New Study Suggests No Difference in Mortality Rate in Two Different Transfusion Ratios

From the study published in the Journal of the American Medicine Association: Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours.”

You can read the NIH press release here.

You can read the abstract for the study here.

The Bombay Phenotype

ABO and H are the most important of the currently characterized blood group systems, since incompatibility between transfused red cells and recipient plasma leads to potentially devastating consequences. Those learning about this system spend lots of time memorizing biochemical details that can be overwhelming. In addition, exam-writers seem to enjoy asking questions about unusual entities in these systems that most blood bankers will never see in real life. Two very rare situations with altered red blood cell appearances (“phenotypes”), known as “Acquired B” and “Bombay,” are among those most frequently discussed on examinations. In a previous post, I discussed the Acquired B Phenotype (see my web page for further details and a video presentation). Today, let’s proceed with details about the very famous Bombay Phenotype.

In the 1950’s, a small group of people were identified in an area in India surrounding the city of Bombay (now called “Mumbai”) that appeared to be blood group O at first glance. As you should know from a basic understanding of the ABO system, group O individuals have antibodies against both A and B antigens, and as a result, can only receive red blood cells from donors who are also group O. The patients reported by Bhende et al (Lancet 1952;1:903-4), however, carried an extra antibody in their plasma that made them INCOMPATIBLE with others that were truly blood group O. These individuals (and others described since) lack a precursor antigen known as “H” both on their RBCs as well as in their secretions and plasma.

In brief, ABO antigens on red blood cells are made in a sequential manner. First, long sugar chains attached to either lipids or proteins (glycolipids or glycoproteins, respectively) on the surface of the RBC must be modified through the work of an enzyme encoded by the H (FUT1) gene (chromosome 19) to display H antigen activity. Only then can the chain be further modified by the action of a second enzyme that adds a single sugar to change that H antigen into either an A or a B antigen. The alleles inherited at the ABO gene site on chromosome 9 (A, B, and/or O) determine which ABO antigens will be expressed on the red cell surface, but again, such a change ONLY happens if the precursor antigen (H) is made first.

ABO antigens are unusual in that they are not only attached to RBCs, but are also present in free-floating forms throughout the body. The same manufacturing principle (first make H, then make A or B) applies to the formation of soluble ABO antigens found in virtually all bodily fluids, including plasma and saliva (and other secretions). The enzyme that is responsible for H antigen formation in these fluids is different than the one described above; it is encoded by the Se (FUT2) gene (also on chromosome 19).

If a person lacks both active forms of both the H (FUT1) and Se (FUT2) alleles (described as having the genotype hh, sese), they are incapable of making H antigen either in secretions and plasma AND on the surface of the RBC (they are described as “H-deficient non-secretors”, and commonly with the shorthand Oh). The genetic mechanism of these changes is well described in the original cohort in India (a particular single nucleotide polymorphism in FUT1 accompanied by a total deletion of FUT2), and multiple additional mutations have been identified that could lead to someone lacking active forms of both alleles.


So, with that out of the way, what does this mean? Well, if a person lacks the ability to make H antigen in both RBC-based and free precursor chains, they will appear to be blood group O, just like someone who inherits two O alleles at the ABO site. However, unlike group O RBCs, which carry more H antigen than any other ABO group, H-deficient non-secretor RBCs have NO H antigen (this can be demonstrated easily in blood banks by showing no reaction when the RBCs are mixed with the H lectin Ulex europaeus). In keeping with the way other ABO system antibodies are formed, Bombay individuals make anti-A, anti-B, and anti-A,B, exactly like others that are group O. However, they also make a strong and very dangerous anti-H. The antibody is primarily IgM, but like most ABO-related antibodies, it reacts strongly at body temperatures, and generally is considered highly capable of giving rise to dangerous hemolytic transfusion reactions. As a result, Bombay patients can really receive blood only from others who completely lack the H antigen (which functionally means they should either get their own blood that has been stored for their future use or blood from another H-deficient non-secretor).


There are variants of Bombay, most notably the “Para-Bombay” phenotype in which the patient is H-deficient on RBCs, but IS capable of making ABO antibodies in secretions and plasma (these patients are H-deficient secretors). The key fact that must be evaluated in all of the Bombay-related phenotypes is whether or not an anti-H has been formed that is capable of reacting at body temperature. If so, Bombay variants must also receive only H-deficient red blood cells.

