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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