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July 1964, Vol 108, No. 1 >
Article | July 1964

Hemolytic Anemias and Folic Acid Deficiency in Children FREE

A MAJID SHOJANIA, MD; SAMUEL GROSS, MD
[+] Author Affiliations

Received for publication Dec 17, 1963.

Present address: (Dr. Shojania) Department of Pediatrics, University of Manitoba, Winnipeg, Canada.

Supported in part by grant (HE 04578), National Institutes of Health, Public Health Service and Wellington, Ohio United Appeal.

Read in part at the Midwestern Society for Pediatric Research Meetings, Nov 2, 1963, Chicago.


Am J Dis Child. 1964;108(1):53-61. doi:10.1001/archpedi.1964.02090010055007.
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References
Comments

For the past several years an increasing number of reports concerning the occurrence of megaloblastic anemia and folic acid deficiency in association with chronic hemolytic anemia have appeared in the literature. The comments regarding this combination have differed widely. Opinions have ranged from a common occurrence and a definite relationship in the pathogenesis of aplastic crises on the one hand to a rare occurrence and no definite relationship on the other hand. In addition, little mention has been made regarding its occurrence in children.

During a six-month period of investigation of folate levels in various hematological conditions, we had the opportunity to study serum folate levels, urinary formiminoglutamic acid excretion (FIGLU), and marrow aspirations in 24 patients with chronic hemolytic anemias. Although this was not a prospective study, we believe that the report of our findings aids in understanding some of the questions relative to folic acid deficiency in chronic

