Body-wide chimerism and mosaicism are predominant causes of naturally occurring ABO discrepancies.

Routine ABO blood group typing of apparently healthy individuals sporadically uncovers unexplained mixed-field reactions. Such blood group discrepancies can either result from a haematopoiesis-confined or body-wide dispersed chimerism or mosaicism. Taking the distinct clinical consequences of these four different possibilities into account, we explored the responsible cause in nine affected individuals. Genotype analyses revealed that more than three-quarters were chimaeras (two same-sex females, four same-sex males, one sex-mismatched male), while two were mosaics. Short tandem repeat analyses of buccal swab, hair root and nail DNA suggested a body-wide involvement in all instances. Moreover, genome-wide array analyses unveiled that in both mosaic cases the causative genetic defect was a unique copy-neutral loss of heterozygosity encompassing the entire long arm of chromosome 9. The practical transfusion- or transplantation-associated consequences of such incidental discoveries are well known and therefore easily manageable. Far less appreciated is the fact that such findings also call attention to potential problems that directly ensue from their specific genetic make-up. In case of chimerism, these are the appearance of seemingly implausible family relationships and pitfalls in forensic testing. In case of mosaicism, they concern with the necessity to delineate innocuous pre-existent or age-related from disease-predisposing and disease-indicating cell clones.

"Don't add fuel to the fire"- Hyperhemolysis Syndrome in a pregnant woman with compound Sickle cell disease/ß0-thalassemia - Case report and review of the literature.

Hyperhemolysis Syndrome (HHS) is a rare and severe post-transfusion complication characterized by the destruction of both recipient and donor red blood cells (RBC). The underlying mechanism of HHS is not fully understood and proper management can be difficult. Furthermore, there are few reports regarding HHS in pregnancy. We report on the development and management of HHS in a pregnant woman with known compound Sickle cell disease/ß-0-thalassemia after transfusion of not fully compatible packed red blood cells (PRBC). We aim to raise awareness on this diagnostically challenging and life-threatening type of hemolysis with this report, and to stress the need to consider the diagnosis of HHS in SCD patients with progressive anemia despite PRBC administration.

Fetal RHD Screening in RH1 Negative Pregnant Women: Experience in Switzerland.

RH1 incompatibility between mother and fetus can cause hemolytic disease of the fetus and newborn. In Switzerland, fetal RHD genotyping from maternal blood has been recommended from gestational age 18 onwards since the year 2020. This facilitates tailored administration of RH immunoglobulin (RHIG) only to RH1 negative women carrying a RH1 positive fetus. Data from 30 months of noninvasive fetal RHD screening is presented. Cell-free DNA was extracted from 7192 plasma samples using a commercial kit, followed by an in-house qPCR to detect RHD exons 5 and 7, in addition to an amplification control. Valid results were obtained from 7072 samples, with 4515 (64%) fetuses typed RHD positive and 2556 (36%) fetuses being RHD negative. A total of 120 samples led to inconclusive results due to the presence of maternal or fetal RHD variants (46%), followed by women being serologically RH1 positive (37%), and technical issues (17%). One sample was typed false positive, possibly due to contamination. No false negative results were observed. We show that unnecessary administration of RHIG can be avoided for more than one third of RH1 negative pregnant women in Switzerland. This reduces the risks of exposure to a blood-derived product and conserves this limited resource to women in actual need.

Serologic and molecular investigations of DAR1 (weak D Type 4.2), DAR1.2, DAR1.3, DAR2 (DARE), and DARA.

BACKGROUND: The partial D variant DAR1 (weak D Type 4.2) is caused by three single-point mutations, 602C>G, 667T>G, and 1025T>C. Here we report a molecular study on different D variants belonging to the DAR category (DAR1, DAR1.2, DAR1.3, and DAR2) and their serologic data. STUDY DESIGN AND METHODS: A total of 42 samples belonging to the DAR category were screened for the presence of the silent mutations 744C>T and 957G>A. The samples were phenotyped for RhD and RhCE, characterized for RhD epitope expression, and sequenced for RHD exons. Flow cytometry was performed to determine RhD antigen density. RESULTS: The silent mutation 744C>T was found in all six samples previously typed as RHD*DAR2 (602C>G, 667T>G, 957G>A, 1025T>C). In addition to the three nucleotide changes originally reported for the RHD*DAR1 allele, the silent mutations 744C>T and 957G>A were found in 14 of 16 samples previously typed as RHD*DAR1. In the remaining two samples one additional silent mutation, 744C>T, was found. Serologically the DAR1.2 and DAR1.3 samples analyzed in this study showed no distinct difference in their anti-D reaction pattern compared to each other. The anti-D reaction pattern of DARA/DAR2 showed some distinct differences compared to those of DAR1.2 and DAR1.3. CONCLUSION: RHD*DARA and RHD*DAR2 are the same allele. Furthermore, the alleles RHD*DAR1.2 and RHD*DAR1.3 both exist; however, the silent mutation 957G>A (V319) showed no influence on the RhD phenotype.