December 19, 2012 by EmerJencyWEBB
Disclaimer: I have no ties, financial or professional, with any pharmaceutical or medical device company.
In the realm of life threatening bleeding and anticoagulant reversal, a paradigm shift is slowly occurring. During most of my training, my hospital’s protocol was solely based on withholding anticoagulant, and adding Vitamin K and FFP. None of these therapies resulted in a reversed INR in the ED. Vitamin K takes time to kick in, and FFP requires more volume than we are comfortable giving some critical patients and doesn’t typically guarantee reversal below 1.7.
Fortunate for us and our patients, the tide is changing. The new push at our institution and many around the country involves the use of prothrombin complex concentrates or PCCs. It narrows the shotgun approach of FFP to laser precision at repleting vitamin K dependent factors. And they do it well.
PCCs come in a variety of flavors. Most hospitals already utilize three factor PCCs such as bebulin which have been in limited use for some time. At my shop, we now have access to a four factor PCC called FEIBA NF (aFVII, IX, X, II) which has the addition of activated factor VII. Here’s a breakdown of this concentrate:
FEIBA NF (Anti-Inhibitor Coagulant Complex), nanofiltered and vapor heated, is a freeze-dried sterile human plasma fraction with Factor VIII inhibitor bypassing activity. In vitro, FEIBA NF shortens the activated partial thromboplastin time (APTT) of plasma containing Factor VIII inhibitor. Factor VIII inhibitor bypassing activity is expressed in arbitrary units. One unit of activity is defined as that amount of FEIBA NF that shortens the APTT of a high titer Factor VIII inhibitor reference plasma to 50% of the blank value.
FEIBA NF contains Factors II, IX, and X, mainly non-activated, and Factor VII mainly in the activated form. The product contains approximately equal unitages of Factor VIII inhibitor bypassing activity and Prothrombin Complex Factors. In addition, 1–6 units of Factor VIII coagulant antigen (FVIII C:Ag) per mL are present. The preparation contains only traces of factors of the kinin generating system. It contains no heparin.
Here’s the simplified version: take a patient with a supratherapeutic INR and life threatening bleed and drop the INR in as little as 30 minutes. There’s still much work to be done in validating whether or not this therapy actually translates to mortality difference, but it’s hard to argue with INRs normalizing in critically ill patients while still in your ED.
If an ICH patient’s INR is unknown or if the INR is known to be < 5 we are giving 500 IU x 1 and rechecking INR in 30 minutes. If they are > 5, we are giving 1000 IU. If we gave 500 IU up front, and their INR comes back > 5 we are giving another 500 IU and rechecking in 30 minutes. Anecdotally, I can say I have been seeing INRs drop like a rock. This is all along with the traditional 10 U Vitamin K IV that we typically give anyway. There are complications in treatment, the most significant being thrombotic event rates. This is thought to be at the rate of 4-8:100,000 hemophiliac patients treated in one study, however these usually occur at doses beyond what is described above. Theoretically, this feels like a low risk for the benefit. And the cost at our institution is similar enough to FFP to justify it’s use.
Like I said, there’s still not a lot of data out on FEIBA NF and reversal of warfarin in critically bleeding patients yet, and more remains to be seen. I invite you to read up on the use of PCCs and life threatening bleeds, I know I will continue to do so. It will be interesting to see if FEIBA NF ultimately shows morbidity/mortality benefit in this population of patients.
Here’s a small taste of what little research has been done so far: