Clinical application of ABO blood typing

Abstract

BACKGROUND:

The ABO blood group is closely related to clinical blood transfusion, transplantation, and neonatal hemolytic disease. It is also the most clinically significant blood group system in clinical blood transfusion.

OBJECTIVE:

The purpose of this paper is to review and analyze the clinical application of the ABO blood group.

METHODS:

The most common ABO blood group typing methods in clinical laboratories are hemagglutination test and microcolumn gel test, while genotype detection is mainly adopted in clinical identification of suspicious blood types. However, in some cases, the expression variation or absence of blood type antigens or antibodies, experimental techniques, physiology, disease, and other factors affect the accurate determination of blood types, which may lead to serious transfusion reactions.

RESULTS:

The mistakes could be reduced or even eliminated by strengthening training, selecting reasonable identification methods, and optimizing processes, thereby improving the overall identification level of the ABO blood group. ABO blood groups are also correlated with many diseases, such as COVID-19 and malignant tumors. Rh blood groups are determined by the RHD and RHCE homologous genes on chromosome 1 and are classified as Rh negative or positive according to the D antigen., the agglutination method is often used in clinical settings, while genetic and sequencing methods are often used in scientific research.

CONCLUSION:

Accurate ABO blood typing is a critical requirement for the safety and effectiveness of blood transfusion in clinical practice. Most studies were designed for investigating rare Rh blood group family, and there is a lack of research on the relationship between Rh blood groups and common diseases.

Keywords

ABO blood type Rh blood type blood group system forward and reverse typing influencing factors diseases

1. Introduction

Blood transfusion safety is of primary concern in clinical transfusion [1], and accurate blood typing is a prerequisite to ensure transfusion safety [2]. At present, it has been found that there are over 20 blood group systems and more than 200 antigens on erythrocytes. Nevertheless, the important guiding role of the ABO blood group system in clinical blood transfusion makes it the most clinically significant blood group system [3, 4, 5, 6]. Laboratory testing of ABO blood groups has also evolved from the initial slide method to the fully automated blood group identification system [7]. In addition, several studies have provided an in-depth analysis of the reasons for identification errors and proposed precautions. The association between blood group antigen A and malignant tumor (i.e., gastric cancer) was first reported in 1953, and followed by studies investigating the association between ABO blood types and other types of malignant tumors in the 1960s [8]. In recent years, the relationships between ABO blood types and diseases have become an interesting research topic [9, 10]. The Rh blood group system, which was discovered in the late 1930s, is composed of at least 49 different antigens. The main clinically relevant antigens are D(Rho), C(rh), E(rh), c(hr) and e(hr). Among then, the D antigen is highly immunogenic and is an important transfusion-responsive antigen and blood group antigen causing neonatal hemolytic disease. With the cloning of the Rh blood group system cDNA, a great breakthrough has been made in the study of the Rh blood group system. the molecular basis of the structure of the RH gene and most variants has been gradually elucidated, and there has been some progress in the study of Rh blood group genotyping and diseases. We aim to provide a review of the above issues in this paper.

