Vol. 20 • Issue 5 • Page 56
Lab Limelight
Authors of a 2008 review in Transfusion Medicine1 predicted the field was ready for widespread application of nucleic acid-based technology. Three years later, laboratories are increasingly utilizing molecular technology.
“It’s mostly being used on the donor side to screen units and on the recipient side when you have patients with complicated antibodies or who are highly transfused,” says Beth Shaz, MD, chief medical officer, New York Blood Center, one of the authors of the 2008 review.
In donor centers, red blood cell (RBC) product genotyping provides phenotype-matched products for patients with alloantibodies, which cause hemolytic transfusion reactions. Dr. Shaz says 2-3% of hospital patients have RBC antibodies, and certain groups are at much higher risk, particularly sickle-cell anemia patients (who suffer from a genetic blood disorder in which RBCs have an abnormal, rigid and sickle shape) and other highly transfused populations.
“The more antibodies they make, the harder it is to find red cells that are compatible to them,” she says.
Sickle-cell anemia patients can become extremely sick when hemolyzing red cells, so donor blood is tested on a molecular platform to search for antigen-negative blood.
In transfusion services, serology isn’t as effective in determining extended antigen typing as nucleic acid testing for patients with antibodies or those who have recently been transfused. This is particularly true in patients with warm autoimmune antibodies (when an individual forms antibodies against their own RBCs) who have higher rates of antibodies to foreign RBCs. Determining presence of these RBC alloantibodies can be difficult; genotyping helps select the appropriate product for transfusion.
“The molecular testing would help you determine the patients’ extended phenotype, then you would select the more closely antigen-matched unit for transfusion,” Dr. Shaz says.
Molecular technologies improve pre-transfusion RBC testing reagents for blood types with typing discrepancies. They are especially useful for the Rh system, specifically the D antigen- the most important antigen after ABO type. For example, a patient who is Rh-positive (D antigen-positive) by serologic testing may be a confusing case because the patient could be missing a portion of RhD protein but be able to make anti-D, known as “partial D” antigen. Molecular testing can detect these cases, but serology cannot, Dr. Shaz says.
In an August 2007 editorial in Transfusion,2 Connie M. Westhoff, SBB, PhD, writes that blood group antigens result from inherited single nucleotide gene polymorphisms (SNPs), so the ability to link SNPs to disease risk and drug response makes SNP profiling promising for personalized medicine. Development of high-throughput SNP genotyping platforms to test blood group antigens is under way. “This approach will enable fast, reliable, cost-effective antigen screening for all major blood group antigens in a single assay,” Dr. Westhoff writes further.
Says Dr. Shaz of the microarrays. “They are not 510(k) approved, but they are being used throughout the country as a screening and research tool. No platform has final FDA approval for labeling blood, so you can’t send a unit out the door without doing serology also.”
Before genotyping becomes universal for pre-transfusion and donor testing, limitations must be addressed through clinical trials, authors in the 2008 review say. For one thing, genotype does not always predict phenotype.
As molecular testing grows, assays will become more comprehensive and detect additional mutations, and laboratorians will be more confident in the tests’ ability to match phenotypes. In addition, increased testing of ethnic groups will provide information on which donors/recipients need further detailed investigation, Dr. Shaz says.
Jill Hoffman is senior associate editor.
References
1. Hillyer CD, Shaz BH, Winkler AM, Reid M. Integrating molecular technologies for red blood cell typing and compatibility testing into blood centers and transfusion services. Transfusion Medicine Reviews 2008; 22(2):117-32.
2. Westhoff CM. Molecular genotyping for RHD: What (not) to do? Transfusion 2007;47: 1337-9.
