“Dr. Chaffin, I started working at a new blood bank recently, and I think they are breaking the rules! A patient came into the emergency room after an auto accident, and the FFP given to him was blood group A! Isn’t AB the ‘universal plasma,’ not A? The patient happened to be group O, so type A FFP turned out to be just fine, but I am worried! Are we doing the wrong thing?”

This exchange illustrates one of the things I love most about blood bankers: They pay attention, and are always on the lookout for unsafe practices. In this case, though, the use of group A plasma transfusions in emergency transfusions is absolutely okay. Despite how wrong it might feel, use of group A FFP in emergency settings is a growing trend – and a good one, for several reasons.

Standard Blood Bank practices

Ever since Dr. Karl Landsteiner described the ABO blood group system in 1901, we have used his findings to define “safe transfusions.” In the ABO blood group system, a person carries either an A or B antigen, both, or neither on his red blood cells, and the opposite antibodies in plasma (this is “Landsteiner’s Law”).

Landsteiner's Law

When transfusing red blood cells (RBCs), blood bank standard practices are designed with the aim of protecting the integrity of the transfused red blood cells. As a result, RBCs should not be transfused to patients carrying incompatible ABO antibodies (e.g., don’t give group A RBCs to a group O recipient, since the recipient’s strong anti-A will destroy the transfused RBCs). A significant proportion of the fatalities reported to the FDA from incompatible transfusions are a result of someone accidentally exposing transfused RBCs to incompatible recipient ABO antibodies. On the other hand, we don’t worry about the small amount (typically less than 50 mL) of potentially incompatible plasma that might be infused along with the RBCs (for example, when a group O RBC is given to a group A recipient); that amount is typically not enough to cause much trouble. The very familiar rules look like this:

ABO Rules for RBCs

ABO Rules for RBC Compatibility

The rules are switched when we choose plasma components for transfusion. We select Fresh Frozen Plasma (FFP) or Plasma Frozen within 24 hours of collection (PF24) units with the intention of protecting the recipient’s RBCs. This is because we are infusing anywhere between 250 and 400 mL of plasma, which contains ABO antibodies, making this scenario significantly more scary than transfusion of smaller amounts of plasma in an RBC transfusion! Note especially that group A donor plasma is only compatible with group A or O recipients, by these rules.

ABO Rules for FFP

ABO Rules for FFP Compatibility

Platelet transfusions cross ABO boundaries

A blood bank would never routinely choose to issue a unit of group A plasma for a group B recipient because of Landsteiner’s Law. However, we have essentially done exactly this with platelet transfusions, safely, for YEARS! Let me explain.

Mostly DeadIt’s really easy for blood bank newcomers to forget that platelet products are actually MOSTLY plasma (which is not the same as being “MOSTLY dead”). Each unit of apheresis platelets in the U.S. (if not collected in platelet additive solution) contains in the range of 250-300 mL of plasma. That amount is fairly close to the volume of a unit of FFP or PF24. So, why don’t we treat ABO antibodies in platelet products with the same respect we treat those in a plasma product?

Unfortunately, blood banks often don’t have enough platelets to go around, let alone adequate supplies to provide ABO-identical platelets for each patient! As a result, most transfusion services accept a somewhat higher degree of risk for out-of-group platelet transfusions than they ever would for plasma-only products. It’s like acquiescing and accepting the risk of allowing your child to walk to school because the risk of harm from having them drive with their eager, teenaged, just-licensed older sibling is greater.

Imagine this situation: The blood bank only has 1 unit of apheresis-derived platelets in inventory, and it is group A. An order for platelets comes in from the operating room, where a testy cardiac surgeon is trying to finish a bypass procedure and wants to help his patient stop bleeding. The patient, however, is group B! Depending on hospital policy, the blood bank technologist might call the blood supplier to see if a group B platelet is available, but in most cases, the blood banker will issue that group A platelet product without hesitation (NOTE: Many hospitals screen platelet units for high-titer ABO antibodies and would not issue one with strong antibodies to an out-of-group patient. This is especially true in the Eastern part of the U.S., but the strategy is not universal). Normal-sized adult patients in this setting do just fine, with no evidence of significant hemolysis of the recipient’s RBCs (though there are some studies suggesting this practice might not be a good idea for other reasons).

