**3.5 Rare type blood donor selection**

Alloimmunized patients require transfusion of RBCs that are negative for a particular antigen. Historically, serology methods, which are labor-intensive and time-consuming, have been used to screen for antigen-negative units. However, the standard practice is likely to change with the high-throughput platforms for blood group genotyping being approved by regulatory bodies and becoming more widely used. High-throughput platforms allow identification of a higher number of antigens compared with serology, increasing the availability of blood characterized for clinically relevant antigens.

The implementation of RBC mass scale genotyping for donor screening has started in blood centers, especially in large collecting facilities [50–53]. The successful establishment of a blood group genotype database has already been accomplished aiming to fulfill antigen-negative requests, especially for SCD patients receiving regular transfusions, and to create an inventory of frozen red cell units with rare blood types [51]. The refereed database comprises 43,066 non-Caucasian blood donors genotyped for 32 single nucleotide polymorphisms, related to the expression of 42 blood group antigens. The report showed that within 4 years of starting RBC genotyping, the blood group antigen database generated on blood donors was fivefold larger than that obtained by serology methods over 30 years. In addition, most antigen-negative units requests to that center were met using exclusively the genotyping database.

Strategies for finding units to fulfill transfusion requests for SCD patients have included RBC genotyping of non-Caucasian blood donors and donors with altered Rh antigen expression [54, 55]. The genotyping selection of donors with a genetic background similar to that of SCD patients' increases the chances of finding compatible blood for these patients, including RH-genotype matching. However, the low percentage of blood donors with African ethnic background combined with the cost of genotyping are limiting factors for widespread use of extended RBC genotyping matching strategy.

*Human Blood Group Systems and Haemoglobinopathies*

C, c, E, e), KEL (K, k), FY (Fya

may be clinically relevant [13, 15].

; Rh: V, VS; Colton: Co<sup>a</sup>

lead to alloimmunization.

**3.4 Thalassaemia**

Extended genotyping including Dombrock: Do<sup>a</sup>

antibodies that can be potentially life-threatening.

, Cob

(D, C/c, E/e) and K [41], while others provide extended matching including RH (D,

the standard ABO and Rh(D). Less frequently, extended matching is performed by genotyping [36]. However, a wide range of institutions do not request phenotypically matched RBC units until the patient has produced an alloantibody [42].

It has been reported that antibodies against Rh antigens are the most frequently identified antibodies in multitransfused SCD patients despite transfusion from Rh phenotype matched donors [15]. The main reason for that is the high frequency of Rh variants in people of African descent. It has been reported that 90% of SCD patients and donors of African ancestry have at least one variant *RHD* or *RHCE* allele [15, 43]. The term "variant" is used when *RHD* and/or *RHCE* genes are carrying genetic alterations that may affect the RhD and RhCe protein expression. Variant alleles can encode weak and/or altered antigens and serological methods are limited in which variant Rh antigens can be identified and might not be reliable [44, 45]. The prophylactic RBC matching performed by serology typing, before exposure to RBC transfusions, can decrease transfusion complications in SCD patients substantially, but does not eliminate the occurrence of alloimmunization against Rh variants and other non-matched antigens that can cause DHTR [41]. Currently available molecular typing methods can predict several blood group antigens allowing a more precise RBC matching and can support transfusion decision-making. *RHD* and *RHCE* genotype matching particularly benefits SCD patients carrying Rh variants. For instance, SCD patients presenting D+ or e+ phenotype can make alloantibodies to these antigens despite receiving Rh phenotyped matching RBCs. The molecular analysis in such individuals may identify polymorphisms in *RH* genes responsible for the phenotypic alteration, confirming the alloimmune status of the antibody. In such cases, provision of *RH* genotype matched units or units negative for the specific antigen would be recommended, because the antibodies produced

An additional benefit of blood group genotyping on transfusion management of SCD patients is the capability of identifying silence mutations like −67T>C in the ACKR1 gene (Duffy gene). Patients carrying the mutation can receive Fy(b+) units, because the mutation only abolishes expression of Fy(b) on red cells but not in other tissues. The detection of this mutation avoids unnecessary use of Fy(b−) and increases the chances to find compatible units available even for highly restrictive

; Cartwright: Yta

; and Scianna: Sc1, Sc2 may help prevent development of clinically significant

Thalassaemia is an inherited blood disorder associated with a mutation in one of the genes involved in hemoglobin production resulting in abnormal form or an inadequate amount of hemoglobin. RBCs carrying abnormal hemoglobin do not function properly and are destroyed in large numbers leading to anemia. People with thalassaemia may have mild or severe anemia depending on the type of thalassaemia. Severe anemia requires regular blood transfusions to maintain the hemoglobin and RBCs levels, and to suppress the ineffective erythropoiesis but can

The prevalence of alloimmunization in patients with thalassaemia varies among geographical locations and may be related to the heterogeneity of population, transfusion exposure frequency, patients age, antigen matching policy, recipient related

, Dob , Joa

; Lutheran: Lua

, Ytb

, Hy; Kell: Kpa

, Lub

, Kpb , Js<sup>a</sup> ,

; Diego: Di<sup>a</sup>

,

, Jkb

), and MNS (S, s) in addition to

), JK (Jk<sup>a</sup>

, Fyb

**206**

matching.

Jsb

Dib
