Anticoagulation Reversal

May 11, 2013

Objectives

• Develop an approach for treating patients with iatrogenic coagulopathy

• Understand recent changes in STEMI care• Review the ICH treatment protocol

Patient Care

Medical Knowledge

Practice-Based Learning and ImprovementInterpersonal and Communication Skills

ProfessionalismSystems-Based Practice

ACGME Competencies Addressed

Tissue factor pathway

Contact activation pathway

Tissue factor pathway

Contact activation pathway

Haemophilia A

Haemophilia B

What is the mechanism of action of warfarin?

What is the mechanism of action of warfarin?

• Inhibits Vitamin K epoxide reductase

The American College of Chest Physicians guideline for the reversal of anticoagulation

therapy (8th ed.).

Vitamin K epoxide reductase

What clotting factors are affected by warfarin?

78 year old with history of PE presents with weakness and UTI. INR = 8.

58 year old with history of atrial fibrillation and HTN on warfarin presents with ICH. GCS = 6 and INR = 4.

67 year old with pmh atrial fibrillation on warfarin presents with brisk nose bleed. INR = 6.

What is the universal donor FFP type?

What is the universal donor FFP type?

• AB

One unit plasma replaced what percent of clotting factors?

One unit plasma replaced what percent of clotting factors?

• 2.5%

How low can you get the INR with FFP?

How low can you get the INR with FFP?

• 1.5

Name two problems with FFP

Name two problems with FFP

• Time• Volume

PCCWhat types of PCC are there?

PCCWhat types of PCC are there?

• 3 factor• 4 factor

3 Factor PCCProfilnine

• II• IX• X• Very small amount of VII

Kcentra

• 4F-PCC– II– VII– IX– X

What is the mechanism of action of Xabans?

What is the mechanism of action of Xabans?

• Xa inhibitor

Xabans-rivaroxaban (Xarelto)

How would you treat major bleeding in someone on Rivaroxaban?

How would you treat major bleeding in someone on Rivaroxaban?

• PCC (?)

XabansRivaroxaban (Xarelto)

• Xa inhibitors• PCC

Dabigatran (Pradaxa)

• What is mechanism of action?

dabigatran(Pradaxa)

Dabigatran (Pradaxa)

• Renal metabolism• Can not be monitored• Normal PTT helpful, but abnormal PTT not

helpful• PCC?• FEIBA (Factor eight inhibitor bypass activity)?

What is the mechanism of action of heparin?

Heparin

• Activates Antithrombin III

HeparinActivates Antithrombin III

You have a patient in the ED with a non-STEMI. You put them on heparin. They develop a severe headache and you diagnose an ICH.

What do you do?

How do you treat a patient with major bleeding on heparin?

• Protamine

LMW Heparin

Low Molecular Weight Heparin

• Blocks Xa• Protamine causes partial reversal

Tissue Plasminogen Activator

• Cryoprecipitate• Platelets• FFP• Heparin reversal if on heparin

TissuePlasminogenActivator

Safest central line site for a patient with an elevated INR

Safest central line site for a patient with an elevated INR

• Internal Jugular

What should the INR be before dong an LP?

What should the INR be before dong an LP?

• 1.5

ICH Protocol

Antiplatelet Therapy

• Cyclooxygenase Inhibitors• P2Y12 receptor antagonists (ADP)• GP Iib/IIIa antagonists

How does aspirin work?

How does aspirin work?

• Irreversible inhibition of COX-1 (cyclooxygenase 1)

• Blocks TXA2 production (thromboxane A2)?

Treatment of major bleeding for a patient on aspirin?

Treatment of major bleeding for a patient on aspirin?

• Platelet transfusion• DDAVP (analog of vasopressin)

1 unit of single donor (pheresis) platelets = how many units of pooled donors?

1 unit of single donor (pheresis) platelets = how many units of pooled donors?

6-10

What is Aggrenox?

What is Aggrenox?

• Aspirin• Dipyridamole

What is the half life of clopidogrel?

What is the half life of clopidogrel?

• 6-7 hours• Binds P2Y12 receptor irreversibly

P2Y12 Inhibitors

• Clopidegrel (Plavix)• Prasugrel• Ticagrelor

What are two drug classes you may want to avoid for patients on clopidogrel?

What are two drug classes you may want to avoid for patients on clopidogrel?

• PPIs• Macrolides

Which P2Y12 inhibitor should you avoid in a patient with a history of TIA or CVA

• Prasugrel

How do you treat a patient on clopidogrel with major bleeding?

How do you treat a patient on clopidogrel with major bleeding?

• Platelets – 2 units• DDAVP?• fFVII?

GPIIbIIIa Inhibitor

• Abciximab (ReoPro)• Triofiban (Aggrastat)• Eptifibatide (Integrillin)

STEMI Protocol

What antiplatelet is given to STEMI patients at SJH and MMC?

What antiplatelet is given to STEMI patients at SJH and MMC?

Ticagrelor (Brilinta)

Ticagrelor

• "David Griffen" wrote: Frank, Could you please refresh my memory - what was the rationale regarding replacing Plavix with ticagrelor for the STEMI orders?

• It's proven clinical superiority in head-to-head ACS clinical trial (PLATO) for which it has received a Class I recommendation in the 2013 ACC/AHA STEMI guidelines and is preferred over plavix in the 2012 European STEMI guidelines.

What has just replaced heparin in the STEMI (Star 80) at MMC?

What has just replaced heparin in the STEMI (Star 80) at MMC?

• Angiomax (bivalirudin)• Revisable inhibitor of thrombin• it is a synthetic congener of the naturally

occurring drug hirudin (found in the saliva of the medicinal leech Hirudo medicinalis

Anticoagulant Therapy to Support Primary PCI

For patients with STEMI undergoing primary PCI, the following supportive anticoagulant regimens are recommended:

• UFH, with additional boluses administered as needed to maintain therapeutic activated clotting time levels, taking into account whether a GP IIb/IIIa receptor antagonist has been administered; or

• Bivalirudin with or without prior treatment with UFH.

I IIa IIb III

I IIa IIb III

Anticoagulant Therapy to Support Primary PCI

In patients with STEMI undergoing PCI who are at high risk of bleeding, it is reasonable to use bivalirudin monotherapy in preference to the combination of UFH and a GP IIb/IIIa receptor antagonist.

Fondaparinux should not be used as the sole anticoagulant to support primary PCI because of the risk of catheter thrombosis.

I IIa IIb III

I IIa IIb III

Harm

Why I get confused

• Aggrenox• Angiomax• Aggrastat

Objectives

• Learn strategies for treating patients with iatrogenic coagulopathy

• Understand recent changes in STEMI care• Review the ICH treatment protocol

• Dr. J. Wall on coagulopathy in trauma June 6th.

Recommended preparation

• CAEP 2012 Annual ConferenceJune 3- June 6, 2012– What's New in the Management of the Massively

Bleeding Trauma PatientDr. Sandro Rizoli