Distribution of Kell phenotype among pregnant women in Sokoto, North Western Nigeria

Distribution of Kell phenotype among pregnant women in Sokoto, North Western Nigeria

 

Erhabor Osaro^1,&, Malami Aisha Ladan¹, Isaac Zama¹, Yakubu Ahmed², Hassan Mairo²

 

¹Department of Haematology and Transfusion Science, Faculty of Medical Laboratory Science, Usmanu Danfodiyo University, Sokoto, Nigeria, ²Department of Obstetrics and Gynaecology Usmanu Danfodiyo University, Sokoto, Nigeria

 

 

^&Corresponding author
Erhabor Osaro, Department of Haematology and Transfusion Science, Faculty of Medical Laboratory Science, Usmanu Danfodiyo University, Sokoto, Nigeria

 

 

 

 

The Kell blood group system is complex and has many antigens which are highly immunogenic. These antigens particularly KEL 1 are second to Rhesus D as a cause of Haemolytic Disease of the Foetus and New-born (HDFN) [1]. Antibodies that target Kell antigens can cause HDFN, as well as Haemolytic Transfusion Reactions (HTR) [2]. Anti-Kell related HDFN causes severe foetal anaemia as maternal anti-Kell target foetal RBC precursors, suppressing the foetal production of RBCs [3, 4]. The Kell blood group system was discovered in 1946 and was named after Mrs. Kelleher, a patient who had anti-Kell antibodies and whose baby had HDFN. The Kell blood group system is important in transfusion medicine and HDFN and is considered to be one of the major human blood group antigens. Antibodies produced against Kell antigens are predominantly IgG and can cross the placental barrier, does not bind complement and therefore causes is extravascular haemolysis. KEL is highly polymorphic, has two major codominant alleles, k and K, which result from a SNP (698C→T) and the corresponding k and K antigens differ by a single amino acid change [4-6]. Individuals without Kell antigens (K₀) who have formed an antibody to a K antigen must be transfused with blood from donors who are also K₀ to prevent severe haemolytic transfusion reaction [2, 7]. Kell isoimmunisation is the third most common cause of HDFN after Rh and ABO. Anti-Kell causes severe foetal anaemia by suppressing foetal RBC synthesis [8]. Anti-Kell is an important cause of HDFN and tends to occur in mothers who have had several Kell incompatible blood transfusions in the past and in mothers who have been sensitized to the Kell antigen during previous pregnancies. HDFN -associated anaemia is caused by the ability of anti-K to cause the suppression of foetal production of RBCs [9]. Unlike Rh and ABO, Kell antigens are expressed on the surface of RBC precursors, and anti-K promotes the immune destruction of K+ erythroid early progenitor cells by macrophages in the foetal liver rather than only mature foetal RBCs [10]. The RBC precursors do not contain haemoglobin and thus less bilirubin is released during the haemolysis, and jaundice in the new-born period is less common in Kell-related HDFN [11]. There is paucity of data on the prevalence of Kell phenotype among pregnant women in Sokoto, Nigeria. The risk of anti- Kell- related HDFN in Sokoto is unknown. Therefore the present study is aimed at determining the prevalence and ethnic variations of the Kell phenotype among pregnant women in Sokoto, Nigeria. Data generated will help improve the obstetrics care offered to pregnant women in the area and may help justify the need to routinely screen pregnant women in the area for clinically significant red cell antigens. Findings from this study will also help blood bank in the area to stock optimum levels of Kell negative units for use among pregnant women and women who are of child- bearing age and are Kell antigen negative as well as those who are positive for anti-Kell antibodies that require antigen negative red cell for transfusion.

 

 

Study area

 

Study site: the selected area for this study is Usmanu Danfodiyo University Teaching Hospital (UDUTH) which is located in Wamakko Local Government within Sokoto Metropolitan city in Sokoto State. Sokoto State is located in the extreme Northwest of Nigeria, near the confluence of the Sokoto River and Rima River. With an annual average temperature of 28.30c (82.9 0F). Sokoto is, on the whole, a very hot area. However, maximum day time temperatures are for most of the year generally under 40 0C (104.0 0F). The warmest months are February to April when daytime temperatures can exceed 45 0C (113.0 0F). The rainy season is from May to October during which showers are a daily occurrence. There are two major seasons, wet and dry which are distinct and are characterized by high and low malarial transmission respectively. Report from the 2007 National Population Commission indicated that the State had a population of 3.6 million [12].