As mentioned, most workers will never see a patient with the Bombay Phenotype. This entity is seen mostly in examination world, but it is nonetheless very important for transfusion service personnel to be aware of this rare phenotype and prepared to take steps to diagnose it. I have seen reports of Bombay cases misdiagnosed as non-ABO high-frequency alloantibodies, and am aware of a case where the diagnosis became apparent when a child was born with an ABO type that seemed impossible based on the ABO types of the parents.


-Joe Chaffin, MD, is the new Vice President and Chief Medical Officer for LifeStream, a Southern California blood center headquartered in San Bernardino, CA. He has a long history of innovative educational efforts and is most widely known as the founder and chief author of “The Blood Bank Guy” website (

Acquired B Phenotype

Students learning about the ABO blood group system commonly get confused about two unique situations: The Acquired B phenotype and the Bombay phenotype.

These two entities are VERY different, but they are similar in this way: people are asked about both on exams all the time, but hardly anyone every actually SEES either one in real life! It is essential for students of blood banking to understand Acquired B clearly, as it remains a real possibility in everyday practice. I’ll cover Acquired B in this month’s blog, and next month I will discuss Bombay.

Routine ABO testing is performed in two distinct (but usually simultaneous) stages, known as “red cell grouping” (forward grouping or “front type”) and “serum grouping” (reverse grouping or “back type”). Here’s an example of how it works: If a person’s red blood cells (RBCs) react strongly with reagent anti-A but not anti-B, we would interpret their red cell grouping as blood group A. If there is no ABO discrepancy, that same person’s serum should have no reaction with reagent group A1 RBCs and strong reaction with reagent group B RBCs (demonstrating the expected presence of anti-B in the serum). Thus, the serum grouping interpretation would also be blood group A, and no ABO discrepancy would exist (see this illustrated in the figure below).


ABO discrepancies occur any time the interpretations of a person’s red cell and serum grouping do not agree. ABO discrepancy takes on many forms, and acquired B is a great, if not terribly common, example.

Students learning about the ABO blood group system commonly get confused about two unique situations: The Acquired B phenotype and the Bombay phenotype.

Usually, Acquired B occurs when the RBCs from a blood group A patient come in contact with bacterial enzymes known as “deacetylases.” These enzymes, commonly carried by bacteria that live in the colon, catalyze the removal of the acetyl group from the residue that gives the A antigen its specificity, N-acetylgalactosamine (GalNAc). This modification leaves the A-specific sugar as galactosamine (N-acetylgalactosamine with the acetyl group removed = galactosamine). Recall that normally, the group B-specific sugar is galactose.


As a result of this modification, anti-B in both human group A serum and especially certain monoclonal reagents will weakly agglutinate the group A RBCs carrying the acquired B antigen. This means that the patient’s RBCs may have a weakly positive reaction with anti-B in serum grouping tests instead of the expected negative (see image below). The serum grouping for these patients is no different from that expected for a group A individual (negative with group A reagent RBCs, strong positive with group B RBCs).


So, what does this actually mean? How do these patients actually get transfused? This is where the recognition of the entity in a transfusion service or reference laboratory is essential. Several simple strategies can be employed to prove that this patient is really NOT group AB. First, I always advise people to check the patient history! The rare cases of acquired B that are still seen will often be associated with colorectal malignancy, gastrointestinal obstruction, or gram-negative sepsis (where those bacteria can contact the RBCs). Second, adding the patient’s own serum to his RBCs (autoincubation) reveals no incompatibility. In other words, this patient’s own very strong anti-B does not recognize the acquired B antigen (which is really just a partially modified group A antigen) as being an actual group B antigen. We already know that this patient has anti-B in his serum from his serum grouping results (see above), but the patient’s own anti-B completely ignores the acquired B antigen on his RBCs (even though human anti-B from other people will react). Third, the technologist can use a different form of monoclonal anti-B in the patient’s red cell grouping test. Certain clones are known to react with acquired B, while others are not (normally specified in the package insert), and choosing a different clone (often easier in reference lab settings) will render the forward grouping consistent with that of a group A person. Also, incubating the Acquired B RBCs with acetic anhydride will lead to “re-acetylation” of the modified A antigen and loss of the B-like activity. Finally, acidifying the reaction mixture of the patient’s RBCs with human anti-B (non-self) can eliminate the incompatibility with that source of anti-B.

