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McLeod syndrome was originally described on the basis of a specific blood group phenotype with weak expression of Kell antigens. This erythrocyte abnormality also causes acanthocytosis. The haematological findings are associated with abnormalities in other organ systems, including neuromuscular manifestations. A 51-year-old patient was followed up for 11 years. He presented with persistent muscle creatine kinase elevation and progressive heart disease and later developed a slowly progressive neuropathy and choreic movements. His younger brother presented with grand mal seizures, involuntary movements and high muscle creatine kinase when aged 43 years. Clinical myopathy was absent in both, yet muscle biopsy showed mild myopathic changes. The presence of a motor axonopathy was supported by electrophysiological findings. One brother also showed sensory axonopathy. The movement disorder suggested accompanying basal ganglia dysfunction. Earlier reports of McLeod syndrome are reviewed with respect to neuromuscular involvement. Absence of the Kx membrane protein seems to be the cause of this multi-system disorder.

Kpa is a low-frequency antigen occurring in less than 2 percent of the Caucasian population. Mild to moderate delayed hemolytic transfusion reactions (DHTR) and hemolytic disease of the fetus and newborn attributable to anti-Kpa have been reported. Severe overt DHTR has not been reported with anti-Kpa. A case of a severe DHTR attributed to anti-Kpa after multiple RBC transfusions is being reported. A 52-year-old Caucasian woman received multiple units of RBCs for a lower gastrointestinal bleed. She was referred to our institution for hepatic and renal failure, which was supported by laboratory findings of peak LDH, bilirubin, BUN, and creatinine elevations. Hemoglobin had dropped on Day 10 after transfusion. The DAT and antibody screen (ABS) were negative. Initial workup and subsequent ABS were negative. Anti-Kpa was identified when an additional RBC panel was tested. One of the RBC units transfused was incompatible by antihuman globulin (AHG) crossmatch with the patient's plasma and typed positive for Kpa. DHTR was confirmed after extensive workup. The patient responded to supportive therapy and experienced an uneventful recovery. DHTR may not be considered when DAT and ABS are negative. However, correlation of recent transfusion with signs and symptoms should alert the clinician to entertain and investigate a DHTR that should include the AHG crossmatch of all implicated RBC units. The severity of the reaction also raises concerns as to when and what antigen specificity should be considered for inclusion in the antibody screening cells.

Anti-RhD allo-immunisation has become rare since anti-D prophylaxis was introduced in the seventies; however, it remains the first cause of fetal anemia. It may cause severe fetal complications such as fetal hydrops, cerebral anoxic lesions and fetal death. In the neonatal period, severe jaundices and anemias requiring transfusion or exsanguino-transfusion are still common in case of severe allo-immunisation. Neonatal death and sequellae due to bilirubin encephalopathy have not fully disappeared. Follow-up of pregnancies with maternal allo-immunisation requires identification of the antibody (anti-RhD, anti-Kell and anti-c are the most frequently responsible for fetal complications), dosage and titration. In RhD allo-immunization, feto-maternal incompatibility may be confirmed by non-invasive RHD genotyping of the fetus in maternal blood. In cases at risk for fetal anemia, weekly Doppler assessment of middle cerebral artery peak systolic velocity (MCA-PSV) allows identification of fetal anemia before the occurrence of fetal hydrops. The reference treatment of fetal anemia is in utero fetal transfusion. The risk of fetal loss due to in utero transfusion (IUT) is 3% per procedure. The cumulated risk of fetal loss can thus exceed 10% in case of early occurrence of fetal anemia requiring up to five or six IUTs in a single pregnancy.

(Full text is available at http://www.manu.edu.mk/prilozi). Introduction. Blood group antigens as integrated parts of the red cell membrane have many essential functions for the cell as well as for the organism, but they are recognized as unique antigens for the purpose of safe blood transfusion. Especially in the case of those with great clinical importance because of their involvement in haemolytic transfusion reactions and hemolytic disease of the newborn, it is very important that they be correctly, and some of them routinely, typed in blood donors as well as in patients. Aim. Evaluation of Rh and Kell blood group antigen frequencies in blood donors as well as the incidence of alloimmunization in transfused patients in the Macedonian population. The need for routine typing of certain blood group antigens in addition to ABO and RhD was also evaluated. Material and method. We evaluated data from 1600 ABO/Rh and Kell typed blood donors (from January 2003 to May 2008), as well as the data from pretransfusion testing (ABO/RhD blood typing, irregular red blood cell antibody screening and compatibility testing) and antibody identification in the period from January 2005 to November 2008. All tests were performed by the DiaMed micro tube gel system. Results. The frequencies of ABO antigens were as follows: A (39.7%), O (38%), B (14.1%), AB (7.4%). The frequencies of Rh antigens were as follows: D pos. (84.2%), D neg. (15.8%), C (58.3%), c (82.4%), E (21.3%), e (97.1%). We found the following frequencies of Kell phenotypes: K+ k- (0.25%), K+ k+ (6.18%), and K- k+ (93.6%) with the total frequency of K antigen of 6.4%. Antibody screening and/or cross-match were positive in the sera from 150 transfused patients. In 75 (50%) sera the following 81 antibodies were identified: anti-K (26), -E (25), -e (1), -C (4), -c (6), -C(w) (2), -k (1), -Fy (a) (3), -Fy(b) (1), -Jk(a) (3), -Lu(b) (1), -Le(b) (2), -Le(a) (1), -M (4), -P1 (1). The most frequent alloantibody was anti-K with 32%, and anti-E with 30.8% of all identified antibodies. Conclusion. Alloimmunization to red cell antigens is still a current problem in our transfusion practice. It is obvious that the additional testing of blood donors for Rh and Kell antigens should be implemented as a routine to prevent as far as possible the incidence of alloimmunization. It would also be cost-effective, bearing in mind the additional laboratory testing necessary to provide compatible blood for alloimmunized patients. Extended blood typing should be implemented for some categories of polytransfused patients as well. This strategy is another step forward to improve the safety of blood transfusion with optimal blood grouping. Key words: Kell phenotypes frequency, alloimmunization, blood grouping, safe transfusion.

