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Pernicious anemia in the second decade of life
Volume 72 Number 3
Brie[ clinical and laboratory observations
T a b l e I. Sensitivity and specificity of copper sulfate and microhematocrit tests for hemoglobin of 10 G i n . % *
Test CuSO4 S.G. ~ 1.0458 CuSO4 S.G. z 1.0468 Hematocrit 32 per cent or less
Sensitivity (% true positives identified)
Specificity (% true negatives identified)
39/55 (70.9)
359/371 (96.7)
46/55 (84.0)
345/371 (92.9)
36/48 (75.0)
339/343 (98.8)
*Hemoglobin value taken as mean cyanmethemoglobin determinations.
of
duplicate
selected for 10 Gin. per cent (see Fig. 1) indicate that either solution is acceptable. For screening purposes the 1.0468 solution detects a significantly higher proportion of anemic patients (83.8 per cent versus 70.9 per cent) but yields more falsely positive results (34 per cent versus 25 per cent) than the 1.0458 solution.
Pernicious anemia in the
second decade of life Beatrice C. L a m p k i n , M.D.,* and William K. Schubert, M.D. CINCINNATI~
OHIO
From the Department of Pediatrics (Division of Hematology) and the Children's Hospital Clinical Research Center, University of Cincinnati College of Medicine. Supported by United States Public Health Service Grant No. FR 00123 [rom the General Clinical Research Centers Branch, National Institutes o[ Health. *Advanced Clinical Fellow of the American Cancer Society, Inc. Address, The Children's Host~ital, Cincinnati, Ohio 45229.
38 7
SUMMARY T h e low cost, portability, and simplicity of the copper sulfate technique are such that it can be highly recommended as an alternative to the microhematocrit for anemia screening in children. REFERENCES 1. Phillips, 17,. A., VanSlyke, D. D., Hamilton, P. B., Dole, V. P., Emerson, K., and Archibald, 17,. M.: Measurement of specific gravities of whole blood and plasma by standard copper sulfate solutions, J. Biol. Chem. 183: 305, 1950. 2. VanSlyke, D. D., Phillips, R. A., Dole, V. P., Hamilton, P. B., Archibald, R. M., and Plazin, J.: Calculation of hemoglobin from blood specific gravities, J. Biol. Chem. 183: 349, 1950. 3. Perkins, H. A., and Torg, B.: Standards for rejection of blood donors: A comparison of CuSO4 specific gravity, microhematocrit, and electronic hematocrit values with hemoglobin values by the cyanmethemoglobin technic, Transfusion 2: 392, 1962. 4. Costeff, H.: Methods of routine hemoglobinometry in childhood: Evaluation of copper sulfate densitometry, Arch. Dis. Childhood 40: 309, 1965.
A N E M I A results from a deficiency of vitamin B12 due to failure of the gastric mucosa to secrete intrinsic factor. Children with pernicious anemia may be divided into two broad groups according to the histology of the gastric mucosa or the secretion of gastric acid? T h e first group, congenital pernicious anemia, is characterized by deficiency of vitamin B12 appearing in early life, and is thought to be the result of a congenital lack of ability to secrete gastric intrinsic factor with no other apparent abnormality of the stomach or its secretion. Antibodies to intrinsic factor and gastric parietal cells are not present. T h e second group consists of children who present with symptoms of a deficiency of vitamin B12 in the second decade of llfe. These children have the same findings as seen in the adult with pernicious anemia: absence of intrinsic factor, achlorhydria, antibodies to parietal PERNICIOUS
3 88
Brie[ clinical and laboratory observations
cells a n d intrinsic factor, and gastric atrophy. This g r o u p m a y or m a y not have an associated endocrinopathy. T h e p u r p o s e of this p a p e r is to point out that, as in the very young child with pernicious anemia, children with pernicious a n e m i a in w h o m symptoms a p p e a r in the second d e c a d e of life m a y have free hydrochloric acid in their gastric juice a n d a normal gastric mucosa. However, because of the delayed onset of pernicious a n e m i a in these children it is unlikely that they were born with inability to secrete intrinsic factor. I n this p a p e r a 13-year-old boy with pernicious a n e m i a w h o h a d free hydrochloric acid in his gastric juice a n d a n o r m a l gastric biopsy is described.
