A rare case report of autoimmune haemolytic anemia in a female child due to a Donath-Landsteiner antibody.

Paroxysmal cold hemoglobinuria is a rare form of autoimmune hemolytic anemia caused by the Donath-Landsteiner autoantibody. The condition is characterized by the presence of an IgG biphasic hemolysin with specificity to the P blood group antigen. The antibody biphasic action may be demonstrated in the Donath-Landsteiner test. While paroxysmal cold hemoglobinuria can be manifested at any age, it typically appears in children following a viral upper respiratory syndrome or immunization, though rarely. This report describes a 23-months old girl presented with 5 days history of fever, erythrocytopenia, leukocytosis and occurrence of dark urine. On admission, the physical examination showed pallor, no scleral icterus, a mild hyperemic throat and no hepatosplenomegaly. The investigations revealed severe anemia with hemoglobin of 44g/L, increased reticulocyte count (10.67%), elevated lactate dehydrogenase (2603IU/L), decreased serum haptoglobin (0.159g/L), normal G6PD. Direct antiglobulin test was positive with C3d and C3c complement components only. Direct and indirect Donath-Landsteiner tests were positive. The girl was treated with a intravenous immunoglobulin infusion and Cefotaxime. She received transfusion of red blood cells, crossmatched, although P antigen untyped. Despite this in vitro serological incompatibility she had a hemoglobin increase. The patient was discharged in stable condition on the seventh day following admission. Paroxysmal cold hemoglobinuria is a hemolytic anemia for which a specific diagnostic test is available. Timely recognition of the disease by pediatricians is crucial as well as the highly skilled hospital blood bank staff performing Donath-Landsteiner testing.

Antibodies detected in samples from 21,730 pregnant women.

Although anti-D is still the main cause of HDN, many other antibodies have been implicated. From September 1995 to April 2000,screening for RBC antibodies was performed on samples from 21,730 pregnant women regardless of RhD type. Standard tube and gel methods were used. Anti-D was identified in 254 samples; other antibody specificities were detected in 376 samples, for a total of 630 antibodies. For this study, 522 antibodies were considered clinically significant. The incidence of potentially clinically significant antibodies was 2.4 percent. The majority belonged to the Rh system, followed by anti-M, -Fya, -S, -Jka, and -Jkb. Among antibodies of no clinical significance, the most frequent were anti- H, -Lea, and -P1.

Molecular defects underlying the Kell null phenotype.

Expression of the Kell blood group system is dependent on two proteins, Kell and XK, that are linked by a single disulfide bond. Kell, a type II membrane glycoprotein, is a zinc endopeptidase, while XK, which has 10 transmembrane domains, is a putative membrane transporter. A rare phenotype termed Kell null (Ko) is characterized by the absence of Kell protein and Kell antigens from the red cell membrane and diminished amounts of XK protein. We determined the molecular basis of eight unrelated persons with Ko phenotypes by sequencing the coding and the intron-exon splice regions of KEL and, in some cases, analysis of mRNA transcripts and expression of mutants on the cell surface of transfected cells. Six subjects were homozygous: four with premature stop codons, one with a 5' splice site mutation, G to A, in intron 3, and one with an amino acid substitution (S676N) in exon 18. Two Ko persons with premature stop codons had identical mutations in exon 4 (R128Stop), another had a different mutation in exon 4 (C83Stop), and the fourth had a stop codon in exon 9 (Q348Stop). Two Ko persons were heterozygous for two mutations. One had a 5' splice site mutation (G to A) in intron 3 of one allele that caused aberrant splicing and exon skipping, and the other allele had an amino acid substitution in exon 10 (S363N). The other heterozygote had the same amino acid substitution in exon 10 (S363N) in one allele and a premature stop codon in exon 6 (R192Stop) in the other allele. The S363N and S676N mutants, expressed in 293T cells, were retained in a pre-Golgi compartment and were not transported to the cell surface, indicating that these mutations inhibit trafficking. We conclude that several different molecular defects cause the Kell null phenotype.