**3.1 Distribution of ABO and other clinically significant blood groups**

The human red blood cell membrane is complex and contains a number of clinically relevant blood group antigens, the most relevant being the ABO and the Rhesus blood group antigens. Apart from the ABO and Rhesus blood group systems, thirty-four other blood group systems have been identified as at November 2014 [7]. In addition to the ABO and Rhesus blood group antigens, 364 other red cell antigens have been identified serologically. The clinical relevance of a blood group system depends on the distribution of antigens of the blood group system in the population, ability of antibodies of the blood group system to cause haemolytic transfusion reaction (HTR) and haemolytic disease of the foetus and newborn (HDFN) [8]. The ABO blood group system is one of the most clinically relevant blood group systems [9]. It was first discovered by Karl Landsteiner in 1901 [10]. The ABO blood group system has three main antigens (A, B and H). Four major ABO groups exist (A, B, AB and O). The ABO blood group system is based on the A and B antigens occurring singly as A or B, doubling as AB or the absence of both as O. Individuals who have lack the A or B antigens on their red cells have the group specific antibody in their serum or plasma. Antibodies of the system are predominantly IgM originally thought to be naturally occurring but are now known to occur in the first years of life as a result of sensitization to ABO-like antigen and environmental substances that occur in nature such as bacteria, viruses and food. Evidence has shown that these antibodies are not present at birth and that animals kept in a sterile room from birth do not produce these antibodies. The ABO blood group system is important in transfusion medicine, HDFN and in organ transplant. Transfusion of ABO incompatible unit can cause severe HTR. Similarly, an immune response can also occur

following ABO incompatible organ transplant. ABO blood group incompatibilities between the mother and child does not normally cause HDFN because antibodies of the ABO blood group system are usually of the large molecular weight IgM type, which do not cross the placenta. However, mothers who were previously sensitised (previous incompatible transfusion and pregnancy) can potentially have IgG ABO antibodies that can potentially cause ABO HDFN. The distribution of ABO blood groups varies across the world according to the population. There are also variations in blood type distribution within human subpopulations.

Nigeria is a significantly varied nation in terms of ethnicity. The gene frequency of ABO and Rh blood group varies significantly within the six geopolitical zones in Nigeria [11–18]. Previous studies in most parts of Nigeria indicates that the ABO blood group distribution is in the order O > A > B > AB [19]. Studies from the United States, Mauritania, Morocco, Cameroun, Tunisia, Ethiopia and Iran reported same order (O > A > B > AB) [20–26]. However, study in Madagascar and Guinea reported a contrary trend (O > B > A > AB) [27, 28]. This observation in Nigeria is also at variance with reports from India and Bangladesh where prevalence of B is highest followed by O and the least was AB (B > O > A > AB) [29, 30]. Reports from Turkey and Colombia indicates an order A > O > B > AB [31, 32].

A multi race/ethnic study in the United States reported that blood type O is the most prevalent (46.6%) with White non-Hispanic, Hispanic, Black non-Hispanic, Asian and North American Indian having varying percentage of 45.5, 56.5, 50.2, 39.8 and 54.6 respectively [21]. Other studies in Turkey, Mauritania, Iran, Ethiopia, Colombia, Cameroun, Bangladesh, Madagascar, Morocco, Guinea and Northern India have reported varying percentage in ABO and Rh blood types [20–23, 25–32].

Phenotypic distribution of Rh(D) in Nigeria varies from one part of the country to the other; Kwara (4.5%) [17], Jos Plateau State (4.32) [14], FCT (4.3) [33], Minna (3.3%0) [11], Lagos (3.0, 6, 6.86%) [16, 34, 35], Ogun (6.65 and 2.9%) [36, 37], Osun (6.3%) [38], Oyo (3.3, 6.68, 4.8, 5.89%) [12, 14, 18, 39], Ekiti (4.3%) [40], Akwa Ibom (5.7%) [41], Bayelsa (2%) [42], Delta (1.8%) [43], Benin (6.0%) [13], Rivers (3.2, 7, 8.3%) [44–46], Kano (5.2%) [47], Sokoto (1.55%) [14], Zamfara (1.2%) [48], Enugu (4.49%) [14], Abia (5.3%) [49], Ebonyi (4.2%) [50], Borno (1.92%) [14], Adamawa (4.6%) [51], Yobe (4.6%) [52]. The prevalence of Rhesus negativity varies from one zone to the other; 4.4, 3.1, 6.0, 4.3, 3.9 and 3.1% respectively for the South East, North East, South, South, South West, North Central and North West zone respectively.

The overall average prevalence of Rhesus negativity is 5.1%. The distribution of Rh(D) in Nigeria is in agreement with others parts of the world [20, 23, 25–28, 30, 31]. Blacks have been found to have a lower frequency of Rhesus D negative phenotype (3–5%) [34, 42, 44] compared to the general Caucasian population (15%) [21, 53]. The lower prevalence of Rh(D)− in Nigeria and other developing is important and a blessing in disguise because clinical situations like fetomaternal haemorrhage during the course of pregnancy can give arise through Rh incompatibility and HDFN. In Nigeria and many of these developing countries RAADP and other anti-D HDFN related prevention strategies are not being implemented. **Table 1** shows the prevalence of Rhesus D group among Nigerians based on zones.

