September 1979
The Journal o f P E D I A T R I C S
447
The spectrum of ABO hemolytic disease of the newborn infant A series ofl,704 infants of blood group 0 mothers have been studied to determine the relation between the degree of red cell sensitization and the cord hemoglobin and bilirubin concentrations. The infants with blood group A or B had significantly higher cord bilirubin and lower cord hemoglobin concentrations than the group 0 babies. Those infants whose red cells had the greatest evidence o f sensitization had the highest bilirubin and lowest hemoglobin levels. The infants in whom no antibody was demonstrable on the red cells or in the red cell eiuaie also had significantly higher cord bilirubin and lower cord hemoglobin levels than the ABO compatible group," it is suggested that these infants had sufficient erythrocyte sensitization to produce mild hemolysis. ABO incompatibility represents a spectrum of hemolytic disease extending from thos e in which there is little laboratory evidence of erythrocyte sensitization, but evidence of hemolysis, to severe hemolytic ~tisease in which erythrocyte sensitization is usually easily demonstrable.
L. Desjardins, M.D., F.R.C.P.(C), M.A. Blajehman, M.D., F.R.C.P.(C),* C. Chintu, M.D., F.R.C.P.(C), M. Gent, M.Se., and A. Zipursky, M.D., F.R.C.P.(C), H a m i l t o n , Ont., C a n a d a
A B O HEMOLYTIC DISEASE is diagnosed by the appearance of jaundice in the firsl 24 hours of life, together with evidence of hemolysis with sphereocytosis. Serologic evidence of the disease and its clinical manifestations are variable? We have examined this problem and have concluded that ABO incompatibility represents a spectrum of disease in newborn infants, which only at its extreme end may manifest clinically as ABO hemolytic disease of the newborn infant.
METHODS The study represents retrospective data from all (1,704) babies of group O mothers born over a 20-month period at the Henderson General Hospital. Hamilton. Ontario. Canada. Cord blood was obtained by syringe at the time of delivery. One sample in EDTA was obtained for complete blood counts, and another clotted sample was From the Department.s of Pathology, Pediatrics, Epidemiology and Biostatistiea, MeMaster University, and the Canadian Red Cross Blood Transfusion Service. *Reprint address: Department of Pathology, MeMaster University Medieal Centre. 1200 Main St. W.. Hamilton, Ont.. L8S 4J9.
0022-3476/79/090447+04500.40/0 9 1979 The C. V. Mosby Co.
obtained for serologic testing and for the determination of cord bilirubin concentration.~ 3 The direct antiglobulin (Coombs) test and the heat elution test were performed using standard techniques?' ~ All statistical comparisons were performed by analysis of variance.
RESULTS In Table I, it can be seen that cord blood from group A and B babies had significantly lower hemoglobin and higher bilirubin concentrations than in group O babies. The cord blood hemoglobin and cord bilirubin concentrations of group A babies were not significantly different from those of group B babies, The group A and B babies were further subdivided into three groups on the basis of the degree of red cell sensitization (Table II).6 Those babies having a positive direct antiglobulin test and a positive heat eluate were considered as one group. A second group consisted of those babies with a negative direct antiglobulin test and a positive heat eluate. The third group had both a negative direct antiglobulin test and a negative eluate. The cord bilirubin concentrations increased as the degree Of sensitization increased. The control group (O babies) had a mean concentration of 1.51 mg/dl. The group A babies
Vol. 95, No. 3, pp. 447-449
448
"Desjardins et al.