 

Study subjects and design: this case study included 150 consecutively- recruited pregnant women vising the antenatal clinic in Usmanu Danfodiyo Hospital Sokoto. Subjects were aged 18-45 years with mean age of 27.19 ±4.69 years. Blood samples were analysed for their Kell antigen status. Verbal informed consent was obtained from all study subjects. The study was approved by the ethical committee of Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria.

 

Inclusion criteria: all consecutively-recruited, consenting and confirmed pregnant (by a consultant obstetrician) women aged 15-45 years visiting the antenatal clinic of Usmanu Danfodiyo University Teaching Hospital (UDUTH) Sokoto were included in this study.

 

Exclusion criteria: the following were excluded from this study; non-pregnant women, non-consenting pregnant women, women who have had a red cell transfusion in the last 4 months and women who have had a recent stem cell or bone marrow transplant.

 

Study site and participating hospital: study will be conducted in the service laboratory of Usmanu Danfodiyo University Teaching Hospital (UDUTH) Sokoto, Nigeria. The hospital is a tertiary health facility rendering quality healthcare services to the people of Sokoto State and the neighbouring states of Zamfara and Kebbi State.

 

Sample collection and testing: three millilitres of blood sample was drawn aseptically with disposable plastic syringe from the median antecubital vein for all the subjects into dipotassium ethylenediamine tetracetic acid (K₂EDTA) blood containers. 2-3% suspension of washed red cells from each study subjects was prepared in low ionic strength solution. Lorne Laboratories (UK) anti-Kell reagents were reacted with red cell suspension from each subject. The Lorne anti-Kell reagent will cause direct agglutination (clumping) of cells that carry K antigen. No agglutination generally indicates absence of K antigen.

 

 

In this study, the Kell phenotype of 150 pregnant women aged 18-45 years and mean age 27.19 ±4.69 years attending antenatal clinic in UDUTH Sokoto Nigeria was determined. Among the 150 subjects 3(2.0%) of subjects were positive for K and 147(98.0) were negative for K antigen. Table 1 shows the prevalence of Kell antigen among subjects.

 

Distribution of Kell antigen based on parity

 

Of the 150 subjects 32 were primigravidae (%) while 118 were multigravidae. Of the 32 primigravidae, 1 woman (3.1%) was Kell positive while 31 (96.9) were Kell negative. Also 2 out of the 118 multigravidae women (1.7%) were Kell positive while 116 (98.3%) were Kell negative. Table 2 show the distribution of K negative phenotype based on parity.

 

Distribution of subjects based on ethnicity

 

The distribution of Kell phenotype among the pregnant subjects was compared based on ethnicity. The Hausa ethnic group constituted the most predominant ethnic groups 94(62.7%) compared to 20(13.3%), Igbo 20(13.3%), Fulani 13(8.7%), others minority ethnic groups 13 (8.7%) and Yoruba 10(6.7%). The prevalence of Kell phenotype was significantly higher among the Hausa ethnic group (3.2%) compared to other ethnic groups that indicated zero prevalence (p=0.001). Kell negative phenotype was ≥ 96.8% among all the ethnic groups. Table 3 shows the prevalence of Kell antigen among subjects based on ethnicity.

 

 