2. Overview of the ABO blood group system

In 1901, Austrian geophysiologist Karl Landesteiner discovered the human ABO blood type, which is located on chromosome 9 (9q31.3 $\sim$ q34.1). The specificity of the various antigens of the ABO blood group system is determined by the carbohydrate chains of glycoproteins or glycolipids located on the erythrocyte membrane. These carbohydrate chains are oligosaccharide chains consisting of a small number of glycosyls exposed on the erythrocyte surface. The specificity of the A and B antigens depends on the composition and link order of these oligosaccharide chains [11]. The A and B antigens are formed on the basis of the H antigen. With the action of the A gene, the A enzyme synthesized in cells can link an acetyl galactosamine group onto the H substance, thus forming the A antigen, and the B enzyme synthesized with the action of the B gene can link a galactosyl group to the H substance, to form the B antigen. Though O phenotype erythrocytes do not contain A and B antigens, they have the H antigen. In fact, the H antigen was formed based on another precursor containing four glycosyl groups. Under the action of fucosyltransferase encoded by the H gene, the H antigen is formed by linking fucose at the end of the precursor galactose. If the H gene is missing, it will lead to fucosyltransferase deficiency and further synthesis failure of H antigen, A antigen, and B antigen. However, with its precursor, the blood type is called Mumbai type [12, 13, 14]. Therefore, genes determine which glycosyl links to the precursor at which position by identifying the synthesized type of glycosyltransferase, thereby indirectly affecting the composition of the oligosaccharide chains, which determines the specificity of blood group antigens and its phenotypes. The A and B antigens can be detected on the erythrocyte membranes in human embryos aged 5 to 6 weeks. The number of A and B antigenic sites on the erythrocyte membranes of infants account for only 1/3 ${}^{\text{rd}}$ of that in adults. These antigenic sites are not fully developed until 2–4 years old. Normally, the antigenicity of A and B antigens remains unchanged throughout life [15]. There are four ABO blood types according to the presence or absence of A antigen and B antigen on the erythrocyte membrane: in the A blood group, only the A antigen is contained on the erythrocyte membrane, in the B blood group, only the B antigen is contained on the erythrocyte membrane, those that contain both A and B antigens are referred to as the AB blood group, while those that have neither A nor B antigens are the O blood group. There are different antibodies in the serum of people with different blood types, however, the serum does not contain antibodies corresponding to their own erythrocyte antigens. Only anti-B antibodies are present in the group A serum, while only anti-A antibodies are present in the group B serum. There are no anti-A and anti-B antibodies in group AB serum, while both anti-A and anti-B antibodies are present in the group O serum. There are also several subtypes of the ABO blood group system, the most important of which are the A1 and A2 subtypes in A blood group. Erythrocytes of A1 blood group contain both the A antigen and A1 antigen, while that of the A2 blood group contain only the A antigen. Similarly, there are also two main subtypes in the AB blood group, namely the A1B and A2B subtypes [16].

3. Overview of the Rh blood grouping system

The Rh blood group is a complex, highly polymorphic blood group system, consisting of at least 49 different antigens. The main clinically relevant antigens are D, C, c, E, and e. The D antigen is highly immunogenic and is an important transfusion-responsive antigen and a blood group antigen causing neonatal hemolytic disease. It is also the second most clinically significant red blood cell antigen after the ABO blood group system [17]. Rh blood groups can be divided into RhD-positive and RhD-negative blood groups according to the presence or absence of D antigen on the surface of red blood cells. (1) RhD-positive: The serology shows the ability to agglutinate with all monoclonal antisera and has all normal RHD genes. (2) RhD-negative: It can be further divided into complete absence of the RHD gene, partial absence of the RHD gene, and complete RHD gene. The Rh blood group is determined by the RHD and RHCE homologous genes on chromosome 1. The RHD gene encodes the D antigen and the RHCE gene encodes the C, c, E, and e antigens, each with 10 exons and up to 94% homology [18]. In Caucasians, RhD-negative blood groups are almost always caused by deletions of the RHD gene that occurs between the upstream and downstream Rh box genes [19]. However, in RhD-negative Asians, the RHD gene exists in various forms, including complete deletions, partial deletions, and point mutations [20]. Hemolytic transfusion reaction due to Rh blood group incompatibility occurs occasionally in clinical practice and are particularly complicated by weak D and partial D variants in clinical transfusions. Because weak D recipients are treated as RhD negative and weak D donors are treated as RhD positive, it is easy to transfuse RhD-positive blood to weak D patients or to transfuse weak D blood to RhD negative patients both of which may produce anti-D and cause hemolytic transfusion reactions. Antibodies produced by a new variant of Del have also been reported to cause transfusion reactions [21].

4. Methods for blood typing

4.1 Hemagglutination test

The visually visible agglutination reaction between antibodies and erythrocytes in liquid media. (1) Slide method: Blood typing is determined by whether there is agglutination reaction between the antibody and antigen on a dry slide. (2) Test tube method: its principle is the same as the slide method. With the test tube as the reaction dish, this method reduces the concentration of non-specific antibodies in blood to a certain extent, thus improving sensitivity and specificity. (3) Instrument method: forward and reverse typing is achieved through standardized sample addition, incubation, centrifugation, suspension, quiescence, and the calculation of the absorbance value before and after reaction [22]. This method has the advantages of rapidity, accurateness, and high degree of automation, while there are also shortcomings like expensive instruments and high costs. This method is simple and easy to implement, but vulnerable to environmental and empirical factors. The accuracy is relatively low, and the operation is difficult to standardize and automate. Also, the test results are not easy to save, only suitable for primary screening.

