Tag Archives: Plasma

Resuscitation

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.

Resuscitation

Liquid Plasma vs FFP: Definitions

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I’ll spend the next two posts 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.

Resuscitation

What’s The Difference? Liquid Plasma vs FFP

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Plasma 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.

Resuscitation

Best Of EAST #2: Pay Attention To Platelet Ratios In Your MTP!

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More MTP stuff! Every trauma center has a massive transfusion protocol, and current literature encourages them to try to achieve an “optimal” transfusion ratio. The literature has converged on a red cell to plasma ratio of somewhere between 1:1 and 2:1. Less has been written about platelet ratios, and trauma centers often don’t pay as much attention to this ratio when reviewing MTPs.

But is it important? The trauma group at the Massachusetts General Hospital examined the impact of platelet ratios on mortality in patients undergoing MTP. This was another TQIP data analysis, performed over a nine year period.

The authors defined massive transfusion as ten or more units of PRBC in the first 24 hours, or any number of units of red cells, plasma, or platelets given within the first four hours. They also defined “balanced” as a ratio of RBC to FFP and RBC to platelets <2. Multivariate regression analysis was performed to gauge the impact of ratios and achievement of a balanced resuscitation on 24-hour mortality.

Here are the factoids:

  • A total of 7,520 patients in the dataset underwent MTP
  • Nearly 83% achieved RBC to FFP balance, but only 6% had RBC to platelet balance (!)
  • Patients with both balanced FFP and platelets had the lowest mortality at 24 hours
  • Mortality increased by 2x with unbalanced plasma, a little more than 2x with unbalanced platelets, and 3x if both were out of balance (see figure)

The authors concluded that the platelet component of the MTP was frequently out of balance, and that it is associated with mortality to a greater degree than with unbalanced plasma.

Bottom line: This paper confirms my observations that trauma centers pay a lot more attention to the red cell to plasma ratio and don’t get as excited when the platelets are out of line. Part of this is probably due to confusion over how to count platelet packs. Typically they are delivered in packs called “pheresis” or “apheresis.” Each is the equivalent of about 6 units of platelets (check with your blood bank for more exact numbers). This means that a ratio of 6 RBC to 5 plasma to 1 platelets would be considered balanced. But a ratio of 28:28:2 would not.

According to this abstract, the use of sufficient platelets is important. This makes sense. However, the exact mechanism cannot be determined from this type of study. It could be a direct effect of not having enough platelets to form good clot. Or it could be something completely outside the clotting mechanism, just an association with something in the care processes that occurs as these patients undergo resuscitation. 

The why doesn’t matter so much, though. This abstract presents compelling data that suggests that we really need to pay attention to the platelet ratios given during the MTP. They should be analyzed just as closely as plasma ratios during PI review, and changes to the MTP process implemented to normalize this important ratio.

Here are my questions for the authors and presenter:

  • There is a statement in the methods section that is not clear. “only patients with steady RBC/PLT and RBC/FFP ratios between 4-and 24-hr were analyzed.” What is your definition of “steady?”
  • Did you see any mortality patterns in the data you analyzed that might suggest why lower platelet volumes were more deadly?

This was a nicely done abstract, and I look forward to the live presentation and the finished manuscript!

Reference: DON’T FORGET THE PLATELETS: BALANCED TRANSFUSION AND THE INDEPENDENT IMPACT OF RBC/PLT RATIO ON MORTALITY IN MASSIVELY TRANSFUSED TRAUMA PATIENTS. EAST 25th ASA, Oral abstract #1.

Complications

Can We Use Type A Plasma For Emergency Transfusion?

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Trauma patients tend to try to bleed to death. And trauma professionals try to stop that bleeding. They also frequently have to replace the blood products that were lost, which includes red blood cells, plasma, platelets, and more.

From a red blood cell standpoint, we have a long history of using group O- packed red cells as the so-called universal donor product. The problem is that only about 5% of the world population has this blood type, so it can be scarce.

To address this, many centers have moved toward using O+ blood for select patients. This blood type is much more prevalent (about 50% worldwide). The only difference is the positive Rh factor which has little impact on males, or females who are not in their child-bearing years. If an allergic reaction occurs, it is typically mild.

But what about plasma? This is interesting stuff. When selecting red cells, we want them to have no ABO group antigens on them so they don’t provoke a reaction. But plasma is just the opposite. We don’t want any ABO group antibodies in it. And the only plasma without antibodies comes from people who have all of them (A and B) on their red cells. This means people with type AB+ blood. Unfortunately, this is the other rare blood type, so there’s not a lot to go around. Worldwide, about 5% of people are AB+ and less than 1% are AB-.

So why couldn’t we do something like we did with packed red cells and substitute a more common blood type that evokes little immune response? The American Association of Blood Banks (AABB) has authorized both AB and A plasma for use in emergency situations. Unfortunately, the safety profile for using group A has not been very well studied, particularly in trauma patients needing massive transfusion.

The authors of the PROPPR study re-analyzed the data from it to try to answer this question. As you may recall, PROPPR was published in 2015 and compared safety and effectiveness of transfusion ratios at 1:1:1 to 1:1:2 (plasma : platelets : red cells).

The study group selected patients from the dataset who received at least one unit of emergency release plasma (ERP), defined as product given before the patient’s ABO type had been determined. Nicely enough, 12 sites transfused group AB ERP and 9 sites gave group A. One site gave both A and AB.

The authors looked at in-hospital mortality at 30 days, and a host of complications. Here are the factoids:

  • A total of 584 of the 680 patients in the PROPPR study received emergency release plasma
  • The median number of units given was 4, and there was no difference between A and AB groups
  • There were statistically significant baseline differences between the groups, including blood type, SBP, percent in shock (SBP<90), blunt mechanism, positive FAST that were probably not very clinically significant
  • The number of transfusions of all products were significantly  higher in the A plasma group
  • Complications were significantly higher in the A plasma group, specifically from SIRS, pulmonary problems, and venous thromboembolism (VTE)
  • There were no acute hemolytic transfusion reactions and three febrile reactions

The authors concluded that, statistically, the use of group A plasma was not inferior to the use of group AB. The authors stated that cautious use of group A is an acceptable option, especially if group AB is not readily available.

Bottom line: Here we go again. Always be careful when reading a study that suggests non-inferiority of one thing compared to another. There are a lot of potential issues here:

  • The PROPPR trial data was not designed to answer questions about plasma usage, so the data is being highjacked a bit
  • Participating centers did not have a standardized way to determine the group that received ERP, so some data anomalies will be present
  • The A and AB study groups were different in many ways at baseline, particularly with respect to how much product they received
  • The primary outcome, 30-day mortality, was underpowered and could never show a significant difference

So with significant baseline differences in study groups and a potentially underpowered study, don’t read non-inferiority as meaning that use of group A plasma is okay. We still just don’t know. What this study really shows is that you can “get away with” using low titer group A plasma if you run out of AB. But it shouldn’t be your go to product yet. To figure out the real safety profile, we need to do a real “PROPPR” study. Get it?

Reference: Group A emergency-release plasma in trauma patients requiring massive transfusion, J Trauma 89(6):1961-1067, 2020.