In this episode I’ll:
1. Review an article about fixed dosing of 4-factor prothrombin complex concentrate for emergent warfarin reversal
2. Answer the drug information question: What is the dose of subcutaneous heparin to provide full therapeutic anticoagulation?
3. Share a resource for information about drug-induced & iatrogenic respiratory disease
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Thank you to Emergency Medicine Alex for sharing this article!
Article
Evaluation of fixed dose 4-factor prothrombin complex concentrate for emergent warfarin reversal
Lead author: Lauren Klein
Published in: The American Journal of Emergency Medicine, May 2015
Background
Four-factor prothrombin complex concentrates (4FPCC) for warfarin reversal are faster to prepare and administer than fresh frozen plasma. The optimal dose of 4FPCC is not known. Current dose recommendations in the US involve calculations based on pretreatment INR. Waiting for the pretreatment INR value to be resulted by the hospital laboratory may delay administration of 4FPCC by 30 minutes or more.
Purpose
The authors sought to characterize the safety and efficacy of 4FPCC in patients who received a fixed dose of 1500 units regardless of pretreatment INR for emergent warfarin reversal.
Methods
The study was a retrospective, single-center review of patients who received 1500 IU of 4FPCC for emergent warfarin reversal between March 2014 and January 2015.
Results
A total of 39 patients were reviewed. The most common indication for treatment was intracranial hemorrhage ( 71.8%). The median INR at presentation was 3.3, and the median INR after a single dose of 1500 IU was 1.4. A total of 36 patients (92.3%) achieved successful reversal with a target INR of less than 2. 28 patients (71.8%) achieved successful reversal with a target INR of 1.5 or less. There were no thrombotic adverse events within 7 days.
Conclusion
The authors concluded that administration of a fixed dose of 1500 units of 4FPCC leads to high rates of successful INR reversal and no related thrombotic adverse events within 7 days.
Discussion
Administering 4FPCC quicker by eliminating the need for a pretreatment INR is great in theory. The advantage 4FPCC has over fresh frozen plasma is speed of administration and this fixed dosing strategy enhances that advantage. The hope is that this will translate into improved clinical outcomes.
It is important to examine the treatment failures in the study which were 3 patients who did not have a post treatment INR below 2:
– A 78 kg patient with a pretreatment INR of 2.5 was in cardiac arrest from ruptured aortic anuerysm in the OR when 4FPCC was administered. INR decreased to 2 after 1500 units of 4FPCC. The patient appeared to have disseminated intravascular coagulation and expired prior to getting another dose of 4FPCC.
– A 99kg patient with a pretreatment INR >10 got 1500 units of 4FPCC and INR decreased to 2.2. The physician elected not to give further 4FPCC doses.
– A 145 kg with a pretreatment INR >10 got 1500 units of 4FPCC and INR decreased to 2.3. The patient was given an additional dose of 500 units 4FPCC and the subsequent INR was 1.8.
An additional consideration is the cost savings realized by the fixed dosing strategy for 4FPCC. Approximately $90,000 USD was spent on 4FPCC for the 39 patients in the study. Had the weight-based dosing of 25-50 units/kg in the prescribing information been used, the cost to treat the same group of patients would have been $40,000 USD higher.
The limitations to this study include that it is a retrospective single center review without a comparator group. I plan to discuss the study further with Emergency Medicine Alex and the pathologist at my institution’s laboratory that oversees blood products. I think there is a good chance our P&T committee would consider adopting this fixed dosing strategy.
I’ve love to know what you think – is this data good enough to present to your P&T committee to change how 4FPCC is dosed for emergent warfarin reversal at your institution? Send me an email with your thoughts – joe@pharmacyjoe.com.
Drug information question
Q: What is the dose of subcutaneous heparin to provide full therapeutic anticoagulation?
A: 333 units/kg subcutaneous loading dose then 250 units/kg subcutaneous q 12 hours.
This particular question was asked in regards to a 100 kg dialysis patient with a DVT and no IV access who needed to be bridged with anticoagulation to warfarin.
The 2012 CHEST Guidelines state:
The results of a randomized trial in patients with VTE that showed that unmonitored weight-adjusted subcutaneous heparin given twice daily in high doses was as safe and effective as unmonitored, weight-adjusted LMWH challenge the requirement for aPTT monitoring of heparin administered subcutaneously.
Resource
The resource I’d like to share in this episode is pneumotox.com. I’d like to give a shout out to @DrugInfoGeek on Twitter for reminding me about this resource.
Pneumotox.com is a place to find updated information about drug-induced & iatrogenic respiratory disease. It is run by the department of pulmonary and intensive care medicine in Dijon, France. You can browse or search the site by drug name or clinical pattern, and get detailed information about drug-induced & iatrogenic respiratory disease.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
We have finger stick INR in our ED thus even though its not the most precise measure, I like to use it to dose Kcentra with targeted INR dosing. Results are available within a few minutes. Additionally most of our bleeds have supratherapeutic INRs > 6, I noticed in the trial their baseline INRs ~ pretty low…I think treatment failure would have been greater if studied in the population of bleed pts that I treat.
Great points, thank you!
PharmacyJoe – do you have an update whether Fixed dose KCentra was adopted at your institution?
Fixed dose was not adopted but we are considering bringing the proposal back in 2018.
have there been any decisions on what dose your institution is planning on standardizing the dose for? 1500 units was used for this study. Is your institution is considering a higher dose?
Thank you.
We decided at the time to not use fixed dosing. I still think it is a good idea though if only because the treatment gets started so much faster because you don’t wait for the INR before giving 4FPCC.