Tag Archives: transfusion

EAST 2018 #10: Fresh Whole Blood And Survival

Decades ago, our blood bank system began disassembling units of donated blood, ushering in the era of component therapy. Now, it seems, we are seeing the light and starting to re-look at the concept of using fresh whole blood. To see the difference between fresh whole blood and “rebuilt” whole blood from components, read this post.

The military has a keen interest in studying the practice of using whole blood, since combat locations have a considerable number of “walking blood banks” (i.e. soldiers) . An abstract being presented tomorrow at EAST was submitted by the US Army Institute of Surgical Research. They performed a straightforward study looking at mortality in combat casualties, comparing troops who received fresh whole blood (FWB) to those who received component therapy (kind of). They used regression analysis to try to identify and control for other variables, and also analyzed a subgroup who required massive transfusion.

Here are the factoids:

  • A total of 215 soldiers received FWB, and 896 did not. Of note, the non-FWB patients did not necessarily receive platelets.
  • Overall, survival was similar in both groups at about 94%
  • After controlling for physiologic injury severity and blood product/crystalloid volumes, the risk of death was twice as high in the group that did not receive FWB
  • Survival was higher in FWB patients who underwent massive transfusion (89% vs 80%), although this was only marginally significant

Bottom line: I see this an an interesting but preliminary study, with many unanswered questions. It’s not really a comparison of patients receiving fresh whole blood vs component therapy, because not all of the latter patients received platelets. It also did not take into account the specific anatomic injury areas, particularly critical ones such as brain injury. But this study should certainly stimulate some better designed projects for followup.

Here are some questions for the authors to consider before their presentation:

  • Did you do a power analysis to estimate how many patients would need to be enrolled to discover a real difference? If so, how many?
  • Have you performed a subanalysis on patients in the non-FWB group who received platelets? This would then be a comparison of FWB vs component therapy.
  • Any idea of the age of the components given vs the day 0 FWB?
  • Be sure to show and interpret your significance testing in the presentation

Reference: EAST 2018 Podium paper #15.

EAST 2018 #2: Blood Product Age And Mortality

Ever since the start of the modern transfusion age (which was really only about 75 years ago), we’ve been trying to extend the life of banked blood products. Currently, we get about 6 weeks of useful life from packed red blood cells, and varying amounts from other frozen or non-frozen products.

What happens at day 42 for red cells? Or day 5 for platelets or thawed plasma? It’s not like a switch gets flipped and it suddenly goes bad. Each of these products slowly degrades over time, and the myriad components that make them up (proteins, clotting factors, etc) do so at varying rates. It has been recognized for years that some of these products “don’t work so well” when they age, and this has been termed the “storage lesion” of blood.

The next EAST paper I’ll review looks for associations between use of older blood products which probably have a storage lesion, and mortality in trauma patients. It re-analyzed the prospectively collected data on the 680 patients enrolled in the PROPPR trial, which was originally designed to examine the mortality difference between patients with specific FFP:platelet:PRBC ratios given during massive transfusion. In this re-analysis, the authors looked at the mortality after 6 hrs, 24 hrs, and 30 days in patients undergoing massive transfusion, and examined the impact of using “older” blood products. “Old” was defined using the median age of the product; RBCs were old after 20/42 days, plasma after 2/5 days, and platelets after 4/5 days.

Here are the factoids:

  • Plasma age decreased with increasing transfusion. There was no similar change in average platelet or RBC age, though.
  • Patients receiving older RBC and younger plasma had higher mortality
  • Receiving older PRBC was associated with mortality at 6 and 24 hrs, but not 30 days

Bottom line: First, this is an association study, not a causation one. Don’t read anything more into it than you see. And what do you think when you see random mortality numbers like this? For me, either mortality is too crude of a variable to use, or the association is just too weak. If you look at the data table for the study, the confidence intervals of the computed “hazard ratios” barely clear the 1.0 line. To me, this looks like an interesting mathematical exercise, but I can’t tease any clinical significance out of it at all. And I don’t think that re-analyzing this dataset will provide any further clarity.

Here are some questions for the authors to consider before their presentation:

  • Did you try to calculate the statistical power of your dataset? As mentioned above, the associations look weak at best.
  • Did you look at other potential factors like injury severity score or massive transfusion volumes? These would seem to have a much more significant impact on the three survival cohorts?
  • Big picture questions: Where can you go from here? What kind of study could you do to see if this is a real effect vs just a statistical anomaly?

Reference: EAST 2018 Podium paper #3.

EAST 2017 #11: Use of Incompatible (Type A) Plasma For Massive Transfusion

Type AB plasma is considered “universal donor” plasma, as it contains no antibodies to red cells with either A or B antigens on their surface. Unfortunately, only about 4% of the US population have this blood type and can provide the product. Due to this shortage, some trauma centers have decided to use Type A plasma initially for massive transfusion, and switch to type specific plasma once patient blood has been typed and screened.

This works, since only about 13% of the population have red cells with B antigens on the surface. But are there any adverse effects in those patients who receive potentially incompatible plasma? The EAST Multicenter Study group performed a retrospective study using trauma registry and blood bank data from 5 trauma centers. They looked at adult patients who received plasma as part of the massive transfusion protocol (MTP) over a 4+ year period. Incompatible type A plasma transfusion was defined to occur if a patient had either Type B or AB blood.

