Over-Anticoagulation
                        ====================
þ Protocol to Reverse Bleeding from Dabigatran Therapy (Conemaugh Memorial 
  Medical Center)
 - BASELINE laboratory STUDIES – PT/aPTT, Thrombin Time (TT), CBC
  1.	Mild bleeding
   a.	delay next dose or discontinue treatment
  2.	Moderate bleeding
   a.	Discontinue treatment
   b.	Mechanical compression
   c.	Surgical intervention
   d.	Fluid replacement with hemodynamic support – IMPORTANT: maintaining 
        urine output will help with the elimination of dabigatran
   e.	Blood product transfusion
  3.	Severe or life-threatening bleeding
   a.	Above measures
   b.	Considering  Reversal
    i.	PCC 50 units/kg IV
    ii.	Factor VIIa 90mcg/kg IV
    iii.Hemodialysis – 60% removal over 2-3 hours
  References:
  Thrombosis and Haemostasis 2010; 103: 
  J Thromb Haemost 2009; 7(suppl 1):107-110

þ Recombinant Factor VIIa
 - significant thromboembolic complications
 - usual dose is 90 mcg (9 mg) IV Q2H until bleeding stops but varies widely

þ FFP:
 - Just need blood type to start thawing.
 - For outside patients coming to ED, can get blood type and start thawing
   FFP.

þ Treatment of too much Coumadin
 - ACCP (American College of Chest Physicians) recommends IV Vitamin K if INR
   is 6 or more (asymptomatic patients).  But IV Vitamin K (at least the older
   preparations) can cause anaphylaxis, and IM works as quickly.  This study
   found that giving vitamin K made no difference in terms of number of
   bleeding complications, but made re-anticoagulation difficult.  Suggests
   that it's safe to manage patients with high INRs (mean in this study was
   11.1, high INR was 80.9!) without Vitamin K.  [Glover JJ, et al.
   Conservative treatment of overanticoagulated patients. Chest 1995;
   108(4):987.]

 - 2.5-10 mg or up to 25 mg (rarely 50 mg) IM or SQ
 
 - Warfarin Reversal with Vitamin K [Mercy Pharmacy Newsletter, 9/08]

  + Warfarin therapy is frequently complicated by patients becoming excessively 
    anticoagulated. This is most often due to interacting medications and 
    superimposed medical conditions (eg, heart failure) which may alter the 
    pharmacokinetics of warfarin.

  + If warfarin reversal is required, the method chosen should reflect both the 
    clinical situation and the INR value.

  + The following table depictes the 2008 American College of Chest Physicians 
    Guidelines for the management of supratherapeutic INRs.

INR 
  Bleeding 
    Interventione

Above normal range, but <5 
  No significant bleeding 
    Lower the warfarin dose or omit a dose
INR = 5 but <9 
  No significant bleeding 
    Omit the next 1-2 doses of warfarin
-If patient is at an increased risk for bleeding
 administer vitamin K 1-2.5 mg orally
-If the patient requires urgent surgery, administer
 vitamin K = 5 mg orally
e
INR = 9 No significant bleeding 
  Hold warfarin
    Administer vitamin K 2.5-5 mg orally

Above normal range 
  Serious bleeding -Hold warfarin
    Administer vitamin K 10 mg by slow IV infusion
    (at a rate of at least 1 mg/min) supplemented with
    fresh frozen plasma (FFP), prothrombin complex
    concentrate (PCC), or recombinant factor VIIa,
e    depending on the urgency of the situation
-Repeat vitamin K administration every 12 hours
for persistent INR elevation

Above normal range 
  Life-threatening bleeding 
    Hold warfarin
-Administer FFP, PCC, or recombinant facteor VIIa
with vitamin K 10 mg by slow IV infusione
-If the INR remains elevated, vitamin K may be
repeated

intravenously. Since there is a risk of anaphylaxis with the intravenous route, 
the oral route is preferred, when possible. Vitamin K should not be administered 
evia the subcutaneous or intramuscular route, due to incomplete and variable 
absorption.