Information about the prevalence of blood group antigens in a population is useful for providing better blood transfusion services and in the effective and evidenced-based management of HDFN. This research work was carried out to determine the prevalence of Kell phenotype among pregnant women in Sokoto, North Western Nigeria. Among the pregnant women studied, we observed a Kell antigen prevalence of (2%). Our finding is consistent with previous report by Lamba and colleagues [13] who observed a Kell antigen prevalence of 2.8% among their cohort of 1,000 healthy and regular repeat blood donors in India. Our finding is also consistent with a previous report by Chaudhary and colleagues [14] among North Indian blood donors which reported a Kell prevalence of 1.92%. Similarly, Ugboma and Nwauche [15] in Port Harcourt investigated the prevalence of Kell antigen among their patients and reported a Kell antigen prevalence of 2%. Our observed prevalence of 2.0% is however lower than a prevalence of 5.56% observed by Thakral and colleagues [16] among North Indian blood donors. Our observed prevalence is also lower than that previously reported among Caucasians (9%) [17-19]. Our observed Kell prevalence is also lower than a 3.5% prevalence obtained by Makroo and colleagues [20] among their cohort of 3073 blood donors in India. Racial differences seem to exist in Kell blood group antigen distributions [13, 19]. A study of randomly selected 123 regular Maldivian blood group O blood donors who were phenotyped for Kell blood group antigen indicated a prevalence of 5.7% [21]. Similarly a previous report among 115 blood donors who were investigated in South Gujarat, India for extended antigen typing, reported no Kell phenotype [22]. Also, a previous study by Lin and colleagues [23] (1988) among Chinese subjects in Taiwan indicated a zero percent Kell prevalence. The prevalence of K phenotype among Senegalese is 0.5% [24]. A previous report on the prevalence of Kell blood group antigen in the Bengalee population observed a Kell phenotype prevalence of 0.8% [25]. Similarly, evaluation of Kell blood group antigen frequencies among Macedonian population by Makarovska-Bojadzieva and colleagues [26] indicated a Kell prevalence of 0.25%.

 

Kell blood group system is the next most clinically significant after the ABO and Rhesus blood group system [27]. Antibodies to the Kell antigen have been incriminated in HDFN and in haemolytic transfusion reactions [28-30]. Anti-K typically presents as IgG class alloantibody. Individuals lacking a specific Kell antigen may develop antibodies against Kell antigens when transfused with blood containing that antigen. This is particularly true for the K antigen which shows a relatively high antigenicity and moderately low frequency in African populations. The Kell antibodies low molecular weight IgG antibodies and can pass through the placenta barrier and cause HDFN in foetus positive for the Kell antigen [31]. The alloantibodies, which frequently develop and are encountered during compatibility testing, are primarily against antigens related to Kell blood group system [28]. Antibodies directed against Kell antigens are implicated in cases of HTRs and HDFN, and are, therefore, regarded as clinically significant particularly if these react in the indirect antiglobulin test at 37°C [28, 32, 33]. It is vital to routinely determine the frequencies of the various blood group antigens among blood donors population particularly with regards to meeting the red cell transfusion-related needs of patients who have developed multiple alloantibodies. This information is necessary to predict the availability of blood units that lack the corresponding antigen(s). A review of the prevalence of antibodies associated with HDFN in reproductive age women revealed a marked decrease in the incidence of anti-Rh D and an increasing incidence of anti-K antibody in the US and in other developed countries [34]. Anti-K was detected with a frequency of 1.0% in a previous study [29] that investigated 500 pregnant women for clinically significant red cell antibodies in Port Harcourt, Nigeria. Anti-K related HDFN can be severe and there is evidence that anti-K can recognize K antigens expressed in the early stage of erythroid development in the foetal liver and can cause anaemia by suppressing erythropoiesis [34, 35]. A previous study investigated the prevalence of red cell antibodies among pregnant women in Sweden and observed eight hundred and twenty-one alloantibodies in 629 immunized pregnant women with 753 foetuses. An overall antibody incidence of 0.57% was observed which included 373 clinically significant antibodies found in 261 mothers (0.24%). Multiple antibodies were present in 8.2% of all samples. Anti-K HDFN was reported in16 Kell-positive babies out of whom three required phototherapy and one required exchange transfusions [36].

