Tag Archives: transfusion

Best Of EAST 2020 #2: Do Platelet Transfusions Fix Sad Platelets?

The next abstract from EAST tackles the question of how we can treat platelets that don’t work right in trauma patients. The literature on using platelet transfusions in patients who are taking anti-platelet agents is getting fairly clear: they don’t work. But what about for platelets that don’t work right due to traumatic hemorrhage?

The trauma group at Penn attacked this problem by performing a prospective study at their Level I trauma center. They investigated platelet function using thromboelastography (TEG) with platelet mapping on trauma patients admitted to the intensive care unit over a two year period. They analyzed platelet function and counts at 3, 6, 9, 12, and 24 hours after admission. Platelet function in patients given platelets during any of the intervals were compared to those who were not. Outcomes studied were improvement in platelet function and mortality.

Here are the factoids:

  • A total of 93 patients were entered into the study
  • About half (57%) had platelet dysfunction detected by TEG
  • Mortality was not different between the groups
  • Neither platelet count nor function improved with transfusion

The authors concluded that platelet dysfunction is common in these patients and that platelet transfusions do not appear to restore platelet function.

My comment: This abstract is a bit hard to follow. Hopefully the manuscript will have more detailed tables that break down which patients got platelets and at what times. It appears that patients could have gotten platelets at various times (any, all, or none) after admission to the ICU, and that pre- and post-transfusion TEG runs were analyzedfor each. It’s also not clear if every patient with dysfunction got a transfusion.

The most obvious issue here is that the total number of patients is small, and the numbers getting platelets at each time interval is even smaller (10-49). The statistical power of such a study is very low. It’s not surprising that no significant differences could be detected. This means that failing to see significance doesn’t means it’s not necessarily there, just that many more patients are needed. So it’s hard to buy into the assertion that platelet transfusions don’t matter.

Here are my questions/comments for the presenter:

  1. Why didn’t all patients get platelets? From the table, it looks like nearly all patients had significant dysfunction (defined as MAadp < 40mm) until the end of the 24 hour study period. It looks like some selection bias is possible if there was no defined protocol for giving transfusions to those who had an abnormal TEG.
  2. Is your study sufficiently powered to draw the conclusion it did? The number of patients seems small overall, and doing measurements serially every 3 hours would seem to further weaken the statistics. Please comment on your choice of analysis and how likely you are to actually be able to detect significance.
  3. Be sure to clarify the details of when platelets were given and why, how many measurements were taken and when, and exact patient numbers. These are not clear in the abstract due to length limitations.

This paper is very interesting and I look forward to its presentation.

Reference: Platelet infusions do not correct trauma induced platelet dysfunction. EAST Annual Assembly abstract #24, 2020.

Massive Transfusion: What’s The Right Ratio?

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.

What’s The Best Trigger For Your Massive Transfusion Protocol?

Every trauma center verified by the American College of Surgeons Committee on Trauma (ACS-COT) must have a massive transfusion protocol (MTP). The details and logistics of the protocol are up to the individual center. The difficult question is: how is a trauma professional to know that the MTP should be activated?

Sometimes it’s extremely obvious. The patient is very hypotensive. Blood is spurting all over the room. But sometimes it’s more subtle and the need just seems to creep up on you. And frequently, this delays activation and the actual arrival of the blood that is so desperately needed.

I’ve previously written about common triggers for the MTP, including psychic powers, shock index, and ABC index. See the links below to read my MTP week posts. But is one better than the other? The group at Vancouver General Hospital in British Columbia, Canada performed a systematic review of the literature to try to answer this question.

A total of 45 pertinent articles were identified in the literature up to 2017. Fifteen different scoring systems were evaluated involving combinations of clinical assessment, laboratory tests, and ultrasound evaluation.

Here are the factoids:

  • The best validated score using clinical assessment plus ultrasound was the Assessment of Blood Consumption score (click here for my post). This was the easiest to score compared to other systems using ultrasound.
  • Shock index (SI) was the only validated system using just the clinical exam
  • Some other studies were promising, with excellent areas under the receiver operating characteristic curve (AUROC), but had not been validated. The best of the bunch was one from Mina et al, but it is complicated enough to require a smartphone tool for calculation.
  • Other promising studies required laboratory evaluations which preclude their use at the time of patient arrival
  • Scoring systems that used more variables generally showed better correlation with actual need for MTP, but were more less likely to provide suficiently early predictions
  • Most validation studies involved single centers
  • No studies were designed to or able to show improved outcomes

Bottom line: There are many, many systems out there for predicting need for activation of the MTP (at least 15 to date)! This review concludes that the system used should be tailored to the center implementing it.

Simpler is better. I still recommend either Shock Index (SI) or ABC. Shock index is quickly calculated based on physical exam as heart rate divided by systolic blood pressure. The normal range is 0.5 to 0.7. The likelihood of MTP escalates 2x with SI > 0.9, 4x if SI > 1.1, and 7x with SI > 1.3. The ratio can easily be calculated based on numbers available from EMS providers prior to arrival. Basically, pick your threshold.

The Assessment of Blood Consumption (ABC) uses four parameters, three of which could be reported prior to patient arrival:

  • Heart rate > 120
  • Systolic blood pressure < 90
  • FAST positive
  • Penetrating mechanism

If two or more criteria are met, the patient has a 41% likelihood of needing MTP.