Since the discovery of blood groups in humans, several hundred new red blood cell antigens have been identified. Multiple terminology modes have been used to denote each new antigen identified, but without any consistent rules, nor international consensus. This was largely due to the many discoverers of these antigens, using either letters of the alphabet, numbers, part of the patient or donor's name, place of discovery or animal names. Besides, alternative terminologies for the Rh system were implemented in the middle of the twentieth century (Rosenfield, Fisher-Race, Wiener). The International Society of Blood Transfusion described for the first time in 1980 the advantages of an alphanumeric and homogeneous nomenclature, keeping with the genetic bases of blood groups, as well as a classification of all RBC antigens within several families. A variant of this new terminology, exclusively numerical, was simultaneously established, mainly designed for computer data exchange. Nearly 30 years later, 308 red blood cell antigens are described within 30 systems, 12 collections, one 700 series and one 901 series of blood groups. Any person involved in the field of immuno-haematology must master both the usual and international nomenclatures. The Wiener nomenclature used for Rh haplotypes, still largely used today, is also important to be known. The systematic use of the international nomenclature should be strongly encouraged, either in the labelling of blood products, clinical laboratory reports or blood type cards.

We describe a male neonate with foetal hydrops due to foetal anaemia caused by Kell isoimmunisation. The severity of anaemia was monitored by Doppler ultrasonography of the middle cerebral artery peak systolic velocity, and this was used to time the foetal blood transfusions. The 33-year-old Indian mother received a total of five foetal blood transfusions from 21 weeks to 31 weeks of gestation, resulting in resolution of the anaemia and hydrops.

BACKGROUND: QWALYS 2 is a fully automated system for ABO/D grouping, Rh phenotyping, K typing, and antibody screening (ABS). Its new erythrocyte-magnetized technology (EMT) is based on the use of magnetic nanoparticles and avoids centrifugation and washing steps. STUDY DESIGN AND METHODS: Overall 499 blood samples were tested with our routine blood bank methods for ABO/D grouping, 313 samples for Rh phenotyping and K typing (microtiter plates; Olympus PK 7200), and 478 samples for ABS (gel centrifugation technique, DiaMed). All samples were tested in parallel with the EMT. RESULTS: In 496 of 499 samples (99.4%), a complete concordance between the observed (QWALYS 2) and the expected results for ABO/D grouping was found. One sample with a weak A in an AB blood group and 2 samples with a weak D were not detected by the QWALYS system. Rh phenotyping and K tests revealed a 100% concordance. In the two ABS techniques, 427 samples were negative in both and 15 samples showed the same antibody specificity in both. Three immunoglobulin M antibodies were as expected negative in EMT and positive by DiaMed. In 32 cases (6.7%), false-positive reactions were observed by EMT due to 22 unspecific reactions (4.6%) and 10 lipemic or fibrinic plasmas (2.1%). One autoantibody was found by EMT only. CONCLUSION: The EMT is reliably suited to ABO/D grouping, Rh phenotyping, and K testing and is suitable to detect immunoglobulin G red blood cell alloantibodies as well. The rate of false-positive reactions in ABS due to lipemic and fibrinic samples needs to be reduced.

BACKGROUND: KEL1 (K) is the most immunogenic red blood cell antigen of the Kell blood group system. The frequently occurring anti-KEL1 alloantibodies may cause hemolytic transfusion reactions as well as severe hemolytic disease of the fetus and newborn. So far, reports on weak KEL phenotypes are scarce. STUDY DESIGN AND METHODS: Blood samples of two unrelated Central European propositi with faint reactions in routine KEL1 typing were analyzed by extended serologic phenotyping, flow cytometry, genotyping by polymerase chain reaction with sequence-specific priming, and genomic DNA sequencing of separated parental KEL alleles. RESULTS: Both propositi exhibited an unusual KEL:1,2,3,4 phenotype: markedly weakened and negative reactions were observed in serologic KEL1 typing in gel and tube technique, respectively. No KEL1 epitope loss was detected using five different monoclonal anti-KEL1 reagents. KEL genotyping confirmed KEL*1/2 and KEL*3/4 (Kpa/Kpb) heterozygosity of both individuals. Importantly, DNA sequencing of the two separated parental alleles of both propositi revealed a KEL*1-specific coding nucleotide T578 and a KEL*3-specific T841 on the same allele. This novel KEL*1,3 (KKpa) allele was associated with an approximately 80 percent reduction in KEL1 expression, compared to KEL:1,2, –3,4 controls. The low KEL1 density was attributed to a cis-modifier effect of KEL3, so far only reported in association with weakened expression of KEL2 (k). CONCLUSION: This is the first description of the KEL*1,3 allele encoding KEL1 and KEL3 on the same molecule. In individuals with weakened KEL1 because of KEL3 in cis, very sensitive serologic or molecular genetic techniques may be required for reliable Kell typing.

The development of alloantibodies and erythrocyte autoantibodies complicates transfusion therapy. The antibodies detection of potential clinical significance in 136 samples of Dr. Max Peralta J Hospital Blood Bank patients, Cartago, Costa Rica between 2004 and February, 2009 were evaluated. Transfusion of phenotypically matched blood for Rh and Kell systems proved to be effective in preventing alloimmunization because it been found in this study that there is good evidence that a high proportion of antibodies produced in response to transfusion are Rh and K specificity.

The transfusion of blood components could be needed in certain types of surgical procedures. Blood type components and the requested number of units will depend on the estimated loss of blood, type of surgery, surgical technique to be employed and risk factors for bleeding. Problems can appear when multiple antibodies against common erythrocyte antigens are detected in blood samples and this situation worsens if blood units are requested as quickly as possible. We report a case of a patient with a non frequent erythrocytic phenotype where multiple antibodies acting against high-frequency antigens were detected and who required urgent surgery.

BACKGROUND: Patients may present with an antibody against a blood group antigen, a negative direct antiglobulin test (DAT), and a null phenotype. Typically, this represents an alloantibody in a null individual. However, on occasion, the antibody disappears coincident with conversion to a positive red blood cell (RBC) phenotype. This has been called antigen loss, antigen suppression, or weakened antigenicity. Herein, a unique serologic profile that mimics this pattern, when in fact antigen loss did not occur, is described. STUDY DESIGN AND METHODS: RBCs and serum were analyzed using a gel microtyping system and flow cytometry. Genomic DNA was amplified by polymerase chain reaction and sequenced. RESULTS: Initially, an anti-Kpb was detected in MTS gel, RBCs typed K−k−Kp(b−), and the DAT was negative for immunoglobulin G (IgG). Later, the anti-Kpb disappeared and RBCs phenotyped as K−k+Kp(b+). Analysis of initial specimens by flow cytometry identified an immunoglobulin M (IgM) anti-Kpb with a positive IgM-specific DAT; eluates contained an anti-Kpb at immediate spin. Supporting the presence of the Kell glycoprotein, RBCs agglutinated with anti-Jsb. Sequencing showed homozygosity for Kpb with no mutations surrounding the Kpb polymorphism. CONCLUSION: In antigen loss, antibody masking is excluded by a negative DAT. However, because typical DAT reagent does not detect IgM, such reasoning was inaccurate in the current case. In addition, an anti-Kpb resulted in RBCs typing k−, even though no anti-k was detected. Overall, this case suggests that an IgM may mask adjacent epitopes and illustrates the potential to mistake a non-IgG autoantibody as antigen loss.