 

Our finding underscores the importance of routine screening of pregnant women for clinically red cell antigens [37]. The phenotype of clinically significant red cell antigens on donor's red cells is important particularly if the blood is intended for transfusion to patients with alloantibodies to facilitate the transfusion of red cells that are negative for the antigens to which patient's antibodies are specific. Routine determination of clinically significant red cell antigens facilitates the planning and running of an efficient blood transfusion service and better management of HDFN. First-trimester screening of pregnant women enables timely identification and treatment of HDFN. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies [38]. The knowledge of clinically significant red cell antigens that are known to cause HDFN, HTR and shortened survival of red cell is important and can help in the prevention and appropriate management of HDFN as well as optimize transfusion among transfusion- dependent patients (sickle cell disease, thalassemia, haematological oncology, myelofibrosis myelodysplasia and aplastic anaemia) particularly those that have developed alloantibodies against clinically significant red cell antigens [39]. One strategy to decrease alloimmunization in transfusion dependent women of child bearing age is provision of phenotype matched RBCs for C, E, and K antigens [40]. Individuals lacking the Kell antigen may develop antibodies against Kell antigen when transfused with Kell positive red cells. These antibodies can potentially cause the destruction of Kell positive red cells in future transfusions. Similarly pregnant women who are Kell negative can be sensitized by feto maternal haemorrhage associated with pregnancy involving a Kell positive foetus [41].

 

Pregnant women with K antibodies will need to be effectively managed by a gynaecologist to reduce the risk of HDFN. Effective management will involve checking the paternal sample for their Kell antigen status. If the husband is Kell positive, there may be need to determine the foetal Kell genotype using maternal plasma at 20 weeks gestation [42]. If the foetal Kell genotype is positive, the anti-K titre will need to be monitored every 4 weeks until 28 weeks gestation and every 2 weeks thereafter. There is a high risk of HDFN if the anti-Kell titre is 32 or greater or if there has been a significant rise since last titration [43, 44]. At delivery it is important to monitor baby's blood group, direct antiglobulin test, haemoglobin and bilirubin [45]. Severely jaundiced baby may be managed with phototherapy or with exchange blood transfusion to prevent Kernicterus. The pathogenesis of HDFN caused by anti-K differs from anti-D. This is because anti-Kell associated HDFN is much harder to predict, as there is little association between anti-K titre and severity of the disease and anti-K associated HDFN is linked with lower concentrations of amniotic fluid bilirubin than in anti-D HDFN of corresponding severity. Also postnatal hyperbilirubinaemia may not present in babies with anaemia caused by anti-K. There is decreased reticulocytosis and erythroblastosis in the anti-K disease. Foetal anaemia in anti-K HDN is due to suppression of erythropoiesis. The Kell glycoprotein emerges on erythroid progenitors, by macrophages in the foetal liver, before they develop into haemoglobinized erythroblasts [46]. As RBC precursors contain no haemoglobin, the release of bilirubin is reduced during haemolysis, therefore jaundice is not as common, but severe anaemia may occur [3]. This is supported by in vitro studies which have shown that antibodies to Kell inhibit growth of KEL 1 progenitor cells. In order to prevent HDFN, it is necessary for the detection of the foetal KEL 1 gene [1]. In pregnant women with anti-KEL1 and who have a partner with KEL 1 and 2, prediction of KEL1 phenotype from tests on foetal DNA allows obstetricians to adjust management of the pregnancy based on whether the foetus is at risk of developing HDFN.

 

 

Our study indicates that blood group antigens can be distributed differently within different nationalities. Our observed prevalence of Kell phenotype is consistent with previous studies among Blacks and Asians but significantly lower than values observed in previous studies among Caucasians.

 

Recommendations

 

We recommend that all pregnant women should be screened for the presence clinically significant red cell antigens including Kell blood group antigens on their first antenatal visit. There is need to introduce routine screening of pregnant women in Sokoto Nigeria for clinically significant red cell antibodies to facilitate the management of HDFN as well as prevent HTR by enabling the selection of antigen negative red cells for women who have alloantibodies and require a red cell transfusion. Kell negative red cell should be routinely provided for all pregnant women with child bearing potential to reduce the risk of Kell-associated HDFN. There is also need for sustained health education of pregnant women in the area to encourage early booking for antenatal care and adherence to prescribed medication.

