Rhesus is the clinically most important protein-based blood group system. It represents the largest number of antigens and the most complex genetics of the 30 known blood group systems. The RHD and RHCE genes are strongly homologous. Some genetic complexity is explained by their close chromosomal proximity and unusual orientation, with their tail ends facing each other. The antigens are expressed by the RhD and the RhCE proteins. Rhesus exemplifies the correlation of genotype and phenotype, facilitating the understanding of general genetic mechanisms. For clinical purposes, genetic diagnostics of Rhesus antigens will improve the cost-effective development of transfusion medicine.
Patients carrying any of the prevalent weak D types 1, 2, 3 or 4.1 are not prone to allo-anti-D immunization and may safely be transfused with D-positive red blood cells. Pregnant women with these weak D types need not receive RhIg. We should pay attention to weak D- or DEL-positive blood units that are labelled D-negative. The clinical benefit of removing DEL blood units from our supply of D-negative red blood cell units should be determined.
Background
Hemolytic reactions (HTRs) can occur from ABO-incompatible platelet transfusions. After a series of cases at our institution, a procedure to screen all plateletpheresis donors for high-titer ABO antibodies was implemented.
Study design and methods
Plasma samples from plateletpheresis donors were screened using pooled 0.8% A1 and 0.8% B RBC in buffered gel. Dilutions of 1 in 150, 1 in 200, and 1 in 250 were sequentially evaluated. A component testing positive for high-titer ABO antibodies is restricted to ABO-identical or group O recipients, or washed.
Results
At the initial dilution of 1 in 150, half of group O components were labeled as high-titer. At the current dilution of 1 in 250, 25% of group O components are labeled as high-titer. No platelet-associated HTR has been reported since screening began.
Conclusion
Universal screening for high-titer ABO antibodies in plateletpheresis donors can be implemented efficiently to reduce the risk of HTRs. The cutoff for classifying a unit as high-titer depends on the serologic method used, and may be customized by the individual facility. Our screening method uses one gel test per donation regardless of blood group, and a plasma dilution of 1 in 250 with pooled A1/B RBCs in buffered gel.
Background: Blood group genotyping is increasingly utilized for prenatal diagnosis and after recent transfusions, but still lacks the specificity of serology. In whites, the presence of antigen D is predicted, if two or more properly selected RHD-specific polymorphism are detected. This prediction must fail, if an antigen D negative RHD positive allele is encountered. Excluding RHDψ and Cde S frequent only in individuals of African descent, most of these alleles are unknown and the population frequency of any such allele has not been determined.
In a limited screen at the molecular level among 1000 random D+ donors in southwestern Germany, 20 donors were found carrying aberrant RHD alleles. Four of these alleles were new and likely sporadic. An estimate was derived of the variety that may be encountered in genotyping approaches, and it was concluded that even within the European population the variety of RHD alleles may be larger than anticipated.
There is considerable variation of Rhesus box sequences associated with distinct RHD alleles. RHD zygosity diagnostics in African persons is best based on quantitative polymerase chain reaction or amplification of the full-length hybrid Rhesus box. Because aberrant Rhesus boxes were observed among European persons, use of more than one method for hybrid Rhesus box detection may even be advisable in European persons.
Since around 2000, molecular tests for blood groups have been widely offered as a routine service. Many samples are shipped to reference laboratories in the German-speaking countries with the specific request for such testing. The advent of Conformité Européenne (CE)-labeled test kits renders it technically and legally possible, within the specifications of the CE-certification process for in vitro diagnostic devices in the European Union, to replace several blood group serology tasks by genotyping.
The characterization of ceRT demonstrated a previously unknown mechanism of antigen D expression that does not require any D-specific amino acid. At least for some D epitopes, D-like structures may be mimicked by RhCE proteins carrying amino acid substitutions not representative for RhD.
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