The lournal of Pediatrics March 1968
over both wrists. With reinforcement, ankle jerks could not be elicited. As seen in Table IA, the patient had a macrocytic anemia. A diagnosis of megaloblastic anemia was confirmed on examination of a bonemarrow aspirate. The serum vitamin B12 level was found to be low, 100 pg. per milliliter as measured by microbiological assay with Lactobacillus leichmannii.* Three stools for ova and parasites were negative and the protein bound iodine was 5.4 ptg per cent. The serum calcium was 10.0 mg. per cent and the serum phosphorus was 5.1 mg. per cent. An upper gastrointestinal series was normal and *The normal range of values in Dr. John Will's Laboratory at the Cincinnati General Hospital is 150 to 500 pg. per milliliter.
T a b l e IB. L a b o r a t o r y d a t a : Special studies CASE R E P O R T An asymptomatic, 13-year-old Caucasian boy was admitted to the Children's Hospital on Aug. 27, 1963, because of anemia. He was born after a fullterm gestational period and weighed 9 pounds 8 ounces. His past history was noncontributory and there was no family history of anemia or endocrine disorders. The parents were not related. Upon physical examination, he was alert, cooperative, but pale, and he was in the fiftieth percentile for height and weight. Several hyperpigmented, discrete spots, approximately 1 cm. in diameter, were present on the lower abdomen. The spleen was palpable 1 to 2 cm. below the left costal margin. There was decreased vibratory sensation over both ankles and to a lesser extent
Be[ore therapy Schilling test Without I.F.* With I.F.
Hemoglobin (Gm./100 ml.) Red cell count (• 106) Reticulocytes (%) Hematocrit (%) Mean corpuscular volume (#c) Mean corpuscular hemoglobin (73') Mean corpuscular hemoglobin concentration (%) Morphology
Normal 1-1 89 yr. after therapy
Antibody to parietal cells
Absent under 3 89 years after starting therapy
Antithyroid antibody
Absent under 3 89 years after starting therapy
39 (Normal 29 -+ 2) 34 (Normal 34 + 2) Macrocytes and hypersegmented neutrophils
intrinsic factor.
T a b l e I C . L a b o r a t o r y d a t a : HC1 in gastric fluid after 0.1 mg. histamine p e r 10 kilograms of b o d y weight
8.2 2.12 1.2 24 113 (Normal 87 + 5)
0.7
0.6 14.7
Gastric biopsy
~I.F. z
T a b l e IA. L a b o r a t o r y d a t a : H e m a t o l o g i c a l data
31,/~ years after starting vitamin B** therapy
Three days after starting B~ therapy Time (minutes) 10 20 30 40 50 60
(degrees)
Free ] Total 17 25 32 32 15 15
---56 41 37
l ~ years after starting BI~ therapy (degrees) Free ] Total 57 108 89 124 105 93
78 120 100 138 121 103
Volume 72 Number 3
there was no protein in 4 urine specimens. As seen in Table IB, the Schilling test was diagnostic of pernicious anemia. Antibodies against human gastric parietal cells and cytoplasm of thyroid cells, with the use of the immunofluorescent technique described by Taylor and co-workers 2 and Doniach and co-workers, a could not be demonstrated at the time of diagnosis and again 3y~ years after starting therapy with vitamin B12. The hemoglobin increased to 12.9 Gm. per cent 11 days after administration of 1,000 /xg of vitamin B12 as part of the Schilling test. Gastric acidity studies are shown in Table IC. One and one-half years after starting vitamin B12 therapy, there was a striking increase in the amount of hydrochloric acid secreted by the stomach. However, there was no improvement in the Schilling test 3 89 years after therapy was begun (Table IB). The child has been observed for 3 ~ years, during which time the hematological values have remained normal and the splenomegaly, hyperpigmentation, and neurological signs have disappeared. The patient continues to receive monthly injections of 100 /~g of vitamin B12. Schilling tests in the father, mother, and two sisters were normal, and no member of the family had antibodies to parietal cells. DISCUSSION
Including our patient, 2 children who had the onset of their symptoms over 8 years of age have been reported to have pernicious anemia associated with free hydrochloric acid in their gastric juice? Both of these patients, a 15~-year-old girl reported by Harris-Jones and associates~ and our patient, had normal gastric biopsies. Since these 2 children did not have achlorhydria or gastric atrophy, they do not meet the diagnostic criteria of the older group of children with pernicious anemia. With the exception of their ages, they fulfill the requirements described for the congenital form of pernicious anemia. However, since the great majority of children with congenital pernicious anemia develop megaloblastic anemia by 2 ~ years of age 1 and since adults following total gastrectomy develop a deficiency of vitamin B~, 3 to 8 years after surgery, ~ it is unlikely that stores of vitamin B12 present at birth would have been suffi-