 

Limitations

 

This study had some limitations. Firstly the sample size for this study was relatively small compared to the huge population of the North West zone in particular and the Nigeria nation in general. The prevalence obtained in this study gives an estimate on the frequencies of the Kell phenotype among pregnant women in Sokoto, North West, Nigeria. Cost implications as well as access to reagents was a limiting factor that affected the number of subjects included in this study. There is need for a nationwide study to determine the prevalence of Kell blood group antigens among Nigerians. Secondly, we used the conventional manual tube method in the screening of our cohort of pregnant women for Kell phenotype. Some previous reports which utilized more sensitive automated testing instrument using commercial antisera and gel card methods. Evidenced -based best practices in most developed countries indicates that the gel and glass beads-based card method has several advantages over the conventional tube method ; paediatric friendly because they require small volume of patient specimen, unlike with tube methods, no washing of the antiglobulin is required, it is more standardized and does not require the use of subjective red cell suspension preparation required with tube testing, results are more objective (clear, eye and analyser readable) and does not require use of microscopes which is a requirement in tube testing, it is easy to automate unlike conventional tube method and thus very useful for high throughput laboratories. It also facilitates large batch testing with no risk of possible mix-up of patient sample common with tube testing and it is more sensitive and specific and has the capacity to detect very weak reactions unlike conventional tube method.

 

 

The authors declare no competing interests.

 

 

All authors read and approved the final version of the manuscript.

 

 

Table 1: prevalence of Kell antigen among subjects

Table 2: distribution of K negative phenotype based on parity

Table 3: distribution of Kell phenotype based on ethnic group of subjects

 

 

1. Li Y, Finning K, Daniels G, Hahn S, Zhong X, Holzgreve W. Non-invasive genotyping foetal Kell blood group (KEL1) using cell-free DNA in maternal plasma by MALDI-TOF mass spectrometry. Prenatal Diagnosis. 2008; 28(3): 203-208. PubMed | Google Scholar


2. Lin M, Wang CL, Chen FS, Ho LH. Fatal haemolytic transfusion reaction due to anti-Ku in a K null patient. Immunohematology. 2003; 19(1):19-21. PubMed | Google Scholar


3. Dean L. Blood Groups and Red Cell Antigens. Bethesda. National Center for Biotechnology Information (US); 2005. PubMed | Google Scholar


4. Dean L. The Kell blood group - Blood Groups and Red Cell Antigens. NCBI Bookshelf. National Center for Biotechnology Information - United States National Institutes of Health. Retrieved 2009-05-04. PubMed | Google Scholar


5. Mohandas N, Narla A. Blood group antigens in health and disease. Current Opinion in Haematology. 2005; 12(12):135-140. PubMed | Google Scholar


6. Wagner T, Resch B, Reiterer F, Gassner C, Lanzer G. Pancytopenia due to suppressed hematopoiesis in a case of fatal hemolytic disease of the newborn associated with anti-K supported by molecular K1 typing. Journal of Pediatric Hematology Oncology. 2004; 26(1):13-15. PubMed | Google Scholar


7. Reid ME, Lomas-Francis C. The Blood Group Antigen Facts Book. Second ed. 2004, New York: Elsevier Academic Press. Google Scholar


8. Vaughan JI, Manning M, Warwick RM, Letsky EA, Murray NA, Roberts IA. Inhibition of erythroid progenitor cells by anti-Kell antibodies in foetal alloimmune anaemia. New England Journal of Medicine. 1998; 338(12):798-803. PubMed | Google Scholar


9. Vaughan JI, Warwick R, Letsky E, Nicolini U, Rodeck CH, Fisk NM. Erythropoietic suppression in fetal anemia because of Kell alloimmunization. Am J Obstet Gynecol. 1994; 171(1):247-252. PubMed | Google Scholar


10. Vaughan JI, Manning M, Warwick RM, Letsky EA, Murray NA, Roberts IA. Inhibition of erythroid progenitor cells by anti-Kell antibodies in fetal alloimmune anemia. N Engl J Med. 1998; 338(12):798-803. PubMed | Google Scholar


11. Daniels G, Hadley A, Green CA. Causes of foetal anemia in hemolytic disease due to anti-K. Transfusion. 2003; 43(1):115-116. PubMed | Google Scholar


12. National Population Commission (NPC). National Census Figures, Abuja, Nigeria. 2007. Google Scholar


13. Lamba DS, Kaur R, Basu S. Clinically Significant Minor Blood Group Antigens amongst North Indian Donor Population. Advances in Hematology. 2013; 2013: 215454. PubMed | Google Scholar