The Journal of Pediatrics September 1979
Table I. Cord hemoglobin and bilirubin concentrations of 1,704 group A, B, and O babies of b l o o d group O mothers Baby's blood group 0 A B
No. of subjects
1,024 (806)* 526 (415)* 154 (119)*
Bilirubin +_ 1 S D (mg / dl)
1.51 + 0.56 1.81 -+ 0.81"~ 1.71 + 0.75+
Hemoglobin +_ 1 SD (gm/dl)
16.59 + 1.71 15.99 -+ 1.7lt 15.78 -+ 2.02+
*The figures in parentheses represent the number of babies in whom hemoglobinconcentrationwas determined.All babieshad cord bilirubin determinationsdone. "l'Analysisof variance showed a significantdifference(P < 0.001) when compared to Group"O babies, had a mean bilirubin concentration of 1.72. 1.75. and 1.93 mg/dl, respectively, with the highest value occurring in the group with greatest sensitization (direct antiglobulin test positive, eluate positive). All values in the group A babies were significantly higher than in the control group (P < 0.01). Conversely, the hemoglobin values were lowest in the most sensitized group. The results of these groups represent a statistically significant shift in the whole group and are not due to a small subpopulation of infants within each group with abnormally high levels of bilirubin or low levels of hemoglobin. Similar results were noted for the blood group B babies; these differences also were statistically significant (P < 0.001 l, except that the bilirubin concentration in the least sensitized group was not different than that of the control group. During the study period. 27 of the 680 ABO incompatible babies were diagnosed independently by their physicians as having clinically significant ABO hemolytic disease. The basis of the diagnosis was either hyperbilirubinemia (bilirubin greater than 12 mg/dl), hemolysis (anemia a n d / o r reticulocytosis), or both. In 22 infants the direct antiglobulin and eluate tests were positive; in four the direct antiglobulin test was negative, and the eluate test was positive; both tests were negative in only one patient. In these infants, diagnosed as having clinically significant ABO hemolytic disease of the newborn infant, there was more evidence of erythrocyte sensitization, based on the greater incidence of a positive direct antiglobulin test, than in the remainder of the series (Table II). This may, in part, stem from the use of the serologic t e s t information by clinicians in reaching a diagnosis. In order to assess more accurately the significance of serologic evidence, we studied another series of eight babies with clinically significant ABO hemolytic disease for which the criteria for diagnosis were strict. In this small series, diagnosis was accepted only if all of the
following were positive: (1) Jaundice within 24 hours of life; (2) anemia (cord Hgb < 14.0 gm/dl or day 1 capi!lary Hgb < 14.8 gm/dl); (3) cord bilirubin (total > 3 mg/dl); (4) hyperbilirubinemia (total > 15 mg/dl); and (5) spherocytosis. Using these criteria, it was shown that all eight of these "proven" cases were direct antiglobulin test positive, eluate positive. DISCUSSION This study has examined a series of infants born of group O mothers in order to assess the effects of ABO incompatibility on the baby's blood and to consider thereby the nature of ABO hemolytic disease. It would appear that the majority of ABO incompatible infants have anti-A or B antibody on their cells, yet only a small number were diagnosed as having ABO hemolytic disease. Clearly, therefore, the finding of anti-A or anti-B on an infant's red blood cells is not diagnostic of ABO hemolytic disease of the newborn infant. Similar findings have been reported by otherss 8 Alter et aP reported that in 61% of ABO incompatible infants, antibody was demonstrable on the red cells. They also noted, as in our series, that the eluate was always positive when the direct antiglobulin test was positive, but that the reverse was not true. It appears that cells with a positive direct antiglobulin test have more antibody on their surface than those cells on which antibody is demonstrable only by elution. 6 It would follow, therefore, that in clinically significant ABO hemolytic disease one would expect that the direct antiglobulin test should nearly always b e positive. That this is the case has been described by Alter et al, 1~ who found a positive direct antiglobulin test in all infants diagnosed as having ABO hemolytic disease, Hemolysis due to IgG antibodies is thought to depend largely on the amount of antibody on the ceil. Romano et al 6 have shown that the strength of the direct antiglobulin test in ABO hemolytic disease is related to the number of antibody molecules or~"the red cell. With this background, the data in Table II become of considerable interest. All three groups of ABO incompatible infants had some evidence of hemolysis (higher cord bilirubin and lower hemoglobin values) when compare d to the ABO compatible group. This was evident even in that group in which no evidence of erythrocyte sensitization was demonstrable in vitro "(i.e., direct antiglobulin test negative, eluate negative), In addition, no statistically significant differences existed when comparing the cord bilirnbin concentration and cord hemoglobin in blood group A with blood group B babies. Using these data, the pathogenesis of ABO hemolytic disease can be revaluated. Anti-A or anti-B antibodies of the IgG class cross the placenta to sensitize the A or B red ceils of the fetus. Low concentrations of antibody may
Volume 95 Number 3
A B O hemolytic disease
449
Table II. Cord h e m o g l o b i n a n d bilirubin c o n c e n t r a t i o n in g r o u p A, B a n d O babies b o r n to 9 group O m o t h e r s
Baby's blood group
No. of babies
DACT~
Eluate
A
195 (157)* 204 (157) 127 (101)
+ -
+ + -
B
28 (18)
+
+
O
57 (45) 69 (56) 1,024 (806)
--
+--
Bilirubin +_ 1 SD (mg / dl) 1.93 1.75 1.72 1.89 1.86 1.52 1.51
_ 0.98 + 0.7 _+ 0.7 _+ 1.1 -+ 0.66 -+ 0.62 _+ 0.56
Hemoglobin +_ 1 SD (gm/ dl) 15.88 + 1.94 15.98 + 1.58 16.18 _+ 1.54 15.13 _+ 1.7 15.59 -!--2.0 16.14 -4- 2.1 16.59 __+ 1.71
*The figures in parentheses represent the number of babies in whom hemoglobin concentrations were determined. Bilirubin concentrations were determined in all. tDAGT = Direct antiglobulin test.