In the end, Acquired B is a serologic problem that is fairly easy to recognize, especially on examinations (I always tell my students that when they see a problem that starts with words like, “A 73 year old male with colon cancer…”, check the answer for Acquired B!). In real life, experienced blood bankers can diagnose and confirm Acquired B fairly easily in the rare times that it is seen. These patients can receive group A blood without a problem, and the ABO discrepancy will disappear as the infection or other situation causing causing contact with bacterial enzymes clears. Thanks for your time and attention. See you next month when I will discuss the Bombay Phenotype!



-Joe Chaffin, MD, is the new Vice President and Chief Medical Officer for LifeStream, a Southern California blood center headquartered in San Bernardino, CA. He has a long history of innovative educational efforts and is most widely known as the founder and chief author of “The Blood Bank Guy” website (

Designer Blood

Recently scientists have discovered transcription pathways that turn pluripotent stem cells into red blood cells and white blood cells. (You can read the article here.) This could be the first step in making patient-specific blood products or a way to increase the nation’s blood supply without having to rely on volunteer donors. What do you think? Could this be the future of transfusion medicine?

What’s In a Name? Chikungunya and Dengue Viruses and the Blood Supply

“Incurable Virus Spreads in US!” In recent weeks, breathless and scary-sounding headlines like this have been seen in newspapers and web sites in the United States, describing an outbreak of emerging viruses with scary names like “Chikungunya” and “Dengue” seen in US travelers to the Caribbean, South America, and other tropical areas. While the news certainly sounds terrifying to the public, Transfusion Medicine professionals must evaluate donors carrying these “emerging” infections (defined as infections whose human incidence has increased in the last 20 years or so) as scientifically as possible to ensure the maximum safety of the blood supply. Let’s take a quick look at two of these infections and their implications for potential blood donors.

Chikungunya virus:

Chikungunya has quite possibly the greatest name in the history of viruses! Sadly, it is a fun-sounding name for a not-so-fun disease. This virus has been on our radar for a few years now, as it spread through Africa, Southeast Asia and parts of Europe. More recently, however, Chikungunya has become quite prominent in the Caribbean islands as well as Central and South America.

  • Vector: Aedes species mosquitoes
  • Spread: Human to human via mosquito vector
  • Illness: High fever, severe joint pain that may last months, severe infections in already ill adults or neonates
  • Treatment: No specific therapy or vaccine; just support symptoms
  • Blood transmission: No cases reported, though theoretically possible
  • Tests for donors: None approved by FDA

Though the CDC is monitoring numerous cases of Chikungunya in US citizens in multiple states exposed through mosquito bites during travel, we currently do not have great ways to track or test blood donors. Fortunately, at least 80% of people infected with this virus are symptomatic, and as a result, would be deferred from blood donation simply because they don’t feel well.


Dengue is another emerging infection that has been recently seen in US citizens, primarily those who travel to Asia and South America (in fact, according to the February 2014 update to the AABB Dengue virus fact sheet, Dengue is the most frequent cause of fever in US travelers returning from those areas; source: AABB web site). Worldwide, Dengue is a MASSIVE problem, affecting millions and killing over 22,000 people every year (source: CDC Dengue web site).

  • Vector: Aedes species mosquitoes
  • Spread: Human to human via mosquito vector
  • Illness: High fever, rash, headache, severe lower back pain known as “break-bone fever”; Rare cases with hemorrhagic or shock
  • Treatment: No specific therapy or vaccine; just support symptoms
  • Blood transmission: Multiple well-proven transmissions from RBCs, platelets, and plasma
  • Tests for donors: None approved by FDA

Dengue and Chikungunya infections can present in a very similar manner (high fever and joint pain). Dengue, however, is associated with much more severe consequences in a few patients, with diffuse hemorrhage and complete systemic collapse seen in a few patients.

