790
LEPERS TO THE EDITOR
4. Skikne BS, Flowers CH, Cook JD. Serum transferrin receptor: a quantitative measure of tissue iron deficiency. Blood 1990;75:1870-6. 5. Zauber NP. Iron supplementation after femoral head replacement for patients with normal iron levels. JAMA 1992;267:525-7.
An anti-K apparently induced by Enterococcus faecalk in
a 30-year-old man
To the Editor: There are several reports describing apparent bacterial stimulation of anti-K production. Marsh et al.’ reported production of the antibody in a 20-day-old child who had acute enterocolitis caused by Escherichia coli 0125:BlS. Possible relationships between infection with Mycobucteriwn tuberculo&J and Morganella morganii‘ and the production of anti-K have been documented. McGinnis et al.5 showed that, while no Klike antigenic structure was demonstrable on intact type D streptococci, such a structure was detectable in a suspension of disrupted organisms. Savalonis et al.6 tested a number of gram-negative bacteria for the presence of K-like antigens. Their only positive finding involved E. coli 0125:B15, subtype 12808, but the cases cited above strongly suggest that other bacteria are able to stimulate production of anti-K in man. We recently encountered a 30-year-old man who was admitted to our hospital with acute necrotizing pancreatitis secondary to alcohol abuse. The patient later became septic and developed adult respiratory distress syndrome and renal insufficiency. On the third hospital day, a blood culture showed the presence of Enterococcus fuecalis, and a culture of the femoral catheter tip grew Enterobucter cloacae. On that same day, the patient became febrile (39.4”C) and hypotensive (RR 80/25). The peripheral blood count showed 10.5 x lo9 white cells per L, and treatment with cephazoline, gentamicin, and metronidazole was started. The patient’s blood type was group 0, Rhpositive, and on Day 3 the antibody screening test was negative. The patient was transfused with 2 units of red cells, retrospectively shown to be K- ,and 6 units of plasma that had been screened and shown not to contain atypical blood group antibodies. Two days later (hospital Day 5 ) , the antibody screening test was repeated when 2 additional units of blood were ordered. This time the test was positive and anti-K was identified by our local blood bank. The rapid production of anti-K by this patient, who did not receive K + red cells, appears to be related to his bacterial infections. Although it is impossible to be sure which, if either, of the organisms was responsible for the stimulation of antibody production, E. fuecalis appears a more likely candidate than E. cloacae, because the latter organism has been shown to lack a K-like structure. Studies are needed to show whether E. fueculis carries a K-like structure. C.J.A. DOELMAN,PHD W.F. WESTERMA”, MD E. VAN VOORSTTOT VOORST,MSc K. MIEDEMA,PHD Departments of Clinical Chemistry, Haematology, and Pulmonary Diseases Ziekenhuis De Weezenlanden Groot Wezenland 20 801I JW Zolle The Netherlands
References 1. Marsh WL. Nichols ME, @en R, et al. Naturally occurring antiKell stimulated by E.coIi enterocolitis in a 20-day-old child. Transfusion 1987;18:149-54.
TRANSFUSION Vol. 32. No. 8-1592
2. Tegoli J, Sausais L, Issitt PD. Another example of a “naturallyoccurring” anti-K1. Vox Sang 1967;12:305-7. 3. Kanel GC, Davis I, Bowhan JE. “Naturally-occurring” anti-K1: possible association with mycobacterium infection. Transfusion 1978;18:472-3. 4. Pereira A, Monteagudo J, Rovira M, Mazzara R, Reverter JC, Castillo R. Anti-K1 of the IgA class associated with Morganellu rnorganii infection. Transfusion 1989;29:549-51. 5 . McGinnis MH, MacLowry JD, Holland PV. Acquisition of K:llike antigen during terminal sepsis. Transfusion 1984;24:28-30. 6. Savalonis JM, Kalish RI, Cummings EA, Ryan RW, Aloisi R. Kell blood group activity of gram-negative bacteria. Transfusion 1988;28:229-32.