Brief clinical and laboratory observations
3 89
cient to prevent signs of a deficiency of vitamin B12 for almost 16 years as in the patient reported by Harris-Jones, or 13 years as in our patient. In order to explain the occurrence of pernicious anemia in the older child who does not have evidence of gastric damage, it may be hypothesized that these patients are born with marginal ability to secrete intrinsic factor at birth and for a period of time thereafter. T h e vitamin B12 absorbed with decreased intrinsic factor plus the amount present in stores at birth could account for the delayed appearance of pernicious anemia. With continued inadequate absorption of vitamin B~2, the stores finally would become depleted and a deficiency of vitamin B12 would develop. This hypothesis is supported by the following observations made by Harris-Jones and co-workers. 1. The result of the Schilling test in their patient was lower than that in normal subjects, but was slightly higher than in adult patients with pernicious anemia. 2. The results of the Schilling test in their patient became normal following the administration of carbachol, which stimulates the secretion of intrinsic factor. Another explanation for the delayed appearance of pernicious anemia in the older child would be that such children are born with adequate stores of vitamin Ba2 and norreal ability to absorb vitamin Ba2 but that the secretion of intrinsic factor stops 4 to 5 years after birth. Children with pernicious anemia in the second decade of life, therefore, may be subdivided into 3 groups: (1) children with free gastric hydrochloric acid and normal gastric mucosa; (2) children with achlorhydria and gastric atrophy; and (3) children with achlorhydria, gastric atrophy, and an associated endocrinopathy. The relationship of the older child with free hydrochloric acid in his gastric fluid and a normal gastric biopsy to the older child with achlorhydria and gastric atrophy without an associated endocrinopathy is not clear. However, since it has been reported that deficiency of vitamin B12
3 90
Brie[ clinical and laboratory observations
may cause transitory intestinal malabsorption of vitamin B12,6 it is conceivable that if the diagnosis of pernicious anemia is delayed in the older child gastric damage may occur, and that these two groups may be related. SUMMARY
A 13-year-old Caucasian boy who had pernicious anemia with normal gastric acidity and a normal gastric biopsy is described. Although these findings are characteristic of the congenital form of pernicious anemia, it is unlikely that he was born with absence of intrinsic factor since he was 13 years of age at the time symptoms of a deficiency of vitamin BI~ developed. The authors wish to thank Dr. John Will, Director, Hematology Division, University of Cincinnati College of Medicine, for his cooperation, and Mrs. Mary Knueven for assaying the sera for vitamin B12.
Aspiration of maternal blood in the etiology of massive pulmonary hemorrhage in the newborn infant
The ]ournat o[ Pediatrics March 1968
REFERENCES
1. Mclntyre, O. R., Sullivan, L. W., Jefffies, G. H., and Silver, R. H.: Pernicious anemia in childhood, New England J. Med. 272: 981, 1965. 2. Taylor, K. B., Roitt, I. M., Doniach, D., Couchman, K. G., and Shapland, C.: Autoimmune phenomena in pernicious anemia: Gastric antibodies, Brit. M. J. 2: 1347, 1962. 3. Doniaeh, D., Roitt, I. M., and Taylor, K. B.: Autoimmune phenomena in pernicious anemia. Serological overlap with thyroiditis, thyrotoxicosis, and systemic lupus erythematosus, Brit. M. J. h 1374, 1963. 4. Harris-Jones, J. N., Swan, H. T., and Tudhope, G. R. : Pernicious anemia without gastric atrophy and in presence of free hydrochloric acid: Report of case, Blood 12: 461, 1957. 5. MacLean, L. D., and Sundberg, R. D.: Incidence of megaloblastic anemia after gastreetomy, New England J. Med. 254: 885, 1956. 6. Lampkin, B. C., and Mauer, A. M.: Congenital pernicious anemia with coexistent transitory intestinal malabsorption of vitamin BI.o,Blood 30: 495, 1967.
