Diversity in the Blood Donor Pool Protects Patients in Need of Rare Blood

*Note: This article originally appeared in AABB News.

The greater the diversity, the higher the likelihood of finding compatible blood.

Often discussions about making the blood donor pool more diverse center around patients who are chronically transfused, such as those with sickle cell disease and thalassemia. Individuals in these groups are more likely to become alloimmunized from receiving ongoing transfusions, developing antibodies to many common antigens. But beyond the frequently transfused, having a diverse donor pool is critical for those with rare blood types. Individuals with rare blood need transfusions of compatible blood, which can be extremely difficult to come by. They need to find a rare blood donor whose blood either lacks the same common antigens or combination of antigens, or lacks immunoglobulin. Having a large, diverse blood donor pool offers the best chance of finding compatible blood quickly. When it comes to rare blood and rare blood donors, nobody knows more than the American Rare Donor Program (ARDP).

The ARDP

Formed in 1998 and headquartered in Philadelphia, the ARDP comprises members that are AABB-accredited blood centers, from both within the American Red Cross and outside of it, said Margaret Keller, PhD, executive director of National Laboratories and senior director of the American Rare Donor Program at the American Red Cross in Philadelphia. Blood centers that are not part of the American Red Cross must be accredited by AABB. ARDP members also include immunohematology reference laboratories — which also need AABB accreditation — and a few hospital blood banks. Most members are located within the United States, but there are also members in Brazil, Italy and Kuwait.

The ARDP began as a collaboration between AABB and the American Red Cross aimed at providing blood for transfusions of patients in need of rare blood. The organizations combined their rare donor databases into one centralized place. The resulting database is called REGGI.

When members of ARDP identify donors with rare blood, they submit that information to be entered in the database, said Keller. When members need to find a unit of rare blood, they can request it from the ARDP. Organizations that are not members can request rare blood units through a member facility, such as their blood supplier. When it gets a request, the ADRP can search in REGGI for blood or donors with the same phenotype.

Requests for Rare Blood

When a hospital patient needs a blood transfusion, they are screened for antibodies against red blood cell antigens in their plasma, said Keller. “Once there is a screen that shows someone has rare blood, the blood bank first looks in-house for matching blood or sends out a request to their blood supplier. They look among fresh and frozen units and among their blood donors. One way or the other will often find a rare phenotype with an antibody.”

One member of the ARDP is OneBlood, headquartered in Florida. Nancy Benitez, vice president of reference laboratories for OneBlood told AABB News that the blood center receives requests for uncommon and rare blood on a daily basis. “Most of the requests we receive are for African American patients with sickle cell disease (SCD). Sickle cell patients have the tendency to produce many alloantibodies, and for some cases, we have to screen over 1,000 donors to find one compatible unit.”

Another member of the ARDP is Vitalant, headquartered in Scottsdale, Ariz., and operating across 28 states. Dolores Figueroa, MT(ASCP)SBB, the immunohematology reference laboratory systems specialist for Vitalant, also said that Vitalant receives requests for rare blood on a daily basis. “Blood types can be rare because they are missing a blood antigen that 99% of the population has, some refer to them as ‘exquisitely rare,’ But blood is also considered rare if it is phenotypically rare, meaning it lacks  multiple antigens in multiple blood group systems, which we commonly refer to as PhenoRare. Multiple requests for PhenoRares are received daily to support patients with chronic conditions like sickle cell disease and thalassemia, or patients who are receiving certain drug therapies or cancer treatment. Rare blood can also be needed for patients with hemolytic disease of the fetus and newborn.”

Beyond the United States

“If no matching blood is found in-house, blood banks can come directly to the ADRP — if they are a member; if they are a blood bank without an attached blood center, they have to go through their blood supplier,” said Keller. “It is only when the blood center cannot fill its own needs that it comes to the ARDP, which will put in a request and search its database to see if any ARDP members have a donor with that phenotype.” If the member blood center has frozen or liquid units or a matching donor with that phenotype, they will recruit them to come in and the ARDP will make sure the unit gets to the appropriate blood bank.”

If blood cannot be found within the U.S., the ARDP goes to the International Rare Blood Panel, headquartered in Bristol, England, explained Keller. “There is a portal that can be accessed to look for compatible blood. If they find compatible blood outside of the U.S., they have to follow a different process:

1. Get consent from the patient.
2. Get consent from the physician.
3. Get an Emergency Use Authorization from the U.S. Food and Drug Administration.

In this situation, once the ARDP locates the blood and obtains the necessary approvals, it must figure out the logistics of getting the blood safely to the patient, continued Keller. This process will vary depending on whether the unit is liquid or frozen and which infectious disease markers the country of origin screens for — which may not match the procedures in the U.S. Other complications include getting the blood to the patient before it expires and, if the label is not in English, entering the unit into the hospital’s computer system.

The Need for Rare Blood

According to Keller, the ARDP receives more than 1,000 requests for rare blood every year. In 2021, they received 1040 requests, which is the highest number of requests ever received in a year. Notably, these requests are only those that the blood centers cannot fill themselves. “The ARDP did a survey of its members about how many requests they got during a 2-month period.” That number translates to 10,000 requests for a whole year. This is important because it shows that the ARDP is handling 1/10 of the total number of requests in the U.S.

Vitalant receives tens of thousands or requests for antigen-negative blood. Of those, Figueroa estimates that Vitalant gets more than 1,500 requests for rare blood each year, which may translate into thousands of units. Since the beginning of the COVID-19 pandemic, Vitalant has been able to fill around 82-87% of these requests. “What is concerning is that approximately 8% of the requests had to be handled by other clinical measures because the rare blood could not be located, even with nationwide searches,” she said.