4.2 Microcolumn gel test

The employment of gel technology in antiglobulin testing can improve sensitivity and specificity. At present, it has been gradually applied as a routine ABO blood typing method in the field of blood transfusion. The microcolumn gel method has changed the traditional manual operation, reduced the manual error, and increased the identification accuracy. The test data can be saved and network transmission. It is the main method of daily blood group typing in hospitals.

4.3 Genotype detection

4.3.1 ABO genotyping

With the cloning and sequencing of cDNA encoding glycosyltransferase, it is possible to identify ABO blood groups at the gene level. As genotyping technology can be used in a variety of samples, with a small sample size required, it is mainly adopted in clinical practice for the identification of suspicious blood types, prenatal fetal blood typing, cases of blood group antigenicity reduction caused by leukemia chemotherapy, paternity tests, and forensic science [23, 24, 25]. Serological techniques are the conventional methods for ABO blood group typing. However, there are some limitations such as $=$ attenuated antigens or antibodies, abnormal plasma proteins, multiple agglutinins or cold agglutinins. With the development of molecular biology technology, ABO blood group genes were cloned, DNA-based genotyping techniques for ABO blood groups were established, and genotyping techniques with different throughputs, such as real-time quantitative PCR and Sanger sequencing, emerged. Genotyping technology has overcome the limitations of serology and has become an indispensable method for solving difficult blood groups, providing strong support for the correct identification of ABO blood groups.

4.3.2 Rh blood group genetic testing

There are four main types of Rh genetic testing. (1) PCR sequence-specific primers (PCR-SSP): Designing sequence-specific primers based on RH gene-specific loci and specifically amplifying RH gene exons or introns is the most commonly used technique for Rh blood group genotyping. (2) PCR restriction fragment length polymorphism (PCRRFLP): restriction enzyme cutting PCR amplification products for length polymorphism analysis can detect single nucleotide substitutions at restriction sites, and PCR-RFI P is used for RHD haplotype identification and D/c/C typing on Rh blood group genotyping. (3) Real-time quantitative PCR: commonly used to detect trace amounts of fetal DNA in the peripheral blood of pregnant women, it is the method of choice for fetal Rh blood group identification and is also suitable for direct detection of RHD congenital phenotypes. Recent studies have shown that this technique is superior to PCR-SSP and PCR-RFLP methods in identifying RHD congeners in non-Caucasian individuals due to the presence of more variants of RHD [26, 27]. (4) PCR direct sequencing (PCR-SBT): direct sequencing of PCR products can detect RH gene polymorphisms and identify various base variant loci. This technique is not only capable of sequence identification and typing, but also has unique advantages in the discovery of new alleles.

5. Influencing factors for blood typing inconsistency

5.1 Experimental techniques

(1) Sample mix up/collection mistakes: medical staff fail to carefully check the patient’s information when collecting samples, or cause collection mistakes because of work overload, which leads to blood typing inconsistency. (2) Improper selection of reagents and samples: The typing reagents have expired or have been contaminated by bacteria, etc., which affects the antigen and antibody reaction, thus resulting in blood typing inconsistency. (3) Non-standard experimental operation: The test is not carried out strictly in accordance with the procedures: the serum of the typing reagent or wrong sample is added into the test tube, or the patient’s erythrocyte suspension concentration is improper, or the centrifugal time and rotational speed are inappropriate, or the results are merely observed with the naked eye, or the test tube is not marked, or the wrong test tube is taken after centrifugation – all of these can lead to blood typing inconsistency. (4) Mistakes in result interpretation: Failure in timely and exhaustively handing over to the next shift, recording the wrong blood typing results, and failure in recognizing the hemolysis phenomenon as a positive reaction during the experiment can lead to misjudgment. (5) Input error: Entering the wrong blood type when the data was input, which eventually leads to blood typing inconsistency.

5.2 Physiological factors

(1) ABO subtypes: Given the fact that agglutination reaction could occur between erythrocytes of A1 blood type and anti-A1 antibodies in A2 group type serum, and the antigenicities of A2 and A2B erythrocytes are more decreased than that of A1 and A1B erythrocytes, it is easy to misidentify A2 and A2B blood types as O and B blood types when using anti-A antibodies for identification. Therefore, the presence of A2 and A2B subtypes should be noted during blood typing. (2) Loss or decrease of antigens: The serum antibody titer of the elderly is very low and the serum ABO antibodies in infants 4–6 months of age are usually negative or weak, which can lead to blood typing inconsistency [28]. (3) Cold autoantibodies: Cold autoantibodies could be induced in some individuals due to some reasons, which often seriously interfere with blood typing interpretation by sensitizing erythrocytes, resulting in blood typing inconsistency [29]. (4) Erythrocyte chimera: Individuals with double fertilization can form erythrocyte chimeras, affecting blood typing results.