Together, these viruses infect millions of people around the world every year. However, to date, neither has proven to be a large issue in US blood donors. In addition to the fact that potential blood donors infected by either virus will often be deferred because they do not feel well, many will also be prohibited from donating because they have traveled to an area where malaria is endemic (the malaria travel deferral covers much of the distribution area for both Dengue and Chikungunya).

It is clear to all Transfusion Medicine professionals that we are not completely “safe,” even though we have not yet seen an abundance of transfusion transmission of Dengue, and none whatsoever with Chikungunya. The presence of these non-treatable infections is simply another reminder that transfusion has risks aside from the ones that clinicians and patients think about most (HIV and hepatitis, for example). A big part of the job of a Transfusion Medicine professional is to help our clinician friends ensure that transfusions are only given when absolutely necessary.



Joe Chaffin, MD, is the new Vice President and Chief Medical Officer for LifeStream, a Southern California blood center headquartered in San Bernardino, CA. He has a long history of innovative educational efforts and is most widely known as the founder and chief author of “The Blood Bank Guy” website (


A Trifecta: It’s About Time!

I am always amazed and interested at how events often occur in 3’s. If you are from Kentucky (or follow the “ponies”) you are likely familiar with the racing 3’s, aka the Triple Crown, of which the Derby is the opening event. There is also the trifecta which is defined as a successful bet for the top three winners in a race: win, place, and show. Well, I believe we have recently (and I might add, finally) achieved a trifecta for Patient Blood Management (PBM).

The trifecta of which I speak is the long-awaited and anticipated national recognition of PBM and thus, transfusion safety.

The first of the three events which initiated my designated trifecta was the American Medical Association and Joint Commission Overuse Summit which took place in 2012. Blood transfusions were recognized and listed within this committee’s top five over-utilized procedures/therapies. A complete discussion of the findings of this summit has been published on the Joint Commission’s website.¹

The second and equally important event was the soon-to-follow Choosing Wisely Campaign, sponsored by the American Board of Internal Medicine (ABIM) Foundation in 2013. Two of the top 5 recommendations pertain to PBM. Restrictive transfusion practices and minimizing overuse of laboratory testing which avoids iatrogenic blood loss anemia were both highlighted.² Several professional societies have embraced the Choosing Wisely Campaign and now have published specific recommendations for their own subspecialties. These include the American Society of Hematologists (ASH), American Association of Blood Banks (AABB), the American Society for Clinical Pathology (ASCP), and the American Society of Anesthesiologists (ASA). The list continues to grow. The American Hospital Association (AHA) has subsequently published a white paper mirroring these recommendations.³

And then the veritable “icing on the cake” has been the recent 2014 release of the AABB Standards for PBM.⁴ These standards place direct focus on the numerous distinct elements of a robust PBM program with levels of activity for all facilities/systems large and small. I imagine many of you have seen the May issue of the AABB News.⁵ This entire publication speaks to the integrated efforts of the ABIM, AHA and other groups that now have joined, in unison, the song of PBM.

Many of us have been beating the PBM drum for several years. Even those of you that are early in your “journey” are embracing it readily in your loco-regional arena. I applaud you! We should be pleased and proud that the drums have finally resonated with leaders of our nationally-recognized societies, accreditation bodies and medical professional groups. This will help to bring PBM and our mission for transfusion safety even more directly into the limelight.

I’m a good old Kentucky girl and I love to score a trifecta. This is a good one and it’s about time!






⁵AABB News, May, 2014; 16: 1-22



-Carolyn D. Burns, MD, is a Board Certified Pathologist who has worked as a medical director for transfusion services and an assistant clinical professor of pathology. She frequently speaks about topics such as transfusion reactions, transfusion in solid organ transplant, and anticoagulant/antiplatelet reversal strategies.


Molecular Testing in Transfusion Medicine

Last week, the FDA approved the Immucor PreciseType Human Erythrocyte Antigen (HEA) Molecular BeadChip assay. This method determines non-ABO antigens on red blood cells and is the first molecular assay for determining blood compatibility to be approved by the FDA.

What do you think, blood bankers? When it comes to blood compatibility, do you trust molecular diagnostics as much as serological methods?