sensitize cells so that a mild degree of hemolysis m a y occur, even t h o u g h there is no in vitro evidence o f sensitization. W i t h higher concentrations o f antibody, the degree o f sensitization increases so that a n t i b o d y c a n b e d e m o n s t r a t e d initially by elution techniques a n d t h e n by a positive direct antiglobulin test. W i t h this greater sensitization there is f u r t h e r shortening o f red cell life span, a n d these infants h a v e more evidence o f hemolysis. W h e n sensitization is sufficiently great, hemolysis m a y b e severe e n o u g h for the babies to b e clinically diagnosed as h a v i n g ABO h e m o l y t i c disease of the n e w b o r n infant. However, red cell life s p a n is p r o b a b l y s h o r t e n e d even in the g r o u p with the least sensitization. W e conclude, therefore, t h a t most if n o t all A B O i n c o m p a t i b l e infants h a v e some degree o f h e m o l y t i c disease. It can b e speculated also t h a t n e o n a t a l h y p e r b i l i r u b i n e m i a due to causes o t h e r t h a n A B O h e m o l y t i c disease m a y be more severe in A B O i n c o m p a t i b l e t h a n in c o m p a t i b l e inlhnts. It is p r o b a b l e that the q u a n t i t y o f a n t i b o d y on the r e d cell is n o t the only factor d e t e r m i n i n g the degree o f fetal red cell destruction. In some instances, low c o n c e n t r a t i o n s of I g G a n t i b o d y h a v i n g a h i g h degree of biologic activity m a y cause significant hemolysis. TM 12 T h a t this m a y b e the case in A B O hemolytic disease of the n e w b o r n i n f a n t is evident f r o m the m a n y instances in which there is d e m o n strable a n t i b o d y o n the red cells with little evidence of clinical hemolysis. Conversely, o t h e r infants with serologically e q u i v a l e n t quantities of a n t i b o d y m a y h a v e sufficient hemolysis to require exchange transfusion. 1~, 14 This p h e n o m e n o n m a y b e related to the subclass o f the I g G a n t i b o d y or to its ability to be involved in m a c r o p h a g e a d h e r e n c e or to both. TM TM REFERENCES
1. Mollison PL: Blood transfusion in clinical medicine, ed 5, Oxford, 1972, Blackwell Scientific Publication, pp 664668. 2. Michaelsson M: Bilirubin determination in serum and urine, Scand J Clin Lab Invest 13(suppl 56):1, 1961.