Red cells (RBCs) contain an abundance of protein methylase II, which catalyzes the transfer of methyl groups from S-adenosylmethionine to carboxyl groups of aspartyl and glutamyl residues in proteins. Enzyme-catalyzed transfer of methyl groups, labeled with 14C or 3H, from S-adenosylmethionine to membrane proteins of McLeod, Ko, and control RBCs was assayed by determining the acceptance of labeled methyl groups under standardized conditions. Membranes of control cells and Ko cells showed about 50 percent greater uptake than did those of McLeod cells. However, when ovalbumin was used as a methyl-accepting substrate, the levels of protein carboxymethyltransferase activity in all three types of cells were found not to differ significantly. In addition, no significant qualitative differences were apparent when methyl-labeled polypeptides from control and McLeod cells were separated by slab gel electrophoresis. The mechanisms responsible for changes in membrane protein methylation of McLeod cells remain unclear. However, these observations provide further evidence of the pleiotropic biochemical lesion associated with the acanthocytic morphology that characterizes McLeod RBCs.

Summary Murine monoclonal antibodies (MoAbs) were produced against the blood group KEL1 glycoprotein (93 kD component) immunopurified from human erythrocytes. One monoclonal antibody, 5A11 (IgGl, K), detects by immunoblotting a 93 and 184 kD component from KEL: 1, -2 or KEL: - 1,2 red cell membrane preparations, separated by SDS polyacrylamide gel electrophoresis (PAGE) under non-reducing conditions. The 184 kD component was not detected under reducing conditions, suggesting that it represented a dimer of the 93 kD KEL glycoprotein. Neither the 93 nor the 184 kD could be detected from KO or McLeod erythrocyte membrane preparations, indicating that the monoclonal antibody reacts with the KEL glycoprotein previously identified as a 93 kD species. Since this antibody does not agglutinate native or protease-treated erythrocytes, it is likely that it reacts with the cytoplasmic domain of the KEL glycoprotein. This was also substantiated by showing that 5A11 could immunoprecipitate the 93 kD component from intact membranes and inside-out vesicles but not from right-side-out vesicles. Immunostaining of membrane proteins prepared from human blood cells (platelets, lymphocytes, monocytes and granulocytes) and non-human erythrocytes revealed that the 93 kD molecule was only present on human red cells. Several other murine monoclonal antibodies obtained from the same fusion experiment gave identical results, but competition analyses on immunoblots indicated that these antibodies reacted with distinct epitopes on the KEL glycoprotein.

To investigate the difference of the transcripts between reticulocyte and non-reticulocyte cells in human blood.Genomic DNA, reticulocyte RNA and total RNA of K-, K+ and Kell-null(K0) were extracted, then PCR, reverse transcription-PCR(RT-PCR) and nested PCR followed by sequencing or cloning-sequencing were used to analyze the KEL gene mRNA exons 1-19 and exons 2-8. Four kinds of monoclonal antibodies were labeled to detect the expression of Kell glycoprotein on red cells or leukocytes with flow cytometry.In reticulocyte, only one normal KEL transcript faithful to the genomic structure was found in all tested samples except K0 which had 4 different transcripts. Sequence analysis of exons 2-8 of total RNA confirmed the alternative KEL transcripts existed in different samples, mostly caused by abnormal splicing, among them, skipping of exon 3 and a 16 bp insertion of intron 6 at the beginning of exon 7 were the most frequent. Although only one band was observed after amplifying the exons 1-19 from total RNA, the sequencing result showed it was a mixture of different sequences. There was strong expression of Kell glycoprotein on red cells except K0, but no or low expression on leucocytes by flow cytometry.Alternative transcripts of KEL gene exist in different cells, which would be responsible for different Kell glycoprotein expression patterns on different cells. This study suggested that reticulocyte RNA was more suitable than total RNA for molecular study of KEL gene transcription.

BACKGROUND: The long-term neurological prognosis of severe fetal anemia is usually considered favorable, especially when fetal hydrops regresses after successful in utero transfusion. CASES: We report two cases of prenatally diagnosed fetal cerebral anoxic lesions associated with severe fetal anemia despite appropriate and successful treatment by in utero transfusion. The two pregnancies were terminated. CONCLUSION: Profound fetal anemia may cause anoxic lesions of the fetal brain that may be diagnosed prenatally. If new onset ventriculomegaly is observed on ultrasonography after in utero transfusion for severe fetal anemia, anoxic lesions could be suspected.

1) We have presented our experiment conducted to detect anti-K antibodies from the Kell-system in pregnant women and their connection with potential destruction of foetal red cells, which may result in haemolytic disease of the foetus and the newborn (HDFN). 2) We have also indicated serological and molecular methods important for a proper diagnosis.27 women with anti-K. Serological diagnosis of K antigen in fathers and children. KEL1 gene examination in foetuses from DNA isolated from foetal cells contained in amniotic fluid, using discrimination of alleles--real-time PCR method.Anti-K were detected in most women after blood transfusion, the fathers were usually K negative. Foetomaternal incompatibility was found in 6 out of 27 women. Haemolytic disease was observed in 5 cases: 3-severe, 1-fatal, 1-mild. Foetal genotyping allowed us to avoid cordocentesis in two pregnant women, it appeared that both foetuses have not received KEL1 gene from heterozygous (Kk) fathers--in the previous pregnancies the children had died because of HDFN.1) In every pregnant woman with anti-K, the K antigen should be examined in the father. 2) In every K+ father the phenotype should be evaluated and if he is heterozygote (Kk), the fetal KEL1 gene must be examined, to avoid unnecessary cordocentesis. 3) If KEL1 gene is not detected in the foetus, HDFN will not occur. 4/Foetal KEL1 genotyping may be performed in all mothers with anti-K and heterozygous father in our Department, after providing the material from the amniocethesis.