Emergency plasma transfusions

In recent years, we have seen a large increase in the proportion of plasma used in emergency situations as compared to RBCs. Trauma surgeons in particular are now accustomed to transfusing their patients with plasma in a ratio of close to 1:1 with RBCs. Since group AB plasma has no ABO antibodies, it has historically been the standard choice when a recipient’s blood type is not known (pretty much the definition of an emergency transfusion). This has resulted in HUGE demands on blood suppliers to provide AB plasma in greater quantities (16.5% more in 2013 than in 2011, per the 2013 “AABB Blood Survey Report,” pg 17). There’s one massive problem, though: AB people make up only 4% of the population! When hospital blood banks try to keep 10-20% AB plasma in their freezers, blood centers really struggle to keep up (we can’t change the dynamics of population genetics, no matter how hard we try!).

So, what to do?

As a result of the increasing AB plasma demand, several academic hospitals decided to try something different. They said (I’m paraphrasing here): “Since 85% of people in the population are either group O or A, group A plasma would work for at least eight of every ten emergency transfusions! What if we provide group A plasma instead of group AB when we don’t know the patient’s type, and play the odds a little bit?” Of course, the remaining 15% or so of the population (the B and AB people) would get INCOMPATIBLE plasma as a result of this strategy. You can read the articles for details (referenced below), but that’s exactly what happened. However, none of the B or AB patients suffered clinically significant hemolysis, and there was no evidence of diminished outcomes in patients receiving incompatible group A plasma. The studies are all a little light on the number of patients enrolled (in particular, the ones getting out-of-group plasma), but the data appears to support the choice of group A FFP for emergency transfusions.

UPDATE: So, you say you want more data? Well, my friend, I’ve got just that for you. Please see Episode 036 of the Blood Bank Guy Essentials Podcast, in which I discuss this very issue with the lead authors of two papers giving LOTS more cumulative data on group B or AB patients receiving group A plasma. I’ll save you a little time: They saw no evidence of hemolysis or bad outcomes!

“But Joe,” you say, “wait a minute! Why the heck aren’t these group B or AB patients harmed by group A plasma?!” There are a few reasons, actually.

  1. The Male Donor Imbalance: As a result of efforts to decrease Transfusion-related Acute Lung Injury (TRALI), almost all group A plasma in the U.S. comes from male donors. In men, the titer of anti-B in group A plasma is generally low (due to the lack of stimulation by incompatible fetal RBCs during pregnancy), making it less likely the antibody will harm the RBCs of group B or group AB recipients . Some facilities using the group A strategy will run an anti-B titer on the plasma product and not use those with strong antibodies, but others have not found titers to be beneficial. (NOTE: This situation is very different, by the way, from group O donor plasma, where the anti-B is often much stronger. Also, a few group A male donors who have taken probiotics have been shown to have very high anti-B titers).
  2. The Dilution Factor: Transfused anti-B is diluted into the patient’s much-larger total blood volume, and as a result, it comprises only a small quantity of the total circulating ABO antibodies.
  3. Look At The Context: Remember that these situations are emergencies! As a result, the patient will likely be receiving lots of group O RBCs. This means there will be fewer “target” B or AB RBCs for the anti-B to attack.
  4. Secretors Rule: Most B or AB patients (80%, to be specific) are “secretors,” meaning they have soluble (free-floating) group B antigen in their plasma. ABO antibodies in general LOVE binding to soluble antigens (it’s a lot easier than trying to get close to a comparatively massive RBC), so many of the anti-B antibodies in non-type specific plasma will be “neutralized” by binding to the soluble B antigen rather than the recipient’s membrane-bound antigen.

So, we shouldn’t really be surprised that group A plasma works just fine as an alternative to AB. It is perfectly reasonable to consider the use of group A plasma in emergency situations where the blood type is unknown.

In The Real World

The use of group A as an automatic choice in emergency settings is growing rapidly, and I am seeing it more and more in hospitals with whom I work. I always caution anyone considering this strategy, though, that I personally believe it is essential to draw a blood sample from the patient as quickly as possible so the transfusion service can switch to ABO-specific products expediently. In the interim, group A FFP, while not truly “universal,” can be used in place of AB FFP without significant risk.

I must remind you, however, that the above does not mean that group A plasma is the right choice for all routine plasma transfusions! I have seen transfusion services try to apply this to non-emergency situations, and that is not a wise strategy! This is a practice shown safe in a specific, emergency situation. Routine plasma transfusions should still follow the ABO compatibility rules (repeated here for emphasis!):

ABO Rules for FFP

ABO Rules for FFP

I’d love to hear your thoughts on the issue in the comments below, especially if your facility has implemented the group A plasma strategy.

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