5.3 Diseases

(1) Leukemia: can cause the decrease of the A or B antigenicities of the patient’s erythrocytes, affecting blood typing results [30]. (2) Acute massive blood loss: can cause decompensation of the hematopoietic system and induce nucleated erythrocytosis, thus affecting blood typing results. (3) Blood transfusion or pregnancy status: can increase the soluble blood group substances in the plasma. The presence of irregular antibodies interferes with ABO antibodies, thus affecting blood typing results [31]. (4) Diseases like multiple myeloma and others: Rouleaux agglutination or pseudoagglutination of the erythrocytes occurs due to plasma protein abnormalities, thus affecting blood typing results. (5) Liver disease or tuberculosis: abnormal plasma proteins can affect ABO antibodies, thus resulting in blood typing inconsistency. (6) Autoimmune diseases: the patient’s autoantibodies can interfere with ABO blood group antigens or antibodies, thus affecting blood typing results. (7) Bone marrow transplantation: in patients who receive compatible bone marrow transplantation with different ABO blood groups, the serum ABO antibodies are inconsistent with the erythrocyte antigen.

5.4 Clinical treatments

(1) Massive infusion or plasmapheresis: it can lead to dilution of ABO antibodies, which can easily cause misinterpretation of reverse typing. (2) Infusion of polymer drugs: Infusions of polymer drugs like mannitol and others could induce non-specific pseudoagglutination of erythrocytes due to the function of polymer proteins. (3) Recent transfusion of heterotypic erythrocytes/plasma: it affects the patient’s ABO antigens and antibodies, thus resulting in blood typing inconsistency. (4) Allogeneic hematopoietic stem cell transplantation: it could lead to chimerism of the ABO genes for a time, thus resulting in blood typing inconsistency.

6. Precautions for ABO blood typing inconsistency

6.1 Strengthen the sense of responsibility of medical staff

Strengthen the sense of responsibility of medical staff; medical staff should be focused, conscientious, and responsible during the blood typing process and carefully check the information. Nurses must be required to strictly implement check systems and medical technical operating procedures.

6.2 Selection of appropriate blood typing methods

Select appropriate blood typing methods based on factors like age, accompanied diseases, and treatments. Some diseases can lead to the weakening of erythrocyte antigens or formation of high-potency cold autoantibodies. In such cases, reverse typing should be conducted after washing and warming of the erythrocytes. For leukemia patients, it is necessary to use standard erythrocytes and antibodies for blood typing, especially when the forward and reverse blood typing results do not match. When the forward blood typing shows the O or B blood group, absorption-elution testing should be conducted on the patient’s blood sample, and genotyping should be carried out if necessary [32].

6.3 Strengthen quality control

Regularly review the reagent, ensure sufficient reaction time, select appropriate centrifugal rotational speed and time, chose proper proportion of antigen and antibody, guarantee the normal operation of the instrument, control possible pollution sources, etc. The agglutination should be observed carefully, and microscope should be adopted if necessary.

6.4 Optimize the blood typing process

By optimizing the process, the sample information can be checked more accurately, and the input results can be correct and reliable. By optimizing the process and reducing ineffective labor, the testing personnel can focus on their work, thus conducting blood typing scientifically, accurately, and efficiently. Contentious samples should be sent to relevant professional institutions for further testing.

7. ABO typing and diseases

The correlation between ABO blood types and COVID-19 has been reported. For instance, Solmaz et al. [33] performed PCR analysis and found that the proportion of type A and AB was significantly higher, while that of type O was significantly lower in patients with COVID-19 than in the healthy population. The proportion of subjects with type B was not significantly different between patients with COVID-19 and the healthy population. Their findings suggested that blood type O may have a protective effect and blood type A may be related to a greater susceptibility to COVID-19. However, the blood type did not affect the course of the disease and was not associated with mortality. In addition, Zhao et al. [34] showed that women with blood type A were more susceptible to COVID-19, whereas blood type B, O, or AB were not associated with the incidence of COVID-19. However, they did not report the method for ABO blood typing. The reports on the relationship between ABO blood types and COVID-19 are currently limited to correlation analysis. No reports on mechanism or genetic analysis are available. In addition, most studies had a large sample size and used simple high-throughput blood typing methods. Sequencing methods are needed for future investigations.