Kell is the most important blood group system after ABO and Rh because all frequently occurring Kell-specific antibodies must be considered clinically significant. The highly immunogenic Kell antigens are usually involved in red cell (RBC) alloimmunization that can cause either hemolytic transfusion

Background and Objectives Kell haemolytic disease in pregnancies has been suggested to be associated with decreased fetal platelet counts. The aim of this study was to evaluate the incidence and clinical significance of fetal thrombocytopenia in pregnancies complicated by Kell alloimmunization. Materials and Methods In this retrospective cohort study, fetal platelet counts were performed in 42 pregnancies with severe Kell alloimmunization prior to the first intrauterine blood transfusion. Platelet counts from 318 first intrauterine transfusions in RhD alloimmunized pregnancies were used as controls. Results Fetal thrombocytopenia (platelet count

BACKGROUND: In 1998 a national program for first-trimester screening for red cell (RBC) antibodies in all pregnant women was implemented. The aim of our study was to assess the impact on perinatal mortality caused by Kell alloimmunization STUDY DESIGN AND METHODS: Prospectively collected data on all pregnant women referred to our center from 1988 until 2005 for intrauterine transfusion (IUT) for fetal anemia due to Kell alloantibodies were analyzed. The cohort was divided into two groups, those treated before 1998 and those treated after 1998. The primary outcome was fetal and neonatal survival. Secondary outcome variables were gestational age, fetal hemoglobin (Hb) levels at first IUT, severity of hydrops, and total number of IUTs per pregnancy. Causes for mortality were analyzed in detail. RESULTS: A total of 43 pregnancies were included, 18 before introduction of screening and 25 thereafter. Perinatal survival increased from 61 percent in the first period to 100 percent after introduction of screening. After 1998, fetal hydrops was generally less severe at first IUT, while gestational age and fetal Hb levels at first IUT were similar. CONCLUSION: Implementation of routine screening for Kell antibodies in pregnancy was associated with an increased referral rate for suspected fetal anemia, more timely referrals, and a higher perinatal survival rate after intrauterine treatment.

Background and Objectives Kell antigens are encoded by the KEL gene on the long arm of chromosome 7. Kx antigen is encoded by the XK gene on the short arm of the X chromosome. Kell and Kx proteins in the red cell membrane are covalently linked by a disulphide bond. The McLeod phenotype is characterized by weakened expression of antigens in the Kell blood group system, absence of Km and Kx antigens, and acanthocytosis. It has an X-linked mode of inheritance with transmission through carrier females. Some males with the McLeod syndrome also have chronic granulomatous disease (CGD). It is generally believed that patients with non-CGD McLeod may develop anti-Km but not anti-Kx, but that those with CGD McLeod can develop both anti-Km and anti-Kx. Materials and Methods We present serological data, DNA genotyping and gene sequencing, monocyte monolayer assay and neutrophil oxidative burst test from a patient with the McLeod phenotype without clinical evidence of CGD. Results We report here the second example of a patient with non-CGD McLeod who developed anti-Kx in addition to anti-Km. Sequencing of our patient's XK gene confirmed the presence of a mutation resulting in a premature stop codon and lack of Kx protein in the red cell membrane, which is consistent with the diagnosis of McLeod syndrome. Neutrophil oxidative burst test was normal, indicating that our patient did not have CGD. The challenge of providing 10 compatible blood units for multiple surgeries was met. Conclusion The second case of a rare entity, a patient with non-CGD McLeod who developed anti-Kx and anti-Km, was managed successfully with a combination of autologous donations and procurement of compatible units from national and international sources.

International audience; The Basques demonstrate peculiar characteristics regarding blood group systems. Although ABO, Rhesus, and Duffy have been extensively studied in this population, the distribution of other groups remains largely unknown. Therefore, we evaluated the frequency of less-explored- or still noninvestigated blood groups using DNA-based assays and interpreted these data in the view of population genetics. Polymorphisms of KEL (Kell), SLCA14A1 (Kidd), GYPA/GYPB (MNS), ART4 (Dombrock), AQP1 (Colton), and ACHE (Yt) blood group genes were determined from a sample of more than 100 autochthonous French Basques using allele-specific primer PCR (PCR-ASP) methods. Our results were compared with those previously obtained by the use of serology from both Basque and nonBasque European populations. MNS*1 and JK*1 allele frequencies were comparable with those reported from Basque samples. Conversely, theKEL*1 allele frequency differed significantly. To our knowledge, this is the first time that the other three systems are studied in the Basque population. DO*1 and CO*1 allele frequencies, being respectively 0.35 and 0.96, were significantly inferior to those published from various European populations. There were some discrepancies regarding these six bloodsystems when comparing molecular typing with serology. These findings may be explained by differences in either criteria for individual selection or technical assays. Nevertheless, these results constitute additional data to be included in the chapter of Basque biological anthropology

Jsb is a high-frequency antigen. Anti-Jsb is a rare alloantibody, and its clinical significance is poorly documented. We report a case in which a 12-year-old boy of Nigerian descent with sickle beta- thalassemia presented with multiple alloantibodies, including a panagglutinin and acute chest syndrome, necessitating the emergent transfusion of five units of phenotype-similar, crossmatchincompatible RBCs, four of which were given during an exchange transfusion. The patient was later found to have anti-Jsb. In addition to routine serologic methods to study the patient's RBCs and plasma, a monocyte monolayer assay (MMA) was performed on the patient's samples obtained 2 and 9 days after transfusion of the Js(b+) RBCs to determine the potential clinical significance of the anti-Jsb. Various laboratory parameters including quantitative hemoglobin fraction analyses were used to monitor for increased RBC destruction. The MMA reactivity of the patient's anti-Jsb increased from 2.3 percent on day 2 after transfusion to strongly positive at 88 percent and 66.5 percent (with and without the addition of fresh serum) 1 week later. MMA reactivity of greater than 5 percent is associated with increased RBC destruction. There was no clinical or laboratory evidence of increased hemolysis above baseline. However, decreased RBC survival was suggested by the relatively brisk decrease of the HbA1 fraction after the transfusions. The current case and others reported in the literature suggest that anti-Jsb may have limited potential for causing overt hemolysis. However, in patients with underlying hematologic disease, even mildly increased RBC destruction may pose problems clinically,and thus transfusion of Js(b+) RBCs should be avoided. In emergent situations, the potential of adverse effects of transfusing incompatible units should be balanced against the risk of withholding transfusion. Family members, especially siblings, should be considered as potential designated donors for patients with antibodies directed against high-frequency antigens. Available reports on anti-Jsb in the literature are also reviewed.

