1. Rapid Reversal of Warfarin Therapy in Patients with Intracranial / Intraspinal Bleeding
Mount Auburn Hospital
Blood Bank, Emergency Department, Critical Care, Neurosurgery, Hem-Onc, Quality and Safety

2. Clinical Questions
What are the treatment options for anticoagulation reversal?
How fast do they work?
What are the risk factors?
What is the Rapid Reversal of Warfarin Order-Set?

3. Background
Life threatening bleeds in patients on wafarin - Timely reversal is IMPERATIVE!
Current Treatment Options:
FFP
Concerns: Delayed treatment (thaw time), volume overload, inadequate correction
Vitamin K IV
Concerns: Length of onset time
Prothrombin Complex Concentrate (PCC)
Desmopressin (DDAVP)
Increases levels of VWF and factor VIII
Now Available

4. Evidence for Use of PCC

5. Evidence continued

6. Main Points:
PCC normalizes INR faster than FFP
PCC is recommended for patients with life-threatening
warfarin related bleeding
PCC, vitamin K IV, and FFP should all be available for this
patient population

7. PCC: What is it? Also called: Bebulin (the brand name)
Factor IX complex concentrate and has high levels of factor II, IX and X (vit K dependent coag. Factors)
Low level of factor VII
Works by temporarily raising the levels of these clotting factors
AHA / ASA class IIb recommendation
Cost: $1500 / dose ($1 / IU)

8. PCC: Adverse Reactions
Allergic reaction
Chills, headache, fever, nausea and vomiting, rash  tx with antihistamines
Anaphylactic reaction  tx immediately
Thrombosis (small risk factor)

9. Rapid Reversal of Warfarin Order-set
Restricted to the ED, Critical Care, and OR
Indications: Confirmed CT with Intracranial or Intraspinal hemorrhage with elevated INR
Exclusions: HIT in previous 3 months
Relative contraindications:
DIC, history of recent thrombosis, MI, Ischemic Stroke

10. Initial Work-up STAT head CT Once Head CT confirmed:
Notify/ CALL blood bank and core lab
Blood bank x 5096
Core Lab x 5060
Neurosurgical Emergency: Patient Name, and MR #
All labs need to be handed to a lab tech
STAT PT/INR, PTT, D-dimer, fibrinogen, CBC, in a bag labeled STAT to core lab
STAT type and screen to blood bank
STAT BMP and LFTs

11. Next Steps (per order-set)
1) Immediately Administer Vitamin K 10 mg slow IV infusion
2) Administer PCC (Bebulin)
INR < ml Bebulin IV (~ 500 IU)
INR > ml Bebulin IV (~ 1000 IU)
Rate: Do not exceed 2 ml per minute IV
3) 2 units FFP given
4) Consider Plt if Plt < 100,000
5) Consider DDAVP (Desmopressin) - If plt dysfunction present

12. Post Initial PCC infusion
Follow up Labs: min AFTER PCC infusion is complete: STAT PT / INR
Goal: Normalization of INR with in shortest time possible
Further management: Per attending MD
Additional labs may be needed per the pathologist or MD
Maximum I.U. per Medical Director of blood bank (~ 3000 IU maximum)

13. Case Study
71 yo M with sudden onset of a severe headache and blurred vision
Vitals: BP 200/90, HR 92, RR 14, Temp 98
PMH: Afib, CAD, HTN, diabetes
Medications:
Warfarin 5mg daily
Lopressor 25mg BID
Lipitor 20mg daily
Glucaphage 10mg BID

14. Case Study Continuted
Head CT shows ICH
Next Steps?

15. Conclusions Coagulopathy puts patients at high risk for ICH Vitamin K
Effective, but slow onset
FFP
Effective, but slow and risk of volume overload
PCC - is effective and fast acting
Order - set is available now
When given together Vit. K, FFP, and PCC can quickly normalize INR

19. References Chest 2008; 133 (6Suppl): 160S - 198S
Stroke 2007; 38;
Yasaka M et al; Optimal dose of PCC for acute reversal of oral anticoagulation. Thromb Res. 2005; 115;
Nat’l Advisory Committee on Blood and Blood Products, September 2008