The correlations between ABO blood types and malignancies, as well as the potential mechanisms have been reported. Liu et al. [35] investigated the population in Xinjiang, China, using the agglutination assay and found that people with blood type A had a higher risk of lung, gastric, and breast cancers. The glycosyltransferases encoded by the ABO genes are involved in intercellular adhesion, cell membrane signaling, and host immune response. Franchini et al. [36] suggested that glycosyltransferases encoded by the ABO genes may affect cell proliferation and promote tumor cell infiltration and metastasis. ABO antigens can regulate host inflammatory responses, leading to the progression and spread of malignant tumors. These antigens can also alter intercellular and cell-extracellular matrix interactions and thus promote tumor development [37, 38]. At present, the relationships between ABO blood types and diseases remain exploration. Cai et al. [39] used the sequencing technique to identify a case of a double-base deletion heterozygous Mumbai-like ABmh in the FUT1 gene encoder, which may provide a basis for future blood transfusion in this patient to avoid transfusion reactions. In addition, Jiang et al. [40] found that pregnant women with RhD-negative blood type had a risk of fetal or neonatal hemolytic disease, which might lead to intrauterine fetal death or neonatal death in severe cases, while the use of anti-D immunoglobulin during pregnancy reduced the risk of occurrence. With the emergence of genetic research tools in recent years, screening for fetal RHD genotype and selective use of anti-D immunoglobulin in pregnant women with RhD-negative blood groups are important for the perinatal management of pregnant women with RhD-negative blood groups. Most studies on Rh blood typing use advanced biological methods, which are difficult to popularize in daily work. More high-quality and cost-efficient testing methods are needed to explore the relationship between Rh and diseases.

8. Conclusion

Accurate ABO blood typing is a critical requirement for the safety and effectiveness of blood transfusion in clinical practice. At present, there are many laboratory testing methods for ABO blood typing, including blood coagulation tests that are simple and easy to operate, as well as microcolumn gel experiments and genotype detection, which provide more reliable results. There are many factors affecting the results of ABO blood typing. It is necessary not only to strengthen the quality assurance of the daily ABO blood typing, but also to review and summarize them regularly. Thus, it would be possible to identify problems and establish feasible, efficient, and simple solutions, to ensure absolute correctness of ABO blood typing results. Since this year, with the rise in bedside testing, the current mainstream detection methods cannot easily ensure the speediness and accuracy of complicated ABO blood typing during emergencies and harsh conditions. Optimizing genotype detection and other methods for difficult individual ABO blood typing under emergency situations, and developing convenient methods such as test strips and colloidal gold may be a trend in clinical blood typing research. In addition, molecular testing methods for Rh blood groups are still difficult to carry out in the daily work of hospitals, and the relationship between Rh blood groups and diseases is still limited to reports of pregnant women, fetuses and family trees, and no studies related to more common diseases have been found. In addition, research on the mechanisms underlying the association of ABO blood groups with many diseases still needs to be further explored.

Footnotes

Conflict of interest

None to report.

References

Dhabangi

Musisi

Kyeyune

. Improving blood transfusion safety in resource-poor countries: A case study of using leucocyte reduced blood in Uganda. Afr Health Sci. 2020 Jun; 20(2): 977-983. doi: 10.4314/ahs.v20i2.54.

Guo

. Blood group testing. Front Med (Lausanne). 2022 Feb 11; 9: 827619.

Stenfelt

Hellberg

Möller

Thornton

Larson

Olsson

. Missense mutations in the C-terminal portion of the B4GALNT2-encoded glycosyltransferase underlying the Sd(a-) phenotype. Biochem Biophys Rep. 2019 Jul 17; 19: 100659. doi: 10.1016/j.bbrep.2019.100659.

Soares

SDS

Aquino

Petrolli

de Oliveira

Almeida

Fiegenbaum

. Frequencies of genetic variants of the Rh, Kell, Duffy, Kidd, MNS and Diego systems of northwest Rio Grande do Sul, Brazil. Hematol Transfus Cell Ther. 2022 Jun 5; S2531-1379(22): 00085-2. doi: 10.1016/j.htct.2022.05.004.

