Rapid Reversal of Warfarin Therapy in Patients

with Intracranial / Intraspinal Bleeding

Mount Auburn HospitalBlood Bank, Emergency Department,

Critical Care, Neurosurgery, Hem-Onc, Quality and Safety

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?

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

Evidence for Use of PCC

Evidence continued

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

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)

PCC: Adverse Reactions

• Allergic reaction

• Chills, headache, fever, nausea and vomiting, rash tx with antihistamines – Anaphylactic reaction tx immediately

• Thrombosis (small risk factor)

Rapid Reversal of WarfarinOrder-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

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

Next Steps (per order-set)1) Immediately Administer Vitamin K 10 mg slow IV

infusion

2) Administer PCC (Bebulin)– INR < 5 20ml Bebulin IV (~ 500 IU)– INR > 5 40ml 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

Post Initial PCC infusion• Follow up Labs: 10 - 15 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)

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

Case Study Continuted

• Head CT shows ICH •Next Steps?

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

References

• Chest 2008; 133 (6Suppl): 160S - 198S

• Stroke 2007; 38; 2001 - 2023

• Yasaka M et al; Optimal dose of PCC for acute reversal of oral anticoagulation. Thromb Res. 2005; 115; 455 - 459

• Nat’l Advisory Committee on Blood and Blood Products, September 2008