3. Thompson RPH: Modification of Michaelsson's methods for measurement of plasma total bilirubin, J Clin Pathol 22:439, 1969. 4. A m e r i c a n Association of Blood Banks: Technical methods and procedures of the American Association of Blood Banks, ed 7, Washington, DC, 1977, p 156. 5. American Association of Blood Banks: Technical methods and procedures of the American Association of Blood Banks, ed 7, Washington, DC, 1977, p 186. 6. Romano EL, Hughes-Jones NC, and Mollison PL: Direct antiglobulin reaction in ABO-hemolytic disease of the newborn, Br Med J 1:524, 1973. 7. Voak D, and Williams MA: An explanation of the failure of the direct antiglobulin test to detect erythrocyte sensitization in ABO Haemolytic disease of the Newborn and observations on pinocytosis of IgG anti-A antibodies by infant (cord) red cells, Br J Haematol 20:9, 1971. 8. Orzaleski M, Gloria F, Lucarelli P, et al: Relationship between direct Coombs test positivity and neonatal jaundice, Pediatrics 51:288, 1973. 9. Alter AA, Prutting DL, Hertz S, et al: Serologic specificity of the positive direct antiglobulin test in ABO heterospecific pregnancies, Obstet Gynecol 34:102, 1969. 10. Alter AA, Feldman F, Tversky J e t al: Direct antiglobulin test in ABO hemolytic disease of the newborn, Obstet Gynecol 33:846, 1969. 11. Gilliland BC, Baxter E, and Evans RS: Red cell antibodies in acquired hemolytic anemia with negative antiglobulin serum tests, N Engl J Med 285:252, 1971. 12. Romano EL, and Mollison PL: Red cell destruction in vivo by low concentrations of IgG anti-A, Br J Haematol 29:121, 1975. 13. Voak D, and Bowley CC: A detailed serological study on the prediction and diagnosis of ABO hemolytic disease of the newborn (ABO HD), Vox Sang 17:321, 1969. 14. Voak D: The pathogenesis of ABO haemolytic disease of the newborn, Vox Sang 17:481, 1969. 15. Vandem Borne AEGKr, Beckers D, and Engelfriet CP: Mechanisms of red cell destruction mediated by noncomplement binding IgG antibodies: the essential role in vivo of the Fc part of IgG, Br J Haematol 36:485, 1977. 16. van der Meulen FW, van der Hart M, Fleer A, et al: The role of adherence to human mononuclear phagocytes in the destruction of red cells sensitized with non-complement binding IgG antibodies, Br J Haematol 38:541, 1978.
The Journal o f P E D I A T R I C S
447
The spectrum of ABO hemolytic disease of the newborn infant A series ofl,704 infants of blood group 0 mothers have been studied to determine the relation between the degree of red cell sensitization and the cord hemoglobin and bilirubin concentrations. The infants with blood group A or B had significantly higher cord bilirubin and lower cord hemoglobin concentrations than the group 0 babies. Those infants whose red cells had the greatest evidence o f sensitization had the highest bilirubin and lowest hemoglobin levels. The infants in whom no antibody was demonstrable on the red cells or in the red cell eiuaie also had significantly higher cord bilirubin and lower cord hemoglobin levels than the ABO compatible group," it is suggested that these infants had sufficient erythrocyte sensitization to produce mild hemolysis. ABO incompatibility represents a spectrum of hemolytic disease extending from thos e in which there is little laboratory evidence of erythrocyte sensitization, but evidence of hemolysis, to severe hemolytic ~tisease in which erythrocyte sensitization is usually easily demonstrable.
L. Desjardins, M.D., F.R.C.P.(C), M.A. Blajehman, M.D., F.R.C.P.(C),* C. Chintu, M.D., F.R.C.P.(C), M. Gent, M.Se., and A. Zipursky, M.D., F.R.C.P.(C), H a m i l t o n , Ont., C a n a d a
A B O HEMOLYTIC DISEASE is diagnosed by the appearance of jaundice in the firsl 24 hours of life, together with evidence of hemolysis with sphereocytosis. Serologic evidence of the disease and its clinical manifestations are variable? We have examined this problem and have concluded that ABO incompatibility represents a spectrum of disease in newborn infants, which only at its extreme end may manifest clinically as ABO hemolytic disease of the newborn infant.
METHODS The study represents retrospective data from all (1,704) babies of group O mothers born over a 20-month period at the Henderson General Hospital. Hamilton. Ontario. Canada. Cord blood was obtained by syringe at the time of delivery. One sample in EDTA was obtained for complete blood counts, and another clotted sample was From the Department.s of Pathology, Pediatrics, Epidemiology and Biostatistiea, MeMaster University, and the Canadian Red Cross Blood Transfusion Service. *Reprint address: Department of Pathology, MeMaster University Medieal Centre. 1200 Main St. W.. Hamilton, Ont.. L8S 4J9.
