Category Archives: Resuscitation

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.

Best Of AAST #8: Whole Blood At The Scene Of Injury

Here’s another abstract with a promising title that suffers from low subject numbers. Whole blood is the new darling of trauma resuscitation. Assembling a unit of whole blood from the components it was broken down into produces an inferior product from the standpoint of resuscitation.

It makes sense from a coagulation standpoint, but there are a few pesky issues that need to be considered, such as antibody titers. So I understand the enthusiasm to get some papers out there that describe the value of it.

A group in the Czech Republic performed a prospective study that assigned patients to receive scene resuscitation with either one unit of packed cells plus one unit of plasma, or two units of low titer group O whole blood. They had a host of primary outcomes, including feasibility, 24-hour and 30-day mortality, 24-hour blood use and fluid balance, and initial INR. They compared the two groups to matched cohort controls from a trauma registry. The study was performed over a three year period.

Here are the factoids:

  • Three groups of about 50 patients each were enrolled
  • There was no difference in 24-hour mortality, but the authors claimed that the 30-day mortality was “better.” However, the numbers were not statistically significant.
  • They found a statistically significant decrease in 24-hour transfusion volume of about 500cc, which is not clinically significant
  • Similarly, there was an increase in fluid balance of about 2L
  • They also found a “significant” decrease in INR from 1.17 to 1.10, which is also not clinically significant
  • There were no transfusion reactions

The authors concluded that whole blood was safe to give at the scene and that there were improvements in the measured parameters.

Bottom line: Sorry, but the abstract does not really support the title. This study is woefully small, and confusing to read. The purpose of the registry control cohort was not clear, and the extra results further muddied the picture. The statistical analyses were not included, and I am skeptical that they fully support the conclusions. There is just no statistical power to achieve significance with the number of subjects in this study. And many of the differences, even if they were statistically significant, were not clinically significant.

I don’t want to be a downer here. I do believe that whole blood is a good thing. Unfortunately, the whole blood in this study could have been better used doing a much bigger, multicenter study to truly show us the benefits.

Reference: Whole blood on the scene of injury improves clinical outcome of the bleeding trauma patient. AAST 2023, Plenary paper #28.

Best Of AAST #7: How Do You Like Your Platelets – Warm Or Cold?

Until the last few years, massive transfusion in trauma consisted of component therapy, an admixture of packed red cells, plasma, and platelets. Whole blood transfusion is making inroads again, but it is used in a minority of centers.

Of the three components, platelets have classically required different handling than the others. They are generally kept at room temperature, while the red cells and plasma are kept very cold to preserve their shelf life. A few centers have toyed with the use of cold platelets, but there have been concerns about their ability to clot and their useful life after transfusion.

Researchers from the US Army performed a retrospective registry study on a sample of military casualties over four years. They identified soldiers who received either room-temperature or cold-stored platelets. The primary outcome was mortality, and secondary outcomes included the need for surgery, fluid and blood infusions, and the use of a massive transfusion protocol.

Here are the factoids:

  • A total of 300 patients were identified, nearly equally split between room temp platelets and cold-stored
  • Demographics of the two groups were similar, but the ISS was somewhat higher in the cold-stored platelet group
  • Significantly fewer cold-stored platelet patients underwent surgery (13% vs. 24%)
  • Survival was the same at 87-88%
  • Blood and product administration was significantly higher in the cold-stored group, as was the use of the MTP (54% vs. 34%)

The authors concluded that the use of cold-stored platelets were not inferior to room temperature platelets.

Bottom line: Huh?? Yes, survival was the same despite a higher ISS in the cold platelet group. But they required more blood and needed massive transfusion significantly more often.

I see two major issues with this study. The most important is that it is a non-inferiority study. To believe that both arms are equal, a power analysis is required. The sample size here is too small to achieve significance unless differences are extreme, like the transfusion and MTP numbers.

The second problem is that this is an association study. Attempting to show that the type of platelets used is a major determinant of survival, need for surgery, or blood product use is shortsighted. There are a myriad of other factors that have more of an impact.

Far more subjects need to be studied, and a retrospective study with limited data points is not enough. I’m surprised that a military registry could only come up with 75 patients a year to analyze. These low numbers and the nature of this particular registry could inject significant bias as well.

Stay with the room temp platelets for now, and wait for a well-powered prospective analysis before changing your MTP.

Reference: An analysis of the use of cold-stored platelets in combat trauma. AAST 2023 Plenary paper #29.

Crafting And Refining Your Massive Transfusion Protocol – Part 3

Let’s continue with my series on the massive transfusion protocol (MTP). I’ll continue today with information on deactivating and analyzing your MTP.

Deactivation. There are two components to this: recognizing that high volume blood products are no longer needed, and communicating this with the blood bank. As bleeding comes under surgical control, and CBC and clotting parameters (and maybe TEG/ROTEM) normalize, the pace of transfusion slows, and ultimately stops. Until this happens, the MTP must stay active. Even a low level of product need should be met with coolers stocked with the appropriate ratios of products.

There are two ways to stop the MTP: the surgeon or their surrogate calls the blood bank (when no more blood products are to be used), or the blood bank calls the surgeon after the next cooler has been waiting for pickup for a finite period of time. This is typically about 30 minutes. It is extremely helpful if the exact deactivation time is recorded in the electronic medical record. However, this information can be obtained from the blood bank.

Analysis. It’s all over, and now the real fun begins. For most trauma centers, the blood bank maintains extensive data about every aspect of each MTP event. They record what units were released and when, when they were returned, which ones were used, were they at a safe temperature on return or were they wasted, and much, much more! Typically, one of the blood bank supervisors or a pathologist then compiles and reviews this data. What happens next varies by hospital.

Ideally, the information from every MTP activation gets passed on to the trauma program. Presentation at your transfusion committee is fine, but this data is most suitable for presentation at the trauma operations committee. And if significant variances are present (e.g. product ratios are way off) then it should also be discussed at your multidisciplinary trauma PI committee as well.

There are relatively few standard tools out there that allow the display of MTP data in an easily digestible form. Here are some of the key points that must be reviewed by the trauma PI program:

  • Demographics
  • Components used (for ratio analysis)
  • Lab values (INR, TEG, Hgb, etc)
  • Logistics
  • Waste

I am aware of two tools, the Broxton form and an MTP audit tool from the Australian National Blood Authority. The Broxton tool covers all the basics and includes some additional data points that cover activation criteria, TXA administration, and administration of uncrossmatched blood. Click here to check it out. The Australian tool is much more robust with more data points that make a lot of sense. You can download a copy by clicking here.

In the next post, I’ll continue with activation criteria for the MTP.