Brief Reports
Severe Hemolytic Disease of the Newborn Associated with Anti-Jsb R. F. LOWE,A. T. MUSENGEZI, A N D P. MOORES From the Harari Central Hospital, Salisbury. and the Natal Blood Transfusion Service, Durban. South Africa
The red blood cells of the group A infant of a group 0 central Afncan Negro woman of the Zezuru tribe with anti-Lea and anti-Jsb in her serum were found to be strongly agglutinated by a commercial antiglobulin reagent six days after birth. The high concentration of bilirubin in the infant's serum gradually decreased but he k a m e profoundly anemic and, in the absence of a suitable donor, was successhlly transfused with blood &om his mother. Subsequent tests using the maternal IUIU-JS~diluted one in ten to avoid agglutination by the Mti-k!' showed that the fkquency of the Js(b-) phenotype in group 0 Z e m is approximately one per cent.
ANTI-JS~ (anti-K7), the antibody specific for Jsb (k7, an antigen in the Kell blood group ~ y s t e m )was , ~ first implicated as having been the cause of mild hemolytic disease of the newborn by Wake et aL5 This report describes the infant son of a central African Negro woman, shown to have anti-Jsbin her serum, who was severely affected by hemolytic disease of the newborn. As compatible blood was not immediately available, the infant was transfused with blood donated by his mother, and he made a good recovery. Case Report
When first seen the infant was six days old with a weight of 2.26 kg, a septic umbilicus, and a history of deepening jaundice. He was referred to Harari Central Hospital where tests showed that his serum bilirubin was 16.5 mg/dl, hemoglobin 7.8 gdl, red blood cell count 2.31 million/ pl, white blood cell count 6,400 per pl, platelet count 524,000 per pl, alkaline phosphatase 19 King-Armstrong units/dl, serum glutamic oxalic transaminase 6 units/liter and serum glutamic Received for publication January 27, 1977; accepted September 21, 1977.
pyruvic transaminase 4 units/liter. The VDRL test was negative and the direct antiglobulin test with a commercial reagent was strongly positive. The umbilical sepsis was successfully treated with antibiotics and during the next two days the infant's spleen and liver became palpable and his serum bilirubin fell to 13.0 mg/dl. By the fourth day (he was now ten days old) his hemoglobin had fallen to 4.6 g/dl. The mother was blood group 0 ccDEe. By indirect antiglobulin tests her serum agglutinated red blood ceils of 66 group 0 central African Negroes, 40 group 0 Whites and all ten samples of a commercial red blood cell antibody identification panel. The infant's blood group was A ccDEe. It was decided to transfuse him without delay with red blood cells from his mother, removing as much as possible of the plasma beforehand. Approximately 40 ml of red blood cells were given, and on the following day the infant's hemoglobin had risen to 9.8 g/dl. Five days later his hemoglobin was 8.1 g/dl, red blood cell count 3.26 million/pI and no further treatment was considered necessary. He was discharged and when seen two months later looked well, his weight had increased to 4.65 kg. His hemoglobin on this occasion was 7.8 g/dl, red blood cell count 3.43 millionlpl, alkaline phosphatase 4 King-Armstrong unitsldl and serum bilirubin 0.8 mgfdl. At one year of age the infant was seen again and was completely well with no clinical signs of anemia. Mrs. Anna, the infant's mother, was 30 years of age and gravida 6 para 5. She was a member of the Zezuru tribe of Central African Negroes from the Salisbury area. Her fourth pregnancy had terminated at six months in an abortion but there was no evidence that her first, second, third or fifth infants had suffered from hemolytic disease at birth. Her second and third infants had died in childhood aged 30 months and 13 months respectively. A sample of her blood was sent to Durban where one of us (P.M.) grouped her red blood cells as follows: 0, MsU, PI, ccDEe, h P + ,
0041-1132-78-0700-0466-0040 0 J. B. Lippincott Co. Transfusion 1uly-A~gust 1978
466
Volume 18
Number 4
Volume 18 Number 4
HDN ASSOCIATED WITH ANTI-Jsb