The Kell blood group is the third most clinically relevant blood group system after ABO and Rhesus. Individuals without Kell antigens (K0) who are transfused with Kell positive donor red cells or Kell negative pregnant women exposed to the Kell positive red cells of their baby carry the risk of developing Kell antibody which can cause HDFN [54]. In the developed world all pregnant women and non-pregnant women of child bearing age are transfused with Kell negative blood. Also, patients with other antibodies are transfused with Kell negative and red cells also lacking the antigen to which their alloantibody is specific. This is to prevent them from potentially developing anti-Kell antibody. Kell sensitization is the third

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management of HDFN.

*Distribution of Clinically Relevant Blood Group Antigens among Nigerians…*

South-East 4.4 95.6 South-South 6.0 94 South-West 4.3 95.7 North-East 3.1 96.9 North-West 3.1 96.9 North-Central 3.9 96.1

most common cause of HDFN after Rh and ABO. Anti-Kell has been shown to cause severe foetal anaemia by suppressing foetal RBC synthesis [55]. HDFN-associated anaemia in Anti-Kell-related HDFN is caused by the ability of anti-K to cause the suppression of foetal production of RBCs [56]. Unlike Rh and ABO, Kell antigens are expressed on the surface of RBC precursors, and anti-K promotes the immune destruction of Kell positive erythroid early progenitor cells by macrophages in the foetal liver rather than only mature foetal RBCs [55]. There are few Kell prevalence studies in Nigeria. Among their cohort of pregnant women in Sokoto, North

**Percentage of Rhesus negative status Percentage of Rhesus negative status**

Western Nigeria, Erhabor and Colleagues [57] obtained a Kell antigen prevalence of 2%. Similarly, Ugboma and Nwauche [58] in Port Harcourt investigated the prevalence of Kell antigen among their patients and reported a Kell antigen prevalence of 2%. The prevalence of Kell antigen among a multi-ethnic cohort of 302 healthy Nigerian individuals indicated a zero prevalence of K antigen [59]. Racial differences seem to exist in Kell blood group antigen distributions [60, 61]. The Nigerian government and governments in other African countries will need to implement this strategy in a bid to reducing Kell-related sensitization and the effect of HDFN. The prevalence of other clinically significant red cell antigens has been determined among Nigerians. The prevalence of Lewis, Kidd, Duffy, Kell and M blood group antigens among blood donors in Aminu Kano Teaching Hospital, Kano, Nigeria [62] were as follows: Lea: 26.4%, Leb: 15.1%, M: 20.8%, k (cellano): 21.7%. The Duffy (anti Fya, anti Fyb) and Kidd (anti Jka anti Jkb) antigens were not detected among the donors. Out of the 162 pregnant women tested for their Duffy antigens status indicated Fya, Fyb and Fya (a+b+) prevalence of 7 (4.3%), 9 (5.6%) and 1 (0.61%) respectively [63]. Kidd blood group phenotypes were determined among pregnant women in Sokoto, North Western Nigeria [63]. The distribution of Kidd antigens among subjects studied indicated a prevalence of Jka, Jkb and Jk(a+b+) of 8 (4.9%), 13 (8.0%) and 0 (0.0%), respectively. There is need for the phenotyping of donor's blood for clinically significant red cell antigens. There is also the need to routinely screen all pregnant women for alloantibodies to facilitate the selection of antigen negative units for those with clinically significant alloantibodies who require a red cell transfusion. This can potentially optimise the obstetric

The prevalence of Rh c and e phenotype among 200 pregnant women attending antenatal clinic (ANC) in Usmanu Danfodiyo University Teaching Hospital Sokoto was determined. The prevalence of Rh c was 92% while Rh e was 98.5% [64]. The frequencies of Rh blood group antigens and phenotypes of the Ibibio, Efik, and Ibo ethnic nationalities in Calabar municipality, Nigeria, were determined using standard serologic techniques. Of the 720 Calabar individuals tested, the frequencies of the Rh antigens within the nationalities were c (100%), e (96.38%),

*DOI: http://dx.doi.org/10.5772/intechopen.90372*

*Prevalence of Rhesus D group among Nigerians based on zones.*

**Zone of Nigeria**

**Table 1.**


*Distribution of Clinically Relevant Blood Group Antigens among Nigerians… DOI: http://dx.doi.org/10.5772/intechopen.90372*