0022-3476/79/090447+04500.40/0 9 1979 The C. V. Mosby Co.
obtained for serologic testing and for the determination of cord bilirubin concentration.~ 3 The direct antiglobulin (Coombs) test and the heat elution test were performed using standard techniques?' ~ All statistical comparisons were performed by analysis of variance.
RESULTS In Table I, it can be seen that cord blood from group A and B babies had significantly lower hemoglobin and higher bilirubin concentrations than in group O babies. The cord blood hemoglobin and cord bilirubin concentrations of group A babies were not significantly different from those of group B babies, The group A and B babies were further subdivided into three groups on the basis of the degree of red cell sensitization (Table II).6 Those babies having a positive direct antiglobulin test and a positive heat eluate were considered as one group. A second group consisted of those babies with a negative direct antiglobulin test and a positive heat eluate. The third group had both a negative direct antiglobulin test and a negative eluate. The cord bilirubin concentrations increased as the degree Of sensitization increased. The control group (O babies) had a mean concentration of 1.51 mg/dl. The group A babies
Vol. 95, No. 3, pp. 447-449
448
"Desjardins et al.
The Journal of Pediatrics September 1979
Table I. Cord hemoglobin and bilirubin concentrations of 1,704 group A, B, and O babies of b l o o d group O mothers Baby's blood group 0 A B
No. of subjects
1,024 (806)* 526 (415)* 154 (119)*
Bilirubin +_ 1 S D (mg / dl)
1.51 + 0.56 1.81 -+ 0.81"~ 1.71 + 0.75+
Hemoglobin +_ 1 SD (gm/dl)
16.59 + 1.71 15.99 -+ 1.7lt 15.78 -+ 2.02+
*The figures in parentheses represent the number of babies in whom hemoglobinconcentrationwas determined.All babieshad cord bilirubin determinationsdone. "l'Analysisof variance showed a significantdifference(P < 0.001) when compared to Group"O babies, had a mean bilirubin concentration of 1.72. 1.75. and 1.93 mg/dl, respectively, with the highest value occurring in the group with greatest sensitization (direct antiglobulin test positive, eluate positive). All values in the group A babies were significantly higher than in the control group (P < 0.01). Conversely, the hemoglobin values were lowest in the most sensitized group. The results of these groups represent a statistically significant shift in the whole group and are not due to a small subpopulation of infants within each group with abnormally high levels of bilirubin or low levels of hemoglobin. Similar results were noted for the blood group B babies; these differences also were statistically significant (P < 0.001 l, except that the bilirubin concentration in the least sensitized group was not different than that of the control group. During the study period. 27 of the 680 ABO incompatible babies were diagnosed independently by their physicians as having clinically significant ABO hemolytic disease. The basis of the diagnosis was either hyperbilirubinemia (bilirubin greater than 12 mg/dl), hemolysis (anemia a n d / o r reticulocytosis), or both. In 22 infants the direct antiglobulin and eluate tests were positive; in four the direct antiglobulin test was negative, and the eluate test was positive; both tests were negative in only one patient. In these infants, diagnosed as having clinically significant ABO hemolytic disease of the newborn infant, there was more evidence of erythrocyte sensitization, based on the greater incidence of a positive direct antiglobulin test, than in the remainder of the series (Table II). This may, in part, stem from the use of the serologic t e s t information by clinicians in reaching a diagnosis. In order to assess more accurately the significance of serologic evidence, we studied another series of eight babies with clinically significant ABO hemolytic disease for which the criteria for diagnosis were strict. In this small series, diagnosis was accepted only if all of the
