Rapid Reversal Warfarin-Associated Hemorrhage

Question 1

Therapeutic Options for Warfarin Reversal: Vitamin K

(1) Content
(2) Source
(3) Brands
(4) Mechanism of Action
(5) Onset
(6) Dose
(7) Advantages relative to other options
(8) Disadvantages relative to other options
(9) Price

Answer 1

(1) Vitamin K1 (Phytonadione)
(2) Manufacture
(3) Generic
(4) Restores intrinsic clotting factor production
(5) 4-6 hours
(6) 10mg IV
(7) Required for sustained reversal of warfarin. Safer in non-life threatening bleeds
(8) Time to maximal effect is 4-6 hours. Duration of action may be too long for patients that only need brief reversal
(9) $17 for 10mg

Question 2

Therapeutic Options for Warfarin Reversal: FFP

(1) Content
(2) Source
(3) Brands
(4) Mechanism of Action
(5) Onset
(6) Dose
(7) Advantages relative to other options
(8) Disadvantages relative to other options
(9) Price

Answer 2

(1) All clotting factors in usual serum concentrations
(2) Donor Plasma
(3) Blood Bank
(4) Restores all clotting factors
(5) 13-48 hours
(6) 15-30mL/kg
- Minimum dose is ~4U for 70kg male
- Effective dose may be 4-12U
(7) No increased risk of thrombosis. Safer in non-life threatening bleeding
(8) Quality of evidence for efficacy low. Slow preparation, administration, and INR reversal. Volume required may lead to CHF. Transfusion related lung injury.
(9) $60 [JS: article unclear if this is per unit]

Question 3

Therapeutic Options for Warfarin Reversal: rFVIIa

(1) Content
(2) Source
(3) Brands
(4) Mechanism of Action
(5) Onset
(6) Dose
(7) Advantages relative to other options
(8) Disadvantages relative to other options
(9) Price

Answer 3

(1) rVIIa
(2) Recombinant DNA
(3) NovoSeven RT
(4) Triggers the final common pathway of the clotting cascade. Facilitates thrombin generation
(5)

Question 4

Therapeutic Options for Warfarin Reversal: 3-factor PCC

(1) Content
(2) Source
(3) Brands
(4) Mechanism of Action
(5) Onset
(6) Dose
(7) Advantages relative to other options
(8) Disadvantages relative to other options
(9) Price

Answer 4

(1) Profilnine contains, per 100-U of FIX, no more than:
- 150U of FII
- 35U of FVII
- 100U of FX

(2) Pooled human plasma concentrate
(3) Profilnine
(4) Replaces FII, FIX, and FX
(5)

Question 5

Therapeutic Options for Warfarin Reversal: 4-factor PCC

(1) Content
(2) Source
(3) Brands
(4) Mechanism of Action
(5) Onset
(6) Dose
(7) Advantages relative to other options
(8) Disadvantages relative to other options
(9) Price

Answer 5

(1) Kcentra contains, per 500-U vial:
- 380-500U of FII
- 200-500U of FVII
- 400-620U of FIX
- 500-1020U FX
- 420-820U protein C
- 240-680U protein S
- 8-40U heparin
- 4-30U ATIII

(2) Pooled Human plasma concentrate
(3) Kcentra
(4) Replaces FII, FVII, FIX, FX, Protein C/S
(5)

Question 6

What are the bleeding risks of Warfarin for ICH?

Answer 6

• Anticoagulation can inc. risk of ICH up to 7-10x
• Mortality can be as high as 60%
• In ~50% of anticoagulated patients, bleeding can continue for more than 12-24 hours

Question 7

What is the major side effect of Vitamin K use? how is this managed?

Answer 7

(1) Anaphylaxis in 3:10,000 patients.

(2) Dose is diluted and delivered over 30 minutes

Question 8

What is the downside of delaying FFP administration?

Answer 8

For every 30 minute delay of giving FFP, the odds of INR reversal in 24 hours decreases by 20%

Question 9

Which PCC has a black box warning suggesting not to be used in “bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors” (e.g Warfarin)

Answer 9

FEIBA NH (contains aFVIIa)

Question 10

What are the relative contraindications for PCCs?

Answer 10

(1) DIC
(2) Decompensated liver disease with antithrombin deficiency
(3) Warfarin treatment for ongoing acute thrombosis (current MI or PE)
(4) HIT
- heparin contained in Bebulin (3F PCC) and Kcentra

Question 11

What is the duration of effect for PCCs?

Answer 11

In absence of major continuing blood loss, PCCs reverse anticoagulation for 6-8 hours

Question 12

What are the elements of Warfarin Reversal Protocols?

as described by the author

Answer 12

(1) Define “Life-threatening” bleeding in the warfarin-anticoagulated patient

(2)
Consider Mechanical, Surgical, and other interventional means of hemorrhage control;
Consider conventional Reversal Therapy (VitK/FFP)

(3) Replace Blood and Components PRN
- Consider massive transfusion

(4) Give vit K IV (10mg) to all patients
(5) Factor replacement options (depend on consultant preferences and availability); treat INR > 1.5
(6) Consent for rFVIIa or 3F PCCs secondary to thrombosis risk

Question 13

What are “life-threatening” bleeds in the warfarin anticoagulated patients?

Answer 13

1. ICH
2. Hemorrhage into the spinal canal
3. Dissecting or rupturing aortic aneurysm
4. Other acute life-threatening bleeds in a patient:
   (a) Needing immediate INR correction, -or-
   (b) Cannot tolerate the volume of FFP therapy

Question 14

What is the factor replacement protocol using FFP?

Answer 14

1. Streamlined blood bank procedures

2. Thawed or liquid universal donor (AB) plasma (15mL/kg)

Question 15

What is the factor replacement protocol using rFVIIa?

Answer 15

Note: Neurosurgery may prefer, often with FFP

1. 1mg rFVIIa
2. Consider FFP
3. Note INR will be inaccurate after rFVIIa

Question 16

What is the factor replacement protocol using 4 factor PCCs (Kcentra)

Answer 16

For INR 2-4: 25U/kg
For INR 4-6: 35U/kg
For INR 6+: 50U/kg

Do NOT exceed 100kg doses

Question 17

What is the factor replacement protocol using 3 factor PCCs (Profilnine)

Answer 17

1. Give 25IU/kg
2. Recheck INR 15 minutes after administration
3. If repeat INR > 1.5 consider second 25IU/kg dose
4. Recheck INR 15 minutes after administration
5. If repeat INR > 1.5 give FFP or rFVIIa