by most authors. We have had the opportunity to study a patient in whom the maternal blood was "tagged" by a congenital hemoglobin defect (A-S hemoglobin) and a definite diagnosis of aspiration of sickled maternal blood was made in a baby with massive pulmonary hemorrhage. Although this represents an isolated observation, the possible role of this pathogenic mechanism should be reconsidered. CASE R E P O R T
Ricardo Ceballos, M.D.* BIRMINGHAM,
MANY
ALA.
PATHOGENIC
MEC I-IANIS M S
have been suggested in the production of socalled "massive pulmonary hemorrhage in the newborn infant." The possibility that the process is simply the result of aspiration of maternal blood is not considered seriously *Address, Director o] Anatomical Pathology, Associate Pro[essor o[ Pathology, University o[ Alabama Medical Center, Birmingham, Ala. 35233.
A 39-year-old Negro woman presented herself to the Obstetric Clinic at University Hospital, Birmingham, Ala., on April 7, 1967, in apparent labor. This was probably her thirteenth pregnancy. Her estimated date of confinement was about April 25. The day before coming to the clinic she had passed small amounts of blood and had felt uterine contractions. Upon admission at 2 A.M., her blood pressure was 150/100, the membranes were intact, and she was having contractions every 4 minutes. At 4:45 A.M. the membranes ruptured. At 5:00 A.M., a prolapsed cord with very weak pulse was found, the cervix being dilated to 3 cm. The head was manually rotated
Brie[ clinical and laboratory observations
T a b l e I. Sensitivity and specificity of copper sulfate and microhematocrit tests for hemoglobin of 10 G i n . % *
Test CuSO4 S.G. ~ 1.0458 CuSO4 S.G. z 1.0468 Hematocrit 32 per cent or less
Sensitivity (% true positives identified)
Specificity (% true negatives identified)
39/55 (70.9)
359/371 (96.7)
46/55 (84.0)
345/371 (92.9)
36/48 (75.0)
339/343 (98.8)
*Hemoglobin value taken as mean cyanmethemoglobin determinations.
of
duplicate
selected for 10 Gin. per cent (see Fig. 1) indicate that either solution is acceptable. For screening purposes the 1.0468 solution detects a significantly higher proportion of anemic patients (83.8 per cent versus 70.9 per cent) but yields more falsely positive results (34 per cent versus 25 per cent) than the 1.0458 solution.
Pernicious anemia in the
second decade of life Beatrice C. L a m p k i n , M.D.,* and William K. Schubert, M.D. CINCINNATI~
OHIO
From the Department of Pediatrics (Division of Hematology) and the Children's Hospital Clinical Research Center, University of Cincinnati College of Medicine. Supported by United States Public Health Service Grant No. FR 00123 [rom the General Clinical Research Centers Branch, National Institutes o[ Health. *Advanced Clinical Fellow of the American Cancer Society, Inc. Address, The Children's Host~ital, Cincinnati, Ohio 45229.