Feng

Jicheng

Rongzi

. Accurate detection of reemergent anti-donor ABO antibody is crucial for safe transfusion in ABO major incompatible HSCT patient after achieved the stages of full switch to donor type. Transfus Clin Biol. 2022 Feb; 29(1): 94-97. doi: 10.1016/j.tracli.2021.10.005.

Ministry of Health of the People’s Republic of China. Technical specification for clinical blood transfusion. [2000] Wei Yi Fa Zi No. 184.

Elliott

Carrascosa

Souchet

Smith

Malaxetxebarria

You

Bendahan

Barnes

Lisle

Whitehouse

. Multicentre evaluation of Erytra Eflexis®, a benchtop fully automated analyser with a compact design for routine use in blood transfusion laboratory. Transfus Med. 2019 Dec; 29(6): 401-407. doi: 10.1111/tme.12619. Epub 2019 Jul 18. PMID: 31321832.

AIRD

LEE

ROBERTS

. ABO blood groups and cancer of oesophagus, cancer of pancreas, and pituitary adenoma. Br Med J. 1960 Apr 16; 1(5180): 1163-6. doi: 10.1136/bmj.1.5180.1163.

Solmaz

Araç

. ABO blood groups in COVID-19 patients; Cross-sectional study. Int J Clin Pract. 2021 Apr; 75(4): e13927. doi: 10.1111/ijcp.13927.

10.

Franchini

Lippi

. The intriguing relationship between the ABO blood group, cardiovascular disease, and cancer. BMC Med. 2015 Jan 16; 13: 7. doi: 10.1186/s12916-014-0250-y.

11.

Franchini

Bonfanti

. Evolutionary aspects of ABO blood group in humans. Clin Chim Acta. 2015, 15; 444: 66-71. doi: 10.1016/j.cca.2015.02.016.

12.

Mallick

Kotasthane

Chowdhury

Sarkar

. Bombay blood group: Is prevalence decreasing with urbanization and the decreasing rate of consanguineous marriage. Asian J Transfus Sci. 2015 Jul-Dec; 9(2): 129-32. doi: 10.4103/0973-6247.162695.

13.

Bhende

Deshpande

Bhatia

Sanger

Race

Morgan

Watkins

. A “new” blood group character related to the ABO system. Lancet. 1952 May 3; 1(6714): 903-4.

14.

Bhagavathi

Das

Prakash

Sahu

Routray

Mukherjee

. Blood group discrepancy in Ah para-Bombay phenotype: A rare blood group variant and its clinical significance. Immunohematology. 2021; 37(4): 160-164. doi: 10.21307/immunohematology-2021-026.

15.

Storry

Olsson

. The ABO blood group system revisited: A review and update. Immunohematology. 2009; 25(2): 48-59.

16.

Nair

Gogri

Kulkarni

Gupta

. Detection of a rare subgroup of A phenotype while resolving ABO discrepancy. Asian J Transfus Sci. 2019 Jul-Dec; 13(2): 129-131. doi: 10.4103/ajts.AJTS_118_17.

17.

, et al. Significance of RhD blood group detection in prenatal diagnosis of HDN. Prac Prev Med. 2009; 16(2): 458-459. doi: 10.3969/j.issn.1006-3110.2009.02.066.

18.

Colin

Chérif-Zahar

Le Van Kim

, et al. Genetic basis of the RhD-positive and RhD-negative blood group polymorphism as determined by Southern analysis. Blood. 1991; 78(10): 2747-2752.

19.

Shao

Maas

, et al. Molecular background of Rh D-positive, D-negative, D(el) and weak D phenotypes in Chinese. Vox Sang. 2002; 83(2): 156-161. doi: 10.1046/j.1423-0410.2002.00192.x.

20.

Takahashi

Migita

Sasaki

, et al. Amplicon sequencing-based noninvasive fetal genotyping for RHD-positive D antigennegative alleles. Clin Chem. 2019; 65(10): 1307-1316. doi: 10.1373/clinchem.2019.307074.

21.

Urbaniak

Greiss

. RhD haemolytic disease of the fetus and the newborn. Blood Rev. 2000; 14(1): 44-61.

