Tag Archives: Massive transfusion

Liquid Plasma vs FFP: Impact On Your Massive Transfusion Protocol

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.

Liquid Plasma vs FFP: Definitions

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.

What’s The Difference? Liquid Plasma vs FFP

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.

Massive Transfusion: What Ratios Are People Using?

Back in the old days (which I remember fondly), we didn’t pay too much attention to the ratio of blood to plasma. We gave a bunch of bags of red cells, then at some point we remembered that we should give some plasma. And platelets? We were lucky to give any! And to top it all off, we gave LOTS of crystalloid. Turns out this was not exactly the best practice.

But things have changed. Some good research has shown us that a nice mix of blood component products is good and too much crystalloid is bad. But what exactly is the ideal mix of blood products? And what is everybody else doing?

What are all the other trauma centers doing? An interesting medley of anesthesia and pathology groups from the University of Chicago, a Dallas-based anesthesia group, and a blood center in my home base of St. Paul, conducted a survey of academic medical centers back in 2016. They wanted to find out how many actually had a MTP and to scrutinize the details.

They constructed a SurveyMonkey survey and sent it to hospitals with accredited pathology residencies across the US. There were 32 questions in the survey, which asked for a lot of detail. As you can probably personally attest, the longer and more complicated the survey, the less likely you are to respond. That certainly happened here. Of 107 surveys sent out, it took a lot of nagging (initial email plus two nags) to get a total of 56 back.

Here are the factoids:

  • Most were larger hospitals, with 74% having 500 or more beds
  • All had massive transfusion protocols
  • Trauma center level: Level I (77%), Level II (4%), Level III (4%), Level IV (2%), no level (14%)
  • Nearly all (98%) used a fixed ratio MTP; very few used any lab-directed (e.g. TEG/ROTEM) resuscitation
  • Target RBC:plasma ratio: 1:1 (70%), 1.5:1 (9%), 2:1 (9%), other (9%)
  • Only 58% had the same RBC:plasma ratio in each MTP cooler
  • More than 86% had thawed plasma available (remember, these were generally large academic centers)
  • Half stored uncrossmatched type O PRBCs outside the blood bank, usually in the ED; only 1 stored thawed plasma in the ED
  • A total of 41% had more than one MTP (trauma, OB, GI, etc.)
  • 84% had some type of formal review process once the MTP was complete
  • About 68% had modified their MTP since the original implementation. Some increased or decreased ratios, expanded MTP to non-trauma services, decreased the number of units in each pack, changed to group A plasma from AB, or switched from ratio to TEG/ROTEM or back.

Bottom line: This is an intriguing snapshot of MTP practices around the country that is about six years old. Also remember, this is a somewhat skewed dataset. The survey was directed toward hospitals with academic pathology programs, not trauma centers. However, there is enough overlap that the results are probably generalizable. 

Most centers are (were) using MTP packs containing six units of PRBCs, and were attempting to achieve a fixed 1:1 ratio. Half of hospitals had the same number of units in each cooler, half varied them by cooler number. Nearly half had multiple flavors of MTP for different specialties. Very few used TEG/ROTEM during the initial phased of MTP. Most modified their MTP over time.

Unfortunately, I’ve not seen a similar survey repeated recently. I’m certain that practices have changed over time as our understanding of balanced resuscitation continues to advance. 

Finally, I’ve written quite a lot on most of these issues. See the links to my “MTP Week” series below.

Reference: Massive Transfusion Protocols: A Survey of Academic
Medical Centers in the United States. Anesth & Analg 124(1):277-281, 2017.

MTP week series:

Best of EAST #1: Ultramassive Transfusion Survival

All right, let’s kick of this EASTfest with an abstract from one of the Eastern Association for the Surgery of Trauma multicenter studies. This one looked at outcomes after what they term “ultra-massive” resuscitation.

There are a number of definitions for “massive transfusion” which I’ve discussed before. They are basically trauma resuscitations in which the massive transfusion protocol is triggered. The group that designed this study defined ultra-massive resuscitation as one that entails transfusing at least 20 units of packed red cells within 24 hours.

The study focused on factors predicting survival in these patients. They used multivariate logistic regression as well as another regression tool, classification and regression tree analysis (CART). They used these tools to control for age, ISS, mechanism of injury, base deficit, and crystalloid use.

Here are the factoids:

  • A total of 400 patients were studied at 15 trauma centers over an eleven year period
  • Subjects were young (mean 37 years), male (81%), severely injured (mean ISS 34) and in shock
  • Median transfused products were 29u PRBCc, 23u FFP, and 24u platelets
  • Mortality was high with half dying in 24 hours and two thirds not surviving to discharge
  • Transfusion ratios > 1.5:1 for both RBC to plasma and RBC to platelets were strongly association with death
  • CART identified severe head injury, resuscitative thoracotomy, and low platelet count (< 169K / microliter) we association with high mortality
  • The best chance for survival occurred in those without a head injury, no thoracotomy, and higher platelet count

The authors concluded that the failure to meet balanced resuscitation goals was the main concern for mortality, and recommended more attention to meeting ratios.

My comments: I’m not so sure I’ve learned a lot from this abstract. I think we already knew that people with severe TBI or thoracotomy don’t do very well, especially if they need that much blood.

I also worry about the heterogeneity of the population. The variables that were controlled still offer quite a bit of variability in the injuries and condition of these trauma patients. I think this will make it difficult to come to many solid conclusions when looking at something as crude as mortality. 

Here are my questions for the authors and presenter:

  1. Why are there so few patients? An eleven year study with 15 centers participating means that each submitted less than 3 cases per year. Most busy Level I centers have many more than that in a single year. Was there some other kind of data selection or limitation that is not described in the abstract? Do you think there is enough power? See question 3 for more on this.
  2. How did you arrive at an admission platelet count threshold of 169,000/ul? This would seem to be a surrogate for something else going on, and I’m not sure what. But it just seems so arbitrary.
  3. The transfusion ratios are a bit confusing. For ratios less than 1.5:1, there are no error bars. Does this mean that every one of those patients survived? That’s remarkable if so. And the error bars for the groups with a ratio > 1.5:1 are perilously close to the 1 line, and they have quite a range. Is the statistical power really there to convincingly show a difference? This is the most interesting part of the abstract, so please expound upon it.
  4. Explain your use of CART. How did you determine the specific  determine the specific thresholds used in the CART model? Why did you choose to use this tool? For my readers, here is the tree presented in the abstract.
  5. What is the real message of the abstract? We already know that if patients who have a severe head injury or get their chest cracked are probably not going to make it. The transfusion ratio information is somewhat interesting, but there is better quality data out there that defines acceptable ratios. The platelet count information… interesting. What more do you have?

I think there is a lot of potential in this dataset once you overcome the small numbers. I’m very interested in the authors’ presentation!

Reference: Ultra-massive transfusion outcomes in a modern era: an EAST multicenter study. EAST 2021, Paper 1.