38 7
SUMMARY T h e low cost, portability, and simplicity of the copper sulfate technique are such that it can be highly recommended as an alternative to the microhematocrit for anemia screening in children. REFERENCES 1. Phillips, 17,. A., VanSlyke, D. D., Hamilton, P. B., Dole, V. P., Emerson, K., and Archibald, 17,. M.: Measurement of specific gravities of whole blood and plasma by standard copper sulfate solutions, J. Biol. Chem. 183: 305, 1950. 2. VanSlyke, D. D., Phillips, R. A., Dole, V. P., Hamilton, P. B., Archibald, R. M., and Plazin, J.: Calculation of hemoglobin from blood specific gravities, J. Biol. Chem. 183: 349, 1950. 3. Perkins, H. A., and Torg, B.: Standards for rejection of blood donors: A comparison of CuSO4 specific gravity, microhematocrit, and electronic hematocrit values with hemoglobin values by the cyanmethemoglobin technic, Transfusion 2: 392, 1962. 4. Costeff, H.: Methods of routine hemoglobinometry in childhood: Evaluation of copper sulfate densitometry, Arch. Dis. Childhood 40: 309, 1965.
A N E M I A results from a deficiency of vitamin B12 due to failure of the gastric mucosa to secrete intrinsic factor. Children with pernicious anemia may be divided into two broad groups according to the histology of the gastric mucosa or the secretion of gastric acid? T h e first group, congenital pernicious anemia, is characterized by deficiency of vitamin B12 appearing in early life, and is thought to be the result of a congenital lack of ability to secrete gastric intrinsic factor with no other apparent abnormality of the stomach or its secretion. Antibodies to intrinsic factor and gastric parietal cells are not present. T h e second group consists of children who present with symptoms of a deficiency of vitamin B12 in the second decade of llfe. These children have the same findings as seen in the adult with pernicious anemia: absence of intrinsic factor, achlorhydria, antibodies to parietal PERNICIOUS
3 88
Brie[ clinical and laboratory observations
cells a n d intrinsic factor, and gastric atrophy. This g r o u p m a y or m a y not have an associated endocrinopathy. T h e p u r p o s e of this p a p e r is to point out that, as in the very young child with pernicious anemia, children with pernicious a n e m i a in w h o m symptoms a p p e a r in the second d e c a d e of life m a y have free hydrochloric acid in their gastric juice a n d a normal gastric mucosa. However, because of the delayed onset of pernicious a n e m i a in these children it is unlikely that they were born with inability to secrete intrinsic factor. I n this p a p e r a 13-year-old boy with pernicious a n e m i a w h o h a d free hydrochloric acid in his gastric juice a n d a n o r m a l gastric biopsy is described.
The lournal of Pediatrics March 1968
over both wrists. With reinforcement, ankle jerks could not be elicited. As seen in Table IA, the patient had a macrocytic anemia. A diagnosis of megaloblastic anemia was confirmed on examination of a bonemarrow aspirate. The serum vitamin B12 level was found to be low, 100 pg. per milliliter as measured by microbiological assay with Lactobacillus leichmannii.* Three stools for ova and parasites were negative and the protein bound iodine was 5.4 ptg per cent. The serum calcium was 10.0 mg. per cent and the serum phosphorus was 5.1 mg. per cent. An upper gastrointestinal series was normal and *The normal range of values in Dr. John Will's Laboratory at the Cincinnati General Hospital is 150 to 500 pg. per milliliter.
T a b l e IB. L a b o r a t o r y d a t a : Special studies CASE R E P O R T An asymptomatic, 13-year-old Caucasian boy was admitted to the Children's Hospital on Aug. 27, 1963, because of anemia. He was born after a fullterm gestational period and weighed 9 pounds 8 ounces. His past history was noncontributory and there was no family history of anemia or endocrine disorders. The parents were not related. Upon physical examination, he was alert, cooperative, but pale, and he was in the fiftieth percentile for height and weight. Several hyperpigmented, discrete spots, approximately 1 cm. in diameter, were present on the lower abdomen. The spleen was palpable 1 to 2 cm. below the left costal margin. There was decreased vibratory sensation over both ankles and to a lesser extent
Be[ore therapy Schilling test Without I.F.* With I.F.
Hemoglobin (Gm./100 ml.) Red cell count (• 106) Reticulocytes (%) Hematocrit (%) Mean corpuscular volume (#c) Mean corpuscular hemoglobin (73') Mean corpuscular hemoglobin concentration (%) Morphology
Normal 1-1 89 yr. after therapy
Antibody to parietal cells
Absent under 3 89 years after starting therapy
Antithyroid antibody
Absent under 3 89 years after starting therapy
39 (Normal 29 -+ 2) 34 (Normal 34 + 2) Macrocytes and hypersegmented neutrophils
intrinsic factor.
