Tag Archives: Massive transfusion

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.

Guidelines

Massive Transfusion: What Ratios Are People Using?

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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:

Abstracts, Resuscitation

Best of EAST #1: Ultramassive Transfusion Survival

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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.

 

Abstracts

Best Of EAST #10: MTP With Whole Blood

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Here’s one last abstract to consider before the EAST meeting kicks off this afternoon. Every trauma center must have a massive transfusion protocol (MTP). But not every one has access to whole blood. And whole blood is all the rage now for transfusion in the trauma world.

Believe it or not, we must still ask the question “is using whole blood safe?” More than 50 years ago, all we had was whole blood. But we didn’t use it in trauma the way we do today. And we didn’t have the tools then to determine whether there were any adverse effects from its use. Now we do, and we are slowly rediscovering the nuances of using it. Some work has shown that small volumes of whole blood appear to be safe. But there is little information on the safety of using large volumes in MTP.

The group at Oregon Health Sciences University in Portland attempted to do this with a quick shot paper to be presented tomorrow morning. They reviewed their experience over a two year period. For the first 18 months, they used standard component therapy (PRBC + plasma + platelets) in their MTP. For the final six months, they used cold-stored uncrossmatched, low-titer group O blood. Any patient who had MTP activated and received even a single unit of blood was included in the study. 

Here are the factoids:

  • 83 patients received component therapy and 42 received whole blood; demographics were the same
  • The component therapy patients received an average of 6 PRBC, 5 plasma, and 0 platelets; the whole blood group received 6.5 units (4 PRBC, 4 plasma, and 1 platelets based on the usual composition of a unit)
  • Plasma:RBC ratio was 0.8:1 for the component group and 0.94:1 in the whole blood group (statistically significant, but not clinically significant, see below)
  • The authors described a component-equivalent unit of product which is not defined. It was 12 for component therapy and 27 for whole blood.
  • There were no differences in 24-hour or 30-day mortality, and no transfusion reactions

The authors concluded that MTP using whole blood is feasible, and that it appeared to be safe and effective. They also commented that it may lead to more balanced resuscitation.

My comment: Alright, this is the last time I’ll mention study power (for a while). If a study does not have the statistical power to show a difference between groups, then seeing no difference means nothing. The absence of a difference does not mean that the two groups are equivalent. And this study of 125 patients is small potatoes for showing any difference in a crude outcome like mortality.

Besides having a small number of subjects, the average number of units given was low for an MTP. For most trauma centers, this was just over one cooler of products. Although ISS was 29, the patients don’t sound like they had huge blood replacement requirements, so it’s no wonder that mortality was the same between the two groups.

And finally, the statement about more balanced resuscitation is open to debate. The difference between 0.8 units of plasma and 0.94 units is 35cc per unit of red cells given, a little over 1 tablespoon. It’s hard to believe that this would ever make a difference clinically.

To those who read only the title or the conclusion of an abstract (or paper for that matter), beware. The devil is in the details. This study is a good start toward addressing the question posed, but needs several hundred more subjects (and a lot more blood products given) to close in on an answer.

Reference: Massive transfusion with whole blood is safe compared to component therapy. EAST Annual Assembly Quick Shot #8, 2020.

Resuscitation

Massive Transfusion: What’s The Right Ratio?

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In my last post, I analyzed a survey that studied the massive transfusion protocol (MTP) practices of academic Level I trauma centers in the US. What centers do is one thing. But what does the literature actually support? A group from Monash University in Melbourne, Australia and the National Health Service in the UK teamed up to review the literature available through 2016 regarding optimal dose, timing, and ratio of products given during MTP.

One would think that this was easy. However, the search for high quality ran into the usual roadblock: the fact that there is not very much of it. The authors scanned MEDLINE for randomized, controlled studies on this topic, and found very few of them. Out of 131 articles that were eligible, only 16 were found to be suitable for inclusion, and 10 of them were still in progress. And only three specifically dealt with the ratio question. Even they  were difficult to compare in a strict apples to apples fashion.

Here are the factoids that could be gleaned from them:

  • There was no difference in 24-hour or 30-day mortality between a ratio of 1:1:1 (FFP:platelets:RBC) vs 1:1:2
  • However, a significantly higher number of patients  achieved hemostasis in the 1:1:1 group (86% vs 78%)
  • There was no difference in morbidity or transfusion reactions in the two groups
  • One study compared 1:1 component therapy with whole blood transfusion and found no difference in short-term or long-term mortality or morbidity

Bottom line: As usual, the quality of available data is poor if one limits the field to randomized, controlled studies. Ratios of 1:1:1 and 1:1:2 appear to be equally effective given the limited information available. A number of papers not included in this review (because of their less rigorous design) do seem to indicate that higher ratios of RBC (1:3-4) appear to be detrimental. And as time passes, more and hopefully better studies will be published.

What does this all mean for your MTP? Basically, we still don’t know the best ratio. However, it is recommended that your final ratios of FFP:RBC end up somewhere between 1:1 and 1:2. The only way to ensure this is to set up your MTP coolers so the the ratio of product they contain is better than 1:2. This means more plasma than 1 unit per 2 units of red cells. 

If you set it at the outside limit of 1:2, then that is the best ratio you can ever get assuming everything goes perfectly. However, if you have to thaw frozen plasma, use too much emergency release PRBC before activating MTP, or someone cherry-picks the coolers to transfuse what they think the patient needs, the ratios will quickly exceed this boundary.

So be sure to load your coolers with ratios that are closer to 1:1 to ensure that your final ratios once MTP is complete are what you want them to be. And monitor the final numbers of every one of your MTP activations through your trauma performance improvement program so you know what your patients are really receiving.

Reference: Optimal Dose, Timing and Ratio of Blood Products in Massive
Transfusion: Results from a Systematic Review. Transfusion Med Reviews 32:6-15, 2018.