REFERENCES

1 +
Waters, A. H., and Mollin, D. L.:  Studies on Folic Acid Activity of Human Serum , J Clin Path 14:335, 1961;.
2 +
Zalusky, R., and Herbert, V.:  Urinary Formiminoglutamic Acid as Test of Folic Acid Deficiency , Lancet 1:108, 1962;.
3 +
Ham, T. H.: Syllabus of Laboratory Examination in Clinical Diagnosis , Cambridge, Mass: Harvard University Press, 1950;.
4 +
Paper Electrophoresis Technique: Method for Hemoglobin, technical bulletin No. TB 6045B, Spinco division, Beckman Instrument, Palo Alto, Calif. 1958.
5 +
Ferris, T. G.; Easterling, R. E.; and Budd, R. E.:  Hemoglobin Electrophoresis in Acrylamide Gel , Blood 19:479, 1962;.
6 +
Ardeman, S.; Chanarin, I.; and Frankland, A. W.:  Pelger-Huët Anomaly and Megaloblastic Anemia , Blood 22:472, 1963;.
7 +
Herbert, V.:  Experimental Nutritional Folate Deficiency in Man , Trans Ass Amer Physicians 75:307, 1962;.
8 +
Shojania, A. M., and Gross, S.:  Folic Acid Deficiency and Prematurity , J Pediat 64:3231964;.
9 +
Gross, S.: Hematological Studies on Erythropoietic Porphyria: New Case With Severe Hemolysis, Chronic Thrombocytopenia and Folic Acid Deficiency, Blood (June) 1964, to be published.
10 +
Gruelund, S.:  Megaloblastic Hemolytic Anemia , Acta Med Scand ( (suppl 239) ) 138:101, 1950;.
11 +
Haenel, J.:  Discussion of Paper by Gasser, C.: Erythroblastopenie aigue dans les anémies hémolytiques , Sang 21:237, 1950;.
12 +
Davidson, L. S. P.:  Thirty Years of Experience With Megaloblastic Anemia , Edinburgh Med J 59:315, 1952;.
13 +
Zuelzer, W. W., and Rutzky, J.:  Megaloblastic Anemia of Infancy , Advances Pediat 6:243, 1953;.
14 +
Dacie, J. V.: Haemolytic Anaemias , New York: Grune and Stratton, Inc., 1954;, p. 70.
15 +
Goldberg, M. A., and Schwartz, S. O.:  Mediterranean Anemia in a Negro Complicated by Pernicious Anemia of Pregnancy , Blood 9:648, 1954;.
16 +
Heffernan, C. K., and Jaswon, N.:  Case of Paroxysmal Nocturnal Haemoglobinuria Associated With Secondary Haemochromatosis, a Lower Nephron Nephrosis and Megaloblastic Anaemia , J Clin Path 8:211, 1955;.
17 +
Baikie, A. G., and Pirrie, R.:  Megaloblastic Erythropoiesis in Idiopathic Acquired Haemolytic Anaemia , Scot Med J 1:330, 1956;.
18 +
Drury, M. I., and Georghegan, F.:  Congenital Haemolytic Anaemia Complicated by Megaloblastic Anaemia of Pregnancy , Brit Med J 2:393, 1957;.
19 +
Greig, H. B. W., et al:  Familial Crisis in Hereditary Spherocytosis , S Afr J Med Sci 23:17, 1958;.
20 +
Willoughby, M. L. N., et al:  Megaloblastic Erythropoiesis in Acquired Haemolytic Anaemia , Blood 17:351, 1961;.
21 +
Oliner, H. L., and Heller, P.:  Megaloblastic Erythropoiesis and Acquired Hemolysis in Sickle Cell Anemia , New Eng J Med 26:19, 1959;.
22 +
Kohler, H. G.; Meynell, M. J.; and Cooke, W. J.:  Spherocytic Anaemia Complicated by Megaloblastic Anaemia , Brit Med J 779, 1960;.
