) $1645
Recombinant Factor VIIa (rFVIIa) $4500
AVAILABLE REVERSAL AGENTS
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30 million prescriptions in the US annually Estimated 3-7% per year of patients on Coumadin require
rapid reversal for major bleeding, need for urgent surgery, other invasive procedures
50-60% of patients are within therapeutic range Risk of major hemorrhage 1% FFP most widely used antidote for VKA reversal
COUMADIN
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Vitamin K reductase inhibitor (VKA) o Inhibits II , VII, IX, X, protein C, S Indication: o DVT/PE (INR 2.5) o Non-valvular Afib (INR 2.5) o Mechanical and Bioprosthetic heart
valves (INR 3.0) o Clearance: Hepatic o Reversal: ??
COUMADIN
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VITAMIN K AND INR 6-10
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VITAMIN K AND INR >10
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Fresh frozen Plasma Prothrombin complex concentrate
Thawing time Safety profile unclear
Transmission infectious agents High cost
Allergic reactions
Fluid overload
FFP VS. PCC
Fresh frozen Plasma Prothrombin complex concentrate
Availability Not blood-type specific
Less cost High clotting factor concentration
Faster reversal
Small volume
PRO
CON
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INR VS. % COAGULATION FACTORS
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27 studies (1992-2010) PCC used for rapid reversal due to major bleeding, need for
surgery, invasive procedure Number of thromboembolic events recorded Results: 1.4% of patients had thromboembolic complications 1.9% incidence in major bleeding vs 0.8% in those treated
before urgent surgery or invasive procedure 1.8% 4-factor PCC vs 0.7% 3-factor PCC
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Kings County Hospital Downstate Richmond University Medical Center Brooklyn VA
Availability of PCC our institutions
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COUMADIN
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BLEEDING ON COUMADIN
II, VII, IX, X
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Binds antithrombin II I Half-life: 30-90 minutes Clearance: Hepatic Reversal: Protamine (100% neutralization)
Degree of reversal assessment: PTT, antifactor Xa activity
HEPARIN
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Factor Xa > IIa inhibitor Indications: o DVT prophylaxis (30 or 40 mg SC daily) o DVT/PE (1.5 mg/kg SC daily, or 1mg/kg SC q12H) o NSTEMI (30mg IV bolus + 1mg/kg SC + 1mg/kg SC q12H) Clearance: Renal (decrease if CrCl <30) Reversal: Protamine (60% neutralization) o Response to dialysis: 20% Monitoring: Anti-Xa activity
ENOXAPARIN (Lovenox)
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Indirect Factor Xa inhibitor (SubQ) Indications: o DVT prophylaxis in orthopedic
surgery (2.5mg subQ daily) o DVT/PE (7.5mg subQ daily) Clearance: renal (contraindicated if
CrCl <30) Monitoring: anti-Xa activity Reversal: no specific antidote o Level reduced by 20% via dialysis o Consider giving PCC
FONDAPARINUX (Arixtra)
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Direct thrombin inhibitor (PO) Indications: o Prevention of DVT/PE after orthopedic
surgery o Prevention of stroke in patients with
non-valvular Afib (150 mg BID) Reversal: no specific antidote o Activated charcoal if ingestion <2 hours
prior o HD for 60% clearance 2-3 hours o Neutralizing monoclonal antibody (in
development) Monitoring: Thrombin test (TCT) Periop management: stop 24-48 hours
prior; restart same evening 6 hrs postop
DABIGATRAN (Pradaxa)
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Direct thrombin inhibitor (IV) Indications: Prophylaxis and
treatment of thrombosis in patients with heparin-induced thrombocytopenia
Clearance: Hepatic Monitor: PTT (1.5-2.5x baseline) Reversal: no specific antidote o 20% plasma concentration can
be cleared via dialysis
ARGATROBAN
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A new risk scheme to predict Warfarin-associated hemorrhage
Population: 9,186 patients with Afib 461 hemorrhage events (median 3.5 years) 5-variable risk score
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Urgent Coumadin reversal issues are complex Recommendation to give PCC-4 and Vitamin K; if not then give
FFP Large volumes quickly, risk of overload 3 and 4-component PCC are prothrombotic, use with caution
in elderly, vasculopaths New oral anticoagulant alternatives have limited use as
reversal of agents is dif ficult
SUMMARY
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M a n a g e m e n t o f b l e e d i n g a n d r e v e r s a l s t r a t e g i e s f o r o r a l a n t i c o a g u l a n t s : C l i n i c a l p r a c t i c e C o n s i d e r a t i o n s ; E d i t h A . N u t E s c u , W i l l i A m E . d A g E r , J A m E s s . K A l u s , J o h N J . l E W i N i i i , A N d m A r K d . c i p o l l , A m J H e a l t h - S y s t P h a r m — V o l 7 0 , 2 0 1 3
h t t p : / / d e pt s . w a s h i n g t o n . e d u / a n t i c o a g / h o m e / s i t e s / d e f a u l t / f i l e s / G U ID E L I NE S % 2 0 F O R % 2 0 R E V E R S AL %2 0 O F % 2 0 A N T I C O A G U L AN T S . p d f
A n u p d a t e o f c o n s e n s us g u i d e l i n e s f o r w a r f a r i n r e v e r s a l , H u y e n A T r a n , S a n j e e v D C h u n i l a l , P a u l L H a r p e r , H u y T r a n , E r i c a M W o o d a n d A l e x S G a l l u s , o n b e h a l f o f t h e A u s t r a l a s i a n S o c i e t y o f T h r o m b o s i s a n d H a e m o s t a s i s , M e d J A u s t 2 0 1 3 ; 1 9 8 ( 4 ) : 1 9 8 - 1 9 9 .
