Tag Archives: Plasma

General

Liquid Plasma vs FFP: Impact On Your Massive Transfusion Protocol

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In my last post, I discussed the growing number of choices for plasma replacement. Today I’ll look at some work that was done that tried to determine if any one of them is better than the others when used for the massive transfusion protocol (MTP).

As noted last time, fresh frozen plasma (frozen within 8 hours, FFP) and frozen plasma (frozen within 24 hours, FP) have a shelf life of 5 days once thawed. Liquid plasma (never frozen, LQP) is good for the 21 days after the original unit was donated, plus the same 5 days, for a total of 26 days.

LQP is not used at most US trauma centers. It is more commonly used in Europe, and a study there suggested that the use of thawed plasma increased short term mortality when compared to liquid plasma. To look at this phenomenon more closely, a group from UTHSC Houston and LSU measured hemostatic profiles on both types of plasma at varying times during their useful life.

All products were analyzed with thromboelastography (TEG) and thrombogram, and platelet count and microparticles, clotting factors, and natural coagulation inhibitors were measured. They chose 10 units of thawed FFP and 10 units of LQP, and assayed them every 5 days during their useful shelf life.

Here are the factoids:

  • Platelet counts were much higher in day 0 LQP (75K) vs day 0 thawed plasma (7.5K). Even at end of shelf life, the LQP was 1.5x higher than thawed (15K vs 10K).
  • Thrombogram showed that LQP had higher endogenous thrombin production until end of shelf life
  • TEG demonstrated that LQP had a higher capacity to clot that gradually declined over time. It became similar to thawed plasma at the end of its shelf life.
                         (TEG MA for liquid (LQP) and thawed (TP) plasma
  • Most clotting factors remained stable in LQP, with the exception of Factors V and VIII, which slowly declined

Bottom line: Liquid plasma sounds like good stuff, right? Although there are a few flaws in the collection aspect of this study, it gives good evidence that never frozen plasma has better coagulation properties when compared to thawed plasma. Will this translate into better survival when used in the MTP for trauma? One would think so, but you never really know until you try it. Our hospital blood bank infrastructure isn’t prepared to handle this product yet, for the most part. What we really need is a study that shows the survival advantage when using liquid plasma compared to thawed. But don’t hold your breath. It will take a large number of patients and some fancy statistical analysis to demonstrate this. I think we’ll have to look to our military colleagues to pull this one off!

Reference: Better hemostatic profiles of never-frozen liquid plasma compared with thawed fresh frozen plasma. J Trauma 74(1):84-91, 2013.

General

Liquid Plasma vs FFP: Definitions

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I’ll spend the next few days discussing plasma. This is an important component of any trauma center’s massive transfusion protocol (MTP). Coagulopathy is the enemy of any seriously injured patient, and this product is used to attempt to fix that problem.

And now there are two flavors available: liquid plasma and fresh frozen plasma. But there is often confusion when discussing these products, especially when there are really three flavors! Let’s review what they are exactly, how they are similar, and how they differ.

Fresh frozen plasma (FFP)
This is plasma that is separated from donated whole blood. It is generally frozen within 8 hours, and is called FFP. However, in some cases it may not be frozen for a few more hours (not to exceed 24 hours total) and in that case, is called FP24 or FP. It is functionally identical to FFP. But note that the first “F” is missing. Since it has gone beyond the 8 hour mark, it is no longer considered “fresh.” To be useful in your MTP, it must be thawed, and this takes 20-40 minutes, depending on technique.

Thawed plasma
Take a frozen unit of FFP or FP, thaw, and keep it in the refrigerator. Readily available, right? However, the clock begins ticking until this unit expires after 5 days. Many hospital blood banks keep this product available for the massive transfusion protocol, especially if other hospital services are busy enough to use it if it is getting close to expiration. Waste is bad, and expensive!

Liquid plasma (never frozen)
This is prepared by taking the plasma that was separated from the donated blood and putting it in the refrigerator, not the freezer. It’s shelf life is that of the unit of whole blood it was taken from (21 days), plus another 5, for a total of 26 days. This product used to be a rarity, but is becoming more common because of its longer shelf life compared to thawed plasma.

Finally, a word on plasma compatibility. ABO compatibility is still a concern, but Rh is not. There are no red cells in the plasma to carry any of the antigens. However, plasma is loaded with A and/or B antibodies based on the donor’s blood type. So the compatibility chart is reversed compared to what you are accustomed to when giving red cells.

Remember, you are delivering antibodies with plasma and not antigens. So a Type A donor will have only Type B antibodies floating around in their plasma. This makes it incompatible with people with blood types B or AB.

Type O red cells are the universal donor type because the cells have no antigens on the surface. Since Type AB donors have both antigens on their red cells, they have no antibodies in their plasma. This makes AB plasma is the universal donor type. Weird, huh? Here’s a compatibility chart for plasma.

Next time, I’ll discuss the virtues of the various types of plasma when used for massive transfusion in trauma.

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.

