Tag Archives: PCC

Abstracts, Resuscitation

Best of EAST #7: Whole Blood Plus 4-Factor Prothrombin Complex Concentrate

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In my last post, I went through some of the basics of whole blood transfusion. However, the focus was more on compatibility than function. Today, I’ll review an abstract that explored functionality of that blood transfused.

In theory, whole blood contains the usual array of clotting factors. It has been shown that high factor levels persist in whole blood, even when stored at room temperature. So in theory, additional clotting factor infusion should not be necessary.

The group at the University of Arizona explored adding 4-factor prothrombin complex concentrate (4-PCC) to whole blood transfusion. The scanned three years of data in the TQIP database. They identified two groups of patients, those who received whole blood alone and those who received 4-PCC in addition to it. They were interested in the impact on total product transfused and the usual crude outcomes of hospital / ICU length of stay and mortality.

Here are the factoids:

  • Only 252 patients in this entire database (tens of thousands of records in three years) received whole blood, and 84 of them also received 4-PCC
  • The patients tended to be young (average age 47), 63% male, with moderate (median ISS 27), and blunt injury in 85%
  • Administration of 4-PCC was associated with a significantly decreased transfusion requirement of both blood (5 vs 8 units) and plasma (3 vs 6 units), but not platelets
  • ICU LOS was significantly lower in the 4-PCC group (5 vs 8 days), but there was no difference in hospital stay or in-hospital mortality

The authors concluded that 4-PCC given with whole blood was associated with a decrease in transfusion requirements and ICU length of stay, and that further studies were needed.

My comments: Well, this is certainly interesting and unexpected.  Why would a clinician even think of giving 4-PCC when giving whole blood? It looks like a very rare occurrence in the dataset. Unfortunately, we can never find out. We can’t just go back and look in the charts. Perhaps these centers were using TEG or ROTEM during the resuscitation?

As always in these big databank analyses, the researchers can only control for the variables they can think of that are already present in the database. Although they were able to match the patient groups for the usual demographics, vital signs, injury patterns, comorbidities, and trauma center level, it is entirely possible that there were other factors in play.

Here are some questions for the authors and presenter:

  • Why did you choose to do this study? Was there some clinical question that arose that triggered it? Something you found in the literature that suggested it?
  • How do you explain the results, given that the factors in 4-PCC have been shown to persist at functional levels in whole blood? Why do you think less blood and plasma were needed?
  • What needs to happen next? I agree that more research is needed to see if this association is real. How would you go about doing it?

Thanks for a very intriguing paper! Details will follow, I’m sure.

Reference: Four factor prothrombin complex concentrate in adjunct to whole blood in trauma-related hemorrhage: does whole blood replace the need of factors? EAST 2021, Paper 18.

Abstracts

EAST 2018 #8: 4-Factor PCC Plus Plasma. What?

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Many trauma centers have moved toward reversing warfarin with prothrombin complex concentrate (PCC) in place of plasma due to the speed and low volume of infusate with the former. In the US, 3-factor PCC was approved by the FDA first, but it has a lower Factor VII content. This usually required infusion of plasma anyway to make up the Factor VII, so what was the point (although there was some debate on this)?

Then 4-factor PCC was approved, and it alone could be used for warfarin reversal. But so far, PCC has not been routinely used for reversal of coagulopathy from trauma. We still rely on plasma infusion for this. The abstract I am discussing today compares reversal with 4-factor PCC alone to reversal with 4-factor PCC and plasma in coagulopathic patients.

This study retrospectively reviewed adult patients who received one of the above treatments over a 3 year period. Patient who were on oral anticoagulants were excluded. The goal INR was 1.5, and time to correction and number of PRBC transfused were measured.

Here are the factoids:

  • There were 516 patients who met criteria, but only 80 FFP patients and 40 PCC+FFP patients were analyzed
  • Patients were an average of 58 years old, had an ISS of 29, and 87% had sustained blunt injury
  • PCC+FFP resulted in faster correction of INR (373 min vs 955 min)
  • PCC+FFP received fewer units of PRBC (7 vs 9 units) and FFP (5 vs 7 units)
  • Mortality rate was lower in the PCC+FFP group (25% vs 33%)
  • There was no difference in thrombotic complications

Bottom line: Well, this is an interesting start. I think this abstract suggests that we should incorporate giving 4-factor PCC into the massive transfusion protocol to try to reduce the INR faster. However, the patient numbers are low and several of the results are only weakly significant (units transfused, mortality, p=0.04). Some additional confirmative studies will be needed before this is ready for prime time!