**Table 1.**

*Prevalence of Rhesus D group among Nigerians based on zones.*

most common cause of HDFN after Rh and ABO. Anti-Kell has been shown to cause severe foetal anaemia by suppressing foetal RBC synthesis [55]. HDFN-associated anaemia in Anti-Kell-related HDFN is caused by the ability of anti-K to cause the suppression of foetal production of RBCs [56]. Unlike Rh and ABO, Kell antigens are expressed on the surface of RBC precursors, and anti-K promotes the immune destruction of Kell positive erythroid early progenitor cells by macrophages in the foetal liver rather than only mature foetal RBCs [55]. There are few Kell prevalence studies in Nigeria. Among their cohort of pregnant women in Sokoto, North Western Nigeria, Erhabor and Colleagues [57] obtained a Kell antigen prevalence of 2%. Similarly, Ugboma and Nwauche [58] in Port Harcourt investigated the prevalence of Kell antigen among their patients and reported a Kell antigen prevalence of 2%. The prevalence of Kell antigen among a multi-ethnic cohort of 302 healthy Nigerian individuals indicated a zero prevalence of K antigen [59]. Racial differences seem to exist in Kell blood group antigen distributions [60, 61]. The Nigerian government and governments in other African countries will need to implement this strategy in a bid to reducing Kell-related sensitization and the effect of HDFN.

The prevalence of other clinically significant red cell antigens has been determined among Nigerians. The prevalence of Lewis, Kidd, Duffy, Kell and M blood group antigens among blood donors in Aminu Kano Teaching Hospital, Kano, Nigeria [62] were as follows: Lea: 26.4%, Leb: 15.1%, M: 20.8%, k (cellano): 21.7%. The Duffy (anti Fya, anti Fyb) and Kidd (anti Jka anti Jkb) antigens were not detected among the donors. Out of the 162 pregnant women tested for their Duffy antigens status indicated Fya, Fyb and Fya (a+b+) prevalence of 7 (4.3%), 9 (5.6%) and 1 (0.61%) respectively [63]. Kidd blood group phenotypes were determined among pregnant women in Sokoto, North Western Nigeria [63]. The distribution of Kidd antigens among subjects studied indicated a prevalence of Jka, Jkb and Jk(a+b+) of 8 (4.9%), 13 (8.0%) and 0 (0.0%), respectively. There is need for the phenotyping of donor's blood for clinically significant red cell antigens. There is also the need to routinely screen all pregnant women for alloantibodies to facilitate the selection of antigen negative units for those with clinically significant alloantibodies who require a red cell transfusion. This can potentially optimise the obstetric management of HDFN.

The prevalence of Rh c and e phenotype among 200 pregnant women attending antenatal clinic (ANC) in Usmanu Danfodiyo University Teaching Hospital Sokoto was determined. The prevalence of Rh c was 92% while Rh e was 98.5% [64]. The frequencies of Rh blood group antigens and phenotypes of the Ibibio, Efik, and Ibo ethnic nationalities in Calabar municipality, Nigeria, were determined using standard serologic techniques. Of the 720 Calabar individuals tested, the frequencies of the Rh antigens within the nationalities were c (100%), e (96.38%),

D (96.38%), E (15.22%), and C (3.62%) for the Ibibios; c (100%), e (95.60%), D (96.70%), E (21.98%), and C (0%) for the Efiks; and c (100%), e (94.29%), D (91.43%), E (28.57%), and C (2.86%) for the Ibos. The overall frequencies of the Rh antigens in these 720 individuals were c (100%), e (95.56%), D (94.44%), E (18.89%), and C (2.78%). Forty (5.56%) were found to be D−, while all were found to possess the c antigen. The most frequently occurring Rh phenotype was Dccee, with a frequency of 73.61%. The alternative allele, C, did not appear in homozygous form (CC) in the population tested [65]. Of the 374 pregnant women studied in Port Harcourt, Nigeria, the frequencies of the Rh antigens within the population were D (89.0%), c (82.0%), e (54.0%), C (24.3%), E (20.1%). The frequencies of the Rh antithetical antigens were DD/Dd (91.2%), Cc (19.5%), cc (84.5%), Ee (13.9%), ee (54.3%), CC (25.1%), EE (19.8%) and dd (10.4%). Seven (1.9%) were found to be Rhnull, sixteen (4.3%) were found to be D− or exalted D. Phenotypes without RhD reactivity were -c- (2.9%), -Cc (0.3%), -C- (0.3%), -Ee (0.5%) and -E- (0.3%) [66]. A multi-ethnic cohort of healthy Nigerian individuals were studied. The antigen status of these individuals for Rh was determined. The prevalence of the Rh antigens in the study cohort was found to be: D (92.7%), C (20.5%), c (97.7%), E (19.5%), and e (97.4%). Dce was the most common Rh phenotype (53.3%) [59]. Few countries in sub-Saharan Africa have systematic testing for antigens C, c, E, and e of the Rh and Kell system antigens in the donor and recipient, thereby exposing transfused patients to the risk of developing antibodies that can cause HTR and HDFN. Among 651 blood donors tested in Abidjan for antigens of the Rh blood group system, the antigen frequencies of D, c, e, C, and E were; 92.93, 99.85, 99.85, 21.97, and 13.82% respectively. K antigen is was found in 0.77% of donors [67].
