Establishment of a case registry that collaborates with a reference laboratory for blood group immunogenetics in Korea

Dear Sir,

The Korean Rare Blood Program (KRBP), established in 2013, is divided into two registries: a transfusion registry (the KRBP database) and a case registry (the KRBP case archive). The transfusion registry is a database of red cell antibodies voluntarily registered by blood banks in Korea. A recent study on the transfusion registry of the KRBP provided data on the frequencies of blood group antigens and the distributions of red cell antibodies¹. The case registry is an archive of challenging cases associated with blood group immunogenetics, and it collaborates with the KRBP reference laboratory. Cases that require specialized immunohematological methods or molecular analysis, such as cases with ABO subgroups, RhD variants, and complex red cell antibodies, are registered and resolved through further analysis. In addition to the recent study¹, our letter described a case registry that was offered as a resource to address and possibly resolve the challenging cases.

Cases that could not be resolved by blood banks in Korea using routine methods were submitted to the case registry. The request forms, which include the reason for the request, patient’s medical history, laboratory findings, and informed consent form, were submitted online (http://bloodgroupimmunogenetics.org). Then the blood samples were sent to the KRBP reference laboratory for further analysis. The specialized tests available through the KRBP reference laboratory included ABO/RHD/RHCE genotyping, antibody identification, specialized immunohematological tests including dithiothreitol treatment, and human erythrocyte/leukocyte/platelet antigen (HEA/HLA/HPA) genotyping. The comprehensive results were reported on a webpage accessible only to the blood banks from which the request had been made. Cases registered from July 2013 to June 2022 were analyzed.

Excluding 44 cases with clerical errors, 801 cases were registered from 66 hospitals (mean bed number: 963.3 ± 468.1), including cases related to the ABO system, Rh system, red cell antibody, and others (225, 183, 317, and 76 cases, respectively) (Table I). CisAB cases accounted for more than half of the cases with molecularly confirmed ABO subgroups, reflecting relatively high proportion in East Asian countries². Twenty-one cases of Asian type DEL were identified. Although doctors in Korea recognize that Asian type DEL individuals are not at risk of alloimmunization after exposure to D+ blood components, D- blood components are in principle selected for transfusion. The previous suggestion that Asian type DEL individuals can be safely transfused with D+ blood components was proven in a recent clinical trial³, although there is an exceptional single case where allo-anti-D was formed⁴.

Table I.

Results of cases registered in the case registry

ABO (No.=225)	Cases	RhD (No.=183)	Cases	Red cell antibodies (No.=317)	Cases
Normal ABO group	90	D+	15	Major alloantibodies a	91
ABO subgroup		D−		Minor alloantibodies a	12
CisAB	62	RHD complete deletion	31	Cold antibodies	27
A subgroup	7	RHD-CE-D hybrid	10	Autoantibodies	32
B subgroup	40	D variant		Alloantibodies to HFA	78
ABO discrepancy		Partial D	26	Alloantibodies to LFA	5
Red cell antibody	13	Weak D	9	Interference	7
Decreased Ig	9	DEL	21	Negative	22
Paraprotein	4	Unspecified	62	Etc. c	43
		D--/D--	1
		Etc. b	8

^aMajor alloantibodies were defined as alloantibodies to antigens that must be expressed in reagent red cell sets licensed by United States Food and Drug Administration (D, C, E, c, e, M, N, S, s, P1, Le^a, Le^b, K, k, Fy^a, Fy^b, Jk^a, and Jk^b). Minor alloantibodies were defined as alloantibodies other than major alloantibodies.

^bCases in which comprehensive serologic typing was not performed.

^cCases that remained inconclusive even after antibody identification based on the tube method and column agglutination using more than 30 reagent cells.

Ig: immunoglobulin; HFA: high frequency antigen; LFA: low frequency antigen.

To resolve complex red cell antibody cases, reagent red cell panels from various manufacturers based on column agglutination technique and tube method were used. HEA genotyping and special immunohematological techniques were also used, such as adsorption and elution, reaction with cord blood, and dithiothreitol treatment.

The case registry could be improved through the following suggestions. Currently, we did not track how the report results affected transfusion-related decisions. The effect of operating the case registry can be enhanced through collecting data on transfusion outcomes. For unresolved cases, collaboration with immunohematology reference laboratories in other countries should be considered.