BACKGROUND: When a pregnant woman has an antibody with the potential to cause hemolytic disease of the fetus and newborn, it is beneficial to determine whether her fetus has the corresponding antigen to assess risk. In many countries this is now done routinely for RhD, by testing cell-free fetal DNA in the maternal plasma. Similar tests for K, C, c, and E are reported. STUDY DESIGN AND METHODS: Real-time quantitative polymerase chain reaction incorporating an allele-specific primer was developed for detecting the K allele of KEL and the C, c, and E alleles of RHCE. These methods were used to test DNA isolated from plasma of pregnant women with antibodies to K, C, c, or E. Accuracy of the tests was determined by comparing results with serologic tests performed on cord red blood cells (RBCs) after delivery or by molecular genotyping on DNA obtained from fetal cells. RESULTS: The K test incorporated an allele-specific primer with two locked nucleic acids and a mismatch. In 70 tests, including 27 K+ fetuses, only one false-negative and no false-positive results were obtained. The C, c, and E tests, performed on 13, 44, and 46 samples, respectively, gave rise to no false results. CONCLUSION: Reliable methods have been developed for predicting fetal K, C, c, and E phenotypes, by testing fetal DNA in the plasma samples of pregnant women whose RBCs lack the corresponding antigens. These methods are now being used routinely in a diagnostic service in the United Kingdom.

Blood bank serology has identified hundreds of red blood cell (RBC) antigens contained within numerous blood group systems. Although most blood group antigens are defined by amino acid polymorphisms in the extracellular domain of membrane proteins, it is also possible that additional nonexofacial polymorphisms (NEPs) may exist within cytoplasmic or transmembrane domains. To assess this possibility, we analyzed several blood group molecules by searching the SNPper database for nonsynonymous single-nucleotide polymorphisms. We report the identification of a number of NEPs in the Kell, Kidd, and Duffy molecules. Because the identified NEPs are not exposed on the surface of intact RBCs and are, thus, not accessible to recipient antibodies, they would neither be detected by blood bank serology in vitro, nor would they be recognized targets in hemolytic transfusion reactions in vivo. The presentation of peptides containing NEPs by recipient MHC Class II molecules, however, would nevertheless produce helper T-cell epitopes. In addition to identifying NEPs in human blood group molecules, we explore a novel hypothesis that the presence of NEPs contributes to the immunogenicity of blood group antigens. We further hypothesize that NEPs provide a mechanism by which transfusion can lead to anti-RBC autoantibodies, which are known to occur in humans after transfusion. The scientific basis, existing evidence, approaches to testing, and predicted biology of this hypothesis are presented.

The X-linked McLeod syndrome is defined by absent Kx red blood cell antigen and weak expression of Kell antigens, and this constellation may be accidentally detected in routine screening of apparently healthy blood donors. Most carriers of this McLeod blood group phenotype have acanthocytosis and elevated serum creatine kinase levels and are prone to develop a severe neurological disorder resembling Huntington's disease. Onset of neurological symptoms ranges between 25 and 60 years, and the penetrance of the disorder appears to be high. Additional symptoms of the McLeod neuroacanthocytosis syndrome that warrant therapeutic and diagnostic considerations include generalized seizures, neuromuscular symptoms leading to weakness and atrophy, and cardiopathy mainly manifesting with atrial fibrillation, malignant arrhythmias and dilated cardiomyopathy. Therefore, asymptomatic carriers of the McLeod blood group phenotype should have a careful genetic counseling, neurological examination and a cardiologic evaluation for the presence of a treatable cardiomyopathy.

BACKGROUND: DNA-based methods are useful for enhancing immunohematology typings. Ready-to-use Conformite Europeenne (CE)-marked test kits based on polymerase chain reaction with sequence-specific priming (PCR-SSP) have been developed, which enable the examination of weak, unexpected, or unclear serologic findings. DEVELOPMENT AND VALIDATION: Primers were designed according to established mutation databases. Proficiency testing for CE marking was performed in accordance with Directive 98/79EC of the European Parliament and of the Council of October 27, 1998 on in vitro diagnostic medical devices using pretyped in-house and external samples. INTENDED USE: BAGene PCR-SSP kits are in vitro diagnostic devices. Genotyping of ABO and RHD/RHCE as well as HPA and KEL, JK, and FY specificities has to be performed after the conclusion of the serologic determination. APPLICATION: Ready-to-use PCR-SSP typing kits allow the determination of common, rare, or weak alleles of the ABO blood group, Rhesus, and Kell/Kidd/ Duffy systems as well as alleles of the human platelet antigens. RESULTS: The investigations showed clear-cut results in accordance with serology or molecular genetic pre-typing. CONCLUSION: PCR-SSP is a helpful supplementary technique for resolving most of the common problems caused by discrepant or doubtful serologic results, and it is an easy-to-handle robust method. Questionable cases in donor, recipient, and patient typing can be examined with acceptable cost.

To determine whether blood groups are genetic markers for primary open angle glaucoma (POAG).ABO, rhesus, and Kell and Duffy blood groups were analyzed in 114 POAG cases and in a control group of age- and sex-matched patients (96 cases).AB groups are significantly more frequent in POAG cases (10.5%) than in the control group (2%). However, no association was found between POAG and ABO, rhesus, and Kell and Duffy blood groups even when men and women were studied separately.AB blood groups seem to be genetic markers of POAG but further studies are needed to confirm this association.

The X-linked McLeod neuroacanthocytosis syndrome (MLS) has originally been denoted as 'benign' McLeod myopathy. We assessed the clinical findings and the muscle pathology in the eponymous index patient, Hugh McLeod, and in nine additional MLS patients. Only one patient had manifested with neuromuscular symptoms. During a mean follow-up of 15 years, however, eight patients including the initial index patient showed elevated skeletal muscle creatine kinase levels ranging from 300 to 3000 U/L, and had developed muscle weakness and atrophy. Two patients had disabling leg weakness. Muscle histology was abnormal in all 10 patients. Clear but unspecific myopathic changes were found in only four patients. All patients, however, had neurogenic changes of variable degree. Post-mortem motor and sensory nerve examinations support the view that muscle atrophy and weakness are predominantly due to an axonal motor neuropathy rather than to a primary myopathy. Multisystem manifestations developed in eight patients at a mean age of 39 years. Three patients manifested with psychiatric features comprising schizophrenia-like psychosis and personality disorder, two presented with generalized seizures and one with chorea. During follow-up, seven patients developed chorea, six had psychiatric disorders, five had cognitive decline and three had generalized seizures. Five patients died because of MLS-related complications including sudden cardiac death, chronic heart failure and pneumonia between 55 and 69 years. In conclusion, our findings confirm that MLS is not a benign condition but rather a progressive multisystem disorder sharing many features with Huntington's disease.