14. Chaudhary RK, Shukla JS, Ray V. Minor red cell antigens in North India blood donor population. Indian Journal of Haematology and Blood Transfusion. 2003; 21:34-35. PubMed | Google Scholar


15. Ugboma HA, Nwauche CA. Kell blood group antigen in Port Harcourt, Nigeria-a pilot study. Port Harcourt Medical Journal. 2009; 4(2): ISSN 0795-3038. PubMed | Google Scholar


16. Thakral B, Saluja K, Sharma RR, Marwaha N . Phenotype frequencies of blood group systems (Rh, Kell, Kidd, Duffy, MNS, P, Lewis and Lutheran) in Northern India blood donors. Transfusion and Apheresis Science. 2010; 43 (1):17-22. PubMed | Google Scholar


17. Chan A, Wong HF, Chui CH, Wong L, Cheng G. The impact of a gel system on routine work in a general hospital blood bank. Immunohaematology. 1996; 12:30-32. PubMed | Google Scholar


18. Nathalang O, Kuvanont S, Punyaprasiddi P, Tasaniyanonda C, Sriphaisal T. A preliminary study of the distribution of blood group systems in Thai blood donors determined by the gel test. Southeast Asian Journal of Tropical Medicine and Public Health. 2001; 32:204-207. PubMed | Google Scholar


19. Redman CM, Russo D, Lee S. Kell, Kx and the McLeod syndrome. Baillière's Clinical Haematology. 1999; 12 (4): 621-635. PubMed | Google Scholar


20. Makroo RN, Bhatia A, Gupta R, Phillip J . Prevalence of Rh, Duffy, Kell, Kidd & MNSs blood group antigens in the Indian blood donor population. Indian Journal of Medical Research. 2013; 137(3):521-526. PubMed | Google Scholar


21. Mohamed S, Muna I. Characterisation of Rh and other blood group systems amongst the Maldivian blood donors. Medical Journal of Malaysia. 2013; 68(5):393-396. PubMed | Google Scholar


22. Kahar MA, Patel RD .Phenotype frequencies of blood group systems (Rh, Kell, Kidd, Duffy, MNS, P, Lewis, and Lutheran) in blood donors of south Gujarat, India. Asian Journal of Transfusion Science. 2014; 8(1):51-55. PubMed | Google Scholar


23. Lin-Chu M, Broadberry RE, Chang FJ. The distribution of blood group antigens and alloantibodies among Chinese in Taiwan. Transfusion. 1988; 28(4):350-352. PubMed | Google Scholar


24. Blavy G, Thiam D, Diakhate L. The Kell system in Senegal: phenotype and gene frequencies. International Journal of Anthropology. 1987; 2(1): 75-76. PubMed | Google Scholar


25. Rahman M. Incidence of important blood groups in Bangladesh. Bangladesh Medical Research Council Bulletin. 1975; 1(1):60-63. PubMed | Google Scholar


26. Makarovska-Bojadzieva T, Blagoevska M, Kolevski P, Kostovska S. Optimal blood grouping and antibody screening for safe transfusion. Prilozi. 2009; 30(1):119-128. PubMed | Google Scholar


27. Westhoff CM, Reid ME. Review: the Kell, Duffy, and Kidd blood group systems. Immunohematology. 2004; 20(1):37-49. PubMed | Google Scholar


28. Lee S, Russo D, Redman CM. Review of the Kell blood group system: Kell and XK membrane proteins. Seminar in Hematology. 2000; 37(2):113-121. PubMed | Google Scholar


29. Jeremiah ZA, Mordi A, Buseri FI, Adias TC. Frequencies of maternal red cell alloantibodies in Port Harcourt, Nigeria. Asian Journal of Transfusion Science. 2011; 5(1):39-41. PubMed | Google Scholar


30. Shah M, Shah FY, Shah FY. Incidence of Kell blood group in Kashmiri population attending blood bank SKIMS as donors. Annals of Tropical Medicine and Public Health. 2013; 6(3):183-187. PubMed | Google Scholar


31. Branch DR. Solving the dilemma of prevention of red cell alloimmunization. Immunotherapy. 2002; 4(9):903-905. PubMed | Google Scholar