hrB+, Cw-, Lu(a-b+), K-k+, Kp(a-b+), Js(a+b-), Le(a-b-), Fy(a-), Fy:-3, Jk(b+), I + , Sd(a+), Co(a+b-), Di(b+), G e + , Gy(a+), Vel+, Yt(a+), Sm+, At(a+), Yk(a+), Lan+, and Jr+. Mrs. Anna's direct antiglobulin test was negative. Anti-A hemolysin was present in her serum and it was not inhibited by 2-mercaptoethanol. Her anti-A also agglutinated A, cells in saline and in enzyme titrations at 22 C to a titer of 256 and at 37 C to a titer of 512. In addition two antibodies, anti-Jsb and anti-Lea, were identified in her serum and confirmed by absorption and elution studies. The anti-Lea agglutinated Le(a+) Js(a+b-) red blood cells moderately well (++) by saline and enzyme techniques at 22 C but not by the indirect antiglobulin test. It was inhibited by 2-mercaptoethanol. The titer of her anti-Jsb, which agglutinated Le(a-) Js(a-b+) red blood cells weakly by enzyme techniques (+) but strongly by indirect antiglobulin test (+ + + +), was 64 both at delivery and in another specimen drawn two months later. This antibody was not inhibited by 2-mercaptoethanol. Reference samples of group 0 Le(a-) KO and Le(a-) Js(a+b-) red blood cells kindly sent by blood grouping laboratories in the USA were not agglutinated by her serum on each occasion, excluding anti-N, -S, -C, -Lua, -Leb, -Fya, -Fyb, and Jk". Anti-K and anti-Kpa were not excluded. Unfortunately an eluate could not be made from the first sample of the red blood cells of Mrs. Anna's infant as the sample was delayed on the journey to Durban and arrived totally hemolysed. However, in a further blood sample drawn from her infant at two years of age the red blood cell groups were found to be as follows: A,, MNs, PI, ccDEe, hP+, hrB+, Cw-, Lu(a-), K-, Kp(a-), Js(a+b+), Le(a-b-), Fy(a-), Fy:-3, Jk(b+), I + , and Sd(a-).
467
more severely affected because of the presence of both immune anti-A and anti-Jsb. It is unlikely that Mrs. Anna's immune anti-A alone was to blame for her infant's severe condition as his red blood cells were clearly well coated with immune globulin, and in hemolytic disease of the newborn due to anti-A and/or anti-B the direct antiglobulin test with normal broad-spectrum antiglobulin reagents is usually negative or only weakly positive. Red blood cells from Mrs. Anna were used for her infant's blood transfusion as it was established that her red blood cells were not agglutinated by her own antibody (her direct antiglobulin test was negative) and she was the only person with serologically compatible red blood cells available when it was decided that her infant needed blood urgently. Fortunately she was group 0, and further harm to her infant's red blood cells was minimized by removing as much plasma as possible before the transfusion was given. A better procedure might have been to have washed the cells free of plasma beforehand, but the hospital did not have the necessary equipment for this. I t is hoped that the successful outcome may encourage others faced with a similar problem to consider using maternal antibody-compatible red blood cells, in instances where the ABO and Rh groups of mother and infant are compatible, before resorting to antibody-incompatible red blood cells from o t h e r persons. Discussion Lowe,* using anti-Jsa only, found five In the absence of an eluate which might Js(a+) individuals in 35 Zezuru tested. This have provided direct evidence of the idencorresponds to a Jsa phenotype frequency of tity of the antibodies attached to the red 7.42 per cent which does not differ signifiblood cells of Mrs. Anna's infant the cantly from the Jsa frequency (9.45 and 4.17 per cent respectively) established by Fraser strongly positive direct antiglobulin test six et al. in 100 and in 98 mixed Bantu respecdays after birth was believed to indicate that the most likely cause of the infant's jaundice lively in nearby Zaire (Congo). Using Mrs. and anemia was Mrs. Anna's anti-Jsb. HowAnna's serum diluted 1 in 10 with saline, ever, in the case reported by Wake ef U I . ~ which at this dilution was shown not to in which anti-Jsb was present, jaundice and agglutinate Le(a+) Js(b-) cells, and in severe anemia did not develop and this may which no other antibodies (excluding anti-K indicate that Mrs. Anna's infant was far and anti-Kpa) were detected, three Js(b-)
468
LOWE ET AL.
individuals were found in 305 random group 0 Zezuru tested, giving a Js(b-) phenotype frequency in them of approximately one per cent. The gene frequencies in the Zezuru kindly calculated for us from this data are: Jsa = 0.0990, and Jsb = 0.9010.