To investigate the polymorphism of Kell blood group system in Chinese and to find a suitable method for large scale screening.An analysis method of polymerase chain reaction-restriction fragment-single strand conformation polymorphism (PCR-RF-SSCP) combined with heteroduplex was established to detect abnormal sample in KEL exon 7-9 area, then sequencing was used to find out the mutation site.Two mutations were found from 500 samples: 966GA mutation in exon 9 and CA mutation in 67th site of intron 7, both with no amino acid change. The mutation rate was 4/1000. No mutation was found as missed in using PCR-RF-SSCP combined with heteroduplex.PCR-RF-SSCP combined with heteroduplex is confirmed as an effective, economical and simple method, it is quite suitable for large scale population screening study with unclear gene background and unavailable positive controls. Since there is special polymorphism for Kell blood group system in Chinese, further study is needed.

Classical immunoadsorbents used for the removal of deleterious molecules in blood such as auto-antibodies are prepared by covalent coupling of antigens onto previously chemically activated supports. Such a chemical treatment may induce a potential toxicity which can be reduced if new immunoadsorbents are prepared by encapsulating erythrocytes-ghosts carrying antigens inside polymeric and porous microparticles.Erythrocyte-ghosts obtained by hemolysis in hypotonic buffer were encapsulated into ethylcellulose microparticles by w/o/w emulsification. The porosity of microparticles was evaluated by mercury porosimetry. The adsorption ability of encapsulated antigens was evaluated by hemagglutination after contact in tube or elution in column with polyclonal antibody solutions or human blood-plasma.The encapsulation process did not significantly alter the evaluated antigens since a significant decrease in anti-A (from 256 to 4) as well as anti-Kell (from 64 to 2) antibody titer has been observed in column after eight chromatographic runs (2 h). The higher the ghost concentration (total protein content of 6 mg/ml), the higher the adsorption capacity.Encapsulation, currently used for drug delivery purposes, may consequently also be applied to the design of new immunoadsorbents as biomaterials.

BACKGROUND: McLeod neuroacanthocytosis syndrome is a late-onset X-linked multisystem disorder affecting the peripheral and central nervous systems, red blood cells (RBCs), and internal organs. A variety of mutations have been found in the responsible gene (XK) including single nonsense and missense mutations, nucleotide mutations at or near the splice junctions of introns of XK, and different deletion mutations. To date no clear phenotype-genotype correlation is apparent. The clinical details of one case of McLeod phenotype without apparent neuromuscular abnormalities have been reported. Here the clinical details of two additional cases are presented, of which the genetic details have previously been published. STUDY DESIGN AND METHODS: Two asymptomatic or minimally symptomatic cases at ages expected to manifest the McLeod syndrome (MLS) were evaluated. The first case had been authenticated as a genuine McLeod both by serology and by genotyping (R222G missense mutation) and the second case had a mutation in XK (IVS2+5G>A) and by serology exhibited very weak Kx antigen and no detectable Kell antigens, except extremely low k antigen by adsorption-elution technique. The patients were examined for hematologic, neurologic, and other clinical abnormalities. RESULTS: Despite documented McLeod phenotype on RBCs, and identified mutations of XK, neurologic and other clinical findings were minimal at ages expected to manifest MLS. CONCLUSIONS: The different XK mutations may have different effects upon the XK gene product and thus may account for the variable phenotype.

BACKGROUND: The KEL2/KEL1 (k/K) blood group polymorphism represents 578C>T in the KEL gene and Thr193Met in the Kell glycoprotein. Anti-KEL1 can cause severe hemolytic disease of the fetus and newborn. Molecular genotyping for KEL*1 is routinely used for assessing whether a fetus is at risk. Red blood cells (RBCs) from a KEL:1 blood donor (D1) were found to have abnormal KEL1 expression during evaluation of anti-KEL1 reagents. STUDY DESIGN AND METHODS: Kell genotyping methods, including KEL exon 6 direct sequencing, were applied. KEL cDNA from D1 was sequenced. Flow cytometry was used to assess KEL1 and KEL2 RBC expression. RESULTS: RBCs from the donor, her mother, and an unrelated donor gave weak or negative reactions with some anti-KEL1 reagents. Other Kell-system antigens appeared normal. The three individuals were homozygous for KEL C578 (KEL*2) but heterozygous for a 577A>T transversion, encoding Ser193. They appeared to be KEL*2 homozygotes by routine genotyping methods. Flow cytometry revealed weak KEL1 expression and normal KEL2, similar to that of KEL*2 homozygotes. CONCLUSION: Ser193 in the Kell glycoprotein appears to result in expression of abnormal KEL1, in addition to KEL2. The mutation is not detected by routine Kell genotyping methods and, because of unpredicted KEL1 expression, could lead to a misdiagnosis.

BACKGROUND: Although antibodies to Jsa and Jsb are clinically significant, reagent-quality anti-Jsa and anti-Jsb are not readily available. A sequence-specific primer–polymerase chain reaction (SSP-PCR) genotyping assay was tested that makes use of two single-nucleotide polymorphisms (SNPs) at positions 1910 and 2019 of KEL. These SNPs distinguish the gene encoding Jsa, KEL6; and Jsb, KEL7. STUDY DESIGN AND METHODS: Four primer sets that selectively amplified KEL6 and KEL7 from genomic DNA were developed. Two sets detected the SNP at bp 1910 and two sets detected the bp 2019 SNP. KEL6 and KEL7 genotyping and Jsa and Jsb phenotyping results were compared among 64 subjects. RESULTS: The SSP-PCRs were specific for KEL6 and KEL7 when testing DNA for three donors of known Js phenotype: Js(a+b–), Js(a–b+), and Js(a+b+). Genotyping results for the 1910 SNP were identical to the phenotyping results in all 64 subjects, but for the 2019 SNP, the genotyping and phenotyping results were identical for only 49 subjects. In 12 subjects with the Js(a–b+) phenotype, the 2019 SNP was heterozygous KEL6, KEL7; in 2 with Js(a–b+) and in 1 with Js(a+b+), the 2019 SNP was homozygous KEL6. CONCLUSION: KEL 2019-bp SNP does not always correlate with the Js phenotype owing to the presence of an atypical KEL gene with a KEL7 polymorphism at 1910 and a KEL6 polymorphism at 2019. The KEL polymorphism at 2019 is silent and this allele yields a Js(a–b+) phenotype. Only analysis of the 1910-bp SNP can be used to genotype KEL6 and KEL7.