“OneBlood provides rare blood to more than 250 hospitals throughout the Southeast,” said Benitez. “We receive orders for uncommon and rare units daily. Additionally, we donate to the ARDP, AABB’s National Blood Foundation and other organizations. In fact, last week we exported a Dib negative, D negative unit to Missouri. This unit is so rare that is appears to have been one of the only few units available in the U.S. In the past 2 months, OneBlood has exported more than 50 units of rare and uncommon blood to other facilities across the country.”

Benitez added that the number of requests for rare blood can vary from year to year. “In general, every year we receive hundreds of orders for local usage and to help other organizations. The increase every year is about 5%.”

Rare Blood Defined

Rare blood can be difficult to find for several reasons, said Keller. Blood that lacks a common  antigen that is common in the general population can make blood rare. Similarly, blood that lacks a common combination of common antigens can make blood hard to find. Finally, individuals can lack the IgA immunoglobulin in their plasma — which is an issue separate from  reasons involving red blood cells — and form antibodies to IgA. If someone in this category receives a transfusion of blood containing IgA, they could suffer from anaphylactic shock, which can be very serious. Patients lacking IgA can donate safely to those having antibodies to IgA in their blood.

In addition, blood can be categorized as rare or exquisitely rare, a term adopted by the ADRP in the past year. Rare blood is defined as blood that is found in less than 1,000 donors in the U.S. Exquisitely rare blood is found in less than 10 individuals in the U.S.

Finding the Elusive Rare Blood Donor

It is important to have a pool of donors with rare blood in the system to find rare blood quickly when it is needed. “The reason it’s so important is because we need rare blood donors to be available at a minute’s notice and we potentially need frozen units right away,” said Keller.

One way in which ARDP member blood centers find donors of rare blood is by screening new  donors, said Keller. ARDP members screen new blood donors who are walking in the door for the first time and phenotype their blood to find out if they have rare blood. “The screening will be by the immunohematology reference lab at the donation center. They can take a retention tube that was collected during the donation or take a segment off of the RBC unit and screen it. Screening can assess antibodies and use reagents (for a serological screening) or molecular methods (for genotyping).”

“At present, it’s standard for the big donor centers to use molecular methods to screen many  donors and screen for many antigens all at the same time,” added Keller. “So, we’re using these screening techniques and different donor centers will have different approaches. Some only screen for type O blood, others only screen repeat donors.”

OneBlood operates in areas with a diverse donor population, which allows them to test for different antigen groups depending on the antigen prevalence among specific ethnicities. For instance, Hispanic donors are screened for two high prevalence antigens, Dib and Ge2, said Benitez. We test African American donors for the U, Jsb, antigens and molecularly to identify RHCE variants,” said Benitez.

Benitez continued, “We use serology and molecular testing to evaluate donors for the presence of multiple antigen combinations for the major red blood cell antigens, which include Rh, Kidd, Duffy and MNS systems. One of our primary forms of screening donors is the use of microplate testing, which enables mass testing while using minimal antisera. The test result information is entered into our regulated software system and identifies the donor based upon their phenotype. Our software system has built in algorithms that are tailored to ensure rare units are identified and forwarded to OneBlood’s Reference Labs.

According to Vitalant’s Figueroa, “We mostly find rare donors by screening donations collected by our organization. Vitalant IRLs have been doing antigen screening for decades. Through the years, different screening methods have been used. Screening using serological (microplates, tube, gel) and now molecular screening methods are used. We have programs to increase the number of phenotype donors and programs with targeted screening, geographically or based on donor demographics to screen for specific rare antigens.”

Recruiting and Maintaining a Pool of Donors With Rare Blood

Education is the first tool in the arsenal of finding and keeping rare blood donors. Sometimes donors start out as patients who are found to have rare blood. Other times women only find out that they have rare blood when they become pregnant, said Keller. If the woman decides to become a donor after the baby has been born, that’s good news for diversity in the blood donor pool, even more so if she has siblings with the same blood type who can be educated and become donors themselves.

“In addition to regular recruitment of donors, we take the opportunity to test siblings from  patients with high prevalence antibodies, which might have the same antigen combination as  their family members,” added Benitez. “Not only will this provide blood units that are compatible with each other, but it can create new donors who can provide for future patients requiring rare blood. We also encourage periodic autologous collection in patients having antibodies against high prevalence antigens.”

Once we find a rare donor, we contact them to tell them that they have rare blood. “Often the donor is unaware they have rare blood,” Benitez said. “It’s important information they need to know about themselves in the event they ever need a transfusion. We also share with them the vital role their blood donation holds in helping patients who have the same rare blood and  encourage them to donate each time they are eligible.” The OneBlood Marketing and Communications teams have ongoing initiatives in place to keep rare donors engaged with donating, she said. “If a rare donor is needed for a specific patient, we will reach out directly to the donor and alert them about the situation and schedule them to come in to donate as soon as possible. Additionally, all rare donors are registered with the American Rare Donor Program.”

“Vitalant has as variety of donor engagement campaigns throughout the year,” said Figueroa. “When a rare donor is identified, we send a packet of information to the donor explaining how they are extra special. We also invite the donors to join the ARDP.”

Identifying rare donors, recruiting them and engaging with them are all necessary parts of the process to provide rare blood to patients wherever and whenever it is needed. This is crucial for patients who are alloimmunized or have a rare blood type and need a transfusion.