Acknowledgments We would like to thank the Secretary for Health, Rhodesia, for permission to publish this case, and Dr. C. Giles, Blood Group Reference Laboratory, London, for kindly confirming the identity of the anti-Jsb.
References 1. Fraser, G.
R., E. R. Giblett, and A. G. Motulsky: Population genetic studies in the Congo. 111. Blood groups (ABO, MNSs, Rh, Jsp). Am. J. Hum. Genet. 18546, 1966. 2. Lowe, R. F.: Personal investigation.
Transfusion July-August 1978
3. Mourant, A. E., A. C. Kopek, and K. DomaniewskaSobczak: The Distribution of the Human Blood Groups and other Polyrnorphisms, 2nd ed. London, Oxford University Press, 1976, p. 537. 4. Stroup, M., M. MacIlroy, R. Walker, and J. V. Aydelotte: Evidence that Sutter belongs to the Kell blood group system. Transfusion 5309, 1965. 5 . Wake, E. J., P. D. Issitt, J. K. Reihart, R. Feldman, and A. L. Luhby: Hemolytic disease of the newborn due to anti-Jsb. Transfusion 9217, 1969.
Dr. R. F. Lowe, MRCS., LRCP., DCP.. DTM & H., Senior Pathologist, Harari Central Hospital Laboratory, Salisbury, Rhodesia. Dr. A. T. Musengezi, MB., ChB., DCH., Registrar, Department of Pediatrics and Child Health, University of Rhodesia, Salisbury, Rhodesia. Miss Phyllis Moores, M.Sc., Nat. Dip. Med. Lab. Tech. S.A., Scientific Officer, Natal Blood Transfusion Service, 149 Prince Street, Durban 4001, South Africa.
Severe Hemolytic Disease of the Newborn Associated with Anti-Jsb R. F. LOWE,A. T. MUSENGEZI, A N D P. MOORES From the Harari Central Hospital, Salisbury. and the Natal Blood Transfusion Service, Durban. South Africa
The red blood cells of the group A infant of a group 0 central Afncan Negro woman of the Zezuru tribe with anti-Lea and anti-Jsb in her serum were found to be strongly agglutinated by a commercial antiglobulin reagent six days after birth. The high concentration of bilirubin in the infant's serum gradually decreased but he k a m e profoundly anemic and, in the absence of a suitable donor, was successhlly transfused with blood &om his mother. Subsequent tests using the maternal IUIU-JS~diluted one in ten to avoid agglutination by the Mti-k!' showed that the fkquency of the Js(b-) phenotype in group 0 Z e m is approximately one per cent.
ANTI-JS~ (anti-K7), the antibody specific for Jsb (k7, an antigen in the Kell blood group ~ y s t e m )was , ~ first implicated as having been the cause of mild hemolytic disease of the newborn by Wake et aL5 This report describes the infant son of a central African Negro woman, shown to have anti-Jsbin her serum, who was severely affected by hemolytic disease of the newborn. As compatible blood was not immediately available, the infant was transfused with blood donated by his mother, and he made a good recovery. Case Report
When first seen the infant was six days old with a weight of 2.26 kg, a septic umbilicus, and a history of deepening jaundice. He was referred to Harari Central Hospital where tests showed that his serum bilirubin was 16.5 mg/dl, hemoglobin 7.8 gdl, red blood cell count 2.31 million/ pl, white blood cell count 6,400 per pl, platelet count 524,000 per pl, alkaline phosphatase 19 King-Armstrong units/dl, serum glutamic oxalic transaminase 6 units/liter and serum glutamic Received for publication January 27, 1977; accepted September 21, 1977.
