40
2.26.14 Patricia Leung SUNY Downstate ANTICOAGULATION REVERSAL IN THE HEMORRHAGING PATIENT www.downstatesurgery.org

Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

  • Upload
    ngothu

  • View
    230

  • Download
    0

Embed Size (px)

Citation preview

Page 1: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

2.26.14 Patricia Leung SUNY Downstate

ANTICOAGULATION REVERSAL IN THE HEMORRHAGING

PATIENT

www.downstatesurgery.org

Page 2: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 3: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 4: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 5: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

www.downstatesurgery.org

Page 6: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

www.downstatesurgery.org

Page 7: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

www.downstatesurgery.org

Page 8: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 9: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 10: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

HOD#4 Labs: Hct 21.6 2 u pRBC given with post-transfusion Hct 26.3 HOD#5 CT C/A/P obtained

www.downstatesurgery.org

Page 11: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

www.downstatesurgery.org

Page 12: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

www.downstatesurgery.org

Page 13: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 14: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

Coagulation cascade Indications for use Agents of reversal Treatment/Guidelines for reversal The decision to continue anticoagulation

OVERVIEW

www.downstatesurgery.org

Page 15: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

COAGULATION CASCADE

www.downstatesurgery.org

Page 16: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

intrinsic extrinsic

common pathway Antithrombin III

www.downstatesurgery.org

Page 17: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

ANTICOAGULANTS

Lovenox Fragmin Innohep

Coumadin

www.downstatesurgery.org

Page 18: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

v

HEPARIN

Antithrombin III

FONDAPARINUX LOVENOX

DABIGATRAN ARGATROBAN

www.downstatesurgery.org

Page 19: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

DVT prophylaxis DVT/PE CVA prophylaxis Afib NSTEMI STEMI

INDICATIONS FOR USE

www.downstatesurgery.org

Page 20: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

ATRIA STUDY 2009

www.downstatesurgery.org

Page 21: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 22: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 23: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 24: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

VITAMIN K AND INR 6-10

www.downstatesurgery.org

Page 25: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

VITAMIN K AND INR >10

www.downstatesurgery.org

Page 26: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 27: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

INR VS. % COAGULATION FACTORS

www.downstatesurgery.org

Page 28: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 29: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

Kings County Hospital Downstate Richmond University Medical Center Brooklyn VA

Availability of PCC our institutions

www.downstatesurgery.org

Page 30: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

COUMADIN

www.downstatesurgery.org

Page 31: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

BLEEDING ON COUMADIN

II, VII, IX, X

www.downstatesurgery.org

Page 32: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

Binds antithrombin II I Half-life: 30-90 minutes Clearance: Hepatic Reversal: Protamine (100% neutralization)

Degree of reversal assessment: PTT, antifactor Xa activity

HEPARIN

www.downstatesurgery.org

Page 33: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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)

www.downstatesurgery.org

Page 34: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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)

www.downstatesurgery.org

Page 35: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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)

www.downstatesurgery.org

Page 36: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 37: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 38: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 39: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

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

www.downstatesurgery.org

Page 40: Anticoagulation Reversal in the Hemorrhaging Patient Reversal in... · ANTICOAGULATION REVERSAL IN THE HEMORRHAGING ... Thrombin test (TCT) ... Management of bleeding and reversal

www.downstatesurgery.org