Findings could lead to new clinical laboratory tests to screen for individuals with increased risk of blood transfusion complications
Pathologists and clinical laboratory scientists who understand the complexities of blood typing from one human to another will be interested to learn that a 50 year-old mystery has brought about an exciting new discovery—a new human blood group.
British and Israeli scientists led by the UK’s NHS Blood and Transplant (NHSBT) and the University of Bristol discovered the meaning behind a missing protein molecule found in a pregnant woman five decades ago. This anomaly has now been given its own blood group identification called MAL, according to a University of Bristol new release.
“Some people can lack this blood group due to the effect of illness, but the rare inherited form of the AnWj-negative phenotype has only been found in a handful of individuals—though due to this discovery it will now be easier to find others in the future,” the news release notes.
This is important because receiving mismatched blood can be fatal.
“AnWj is a high-prevalence red blood cell (RBC) antigen in the ISBT 901 series. Only nine reports of anti-AnWj have been published since it was first documented in 1972,” according to a 2012 article published by the American Association of Blood Banks, now known as the Association for the Advancement of Blood and Biotherapies (AABB).
For even the small proportion of the population with this new blood group, diagnosing its presence can have a major impact while preventing unwanted harm.
“The work was difficult because the genetic cases are very rare. We would not have achieved this without exome sequencing, as the gene we identified wasn’t an obvious candidate and little is known about Mal protein in red cells,” said Louise Tilley, PhD, Senior Research Scientist, IBGRL Red Cell Reference at NHS Blood and Transplant, in the news release.
“The genetic background of AnWj has been a mystery for more than 50 years, and one which I personally have been trying to resolve for almost 20 years of my career,” said Louise Tilley, PhD (above), Senior Research Scientist, IBGRL Red Cell Reference at NHS Blood and Transplant, in the news release. “It represents a huge achievement, and the culmination of a long term effort, to finally establish this new blood group system and be able to offer the best care to rare, but important, patients,” she added. Clinical laboratory scientists involved in blood banking will want to keep updated as further research into this new blood group is published. (Photo copyright: NHS Blood and Transplant.)
Unraveling the Mystery
In 1972, scientists were stumped by a pregnant woman with a blood sample that was “mysteriously missing a surface molecule found on all other known red blood cells at the time,” Science Alert reported. The AnWj antigen that was missing in that patient’s blood is present in 99.9% of human blood samples.
“Researchers found that the AnWj antigen is carried on the Mal protein. While illness can cause some people to lose the AnWj antigen, inherited cases of the AnWj-negative phenotype are extremely rare. Using whole exome sequencing on five genetically AnWj-negative individuals, researchers confirmed that, in these cases, the participants lacked the antigen due to homozygous deletions in the MAL gene,” an AABB news release stated.
The researchers named the group with the missing antigen the MAL blood group (short for Myelin and Lymphocyte Protein) which is where the antigen resides.
Genetic sequencing enabled the scientists to locate the gene when they “inserted the normal MAL gene into blood cells that were AnWj-negative. This effectively delivered the AnWj antigen to those cells,” Science Alert noted.
Mutated MAL genes result in the AnWj-negative blood type. The team discovered three patients with the blood type and no mutation, “Suggesting that sometimes blood disorders can also cause the antigen to be suppressed,” Science Alert added. The researchers also discovered that AnWj isn’t present in newborns but arrives sometime after they are born.
“Interestingly, all the AnWj-negative patients included in the study shared the same mutation. However, no other cell abnormalities or diseases were found to be associated with this mutation,” Science Alert said.
The discovery that “the Mal protein is responsible for binding AnWj antibodies” could lead to new clinical laboratory tests to screen for patients at risk from blood transfusions, AABB noted in its news release.
Facing the Challenge
Scientists had to overcome many challenges to uncover the details of this blood type. The complexity of the protein further hindered their efforts.
“MAL is a very small protein with some interesting properties which made it difficult to identify, and this meant we needed to pursue multiple lines of investigation to accumulate the proof we needed to establish this blood group system,” said Tim Satchwell, PhD, senior lecturer and cell biologist at the University of the West of England, in the University of Bristol news release.
“Resolving the genetic basis for AnWj has been one of our most challenging projects,” Nicole Thornton, head of IBGRL Red Cell Reference at NHSBT told the AABB. “There is so much work that goes into proving that a gene does actually encode a blood group antigen, but it is what we are passionate about, making these discoveries for the benefit of rare patients around the world.”
It’s hard to pinpoint how many individuals will benefit by testing for the blood group, Tilley told the BBC. Nevertheless, “the NHSBT is the last resort for about 400 patients across the world each year,” the BBC reported.