pyruvic transaminase 4 units/liter. The VDRL test was negative and the direct antiglobulin test with a commercial reagent was strongly positive. The umbilical sepsis was successfully treated with antibiotics and during the next two days the infant's spleen and liver became palpable and his serum bilirubin fell to 13.0 mg/dl. By the fourth day (he was now ten days old) his hemoglobin had fallen to 4.6 g/dl. The mother was blood group 0 ccDEe. By indirect antiglobulin tests her serum agglutinated red blood ceils of 66 group 0 central African Negroes, 40 group 0 Whites and all ten samples of a commercial red blood cell antibody identification panel. The infant's blood group was A ccDEe. It was decided to transfuse him without delay with red blood cells from his mother, removing as much as possible of the plasma beforehand. Approximately 40 ml of red blood cells were given, and on the following day the infant's hemoglobin had risen to 9.8 g/dl. Five days later his hemoglobin was 8.1 g/dl, red blood cell count 3.26 million/pI and no further treatment was considered necessary. He was discharged and when seen two months later looked well, his weight had increased to 4.65 kg. His hemoglobin on this occasion was 7.8 g/dl, red blood cell count 3.43 millionlpl, alkaline phosphatase 4 King-Armstrong unitsldl and serum bilirubin 0.8 mgfdl. At one year of age the infant was seen again and was completely well with no clinical signs of anemia. Mrs. Anna, the infant's mother, was 30 years of age and gravida 6 para 5. She was a member of the Zezuru tribe of Central African Negroes from the Salisbury area. Her fourth pregnancy had terminated at six months in an abortion but there was no evidence that her first, second, third or fifth infants had suffered from hemolytic disease at birth. Her second and third infants had died in childhood aged 30 months and 13 months respectively. A sample of her blood was sent to Durban where one of us (P.M.) grouped her red blood cells as follows: 0, MsU, PI, ccDEe, h P + ,
0041-1132-78-0700-0466-0040 0 J. B. Lippincott Co. Transfusion 1uly-A~gust 1978
466
Volume 18
Number 4
Volume 18 Number 4
HDN ASSOCIATED WITH ANTI-Jsb
hrB+, Cw-, Lu(a-b+), K-k+, Kp(a-b+), Js(a+b-), Le(a-b-), Fy(a-), Fy:-3, Jk(b+), I + , Sd(a+), Co(a+b-), Di(b+), G e + , Gy(a+), Vel+, Yt(a+), Sm+, At(a+), Yk(a+), Lan+, and Jr+. Mrs. Anna's direct antiglobulin test was negative. Anti-A hemolysin was present in her serum and it was not inhibited by 2-mercaptoethanol. Her anti-A also agglutinated A, cells in saline and in enzyme titrations at 22 C to a titer of 256 and at 37 C to a titer of 512. In addition two antibodies, anti-Jsb and anti-Lea, were identified in her serum and confirmed by absorption and elution studies. The anti-Lea agglutinated Le(a+) Js(a+b-) red blood cells moderately well (++) by saline and enzyme techniques at 22 C but not by the indirect antiglobulin test. It was inhibited by 2-mercaptoethanol. The titer of her anti-Jsb, which agglutinated Le(a-) Js(a-b+) red blood cells weakly by enzyme techniques (+) but strongly by indirect antiglobulin test (+ + + +), was 64 both at delivery and in another specimen drawn two months later. This antibody was not inhibited by 2-mercaptoethanol. Reference samples of group 0 Le(a-) KO and Le(a-) Js(a+b-) red blood cells kindly sent by blood grouping laboratories in the USA were not agglutinated by her serum on each occasion, excluding anti-N, -S, -C, -Lua, -Leb, -Fya, -Fyb, and Jk". Anti-K and anti-Kpa were not excluded. Unfortunately an eluate could not be made from the first sample of the red blood cells of Mrs. Anna's infant as the sample was delayed on the journey to Durban and arrived totally hemolysed. However, in a further blood sample drawn from her infant at two years of age the red blood cell groups were found to be as follows: A,, MNs, PI, ccDEe, hP+, hrB+, Cw-, Lu(a-), K-, Kp(a-), Js(a+b+), Le(a-b-), Fy(a-), Fy:-3, Jk(b+), I + , and Sd(a-).