T a b l e I C . L a b o r a t o r y d a t a : HC1 in gastric fluid after 0.1 mg. histamine p e r 10 kilograms of b o d y weight
8.2 2.12 1.2 24 113 (Normal 87 + 5)
0.7
0.6 14.7
Gastric biopsy
~I.F. z
T a b l e IA. L a b o r a t o r y d a t a : H e m a t o l o g i c a l data
31,/~ years after starting vitamin B** therapy
Three days after starting B~ therapy Time (minutes) 10 20 30 40 50 60
(degrees)
Free ] Total 17 25 32 32 15 15
---56 41 37
l ~ years after starting BI~ therapy (degrees) Free ] Total 57 108 89 124 105 93
78 120 100 138 121 103
Volume 72 Number 3
there was no protein in 4 urine specimens. As seen in Table IB, the Schilling test was diagnostic of pernicious anemia. Antibodies against human gastric parietal cells and cytoplasm of thyroid cells, with the use of the immunofluorescent technique described by Taylor and co-workers 2 and Doniach and co-workers, a could not be demonstrated at the time of diagnosis and again 3y~ years after starting therapy with vitamin B12. The hemoglobin increased to 12.9 Gm. per cent 11 days after administration of 1,000 /xg of vitamin B12 as part of the Schilling test. Gastric acidity studies are shown in Table IC. One and one-half years after starting vitamin B12 therapy, there was a striking increase in the amount of hydrochloric acid secreted by the stomach. However, there was no improvement in the Schilling test 3 89 years after therapy was begun (Table IB). The child has been observed for 3 ~ years, during which time the hematological values have remained normal and the splenomegaly, hyperpigmentation, and neurological signs have disappeared. The patient continues to receive monthly injections of 100 /~g of vitamin B12. Schilling tests in the father, mother, and two sisters were normal, and no member of the family had antibodies to parietal cells. DISCUSSION
Including our patient, 2 children who had the onset of their symptoms over 8 years of age have been reported to have pernicious anemia associated with free hydrochloric acid in their gastric juice? Both of these patients, a 15~-year-old girl reported by Harris-Jones and associates~ and our patient, had normal gastric biopsies. Since these 2 children did not have achlorhydria or gastric atrophy, they do not meet the diagnostic criteria of the older group of children with pernicious anemia. With the exception of their ages, they fulfill the requirements described for the congenital form of pernicious anemia. However, since the great majority of children with congenital pernicious anemia develop megaloblastic anemia by 2 ~ years of age 1 and since adults following total gastrectomy develop a deficiency of vitamin B~, 3 to 8 years after surgery, ~ it is unlikely that stores of vitamin B12 present at birth would have been suffi-
Brief clinical and laboratory observations
3 89
cient to prevent signs of a deficiency of vitamin B12 for almost 16 years as in the patient reported by Harris-Jones, or 13 years as in our patient. In order to explain the occurrence of pernicious anemia in the older child who does not have evidence of gastric damage, it may be hypothesized that these patients are born with marginal ability to secrete intrinsic factor at birth and for a period of time thereafter. T h e vitamin B12 absorbed with decreased intrinsic factor plus the amount present in stores at birth could account for the delayed appearance of pernicious anemia. With continued inadequate absorption of vitamin B~2, the stores finally would become depleted and a deficiency of vitamin B12 would develop. This hypothesis is supported by the following observations made by Harris-Jones and co-workers. 1. The result of the Schilling test in their patient was lower than that in normal subjects, but was slightly higher than in adult patients with pernicious anemia. 