following were positive: (1) Jaundice within 24 hours of life; (2) anemia (cord Hgb < 14.0 gm/dl or day 1 capi!lary Hgb < 14.8 gm/dl); (3) cord bilirubin (total > 3 mg/dl); (4) hyperbilirubinemia (total > 15 mg/dl); and (5) spherocytosis. Using these criteria, it was shown that all eight of these "proven" cases were direct antiglobulin test positive, eluate positive. DISCUSSION This study has examined a series of infants born of group O mothers in order to assess the effects of ABO incompatibility on the baby's blood and to consider thereby the nature of ABO hemolytic disease. It would appear that the majority of ABO incompatible infants have anti-A or B antibody on their cells, yet only a small number were diagnosed as having ABO hemolytic disease. Clearly, therefore, the finding of anti-A or anti-B on an infant's red blood cells is not diagnostic of ABO hemolytic disease of the newborn infant. Similar findings have been reported by otherss 8 Alter et aP reported that in 61% of ABO incompatible infants, antibody was demonstrable on the red cells. They also noted, as in our series, that the eluate was always positive when the direct antiglobulin test was positive, but that the reverse was not true. It appears that cells with a positive direct antiglobulin test have more antibody on their surface than those cells on which antibody is demonstrable only by elution. 6 It would follow, therefore, that in clinically significant ABO hemolytic disease one would expect that the direct antiglobulin test should nearly always b e positive. That this is the case has been described by Alter et al, 1~ who found a positive direct antiglobulin test in all infants diagnosed as having ABO hemolytic disease, Hemolysis due to IgG antibodies is thought to depend largely on the amount of antibody on the ceil. Romano et al 6 have shown that the strength of the direct antiglobulin test in ABO hemolytic disease is related to the number of antibody molecules or~"the red cell. With this background, the data in Table II become of considerable interest. All three groups of ABO incompatible infants had some evidence of hemolysis (higher cord bilirubin and lower hemoglobin values) when compare d to the ABO compatible group. This was evident even in that group in which no evidence of erythrocyte sensitization was demonstrable in vitro "(i.e., direct antiglobulin test negative, eluate negative), In addition, no statistically significant differences existed when comparing the cord bilirnbin concentration and cord hemoglobin in blood group A with blood group B babies. Using these data, the pathogenesis of ABO hemolytic disease can be revaluated. Anti-A or anti-B antibodies of the IgG class cross the placenta to sensitize the A or B red ceils of the fetus. Low concentrations of antibody may
Volume 95 Number 3
A B O hemolytic disease
449
Table II. Cord h e m o g l o b i n a n d bilirubin c o n c e n t r a t i o n in g r o u p A, B a n d O babies b o r n to 9 group O m o t h e r s
Baby's blood group
No. of babies
DACT~
Eluate
A
195 (157)* 204 (157) 127 (101)
+ -
+ + -
B
28 (18)
+
+
O
57 (45) 69 (56) 1,024 (806)
--
+--
Bilirubin +_ 1 SD (mg / dl) 1.93 1.75 1.72 1.89 1.86 1.52 1.51
_ 0.98 + 0.7 _+ 0.7 _+ 1.1 -+ 0.66 -+ 0.62 _+ 0.56
Hemoglobin +_ 1 SD (gm/ dl) 15.88 + 1.94 15.98 + 1.58 16.18 _+ 1.54 15.13 _+ 1.7 15.59 -!--2.0 16.14 -4- 2.1 16.59 __+ 1.71
*The figures in parentheses represent the number of babies in whom hemoglobin concentrations were determined. Bilirubin concentrations were determined in all. tDAGT = Direct antiglobulin test.