Cold agglutinin autoimmune hemolytic anemia as a severe complication in B-cell acute lymphocytic leukemia To the Editor: Cold agglutinin autoimmune hemolytic anemia (CA-AIHA) is a rare event in reticuloendothelial neoplasias (e.g., chronic lymphocytic leukemia, Hodgkins’ disease, multiple myeloma) and some infectious diseases (e.g., mycoplasma and viral infections).’P2 However, there are no data regarding any association between acute lymphocytic leukemia and CA-AIHA. We describe a 27-year-old man whose B-cell acute lymphocytic leukemia (B-ALWAB-subtype L3) was complicated by severe CA-AIHA. After induction chemotherapy (including prednisone, asparaginase, and methotrexate), anemia was treated with 2 units of packed red cell concentrates that effected an adequate rise in hemoglobin level from 79 to 101 g per L. Two days later, the patient developed significant jaundice and pallor and experienced a fall in hemoglobin level to 51 g per L. Signs of hemolysis were evident: increase in indirect bilirubin from 5.3 to 18.8 Fmol per L, increase in lactate dehydrogenase from 151 to 420 U per L, and decrease in haptoglobin to less than 0.1 g per L. Immunohematologic testing revealed a positive indirect antiglobilin test (IAT) and direct antiglobulin test (DAT). The IAT was positive with all red cells tested using albumin or low-ionic-strength saline, as was a one-stage enzyme test at 37°C using bromelin (Ortho Diagnostic Systems, Raritan, NJ). The DAT was positive with polyspecific anti-human globulin and monospecific anti-C3d-antiglobulin serum (Biotest, Frankfurt, Germany) with a maximum titer of 8. The DAT was negative with monospecific anti-IgG and anti-IgA (Ortho). Treatment of the serum with dithiothreitol led to a negative IAT. Tests for cold agglutinins (4°C) were positive with a titer of 2000. An ether eluate did not react with antibody screening cells or with cells from donors of the packed red cell concentrates previously transfused. Additional tests showed that the antibody did not react with cord blood cells, which confirmed its specificity as auto-anti-I (IgM). Infectious diseases were excluded (mycoplasma, viral infections), as were a biphasic hemolysin (Donath Landsteiner), paroxysmal nocturnal hemoglobinuria, lues, rheumatologic disease, and neuraminidase-induced T activation. The patient was treated with prednisone (2 m a g ) ; subsequent transfusions were at 37°C and were tolerated well. After conditioning treatment with cyclophosphamide (120 m a g ) and hyperfractionated whole body irradiation (12 Gy), an allogeneic bone marrow transplantation (BMT) was performed using marrow form the patient’s HLA-identical, mixed lymphocyte culture-negative sister who was blood group A l , Rh-positive, as was the donor. Compatibility testing of red cells was positive with serum of the patient and donor red cells (IAT), but negative with red cells of the patient and the donor’s
LEPERS TO THE EDITOR
4. Skikne BS, Flowers CH, Cook JD. Serum transferrin receptor: a quantitative measure of tissue iron deficiency. Blood 1990;75:1870-6. 5. Zauber NP. Iron supplementation after femoral head replacement for patients with normal iron levels. JAMA 1992;267:525-7.
An anti-K apparently induced by Enterococcus faecalk in
a 30-year-old man
To the Editor: There are several reports describing apparent bacterial stimulation of anti-K production. Marsh et al.’ reported production of the antibody in a 20-day-old child who had acute enterocolitis caused by Escherichia coli 0125:BlS. Possible relationships between infection with Mycobucteriwn tuberculo&J and Morganella morganii‘ and the production of anti-K have been documented. McGinnis et al.5 showed that, while no Klike antigenic structure was demonstrable on intact type D streptococci, such a structure was detectable in a suspension of disrupted organisms. Savalonis et al.6 tested a number of gram-negative bacteria for the presence of K-like antigens. Their only positive finding involved E. coli 0125:B15, subtype 12808, but the cases cited above strongly suggest that other bacteria are able to stimulate production of anti-K in man. We recently encountered a 30-year-old man who was admitted to our hospital with acute necrotizing pancreatitis secondary to alcohol abuse. The patient later became septic and developed adult respiratory distress syndrome and renal insufficiency. On the third hospital day, a blood culture showed the presence of Enterococcus fuecalis, and a culture of the femoral catheter tip grew Enterobucter cloacae. On that same day, the patient became febrile (39.4”C) and hypotensive (RR 80/25). The peripheral blood count showed 10.5 x lo9 white cells per L, and treatment with cephazoline, gentamicin, and metronidazole was started. The patient’s blood type was group 0, Rhpositive, and on Day 3 the antibody screening test was negative. The patient was transfused with 2 units of red cells, retrospectively shown to be K- ,and 6 units of plasma that had been screened and shown not to contain atypical blood group antibodies. Two days later (hospital Day 5 ) , the antibody screening test was repeated when 2 additional units of blood were ordered. This time the test was positive and anti-K was identified by our local blood bank. The rapid production of anti-K by this patient, who did not receive K + red cells, appears to be related to his bacterial infections. Although it is impossible to be sure which, if either, of the organisms was responsible for the stimulation of antibody production, E. fuecalis appears a more likely candidate than E. cloacae, because the latter organism has been shown to lack a K-like structure. Studies are needed to show whether E. fueculis carries a K-like structure. C.J.A. DOELMAN,PHD W.F. WESTERMA”, MD E. VAN VOORSTTOT VOORST,MSc K. MIEDEMA,PHD Departments of Clinical Chemistry, Haematology, and Pulmonary Diseases Ziekenhuis De Weezenlanden Groot Wezenland 20 801I JW Zolle The Netherlands
References 1. Marsh WL. Nichols ME, @en R, et al. Naturally occurring antiKell stimulated by E.coIi enterocolitis in a 20-day-old child. Transfusion 1987;18:149-54.