22.

Lim

Park

Cho

. Investigation of discrepant ABO blood grouping results from an autoanalyzer. Ann Lab Med. 2022 Nov 1; 42(6): 650-658. doi: 10.3343/alm.2022.42.6.650.

23.

Bugert

Rink

Kemp

Klüter

. Blood group ABO genotyping in paternity testing. Transfus Med Hemother. 2012 Jun; 39(3): 182-186. doi: 10.1159/000339235.

24.

Quirino

Colli

Macedo

Sell

Visentainer

JEL

. Methods for blood group antigens detection: Cost-effectiveness analysis of phenotyping and genotyping. Hematol Transfus Cell Ther. 2019 Jan-Mar; 41(1): 44-49. doi: 10.1016/j.htct.2018.06.006.

25.

Fürst

Tsamadou

Neuchel

Schrezenmeier

Mytilineos

Weinstock

. Next-generation sequencing technologies in blood group typing. Transfus Med Hemother. 2020 Feb; 47(1): 4-13. doi: 10.1159/000504765.

26.

Wagner

Moulds

Flegel

. Genetic mechanisms of Rhesus box variation. Transfusion. 2005; 45(3): 338-344.

27.

Grootkerk-Tax

Maaskant-van Wijk

van Drunen

, et al. The highly variable RH locus in nonwhite persons hampers RHD zygosity determination but yields more insight into RH-related evolutionary events. Transfusion. 2005; 45(3): 327-337.

28.

Sun

Han

Ren

. Blood group gene analysis of 20 ABO blood group antigen abnormal expression samples. Journal of Southern Medical University. 2021; 09: 1431-1435.

29.

Xiao

Tashi

. Distribution of ABO blood groups among patients in Nagqu area of Tibet. Chin J Blood Transfusion. 2021; 03: 266-270.

30.

Nambiar

Narayanan

Prakash

Vijayalakshmi

. Blood group change in acute myeloid leukemia. Proc (Bayl Univ Med Cent). 2017 Jan; 30(1): 74-75. doi: 10.1080/08998280.2017.11929536.

31.

Jiang

Zhou

Guo

Liu

. Intrauterine blood transfusion for the treatment of maternal and fetal Rh incompatibility fetal anemia: Report of 2 cases. J Reproductive Medicine. 202; 08: 1137-1140.

32.

Zhu

Zhong

. Investigation and analysis of 75 cases of ABO blood group inconsistent with positive and negative stereotyping. Chin J Blood Transfusion. 222; 07: 751-754.

33.

Solmaz

Araç

. ABO blood groups in COVID-19 patients; Cross-sectional study. Int J Clin Pract. 2021 Apr; 75(4): e13927. doi: 10.1111/ijcp.13927.

34.

Zhao

Yang

Huang

Zhang

Liu

Sun

Wei

Yang

Wang

Zhang

Zhou

Xing

Wang

. Relationship between the ABO blood group and the coronavirus disease 2019 (COVID-19) susceptibility. Clin Infect Dis. 2021 Jul 15; 73(2): 328-331. doi: 10.1093/cid/ciaa1150.

35.

Liu

Song

Xie

. Analysis of the correlation between ABO blood group and the incidence of common malignant tumors in Xinjiang. Journal of Modern Medicine and Health Research (Electronic Edition). 202; 19: 37-41.

36.

Franchini

Liumbruno

Lippi

. The prognostic value of ABO blood group in cancer patients. Blood Transfus. 2016 Sep; 14(5): 434-40. doi: 10.2450/2015.0164-15.

37.

Singh

Mishra

Aggarwal

. Inflammation, immunity, and cancer. Mediators Inflamm. 2017; 2017: 6027305. doi: 10.1155/2017/6027305.

38.

Greten

Grivennikov

. Inflammation and cancer: Triggers, mechanisms, and consequences. Immunity. 2019 Jul 16; 51(1): 27-41. doi: 10.1016/j.immuni.2019.06.025.

39.

Cai

Zhang

Zhou

Xie

. Sequence analysis of FUT1 gene in a case of AB Bombay blood group. Chinese Journal of Medical Genetics. 2021; 08: 809-811.

40.

Jiang

Duan

. Research progress of fetal RhD genotype detection in Asian pregnant women with RHD negative blood type. Chinese Journal of Perinatal Medicine. 201; 10: 793-797.