2. The results of the Schilling test in their patient became normal following the administration of carbachol, which stimulates the secretion of intrinsic factor. Another explanation for the delayed appearance of pernicious anemia in the older child would be that such children are born with adequate stores of vitamin Ba2 and norreal ability to absorb vitamin Ba2 but that the secretion of intrinsic factor stops 4 to 5 years after birth. Children with pernicious anemia in the second decade of life, therefore, may be subdivided into 3 groups: (1) children with free gastric hydrochloric acid and normal gastric mucosa; (2) children with achlorhydria and gastric atrophy; and (3) children with achlorhydria, gastric atrophy, and an associated endocrinopathy. The relationship of the older child with free hydrochloric acid in his gastric fluid and a normal gastric biopsy to the older child with achlorhydria and gastric atrophy without an associated endocrinopathy is not clear. However, since it has been reported that deficiency of vitamin B12
3 90
Brie[ clinical and laboratory observations
may cause transitory intestinal malabsorption of vitamin B12,6 it is conceivable that if the diagnosis of pernicious anemia is delayed in the older child gastric damage may occur, and that these two groups may be related. SUMMARY
A 13-year-old Caucasian boy who had pernicious anemia with normal gastric acidity and a normal gastric biopsy is described. Although these findings are characteristic of the congenital form of pernicious anemia, it is unlikely that he was born with absence of intrinsic factor since he was 13 years of age at the time symptoms of a deficiency of vitamin BI~ developed. The authors wish to thank Dr. John Will, Director, Hematology Division, University of Cincinnati College of Medicine, for his cooperation, and Mrs. Mary Knueven for assaying the sera for vitamin B12.
Aspiration of maternal blood in the etiology of massive pulmonary hemorrhage in the newborn infant
The ]ournat o[ Pediatrics March 1968
REFERENCES
1. Mclntyre, O. R., Sullivan, L. W., Jefffies, G. H., and Silver, R. H.: Pernicious anemia in childhood, New England J. Med. 272: 981, 1965. 2. Taylor, K. B., Roitt, I. M., Doniach, D., Couchman, K. G., and Shapland, C.: Autoimmune phenomena in pernicious anemia: Gastric antibodies, Brit. M. J. 2: 1347, 1962. 3. Doniaeh, D., Roitt, I. M., and Taylor, K. B.: Autoimmune phenomena in pernicious anemia. Serological overlap with thyroiditis, thyrotoxicosis, and systemic lupus erythematosus, Brit. M. J. h 1374, 1963. 4. Harris-Jones, J. N., Swan, H. T., and Tudhope, G. R. : Pernicious anemia without gastric atrophy and in presence of free hydrochloric acid: Report of case, Blood 12: 461, 1957. 5. MacLean, L. D., and Sundberg, R. D.: Incidence of megaloblastic anemia after gastreetomy, New England J. Med. 254: 885, 1956. 6. Lampkin, B. C., and Mauer, A. M.: Congenital pernicious anemia with coexistent transitory intestinal malabsorption of vitamin BI.o,Blood 30: 495, 1967.
by most authors. We have had the opportunity to study a patient in whom the maternal blood was "tagged" by a congenital hemoglobin defect (A-S hemoglobin) and a definite diagnosis of aspiration of sickled maternal blood was made in a baby with massive pulmonary hemorrhage. Although this represents an isolated observation, the possible role of this pathogenic mechanism should be reconsidered. CASE R E P O R T
Ricardo Ceballos, M.D.* BIRMINGHAM,
MANY
ALA.
PATHOGENIC
MEC I-IANIS M S
have been suggested in the production of socalled "massive pulmonary hemorrhage in the newborn infant." The possibility that the process is simply the result of aspiration of maternal blood is not considered seriously *Address, Director o] Anatomical Pathology, Associate Pro[essor o[ Pathology, University o[ Alabama Medical Center, Birmingham, Ala. 35233.
A 39-year-old Negro woman presented herself to the Obstetric Clinic at University Hospital, Birmingham, Ala., on April 7, 1967, in apparent labor. This was probably her thirteenth pregnancy. Her estimated date of confinement was about April 25. The day before coming to the clinic she had passed small amounts of blood and had felt uterine contractions. Upon admission at 2 A.M., her blood pressure was 150/100, the membranes were intact, and she was having contractions every 4 minutes. At 4:45 A.M. the membranes ruptured. At 5:00 A.M., a prolapsed cord with very weak pulse was found, the cervix being dilated to 3 cm. The head was manually rotated