Here are some questions for the authors to consider before their presentation:

  • Why did your study group drop from 516 to 120? What impact might this have had on you analyses?
  • Did you look at the correction times stratified by initial INR? Severely coagulopathic patients could skew the numbers, especially if they were predominantly in only one of the study groups.
  • It did not look like the patients received much PRBC or plasma (<10 units of each). How injured / coagulopathic were they?
  • The mortality rates are rather high for an average ISS of 29. Did you analyze to see what impact ISS had on mortality? Could this have influenced your analysis?
  • Big picture question: Should we consider routinely giving PCC as part of the massive transfusion protocol in patients who are known to be coagulopathic? Based on the graph, it looks like patients will need more than a single dose. Reversal time was still very long for PCC+FFP.

Thanks for an intriguing abstract!

Reference: EAST 2018 Podium paper #12.

General

Warfarin Reversal For Emergent Surgery Using PCC

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Yesterday I published a protocol that Regions Hospital uses for rapid reversal of warfarin in patients with life-threatening bleeding. This is very useful in trauma patients, but a number of other specialties use it as well (GI, etc). But what about that patient who doesn’t have a major bleeding problem, but needs emergency surgery or some invasive procedure? If something isn’t done prior to the case, the surgeon or interventionalist may inflict life-threatening bleeding!

We use a variant of the protocol I posted yesterday. The differences arise from the fact that, in this case, there is a little bit of time to find out some of the patient’s medical history. Certain things may modify the protocol, or contraindicate it entirely, such as:

  • Is the patient in DIC?
  • Do they have heparin induced thrombocytopenia (HIT)?
  • Do they have a history of significant peripheral vascular disease or thrombotic tendencies?
  • Will they need to be re-anticoagulated afterwards?

Again, feel free to download this protocol and modify it as you wish. Comments and questions are welcome!

Download the warfarin reversal for emergent surgery protocol here

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General

Warfarin Reversal With Prothrombin Complex Concentrate

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Everybody is looking for good algorithms. They’re very helpful in standardizing care and they are a great teaching tool to show one good way to do something. All trauma centers have at least a few, like the Massive Transfusion Protocol.

Well, as the population ages and more of our elders are placed on drugs like warfarin, they run the risk of life-threatening bleeding if an accident occurs. Why reinvent the wheel? Don’t spend the time combing through the literature and designing your own protocol if someone else has already done the leg work!

Here’s a copy of our protocol for rapid reversal of warfarin with prothrombin complex concentrate (PCC) when life-threatening bleeding is present (e.g. blood in the head). Please note that the INR must be 2 or above to use this protocol, or the risks of giving the drug begin to outweigh the benefits.

Once the patient is found to be eligible, a single dose of PCC based on INR is given, as well as 10mg of vitamin K. The INR usually returns to near normal within about 30-45 minutes. If it’s still elevated, then begin administering plasma.

Feel free to copy and share. Also, any and all comments are welcome!

Download the protocol by clicking here

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General

Q&A: Prothrombin Complex Concentrate

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An anonymous user recently asked about decision-making with regard to anticoagulation reversal. Specifically, they were interested in using prothrombin complex concentrate (PCC) vs activated Factor VII (FVIIa). I’ve done a little homework on this question, and am going to include some information on the use of fresh frozen plasma (FFP), too.

Unfortunately, there’s not a lot of good data out there comparing the three. Enthusiasm for using FVIIa is waning because it is extremely expensive and the risk/benefit ratio is becoming clearer with time (more risk and less benefit than originally thought). PCC is attractive because it provides most of the same coagulation factors as FFP, but with far less volume. However, it is very expensive, too.

What to do? One of the best papers out there comes from the UK, where they looked at the cost effectiveness of PCC vs FFP in warfarin reversal. They reviewed a year’s worth of National Health Service patients from the standpoint of what it costs to gain a year of life after hemorrhage. They found that the cost was £1000-£2000 per life-year, and £3000 per quality adjusted life-year. This was more cost effective than using FFP. Unfortunately, I do not have access to the full text to review the details.

PCC has only been compared to FFP in the treatment of hemophilia, so it’s not possible to draw any conclusions. The course of therapy for perioperative management of hemophiliacs is lengthy (meaning hideously expensive), and there was a cost-savings seen ($400,000)! Since we use only short duration therapy in trauma patients, the savings will be far less.

Bottom line: PCC is probably as effective as FFP, with less risk of volume overload. It is probably more cost effective as well. As the population of people that are placed on warfarin ages and becomes more susceptible to volume overload from plasma infusions, I think that PCC is going to become the reversal agent of choice. Use of Factor VIIa will continue to wane. However, someone needs to do some really good studies so we don’t get suckered.

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Reference: Modeling the cost-effectiveness of prothrombin complex concentrate compared with fresh frozen plasma in emergency warfarin reversal in the United Kingdom. Clinical Therapeutics 32(14):2478-2493, 2010.