23 +
Heller, P., and Venger, N.:  Problems in Differentiation of Megaloblastic Anemias , Med Clin N Amer 46:121, 1962;.
24 +
Robinson, M. G., and Watson, R. J.:  Megaloblastic Anemia Complicating Thalassemia Major , Amer J Dis Child 105:275, 1963;.
25 +
Jonsson, U.: "Nutritional Megaloblastic Anemia in Sickle Cell States and Relation of Folic Acid to Blastic Crisis in Haemolytic Anaemia," in the Proceedings of the Seventh Congress of the International Society of Hematology, Rome, 1958, New York: Intercontinental Medical Book Corporation, 1960, p 155.
26 +
Jonsson, U.; Rath, O. S.; and Kirkpatrick, C. I. F.:  Nutritional Megaloblastic Anemia Associated With Sickle Cell States , Blood 14:535, 1959;.
27 +
Pierce, L. E., and Rath, C. E.:  Evidence for Folic Acid Deficiency in Genesis of Anemic Sickle Cell Crisis , Blood 20:19, 1962;.
28 +
Chanarin, I.; Burman, D.; and Bennet, M.:  Familial Aplastic Crisis in Hereditary Spherocytosis: Urocanic Acid and FIGLU Excretion Studies in Case of Megaloblastic Anemia , Blood 20:33, 1962;.
29 +
Spray, G. H., and Witts, L. J.:  Utilization of Folic Acid in Anemia and Leukemia , Clin Sci 12:385, 1953;.
30 +
Chatterjea, J. B.:  "Section on Haemoglobin in India"  in Abnormal Haemoglobins , J. H. P. Jonxis, and J. F. Delafresnaye, ed., Springfield, Ill: Charles C Thomas, 1959;.
31 +
Chanarin, I.; Dacie, J. V.; and Mollin, D. L.:  Folic Acid Deficiency in Haemolytic Anaemia , Brit J Haemat 5:245, 1959;.
32 +
MacIver, J. E., and Went, L. N.:  Sickle Cell Anaemia Complicated by Megaloblastic Anaemia of Infancy , Brit Med J 1:775, 1960;.
33 +
Luhby, A. L., and Cooperman, J. M.:  Folic Acid Deficiency in Thalassemia Major , Lancet 2:490, 1961;.
34 +
Pearson, H. A.: "Megaloblastic Crisis of Sickle Cell Anaemia, Coincidence or Fact," in the Society for Pediatric Research program abstracts, 33rd Annual Meeting, Atlantic City, New Jersey, May, 1963, p 74.
35 +
Chanarin, I.:  Urocanic Acid and Formiminoglutamic Acid Excretion in Megaloblastic Anaemia and Other Conditions: Effect of Specific Therapy , Brit J Haemat 9:141, 1963;.
36 +
Grasbeck, R.; Björksten, B.; and Nyberg, W.:  Formiminoglutamic Acid in Urine of Folic Acid Deficiency , Nord Med 66:1343, 1961;.
37 +
Watson-Williams, E. J.:  Folic Acid Deficiency in Sickle-Cell Anaemia , E Afr Med J 39:213, 1962;.
38 +
Herbert, V.:  Minimal Daily Adult Folate Requirement , AMA Arch Intern Med 110:649, 1962;.
39 +
Zalusky, R., and Herbert, V.:  Megaloblastic Anemia in Scurvy With Response to 50 Micrograms of Folic Acid Daily , New Eng J Med 265:1033, 1961;.
40 +
Jandl, J. H., and Greenberg, M. S.:  Bone Marrow Failure Due to Relative Nutritional Deficiency in Cooley's Hemolytic Anemia: Painful "Erythropoietic Crisis" in Response to Folic Acid , New Eng J Med 260:461, 1959;.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