TRANSFUSION Vol. 32. No. 8-1592
2. Tegoli J, Sausais L, Issitt PD. Another example of a “naturallyoccurring” anti-K1. Vox Sang 1967;12:305-7. 3. Kanel GC, Davis I, Bowhan JE. “Naturally-occurring” anti-K1: possible association with mycobacterium infection. Transfusion 1978;18:472-3. 4. Pereira A, Monteagudo J, Rovira M, Mazzara R, Reverter JC, Castillo R. Anti-K1 of the IgA class associated with Morganellu rnorganii infection. Transfusion 1989;29:549-51. 5 . McGinnis MH, MacLowry JD, Holland PV. Acquisition of K:llike antigen during terminal sepsis. Transfusion 1984;24:28-30. 6. Savalonis JM, Kalish RI, Cummings EA, Ryan RW, Aloisi R. Kell blood group activity of gram-negative bacteria. Transfusion 1988;28:229-32.
Cold agglutinin autoimmune hemolytic anemia as a severe complication in B-cell acute lymphocytic leukemia To the Editor: Cold agglutinin autoimmune hemolytic anemia (CA-AIHA) is a rare event in reticuloendothelial neoplasias (e.g., chronic lymphocytic leukemia, Hodgkins’ disease, multiple myeloma) and some infectious diseases (e.g., mycoplasma and viral infections).’P2 However, there are no data regarding any association between acute lymphocytic leukemia and CA-AIHA. We describe a 27-year-old man whose B-cell acute lymphocytic leukemia (B-ALWAB-subtype L3) was complicated by severe CA-AIHA. After induction chemotherapy (including prednisone, asparaginase, and methotrexate), anemia was treated with 2 units of packed red cell concentrates that effected an adequate rise in hemoglobin level from 79 to 101 g per L. Two days later, the patient developed significant jaundice and pallor and experienced a fall in hemoglobin level to 51 g per L. Signs of hemolysis were evident: increase in indirect bilirubin from 5.3 to 18.8 Fmol per L, increase in lactate dehydrogenase from 151 to 420 U per L, and decrease in haptoglobin to less than 0.1 g per L. Immunohematologic testing revealed a positive indirect antiglobilin test (IAT) and direct antiglobulin test (DAT). The IAT was positive with all red cells tested using albumin or low-ionic-strength saline, as was a one-stage enzyme test at 37°C using bromelin (Ortho Diagnostic Systems, Raritan, NJ). The DAT was positive with polyspecific anti-human globulin and monospecific anti-C3d-antiglobulin serum (Biotest, Frankfurt, Germany) with a maximum titer of 8. The DAT was negative with monospecific anti-IgG and anti-IgA (Ortho). Treatment of the serum with dithiothreitol led to a negative IAT. Tests for cold agglutinins (4°C) were positive with a titer of 2000. An ether eluate did not react with antibody screening cells or with cells from donors of the packed red cell concentrates previously transfused. Additional tests showed that the antibody did not react with cord blood cells, which confirmed its specificity as auto-anti-I (IgM). Infectious diseases were excluded (mycoplasma, viral infections), as were a biphasic hemolysin (Donath Landsteiner), paroxysmal nocturnal hemoglobinuria, lues, rheumatologic disease, and neuraminidase-induced T activation. The patient was treated with prednisone (2 m a g ) ; subsequent transfusions were at 37°C and were tolerated well. After conditioning treatment with cyclophosphamide (120 m a g ) and hyperfractionated whole body irradiation (12 Gy), an allogeneic bone marrow transplantation (BMT) was performed using marrow form the patient’s HLA-identical, mixed lymphocyte culture-negative sister who was blood group A l , Rh-positive, as was the donor. Compatibility testing of red cells was positive with serum of the patient and donor red cells (IAT), but negative with red cells of the patient and the donor’s