467
more severely affected because of the presence of both immune anti-A and anti-Jsb. It is unlikely that Mrs. Anna's immune anti-A alone was to blame for her infant's severe condition as his red blood cells were clearly well coated with immune globulin, and in hemolytic disease of the newborn due to anti-A and/or anti-B the direct antiglobulin test with normal broad-spectrum antiglobulin reagents is usually negative or only weakly positive. Red blood cells from Mrs. Anna were used for her infant's blood transfusion as it was established that her red blood cells were not agglutinated by her own antibody (her direct antiglobulin test was negative) and she was the only person with serologically compatible red blood cells available when it was decided that her infant needed blood urgently. Fortunately she was group 0, and further harm to her infant's red blood cells was minimized by removing as much plasma as possible before the transfusion was given. A better procedure might have been to have washed the cells free of plasma beforehand, but the hospital did not have the necessary equipment for this. I t is hoped that the successful outcome may encourage others faced with a similar problem to consider using maternal antibody-compatible red blood cells, in instances where the ABO and Rh groups of mother and infant are compatible, before resorting to antibody-incompatible red blood cells from o t h e r persons. Discussion Lowe,* using anti-Jsa only, found five In the absence of an eluate which might Js(a+) individuals in 35 Zezuru tested. This have provided direct evidence of the idencorresponds to a Jsa phenotype frequency of tity of the antibodies attached to the red 7.42 per cent which does not differ signifiblood cells of Mrs. Anna's infant the cantly from the Jsa frequency (9.45 and 4.17 per cent respectively) established by Fraser strongly positive direct antiglobulin test six et al. in 100 and in 98 mixed Bantu respecdays after birth was believed to indicate that the most likely cause of the infant's jaundice lively in nearby Zaire (Congo). Using Mrs. and anemia was Mrs. Anna's anti-Jsb. HowAnna's serum diluted 1 in 10 with saline, ever, in the case reported by Wake ef U I . ~ which at this dilution was shown not to in which anti-Jsb was present, jaundice and agglutinate Le(a+) Js(b-) cells, and in severe anemia did not develop and this may which no other antibodies (excluding anti-K indicate that Mrs. Anna's infant was far and anti-Kpa) were detected, three Js(b-)
468
LOWE ET AL.
individuals were found in 305 random group 0 Zezuru tested, giving a Js(b-) phenotype frequency in them of approximately one per cent. The gene frequencies in the Zezuru kindly calculated for us from this data are: Jsa = 0.0990, and Jsb = 0.9010.
Acknowledgments We would like to thank the Secretary for Health, Rhodesia, for permission to publish this case, and Dr. C. Giles, Blood Group Reference Laboratory, London, for kindly confirming the identity of the anti-Jsb.
References 1. Fraser, G.
R., E. R. Giblett, and A. G. Motulsky: Population genetic studies in the Congo. 111. Blood groups (ABO, MNSs, Rh, Jsp). Am. J. Hum. Genet. 18546, 1966. 2. Lowe, R. F.: Personal investigation.
Transfusion July-August 1978
3. Mourant, A. E., A. C. Kopek, and K. DomaniewskaSobczak: The Distribution of the Human Blood Groups and other Polyrnorphisms, 2nd ed. London, Oxford University Press, 1976, p. 537. 4. Stroup, M., M. MacIlroy, R. Walker, and J. V. Aydelotte: Evidence that Sutter belongs to the Kell blood group system. Transfusion 5309, 1965. 5 . Wake, E. J., P. D. Issitt, J. K. Reihart, R. Feldman, and A. L. Luhby: Hemolytic disease of the newborn due to anti-Jsb. Transfusion 9217, 1969.
Dr. R. F. Lowe, MRCS., LRCP., DCP.. DTM & H., Senior Pathologist, Harari Central Hospital Laboratory, Salisbury, Rhodesia. Dr. A. T. Musengezi, MB., ChB., DCH., Registrar, Department of Pediatrics and Child Health, University of Rhodesia, Salisbury, Rhodesia. Miss Phyllis Moores, M.Sc., Nat. Dip. Med. Lab. Tech. S.A., Scientific Officer, Natal Blood Transfusion Service, 149 Prince Street, Durban 4001, South Africa.