Here are the factoids:

  • There were a total of 1212 patients in the study; 93% were compatible and 7% were incompatible type A initial transfusions
  • The usual trauma demographics were seen (young, male) and the average ISS was 25 (they triggered an MTP, remember?)
  • By chance, the incompatible group had a slightly higher ISS (29) and penetrating injury rate (45% vs 33%)
  • The incompatible group received significantly more plasma during the first 4 hours and during the first day
  • There was no difference in mortality sepsis, ARDS, thromboembolic events, or renal failure
  • Regression analysis showed that incompatible plasma was not a predictor of mortality or morbidity
  • There was one hemolytic reaction and one occurrence of TRALI, both in the compatible group

Bottom line: This is the largest study around on the topic, and it does not show any significant problems (at least the ones that were studied) with giving incompatible plasma in acute trauma. How can this be, you ask? Remember, only the first one or two units (the first MTP pack) is potentially incompatible. Hopefully, by the time the second pack is delivered, the blood has been typed. And these patients are potentially receiving multiple units of typed plasma after the initial transfusion which dilutes the incompatible, and multiple transfusions overall which may blunt their immune response. 

This is an important paper that all centers should consider as they update their massive transfusion protocols!

Questions and comments for the authors/presenters:

  1. The abstract states that 5 centers participated, but the tables only list 4. Please explain this.
  2. It is not stated explicitly whether all centers used type A plasma initially. Is this the case?
  3. This is important work! Have any other centers converted to initial use of type A plasma?

Click here to go the the EAST 2017 page to see comments on other abstracts.

Related posts:

Reference: Use of incompatible type A plasma transfusion in patients requiring massive transfusion protocol: outcomes of an EAST multicenter study. Paper #16, EAST 2017.

EAST 2017 #4: A More Restrictive Transfusion Trigger?

For many years, patients were automatically given not one, but two units of blood anytime they got “anemic” while in the hospital. And anemia was defined as a hemoglobin (Hgb) value < 10. Wow! Then we recognized that blood was a dangerous drug, with many potential complications.

We’ve come a long way, with our transfusion trigger slowly dropping and giving just one unit of blood at a time when needed. Many trauma centers use a transfusion trigger Hgb of 7 in younger, healthier patients. The question is, how low can you (safely) go?

The trauma program at Wake Forest University analyzed their data, and found that there was no “physiologic advantage” to transfusions in patients with Hgb of 6.5 to 7. Therefore, they lowered their transfusion trigger from 7 to 6.5 and retrospectively studied the results for the six months before and six months after the switch. Patients with hemorrhage, anticipated surgical procedures, or unreconstructed coronary artery disease were excluded.

Here are the factoids:

  • Of 852 patients admitted to the ICU, 131 met criteria and had a Hgb < 7
  • 72 patients were transfused with a trigger of 7, and 59 with a trigger of 6.5
  • There was no difference in ventilator, ICU, or hospital days, or mortality
  • The transfusion rate dropped by 27%, saving 72 units of blood

Bottom line: We continue to determine how low we can go with this. In healthy patients, the magic number is probably even lower. But we are increasingly seeing older, less healthy trauma patients. The next step is to start looking at subsets to determine what is safe for each group.

Questions and comments for the authors/presenter

  • Tell us the nature of the “preliminary work” that led to this paper. Was it animal data, or some kind of analysis of your patient data?
  • Since coronary artery disease was an exclusion criterion, how did you know a patient had it? By history alone?
  • Please show an age histogram of all units given at each threshold. This will let us see if there is any age bias present.
  • How low did the Hgb actually get in both groups? A histogram would be nice on this one, too.
  • Do you have any recommendations regarding selection based on age, frailty, or other parameters? What is your practice now?
  • Your outcome measures are somewhat crude, meaning that one would not really expect much of a change in those variables due to an extra unit or two of blood. What about adverse reactions that necessitated a fever workup or other intervention? Any differences between the groups there?

Click here to go the the EAST 2017 page to see comments on other abstracts.

Related posts:

Reference:   Effects of a more restrictive transfusion trigger in trauma patients. Poster #38, EAST 2017.

EAST 2016: (F)utility Of Transfusion In Flight

Air transport of trauma patients has resulted in the creating a mobile intensive care unit in the passenger compartment of the aircraft. Since trauma patients frequently need blood, it was logical to begin stocking blood products on board. Once again, though, it sounds like a good idea. But does it make a difference?

Vanderbilt University carried out a retrospective review of aeromedical transports to its Level I trauma center. The authors chose overall mortality and 24-hour mortality as their endpoints.

Here are the factoids:

  • 5581 patients were entered into the study. This represented all trauma scene transports to this trauma center over 7 years.
  • Only 4% of these patients (231) received blood in the aircraft.
  • Multivariate regression analyses were performed with and without propensity score matching. (Sorry, just had to throw that in there to make your head spin!)
  • There was no significant improvement in 24-hour or overall mortality when blood was given. This was true using all of their statistical methods.

Bottom line: This abstract seems to corroborate a few other studies that show no benefit to prehospital blood administration. So why do we still do it? Because we don’t know the full answer yet. Using mortality alone is a very crude outcome measure. What about early complications, ventilator times, time in the ICU, and other soft measures? More work is needed to slice and dice this appropriately enough to answer the question.

Reference: Blood transfusion: in the air tonight? EAST 2016 Oral abstract #5, resident research competition.