Abstracts

EAST 2018 #1: Plasma Over-Resuscitation And Mortality In Pediatric TBI

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The first EAST abstract I will discuss is the very first to be presented at the annual meeting. This is a prospective, observational studied that was carried out at the University of Pittsburgh. It looked at the association between repeated rapid thromboelastography (rTEG) results in pediatric patients and their death and disability after plasma administration. They specifically looked at the degree of fibrinolysis 30 minutes after maximum clot amplitude and tried to correlate this to mortality.

For those of you who need a refresher on TEG, the funny sunfish shape above shows the clot amplitude as it increases from nothing at the end of R, hits its maximum at TMA, then begins to lyse. The percent that has lysed at 30 mins (LY30%) gives an indication if the clot is dissolving too quickly (LY30% > 3%) or too slowly (LY30% < 0.8%).

The authors selected pediatric patients with TBI and performed an initial rTEG, then one every day afterward. They looked at correlations with transfusion of blood, plasma, and platelets.

Here are the factoids:

  • A total of 101 patients under age 18 were studied, with a median age of 8, median ISS of 25, and 47% with severe TBI (head AIS > 3)
  • Overall mortality was 16%, with 45% having discharge disability
  • On initial analysis, it appeared that transfusion of any product impeded fibrinolysis, but when controlling for the head injury, only plasma infusion correlated with this
  • Increasing plasma infusion was associated with increasing shutdown of fibrinolysis
  • The combination of severe TBI and plasma transfusion showed sustained fibrinolysis shutdown, and was associated with 75% mortality and 100% disability in the remaining survivors
  • The authors conclude that transfusing plasma in pediatric patients with severe TBI may lead to poor outcomes, and that TEG should be used for guidance rather than INR values.

Bottom line: There is a lot that is not explained well in this abstract. It looks like an attempt at justification for using TEG in place of chasing INR in pediatric TBI patients. This may be a legitimate thing, but I can’t really come to any conclusions based on what has been printed in this abstract so far.

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

  • There seem to be a lot of typos, especially with < and > signs in the methods.
  • Disability is a vague term. What was it exactly? Was it related to TBI or the other injuries as well?
  • These children also appear to have had other injuries, otherwise why would they need what looks like massive transfusion activation? Why did they need so much blood? Could that be the reason for their fibrinolysis changes and poor outcomes?
  • I can see the value of the initial rTEG, and maybe one the next day. But why daily? What did you learn from the extra days of measurements? Would a pre- and post-resuscitation pair have been sufficient?
  • Plasma is the focus of this abstract, but it does not describe how much plasma was given, or whether there was any departure from the usual acceptable ratios of PRBC to plasma administration.
  • Big picture questions: Most importantly, why would you think that poor outcomes, which are the focus of this paper, are related to plasma administration? Why haven’t we noticed this correlation before? And how does daily TEG testing help you identify and/or avoid this? What questions raised here are you going to pursue?

Reference: EAST 2018 Podium paper #1.

Laboratory

How Much Plasma Does It Take To Reverse Warfarin?

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For decades, plasma (with vitamin K) was the mainstay for reversing warfarin. Over the past several years, prothrombin complex concentrates (PCC) have made inroads in the management of this problem because of its sheer speed of action.

There are two problems with plasma. First, most hospitals still have only fresh frozen plasma (FFP), and it takes 20-30 minutes to thaw. This adds some up-front time to administration. Then, it takes time to infuse the 250cc or so of volume in each unit. This may be 1 or 2 hours, depending on policy and patient tolerance of a bolus of colloid.

If it always just took one unit of plasma to correct the INR to a desirable range (typically 1.5-1.6), then the whole PCC conversation might be moot. You could potentially have the INR corrected in 30-60 minutes depending on your patient’s cardiovascular system.

But how many does it really take? A group at Eastern Virginia Medical School in Norfolk, VA looked at this problem and tried to come up with a mathematical formula. They examined a year of warfarin reversal data at their hospital. Patients with severe clotting disturbances (advanced cirrhosis, DIC) and those who received additional products (PCC or activated Factor VII) were excluded.

Using data from nearly 1,000 patients, the following formula was derived and validated:

∆ INR = (0.57 ∙ preINR) – 0.72

So a patient with an INR of 3.0 would be expected to show a decrease of 0.99 to about 2.0 after one unit. This formula can be used iteratively to figure out how many units will drop the INR to the goal range.

I don’t know about you, but I hate doing math in the middle of a trauma resuscitation. I need something quick and dirty. A physician from NYU Langone in NYC commented on the article, and derived a nice little table to simplify the process. He calculated the number of plasma units based on some common INR ranges, assuming that the goal was to get it down under 1.5. Here is the table:

Bottom line: This is a nice little piece of information to tuck into your pocket or phone. For patients inside the usual therapeutic values, it will take 2-3 units of plasma to reverse. For your average older human with average comorbidities, expect this to take 4-6 hours, not counting ordering, thawing, and delivery. If my definitions of “life-threatening bleeding” are met (see below), your patient may have significant adverse events during this time frame. So think very seriously about using PCC instead.

Related posts:

Reference: Fresh Frozen Plasma Dosing for Warfarin Reversal: A Practical Formula. Mayo Clin Proc 88(3):244-250, 2013.