S h o u l d P a t i e n t C h a r a c t e r i s t i c s I n f l u e n c e T a r g e t A n t i c o a g u l a t i o n I n t e n s i t y f o r S t r o k e P r e v e n t i o n i n N o n v a l v u l a r A t r i a l F i b r i l l a t i o n ? T h e A T R I A S t u d y D a n i e l E . S i n g e r C i r c u l a t i o n : C a r d i o v a s c u l a r Q u a l i t y a n d O u t c o m e s . 2 0 0 9 ; 2 : 2 9 7 - 3 0 4 P u b l i s h e d o n l i n e b e f o r e p r i n t J u n e 9 , 2 0 0 9
C o m p a r i s o n o f O r a l v s I n t r a v e n o u s P h y t o n a d i o n e ( V i t a m i n K 1 ) i n P a t i e n t s W i t h E x c e s s i v e A n t i c o a g u l a t i o n A P r o s p e c t i v e R a n d o m i z e d C o n t r o l l e d S t u d y A h a r o n L u b e t s k y e t a l A r c h I n t e r n M e d . 2 0 0 3 ; 1 6 3 ( 2 0 ) : 2 4 6 9 - 2 4 7 3 . d o i : 1 0 . 1 0 0 1 / a r c h i n t e . 1 6 3 . 2 0 . 2 4 6 9
A p p l H e a l t h E c o n H e a l t h P o l i c y . 2 0 1 1 ; 9 ( 1 ) : 2 9 - 3 7 . d o i : 1 0 . 2 1 6 5 / 1 1 5 3 0 7 4 0 - 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 . C o s t s t o h o s p i t a l s o f a c q u i r i n g a n d p r o c e s s i n g b l o o d i n t h e U S : a s u r v e y o f h o s p i t a l - ba s e d b l o o d b a n k s a n d t r a n s f u s i o n s e r v i c e T o n e r R W 1 , P i z z i L , L e a s B , B a l l a s S K , Q u i g l e y A , G o l d f a r b N I .
M e c h a n i s m o f A c t i o n a n d P h a r m a c o l o g y o f U n f r a c t i o n a t e d H e p a r i n J a c k H i r s h A r t e r i o s c l e r o s i s , T h r o m b o s i s , a n d V a s c u l a r B i o l o g y . 2 0 0 1 ; 2 1 : 1 0 9 4 - 1 0 9 6 d o i : 1 0 . 1 1 6 1 / h q 0 7 0 1 . 0 9 3 6 8 6
U p d a t e o n A n t i t h r o m b o t i c T h e r a p y : N e w A n t i c o a g u l a n t s J o h n W . E i k e l b o o m , M B B S ; C i r c u l a t i o n . 2 0 1 0 ; 1 2 1 : 1 5 2 3 - 1 5 3 2
G u i d e t o A n t i c o a g u l a n t T h e r a p y : H e p a r i n : A S t a t e m e n t f o r H e a l t h c a r e P r o f e s s i o n a l s F r o m t h e A m e r i c a n H e a r t A s s o c i a t i o n J a c k H i r s h , M D ; C i r c u l a t i o n . 2 0 0 1 ; 1 0 3 : 2 9 9 4 - 3 0 1 8
L u b e t s k y e t a l ; C o m p a r i s o n o f O r a l v s I V V i t a m i n K i n P a t i e n t s w i t h E x c e s s i v e A n t i c o a g u l a t i o n ; A r c h I n t e r n M e d 2 0 0 3 ; 1 6 3 : 2 4 6 9 - 2 4 7 3
REFERENCES
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