The Kell blood group is constituted by two covalently linked antigens at the surface of red blood cells, Kell and Kx. Whereas Kell is a metalloprotease with demonstrated in vitro enzymatic activity, the role of Kx thereon, and/or alone, remains unknown, although its absence is linked to the McLeod syndrome, a neuroacanthocytosis. In the central nervous system, the expression of Kell and XK has been suggested, but their expression patterns remain uncharacterized, as are the post-translational pathogenic mechanisms involved in the development of the McLeod syndrome. The distributions of Kell and XK were thus studied by in situ hybridization as well as immunohistochemistry in rodent and human brain. The results reveal an independent localization of the two constituents of the Kell blood group, XK (Kx) being expressed throughout this tissue, whereas Kell expression is restricted to red blood cells in cerebral vessels. The XK protein is shown to be neuronal, located mainly in intracellular compartments, suggesting a cell specific trafficking pattern, possibly associated with specific physiological functions.

BACKGROUND: The Kell blood group system consists of 25 antigens that result from single-nucleotide polymorphisms. Most polymorphic Kell antigens reside on the N-terminal domain of Kell before the zinc-binding catalytic motif, which is the major site for endothelin-3–converting enzyme activity. Kell antigens are important in transfusion medicine owing to their strong immunogenicity, and the corresponding antibodies are clinically significant. Two probands were studied whose serum samples contained antibodies to different high-prevalence Kell antigens. STUDY DESIGN AND METHODS: Standard hemagglutination methods were used for serologic testing of Proband 1 and Proband 2. DNA was prepared from both probands and family members. The 19 exons and the intron-exon regions of KEL from both probands were amplified by polymerase chain reaction, and the sequences were compared with that of common KEL. The identified substitutions were located on a three-dimensional model of Kell generated based on the crystal structure of neutral endopeptidase, a homolog of Kell. RESULTS: In Proband 1, a homozygous 1988G>A mutation (Arg623Lys) in Exon 17 was present. One sibling of Proband 1 was homozygous for 1988G>A. In Proband 2, a homozygous 1033G>A mutation (Asp305Asn) in Exon 8 was present. Three siblings of Proband 2 were heterozygous for 1033G>A. CONCLUSION: The identified KEL mutations of the two probands are novel and inherited. The antigen absent from the red blood cells (RBCs) of Probands 1 and 2 are named KALT and KTIM, respectively. KALT is unique in that it is the only Kell antigen sensitive to treatment of RBCs by trypsin.

We describe a case of incidental detection of anti Kell antibody in a child with transfusion dependent thalassaemia. Kell antibody detection may be missed by routine indirect antiglobulin test (IAT) crossmatch procedure because of low prevalence of Kell antigen in the general population. A false negative result can be avoided by using sensitive cross matching techniques and screening cells representing antigens in homozygous state, against all clinically significant antibodies. A transfusion alert card describing the nature of antibody and future transfusion policy should be given to such allo-immunized patients.

The Kell blood group protein is a metalloendopeptidase that preferentially cleaves a Trp(21)-Ile(22) bond of big endothelin-3 producing bioactive endothelin-3. Kell is a polymorphic protein, and 25 different phenotypes, because of point mutations resulting in single amino acid substitutions, have been described. It was recently reported that a recombinant form of KEL1 (K, K1) phenotype, expressed in K562 and HEK293 cells, had no endothelin-3-converting activity, in contrast to the common KEL2 (k, K2) phenotype. We demonstrate that KEL1 red blood cells and also a soluble recombinant form of KEL1 protein (s-Kell KEL1) have similar enzymatic activity as the common Kell phenotype. In addition we show that KEL6 red blood cells, which are more prevalent in persons of African heritage than in Caucasians also have endothelin-3-converting enzyme activity and that the recombinant soluble form of KEL6 protein (s-Kell KEL6) has similar K(m) values as the wild-type.

K immunisation is observed in some polytransfused patients and pregnant women but does not occur in all cases of K incompatibility. This study analysed the role of genetic background in this selective response to K antigen by investigating HLA-DRB1 alleles associated with K immunisation in a southern European population. HLA-DRB1 genotyping was performed by polymerase chain reaction sequence-specific oligonucleotide/sequence-specific primer procedures in 54 K immunised patients and 200 healthy controls. The frequency of HLA-DRB1*11 was significantly higher in K immunised patients than healthy controls: 31 of 54 (57%) vs. 56 of 200 (28%) (P(c)0.001). In the remaining K immunised HLA-DRB1*11-negative patients, the frequency of HLA-DRB1*13 was increased: 14 of 23 (61%) vs. 49 of 144 in healthy controls (34%) (P0.02). The combined frequency of the two HLA-DRB1 alleles (HLA-DRB1*11 and HLA-DRB1*13) was 83% in K immunised patients when compared with 52% in healthy controls (P(c)0.001). K and k differ by a single amino acid T193 (M). The DRB1*11 and DRB1*13 alleles share a HLA-DRB1 gene sequence containing S in position 13, D in 70 and A in 74, and coding for the P4 pocket within the HLA-DR binding groove. This feature of the HLA-DRB1 gene could be involved in the K peptide presentation through a polymorphism ligand specific for the T193 (M) of K. In conclusion, this study demonstrated a high frequency of HLA-DRB1*11 or HLA-DRB1*13 alleles in K immunised patients, which could be due to specific K peptide presentation by HLA-DR molecules.

Summary Twenty Mabs of human or murine origin were studied. Serological characterization was achieved by the gel technique with common, rare, and enzyme-modified RBCs. Three clones bound to cell surface proteins on immunoblots: 1 anti-Lu b and 2 Mabs raised to a purified Kell glycoprotein. Four anti-K Mabs precipitated the expected 93kD protein and a dimeric form under non-reducing conditions.

