Red blood cell (RBC) transfusions are a milestone in the treatment for sickle cell anaemia (SSA) and for thalassaemia. RBC alloimmunization remains a major challenge of chronic transfusion therapy, and it can lead to adverse life-threatening events. The alloimmunization risk could depend on multiple factors such as the number of transfusions and, most of all, the genetic background. Different ethnic groups are predisposed to immunization because of a significant degree of RBC antigenic mismatch between donor and recipient. There is no universal agreement and standards for the most appropriate selection of RBC units in chronically transfused subjects. Current practice only deals with compatibility of ABO, Rh and K antigens. Molecular RBC antigenic matching extended to other blood group systems is an innovative strategy to ensure a better quality and effectiveness of transfusion therapy.

Serological ABO HDFN is a relatively frequent event when an O-A/O-B incompatibility between mothers and their newborn occurs and, in most cases, translates into a self-limiting disease, with a small number of newborns requiring invasive treatments. The DAT test, although not predictive of disease severity, appears to be a useful tool to monitor babies born from O-A/O-B-incompatible pregnancies and to identify those who may require treatment.

Fungal infections are a common complication in hematological and oncological patients. In the study the results of a retrospective analysis of the onset of fungal infections among 383 patients admitted at the hematology unit of San Camillo Hospital, Rome, from 1980 to 1995 are reported. In the eleven years prior to 1991 only four cases of fungal infection were detected in high risk patients (1.8% of the high risk patients). From 1991 to 1993 there was a dramatic increase of fungal infections (Candida and Aspergillus). Thirteen cases of infections were observed during this period, eight of which were due to Aspergillus (12% of the high risk patients). For this reason it was decided to introduce a different prophylactic treatment for all high risk patients consisting of combined conventional intravenous (i.v.) amphotericin B, oral amphotericin B and nebulized amphotericin B, starting from the first day of hospitalization. Since the introduction of this new prophylactic regimen no cases of invasive fungal infections were observed in the 48 high risk patients examined. The prophylactic treatment was well tolerated by all patients. The results suggest that the combined use of oral, nebulized and i.v. amphotericin B is very effective in preventing invasive fungal infections in high risk patients.

The indication for IUT in our institution has to date been limited to red cell alloimmunization due to anti-D. Alpha thalassaemia and congenital infections such as Parvovirus are not uncommon in this region of the world, but the foetal and neonatal specialists in our centre have generally not advocated IUT for them. Certainly, we would not embark on an IUT programme for HbBarts that would be considered as incompatible with life. Question 2 Anti-D has been the only reason for IUT in our population. We identify anti-D in 0Á35% of our non-transfused female population, mainly from the antenatal clinic. The majority of this is due to anti-D administered through the antenatal anti-D prophylaxis programme, but we do get 1-2 cases that occur as a result of RhD immunization resulting in moderate to severe HDFN. The common antibodies we otherwise identify in our nontransfused female population (prevalence in parentheses) are anti-Mi a (0Á24%), anti-Le a (0Á24%), anti-E (0Á14%) and anti-M (0Á12%). As you would note, these antibodies are rarely associated with HDFN. Anti-K and anti-c which are more commonly associated with HDFN has a prevalence of only 0Á01% in our population of non-transfused females. Question 3 We only perform 1-2 IUTs per year. In 2018, we had no IUT procedures and in 2019, we have only performed one procedure to date. Blood sample testing Question 4 Foetal red cell typing is limited to ABO and RhD, C, c, E and e phenotyping. Blood product selection (Red blood cell (RBC) concentrates): Question 5 We select Group O red cells, preferably from a donor with low titres of anti-A/B. If a suitable donor with low anti-A/ B titre cannot be located, we will elect to reconstitute the red cells with AB plasma. Question 6 We obtain allogeneic red cells from our pool of selected donors. Question 7 All red cell units supplied are K negative as well as antigen matched as close as possible to the maternal phenotype. At the minimum, the red cells supplied must be CcEe-matched. Question 8 Units supplied would be considered Day-0, as we prepare red cells from a fresh bleed on the day of the IUT procedure. The donor workup which includes ABO and RhD typing, red cell phenotyping, antibody screening, IAT crossmatch with maternal plasma, anti-A/B titration as well as microbiology testing (HIV, HBV, HCV, TPPA, NAT) would be completed prior to the donation from a sample obtained from the donor not more than 72 h before the planned blood collection. e18 Question 9 Whole blood is collected into a collection bag containing CPD (Citrate, Phosphate and Dextrose) prior to processing. Question 10 No, we do not assess CMV status. CMV prevalence is high within our population, and we therefore have found it difficult to maintain a pool of suitable CMV donors.

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Conclusion Despite some differences among countries, the Rh disease prevention policies are very efficient in Europe, but HDFN cases due to maternal anti-RH1 immunization have not completely disappeared. It therefore remains important to share best practices for continuous improvement in reducing anti-RH1 alloimmunization.

Molecular investigation is an important complement to routine serologic analyses of Kell antigens. Discrepancies between genotype and phenotype may reveal the presence of K(mod) or K0 phenotypes. Our description of three new KEL alleles suggests a role for a wider diagnostic approach to typing of the Kell system.