While more research needs to be done, the initial discovery is promising and may lead to new clinical laboratory tests to identify individuals who could be severely harmed should they receive the wrong blood type during a transfusion.
Funded by the CDC, the program hopes to alleviate personnel shortages in Baltimore area clinical labs while also producing a knowledge base for lab managers nationwide
Clinical laboratory managers struggling to fill vacant phlebotomy and accessioning positions will be interested to learn about a pilot program being conducted by the City of Baltimore and the University of Maryland School of Medicine to train people “for employment in hospital laboratories, phlebotomy draw sites, and reference laboratory processing centers,” according to The Elm, a publication of the University of Maryland, Baltimore.
The 14-week “Mayor’s Workforce Development Program” began on April 19 and will continue through the end of July. Participants meet twice a week for lectures and experience working with specimens in actual medical laboratories or in a “hybrid learning environment,” The Elm reported.
“I came up with the idea of doing cross-training for laboratory people and public health people in case there is another pandemic,” explained Lorraine Doucette in an exclusive interview with Dark Daily. Doucette, who is managing the pilot program, is an Assistant Professor and Medical Laboratory Science Program Director, Department of Medical and Research Technology, University of Maryland School of Medicine.
“There is already a huge shortage of laboratory people, but an enormous amount left in droves during the pandemic because they got physically burned out. Some just could not do the work anymore because of things like carpal tunnel syndrome and repetitive stress injuries,” she added.
“I’m confident that all 15 or 16 students who complete this workforce program will be employed within weeks of finishing as accessioners,” said Lorraine Doucette (above), Assistant Professor and Medical Laboratory Science Program Director, Department of Medical and Research Technology, University of Maryland School of Medicine, in an exclusive interview with Dark Daily. “This has been so successful. This is making a difference in people’s lives. This is changing them from being unemployed to actually having a career in a clinical laboratory. They love it. They are so proud of themselves.” (Photo copyright: LinkedIn.)
CDC Funding Part of National Program to ‘Enhance’ Clinical Lab Workforce
The collaboration is part of a CDC project titled, “Enhancing US Clinical Workforce Capacity.’ Doucette will receive a total of one million dollars over the course of three years to facilitate the program in stages.
“It is not necessarily an old-fashioned grant where they just gave me a pile of money,” Doucette told Dark Daily. “The CDC works with me constantly via reports and Zoom meetings.”
This CDC project is designed to both cross train clinical laboratory professionals in public health, clinical chemistry, microbiology, and hematology, as well as to train individuals in the workforce development program to become laboratory accessioners.
“They are going to be qualified to work as an accessioner in any local hospital,” Doucette noted. “The people who pick up the lab samples out of the tube system are the accessioners and there is a huge shortage of them also. We’re teaching them the basics so the more advanced lab personnel can perform the higher-level work.”
Students in the program learn all about lab safety and the proper handling of lab samples as well as proper data entry, professionalism, and how to communicate with medical and laboratory personnel. They work with urine and blood samples and fabricated spinal fluid samples.
“They are taught about the different tubes, what the anticoagulants are, what makes each tube unique, why you can’t mix samples, balancing a centrifuge, and how to properly put on and remove safety gear like lab coats, gloves, and goggles,” Doucette explained.
The Mayor’s Workforce Development Program is free for Baltimore residents looking for employment via the workforce office. The only requirements for enrolling are having a high school education and being fully vaccinated.
Phlebotomy and Additional Cross-training to Be Added
Doucette would eventually like to add a phlebotomy segment to future training sessions. “We would like to develop an additional partnership with BCCC (Baltimore City Community College) for the phlebotomy piece. That would definitely increase the people and the program’s marketability,” she said. “They could not only draw the blood, but they could also process the sample.”
After assessing the success of the current program and determining what did and did not work, there will be an additional training session held in the fall. Next year, there will be more sessions held for individuals in the workforce program and cross-training classes for current clinical laboratory professionals.
The strategy for the third year of the grant includes sharing the specifics of the program with medical laboratory professionals via the CDC’s free OneLab REACH platform. This portion includes the online delivery of documentation such as training sheets, lab exercises, Microsoft PowerPoint presentations, and videos used in both the accessioning and cross-training coursework.
“We’re going to do the OneLab REACH,” Doucette said. “I’m going to be putting it all online and marketing it all around the country in stages and increments. I will be going to a lot of professional society meetings and talking to lab managers to help them understand the concept of how this all benefits them.”
This unique collaboration between the City of Baltimore and University of Maryland School of Medicine, funded by the CDC, should help alleviate some of the clinical laboratory worker shortages that exist in the Baltimore area. Hopefully, the effort will result in additional knowledge, resources, and tools to assist medical lab managers across the country to recruit and retain talented, highly-skilled workers.
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