BACKGROUND: The management of a pregnant woman with the rare Ko phenotype and anti-Ku is a special challenge, because matched blood is extremely rare and the possibility of severe hemolytic disease of the newborn is high. CASE REPORT: A 30-year-old woman with rare Ko (Knull) phenotype presented at 18 weeks of gestation with positive indirect agglutination test results. She had anti-Ku due to previous blood transfusion, one pregnancy, and two abortions. STUDY DESIGN AND METHODS: During this pregnancy, anti-Ku titers ranged from 1024 to 4096. At the 26th week of gestation ultrasound showed a hydropic fetus and urgent intrauterine exchange transfusion was performed with the maternal red blood cells (RBCs). Recombinant human erythropoietin (rHu-EPO) and intravenous (IV) iron were administered to the mother to ensure an adequate supply of matched RBCs for intrauterine transfusions and possible perinatal hemorrhage. RESULTS: Intrauterine transfusions were repeated every 1 to 3 weeks. By 35 weeks 2 days of gestation, the mother had donated 4 units of blood, and four intrauterine transfusions had been performed. Cesarean section was then decided and a healthy male newborn was born. He was treated with phototherapy but without exchange transfusions. By the 15th day of life rHu-EPO was administrated to the newborn because of anemia. The maternal RBCs completely disappeared from the child's blood by Day 100. CONCLUSIONS: As shown in this case, treatment with rHu-EPO and IV Fe has effectively increased the mother's capacity to donate RBCs for autologous use and intrauterine transfusions, with no adverse effects to the mother or the child.

BACKGROUND: Kell and XK, two distinct red blood cell membrane proteins, are linked by a disulfide bond and form the Kell blood group complex. Kell surface antigens are expressed early during erythropoiesis but the onset of expression of XK which carries the Kx antigen is unknown. STUDY DESIGN AND METHODS: To determine whether Kell and XK are synchronously expressed, sorted human hematopoietic progenitor cells and mouse progenitor cells of defined lineage were studied. To determine the onset of expression, human marrow and cord blood cells were sorted into three subpopulations, representing stem, multipotent, and erythroid progenitor cells, and the expression of Kell and XK was determined by reverse transcription–polymerase chain reaction (RT-PCR) and fluorescence-activated cell sorting (FACS) analysis. Mouse Kell and XK transcripts were determined by cDNA blotting of progenitor cells of defined lineage. RESULTS: By RT-PCR, human peripheral blood progenitor cells had weak expression of Kell and XK transcripts but FACS analysis did not detect surface antigens. Kell and XK transcripts are expressed in multipotent progenitor cells and these cells express Kell surface antigens. The expression of Kx antigen in progenitor cells was not determined owing to nonspecific reactions with the antibody. By cDNA blotting, mouse Kell expression was detected in bipotential megakaryocytes-erythroid cells and in colony-forming units–erythroid (CFU–E) and burst-forming units–erythroid (BFU–E), whereas XK was only detected in CFU-E and BFU-E. CONCLUSION: Both Kell and XK transcripts occur early during erythropoiesis; however, expression may not be coincident because, in mice, Kell transcripts, but not XK, occur in bipotential megakaryocytes-erythroid progenitor cells.

Anti-k is a Kell-related antibody. There is little correlation between the maternal antibody titre and the severity of haemolytic disease of the foetus and newborn, and anaemia is usually associated with low bilirubin levels. Severe erythroblastosis has been reported with a low titre anti-k (IAT 8-16). We report a case of severe haemolytic disease of the newborn (HDN) due to anti-k. HDN was associated with a normal bilirubin level and reticulocytopenia. The foetus was monitored by ultrasound, and delivery by elective caesarean section (CS) was planned. The mother was admitted 1 week before the expected date of delivery, and the infant was delivered by urgent CS. The infant required exchange transfusion. As suitable plasma-reduced (k antigen(-)) red cell units were not readily available, k- SAGM red cell units (preserved in extended storage media: SAGM sodium chloride, adenine, glucose and mannitol) were provided. The post-transfusion Hb remained stable, and the infant did not require further transfusion support. Our findings (reticulocytopenia and normal bilirubin levels) support the hypothesis that the pathogenesis of anaemia and haemolysis in anti-k HDN may be similar to that in anti-K (suppression of erythropoesis and immune destruction of K+ erythroid progenitor cells by macrophages in the foetal liver). The ideal product for exchange transfusion is plasma-reduced RBC, less than 5-days old. We provided a 4-day-old SAGM red cell unit for exchange transfusion in a term infant, and this was uneventful. Caution should be taken, however, and renal function and electrolyte levels should be monitored closely. More information is required regarding the safety of SAGM units for exchange transfusion.

The absence of all Kell blood group antigens (K(0) phenotype) is very rare. K(0) persons, however, can produce clinically significant anti-Ku (K5) after transfusion and/or pregnancy and require K(0) blood for transfusion. Ten alleles giving rise to the K(0) phenotype have been reported: different populations were studied although none from Scandinavia.Three K(0) samples were identified by blood banks in Sweden (Uppsala, Umeå, and Linköping) during a 20-year period. Kell antigen typing was performed with standard serologic techniques by the respective blood banks and K(0) status was confirmed by the International Blood Group Reference Laboratory in Bristol, England. Polymerase chain reaction and DNA sequencing of the KEL coding region (exons 1-19) was performed on genomic DNA.The Uppsala K(0) was homozygous for a 1540CT substitution in exon 13, leading to an immediate stop codon. The Umeå K(0) was homozygous for 1023delG in exon 8 that results in a frameshift and a premature stop codon in exon 9. In the Linköping K(0), a previously reported mutation ga at +1 of intron 3 was found.Two novel and one previously reported null alleles at the KEL locus are described. The identified nonsense mutations abolish expression of the Kell glycoprotein and are thus responsible for the K(0) phenotype in these Swedish families.

Objectives Few reports have been published of the current clinical management of anti-Kell alloimmunization in pregnancy; its low frequency of occurrence means that the few long series published have covered very ample time periods in which different kinds of clinical management have overlapped. The objective of the present paper is to present our experience in the current clinical management of pregnant women who are positive for the anti-Kell antibody. Study design A retrospective analysis was carried out of the case histories of pregnant women who were alloimmunized for the Kell antigen and who were studied and/or treated at the Department of Fetal Medicine in the Virgen de las Nieves University Hospital in Granada (Spain), between 2000 and 2004. The clinical management included the basal measurement of the titre of antibodies, the identification of the paternal phenotype (and that of the fetus, if necessary), the ultrasonographic monitoring of the fetus to detect signs of anaemia, sampling of fetal blood by cordocentesis when fetal anaemia was suspected, and fetal intravascular transfusion when necessary. Results Of the 10 pregnancies with anti-Kell antibodies, The Kell antigen was confirmed in the fetus in three cases, in all of which moderate to severe fetal anaemia developed, requiring fetal intravascular transfusions. Although one of the fetus developed antenatal hydrops, a good perinatal result was advised. Conclusions The current approach to anti-Kell alloimmunization enables pregnant women who have Kell-positive fetuses to be treated successfully.