sensitize cells so that a mild degree of hemolysis m a y occur, even t h o u g h there is no in vitro evidence o f sensitization. W i t h higher concentrations o f antibody, the degree o f sensitization increases so that a n t i b o d y c a n b e d e m o n s t r a t e d initially by elution techniques a n d t h e n by a positive direct antiglobulin test. W i t h this greater sensitization there is f u r t h e r shortening o f red cell life span, a n d these infants h a v e more evidence o f hemolysis. W h e n sensitization is sufficiently great, hemolysis m a y b e severe e n o u g h for the babies to b e clinically diagnosed as h a v i n g ABO h e m o l y t i c disease of the n e w b o r n infant. However, red cell life s p a n is p r o b a b l y s h o r t e n e d even in the g r o u p with the least sensitization. W e conclude, therefore, t h a t most if n o t all A B O i n c o m p a t i b l e infants h a v e some degree o f h e m o l y t i c disease. It can b e speculated also t h a t n e o n a t a l h y p e r b i l i r u b i n e m i a due to causes o t h e r t h a n A B O h e m o l y t i c disease m a y be more severe in A B O i n c o m p a t i b l e t h a n in c o m p a t i b l e inlhnts. It is p r o b a b l e that the q u a n t i t y o f a n t i b o d y on the r e d cell is n o t the only factor d e t e r m i n i n g the degree o f fetal red cell destruction. In some instances, low c o n c e n t r a t i o n s of I g G a n t i b o d y h a v i n g a h i g h degree of biologic activity m a y cause significant hemolysis. TM 12 T h a t this m a y b e the case in A B O hemolytic disease of the n e w b o r n i n f a n t is evident f r o m the m a n y instances in which there is d e m o n strable a n t i b o d y o n the red cells with little evidence of clinical hemolysis. Conversely, o t h e r infants with serologically e q u i v a l e n t quantities of a n t i b o d y m a y h a v e sufficient hemolysis to require exchange transfusion. 1~, 14 This p h e n o m e n o n m a y b e related to the subclass o f the I g G a n t i b o d y or to its ability to be involved in m a c r o p h a g e a d h e r e n c e or to both. TM TM REFERENCES
1. Mollison PL: Blood transfusion in clinical medicine, ed 5, Oxford, 1972, Blackwell Scientific Publication, pp 664668. 2. Michaelsson M: Bilirubin determination in serum and urine, Scand J Clin Lab Invest 13(suppl 56):1, 1961.
3. Thompson RPH: Modification of Michaelsson's methods for measurement of plasma total bilirubin, J Clin Pathol 22:439, 1969. 4. A m e r i c a n Association of Blood Banks: Technical methods and procedures of the American Association of Blood Banks, ed 7, Washington, DC, 1977, p 156. 5. American Association of Blood Banks: Technical methods and procedures of the American Association of Blood Banks, ed 7, Washington, DC, 1977, p 186. 6. Romano EL, Hughes-Jones NC, and Mollison PL: Direct antiglobulin reaction in ABO-hemolytic disease of the newborn, Br Med J 1:524, 1973. 7. Voak D, and Williams MA: An explanation of the failure of the direct antiglobulin test to detect erythrocyte sensitization in ABO Haemolytic disease of the Newborn and observations on pinocytosis of IgG anti-A antibodies by infant (cord) red cells, Br J Haematol 20:9, 1971. 8. Orzaleski M, Gloria F, Lucarelli P, et al: Relationship between direct Coombs test positivity and neonatal jaundice, Pediatrics 51:288, 1973. 9. Alter AA, Prutting DL, Hertz S, et al: Serologic specificity of the positive direct antiglobulin test in ABO heterospecific pregnancies, Obstet Gynecol 34:102, 1969. 10. Alter AA, Feldman F, Tversky J e t al: Direct antiglobulin test in ABO hemolytic disease of the newborn, Obstet Gynecol 33:846, 1969. 11. Gilliland BC, Baxter E, and Evans RS: Red cell antibodies in acquired hemolytic anemia with negative antiglobulin serum tests, N Engl J Med 285:252, 1971. 12. Romano EL, and Mollison PL: Red cell destruction in vivo by low concentrations of IgG anti-A, Br J Haematol 29:121, 1975. 13. Voak D, and Bowley CC: A detailed serological study on the prediction and diagnosis of ABO hemolytic disease of the newborn (ABO HD), Vox Sang 17:321, 1969. 14. Voak D: The pathogenesis of ABO haemolytic disease of the newborn, Vox Sang 17:481, 1969. 15. Vandem Borne AEGKr, Beckers D, and Engelfriet CP: Mechanisms of red cell destruction mediated by noncomplement binding IgG antibodies: the essential role in vivo of the Fc part of IgG, Br J Haematol 36:485, 1977. 16. van der Meulen FW, van der Hart M, Fleer A, et al: The role of adherence to human mononuclear phagocytes in the destruction of red cells sensitized with non-complement binding IgG antibodies, Br J Haematol 38:541, 1978.