32. Natukunda B, Schonewille H, van de Watering L, Brand A. Prevalence and specificities of red blood cell alloantibodies in transfused Ugandans with different diseases. Vox Sanguine. 2010; 98(2):167-171. PubMed | Google Scholar


33. Zimring JC, Spitalnik SL, Roback JD, Hillyer CD. Transfusion-induced autoantibodies and differential immunogenicity of blood group antigens: a novel hypothesis. Transfusion.2007; 47(12):2189-196. PubMed | Google Scholar


34. Moise KJ Jr. Non-anti-D antibodies in red-cell alloimmunization. European Journal of Obstetrics, Gynecology and Reproductive Biology. 2000; 92(1):75-81. PubMed | Google Scholar


35. Hadley AG. In vitro a comparison of test for predicting the severity of haemolytic disease of the foetus and newborn. Vox Sanguine. 1998; 74(suppl 2): 375-383. PubMed | Google Scholar


36. Malhotra S, Kaur G, Basu S, Kaur R, Jindal G. Alloimmunization to Kell blood group system antigen owing to unmatched blood transfusion in a resource-poor setting. Immunohematology. 2002; 28(2):45-48. PubMed | Google Scholar


37. Koelewijn JM, Vrijkotte TG, van der Schoot CE, Bonsel GJ, de Haas M. Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands. Transfusion. 2008; 48(5):941-952. PubMed | Google Scholar


38. Azarkeivan A, Ansari S, Ahmadi MH, Hajibeigy B, Maghsudlu M, Nasizadeh S, Shaigan M, Toolabi A, Salahmand M. Blood transfusion and alloimmunization in patients with thalassemia: multicenter study. Pediatric Hematology and Oncology. 2011; 28(6):479-485. PubMed | Google Scholar


39. Castro O, Sandler SG, Houston-Yu P, Rana S. Predicting the effect of transfusing only phenotype-matched RBCs to patients with sickle cell disease: theoretical and practical implications. Transfusion. 2002; 42(6):684-690. PubMed | Google Scholar


40. Gariod S, Brossard Y, Poissonnier MH, Vuilliez B, Deutsch V, Jouk PS, Pons JC. Kell alloimmunization in pregnancy. Journal of Gynecology, Obstetrics, Biology and Reproduction. 2004; 33(7):637-648. PubMed | Google Scholar


41. Liu Z, Zeng R, Chen Q, Li M, Shi GY, Wei P, Huang CY, Tang RC, Sun J, Zhang XG. Genotyping for Kidd, Kell, Duffy, Scianna, and RHCE blood group antigens polymorphisms in Jiangsu Chinese Han. Chin Med J (Engl). 2012; 125(6):1076-81. PubMed | Google Scholar


42. van Wamelen DJ, Klumper FJ, de Haas M, Meerman RH, van Kamp IL, Oepkes D. Obstetric history and antibody titer in estimating severity of Kell alloimmunization in pregnancy. Obstetrics and Gynecology. 2007; 109(5):1093-1098. PubMed | Google Scholar


43. Ahaded A, Brossard Y, Debbia M, Lambin P. Quantitative determination of anti-K (KEL1) IgG and IgG subclasses in the serum of severely alloimmunized pregnant women by ELISA. Transfusion. 2000; 40(10):1239-45. PubMed | Google Scholar


44. Santiago JC, Ramos-Corpas D, Oyonarte S, Montoya F. Current clinical management of anti-Kell alloimmunization in pregnancy. European Journal of Obstetrics, Gynecology and Reproductive Biology. 2008; 136(2):151-154. PubMed | Google Scholar


45. Finning K, Martin P, Summers J, Daniels G. Foetal genotyping for the K (Kell) and Rh C, c, and E blood groups on cell-free foetal DNA in maternal plasma. Transfusion. 2007; 47(11): 2126-2133. PubMed | Google Scholar


46. Poole J, Nicole W, Hustinx H, Taleghani BM, Martin P, Finning K, Crew VK, Green C, Bromilow I, Daniels G. A KEL gene encoding serine at position 193 of the Kell glycoprotein results in expression of KEL1 antigen. Transfusion. 2006; 46(11): 1879-1885. PubMed | Google Scholar