References

1 +
Waters, A. H., and Mollin, D. L.:  Studies on Folic Acid Activity of Human Serum , J Clin Path 14:335, 1961;.
2 +
Zalusky, R., and Herbert, V.:  Urinary Formiminoglutamic Acid as Test of Folic Acid Deficiency , Lancet 1:108, 1962;.
3 +
Ham, T. H.: Syllabus of Laboratory Examination in Clinical Diagnosis , Cambridge, Mass: Harvard University Press, 1950;.
4 +
Paper Electrophoresis Technique: Method for Hemoglobin, technical bulletin No. TB 6045B, Spinco division, Beckman Instrument, Palo Alto, Calif. 1958.
5 +
Ferris, T. G.; Easterling, R. E.; and Budd, R. E.:  Hemoglobin Electrophoresis in Acrylamide Gel , Blood 19:479, 1962;.
6 +
Ardeman, S.; Chanarin, I.; and Frankland, A. W.:  Pelger-Huët Anomaly and Megaloblastic Anemia , Blood 22:472, 1963;.
7 +
Herbert, V.:  Experimental Nutritional Folate Deficiency in Man , Trans Ass Amer Physicians 75:307, 1962;.
8 +
Shojania, A. M., and Gross, S.:  Folic Acid Deficiency and Prematurity , J Pediat 64:3231964;.
9 +
Gross, S.: Hematological Studies on Erythropoietic Porphyria: New Case With Severe Hemolysis, Chronic Thrombocytopenia and Folic Acid Deficiency, Blood (June) 1964, to be published.
10 +
Gruelund, S.:  Megaloblastic Hemolytic Anemia , Acta Med Scand ( (suppl 239) ) 138:101, 1950;.
11 +
Haenel, J.:  Discussion of Paper by Gasser, C.: Erythroblastopenie aigue dans les anémies hémolytiques , Sang 21:237, 1950;.
12 +
Davidson, L. S. P.:  Thirty Years of Experience With Megaloblastic Anemia , Edinburgh Med J 59:315, 1952;.
13 +
Zuelzer, W. W., and Rutzky, J.:  Megaloblastic Anemia of Infancy , Advances Pediat 6:243, 1953;.
14 +
Dacie, J. V.: Haemolytic Anaemias , New York: Grune and Stratton, Inc., 1954;, p. 70.
15 +
Goldberg, M. A., and Schwartz, S. O.:  Mediterranean Anemia in a Negro Complicated by Pernicious Anemia of Pregnancy , Blood 9:648, 1954;.
16 +
Heffernan, C. K., and Jaswon, N.:  Case of Paroxysmal Nocturnal Haemoglobinuria Associated With Secondary Haemochromatosis, a Lower Nephron Nephrosis and Megaloblastic Anaemia , J Clin Path 8:211, 1955;.
17 +
Baikie, A. G., and Pirrie, R.:  Megaloblastic Erythropoiesis in Idiopathic Acquired Haemolytic Anaemia , Scot Med J 1:330, 1956;.
18 +
Drury, M. I., and Georghegan, F.:  Congenital Haemolytic Anaemia Complicated by Megaloblastic Anaemia of Pregnancy , Brit Med J 2:393, 1957;.
19 +
Greig, H. B. W., et al:  Familial Crisis in Hereditary Spherocytosis , S Afr J Med Sci 23:17, 1958;.
20 +
Willoughby, M. L. N., et al:  Megaloblastic Erythropoiesis in Acquired Haemolytic Anaemia , Blood 17:351, 1961;.
21 +
Oliner, H. L., and Heller, P.:  Megaloblastic Erythropoiesis and Acquired Hemolysis in Sickle Cell Anemia , New Eng J Med 26:19, 1959;.
22 +
Kohler, H. G.; Meynell, M. J.; and Cooke, W. J.:  Spherocytic Anaemia Complicated by Megaloblastic Anaemia , Brit Med J 779, 1960;.
23 +
Heller, P., and Venger, N.:  Problems in Differentiation of Megaloblastic Anemias , Med Clin N Amer 46:121, 1962;.
24 +
Robinson, M. G., and Watson, R. J.:  Megaloblastic Anemia Complicating Thalassemia Major , Amer J Dis Child 105:275, 1963;.
25 +
Jonsson, U.: "Nutritional Megaloblastic Anemia in Sickle Cell States and Relation of Folic Acid to Blastic Crisis in Haemolytic Anaemia," in the Proceedings of the Seventh Congress of the International Society of Hematology, Rome, 1958, New York: Intercontinental Medical Book Corporation, 1960, p 155.
26 +
Jonsson, U.; Rath, O. S.; and Kirkpatrick, C. I. F.:  Nutritional Megaloblastic Anemia Associated With Sickle Cell States , Blood 14:535, 1959;.
27 +
Pierce, L. E., and Rath, C. E.:  Evidence for Folic Acid Deficiency in Genesis of Anemic Sickle Cell Crisis , Blood 20:19, 1962;.
28 +
Chanarin, I.; Burman, D.; and Bennet, M.:  Familial Aplastic Crisis in Hereditary Spherocytosis: Urocanic Acid and FIGLU Excretion Studies in Case of Megaloblastic Anemia , Blood 20:33, 1962;.
29 +
Spray, G. H., and Witts, L. J.:  Utilization of Folic Acid in Anemia and Leukemia , Clin Sci 12:385, 1953;.
30 +
Chatterjea, J. B.:  "Section on Haemoglobin in India"  in Abnormal Haemoglobins , J. H. P. Jonxis, and J. F. Delafresnaye, ed., Springfield, Ill: Charles C Thomas, 1959;.
31 +
Chanarin, I.; Dacie, J. V.; and Mollin, D. L.:  Folic Acid Deficiency in Haemolytic Anaemia , Brit J Haemat 5:245, 1959;.
32 +
MacIver, J. E., and Went, L. N.:  Sickle Cell Anaemia Complicated by Megaloblastic Anaemia of Infancy , Brit Med J 1:775, 1960;.
33 +
Luhby, A. L., and Cooperman, J. M.:  Folic Acid Deficiency in Thalassemia Major , Lancet 2:490, 1961;.
34 +
Pearson, H. A.: "Megaloblastic Crisis of Sickle Cell Anaemia, Coincidence or Fact," in the Society for Pediatric Research program abstracts, 33rd Annual Meeting, Atlantic City, New Jersey, May, 1963, p 74.
35 +
Chanarin, I.:  Urocanic Acid and Formiminoglutamic Acid Excretion in Megaloblastic Anaemia and Other Conditions: Effect of Specific Therapy , Brit J Haemat 9:141, 1963;.
36 +
Grasbeck, R.; Björksten, B.; and Nyberg, W.:  Formiminoglutamic Acid in Urine of Folic Acid Deficiency , Nord Med 66:1343, 1961;.
37 +
Watson-Williams, E. J.:  Folic Acid Deficiency in Sickle-Cell Anaemia , E Afr Med J 39:213, 1962;.
38 +
Herbert, V.:  Minimal Daily Adult Folate Requirement , AMA Arch Intern Med 110:649, 1962;.
39 +
Zalusky, R., and Herbert, V.:  Megaloblastic Anemia in Scurvy With Response to 50 Micrograms of Folic Acid Daily , New Eng J Med 265:1033, 1961;.
40 +
Jandl, J. H., and Greenberg, M. S.:  Bone Marrow Failure Due to Relative Nutritional Deficiency in Cooley's Hemolytic Anemia: Painful "Erythropoietic Crisis" in Response to Folic Acid , New Eng J Med 260:461, 1959;.

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