So basically, use a system that works for you. From my experience, centers that use a system tend to use ABC. But definitely pick a system, don’t leave it up to chance with the trauma surgeon. And use your trauma PI program to assess utilization to see if it’s the best tool for your center.

Related posts:

Reference: Systematic Reviews of Scores and Predictors to Trigger Activation of Massive Transfusion Protocols. Accepted ahead of print, J Trauma, 2019.

Little-Known Whole Blood Transfusion Program: Part 2

In my last post, I described a long-standing whole blood transfusion program that was implemented by Royal Caribbean Cruise Lines (RCCL)about 10 years ago. Today, I’ll dig into the specifics of their protocol and review their results.

Here is an image of the protocol. You can click it to download a full-size pdf copy.

Here are the key points in the protocol:

  • It is only implemented if it will take more than 4 hours to get the patient ashore for more advanced care
  • If the patient is hemodynamically stable, permissive hypotension to MAP 75 is encouraged and TXA infusion / Vitamin K administration are considered when appropriate. The patient disembarks at the next port of call with advanced hospital capabilities.
  • If hemodynamically unstable, two large bore IVs are maintained, TXA and Vitamin K are given when appropriate, and whole blood collection and administration are initiated. Helicopter / coast guard transport is deemed acceptable to closest advanced hospital.

And here are the guidelines for donor selection:

  • The donor hierarchy is:
    • sexual partner of the patient
    • male passenger with blood donor card
    • male passenger without blood donor card
    • female passenger with blood donor card (beware of TRALI)
    • medical staff members
    • crew
  • Only one unit is taken from each donor, and they must not be anemic

Here are the factoids describing RCCL’s seven year experience with the program:

  • 73 patients received transfusions, including 67 passengers and 6 crew
  • Mean hemoglobin on presentation was 6
  • A total of 1-6 units were given
  • Six patients ultimately died; no details were given
  • There were no ABO seroconversions, and only two adverse reactions occurred, both allergic
  • The majority of the medical staff felt that this was a valuable program

Bottom line: This is the first whole blood transfusion program I have seen outside of hospitals and the military. Royal Caribbean has incorporated lessons learned from both in developing their protocol. It includes all the principles of balanced resuscitation, including limiting crystalloids, permissive hyportension, and 1:1:1 transfusion ratios. There are many other opportunities to implement similar protocols in areas where medical capabilities are austere, and this protocol should be used as a model to develop them.

Use Of Whole Blood For Massive Transfusion

We’ve been using fractionated blood components in medicine, and trauma specifically, for over 50 years. So why doesn’t component therapy work so well for trauma? Refer to the following diagram. Although when mixed together the final unit of reconstituted blood looks like whole blood, it’s not. Everything about it is inferior.

Then why can’t we just switch back to whole blood? That’s what our trauma patients are losing, right? Unfortunately, it’s a little more complicated than that. The military has been able to use fresh warm whole blood donated by soldiers which has been stored for just a few hours. That is just not practical for civilian use. We need bankable blood for use when the need arises.

This ultimately means that we need to preserve the blood, and this requires a combination of preservatives to prevent clotting and keep the cellular components fresh, and refrigeration to avoid bacterial growth. This is not as simple as it sounds. Adding such a preservative to whole blood dilutes it by about 12%. And there are concerns that cooling it may have effects on platelet function. Recent data suggests that platelet function in cooled whole blood is preserved, but platelet longevity is decreased.

There are other issues with the use of whole blood as well. It contains a full complement of white blood cells, and this may be related to reports of venous thrombosis, respiratory distress, and even graft vs host disease. Unfortunately, removing the white cells (leukoreduction) also tends to remove the platelets, and there is little literature detailing the safety of this practice.

Another problem is the plasma component in whole blood. Universal donor (type O) whole blood may contain significant amounts of anti-A and anti-B antibodies. For these reasons, most blood banks limit the number of whole blood units transfused to a handful. A recent paper from OHSU in Portland details a massive transfusion in which 38 units were given to one patient. There was no transfusion reaction, but platelet counts dipped precipitously. All centers currently using whole blood utilize only low-titer anti-A and anti-B units.

So does whole blood work as expected in the civilian arena? The data is still incomplete, but the total transfusion volume appears to be decreased in patients without severe brain injury. With the increased interest and use of whole blood, it is imperative that more safety and efficacy studies are forthcoming.

Here are some tips on getting started with your own whole blood program:

  • Develop a relationship with a supplier of whole blood. Hammer out the details of the exact product (product age, leukoreduction, titer levels, returnability if not used).
  • Obtain approval from your hospital’s Transfusion Committee!
  • Work with your blood bank to develop processes to ensure proper availability and accountability. What is the maximum number of units that can be used in a patient? When should units be returned to the general pool to ensure they are not wasted?
  • Decide where whole blood will be available. Obviously, the blood bank will house the majority of the product. But should you have it in an ED refrigerator? On air or ground EMS units? These situations demand several extra layers of oversight and add greatly to complexity.
  • Educate, educate, educate! Make sure everyone involved, in all departments, are familiar with your new MTP!

References:

  1. Whole blood for resuscitation in adult civilian trauma in 2017: a narrative review. Anesth Analg 127(1):157-162, 2018.
  2. Massive transfusion of low-titer cold-stored O-positive whole blood in a civilian trauma setting. Transfusion, Epub Dec 27, 2018.