Staten Island Corner: Coumadin Toxicity!

Welcome everybody to this month’s edition of Staten Island Corner.  I recently had a case that we see on a regular basis in the ED that is the motivation for this month’s topic.  Supratherapeutic INR is something we see all the time, but it is something that I feel is managed differently depending on who you speak with.  I decided to look up the current literature on the topic to come up with an answer.  Luckily for me, the recent October edition of EMCAST by Dr. Mattu had this specific topic and it was based on a June 2012 article in Circulation.

This article broke down reversal of warfarin in a case-based format, which I find relevant for EM docs.  Three out of the four cases pertain to typical emergency medicine situations and I thought that it would be a good idea to summarize these cases.  I am sure that many of you will question some of these recommendations, which I think will spark an interesting discussion.

The first case is an elderly person with AFib on Coumadin who presents with an INR of 8.6.  This case addresses the very common presentation of asymptomatic supratherapeutic INR.  In this situation, a thorough history and physical must be performed to ensure that there is no active bleeding.  The question is whether or not to give oral Vitamin K in addition to withholding Coumadin.  The risk of major hemorrhage within thirty days in these patients with an INR between 5.0 and 9.0 is very low (with one large observational cohort study showing a rate of 0.96%.)  The authors randomized 355 nonbleeding patients with INR between 5 and 9 and compared those treated with 1.25 mg of Vitamin K and placebo.  The results were that there were no major bleeds at 7 days in either group and a rate of bleeding of 2.5% in the Vitamin K and 1.1% in the placebo at 90 days.  Therefore, this article recommends that in asymptomatic patients with an INR between 5 and 9, low-dose oral Vitamin K will lower the INR more quickly, but WILL NOT lower the risk of major hemorrhage.  Low-dose oral Vitamin K is recommended in patients with high risk of bleeding or with predictors of slow INR decay including advanced age, decompensated heart failure, low weekly warfarin dose, and active malignancy.

The second case is a patient with no active bleeding with an INR of 15.7.  Once again, the important point is that the patient has no current signs of active bleeding.  It has been found that a large proportion of patients with an INR > 10 will have their INR return to a safer range within 24 hours after 2-5 mg of oral Vitamin K.  These patients can be discharged, but should have their INR checked in 24-48 hours to guide further therapy.  If these patients have any sign of bleeding, they should be admitted for further treatment.

The final case is a patient with an INR of 7.3 who presents with melena and hematemsis.  These patients require emergent resuscitation including ABCs, IVF, possible intubation, O2, monitor, PPI, blood transfusion, octreotide, and….warfarin reversal.  Warfarin associated major bleeding is life threatening with a mortality rate of 10% within 30 days.  The most dangerous form of bleeding is intracranial hemorrhage which carries a 50% mortality rate.  IV Vitamin K is indicated in these patients (5-10 mg) which will normalize the INR in most patients, but will take 24 hours for its full effect.  Fresh frozen plasma (FFP 15-30 ml/kg) is what many of us use on a regular basis.  There are many problems with FFP with the two most important being the time needed to thaw the product as well as the significant amount of product required in severe cases.  Many would argue that prothrombin complex concentrates (25-50 IU/kg) should be used in these situations because it contains much higher amounts of Vitamin K dependent factors per unit of volume allowing you to use significantly less volume.  4-factor PCC (not used in the US) which contain factors II, VII, IX, and X, are preferred and reverse warfarin quickly at the time of administration.  3- factor PCC (what we have and have little or no factor VII) are still recommended, but many believe must be given with FFP in order to normalize the INR.  There is debate on this topic as to whether or not FFP needs to be given in addition to the 3-factor PCC.  PCC does carry a risk of thrombosis and therefore should only be given to patients with major or life-threatening hemorrhage.

Summary:

1)      Elevated INR and signs of major bleeding:  Admit, Vitamin K IV 10 mg, and FFP (15-30 ml/kg) or PCC (25-50 IU/kg)

2)      INR between 4-10 with no bleeding:  stop warfarin, outpatient follow up, and consider Vitamin K 1-2.5 mg PO especially for patients at high risk of bleeding.

3)      INR greater than 10 with no bleeding:  stop warfarin, Vitamin K 2.5-5 mg PO, and 24-48 hour follow up.

I am curious to see what people think about these recommendations (especially the third one which suggests discharging a patient with an asymptomatic patient with an INR over 10)??

References:

Garcia DA, Crowther MA.  Reversal of warfarin: case-based practice recommendations.  Circulation.  2012 Jun 12;125(23):2944-7.

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basile

Latest posts by basile (see all)

• Staten Island Corner: VBG for DKA? - April 9, 2013
• Staten Island Corner: Coumadin Toxicity! - February 25, 2013
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