PERNICIOUS ANEMIA AND RELATED ANEMIAS TREATED WITH VITAMIN B12

Blood ◽  
1949 ◽  
Vol 4 (7) ◽  
pp. 827-844 ◽  
Author(s):  
EDGAR JONES ◽  
WILLIAM J. DARBY ◽  
JOHN R. TOTTER
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Maximum Rate ◽  
Reticulocyte Count ◽  
Liver Extract ◽  
Average Daily Dose ◽  
Quantitative Criterion ◽  
Adequate Treatment ◽  
Neurologic Involvement ◽  
Daily Dose

Abstract Eleven cases treated with vitamin B12 have been presented. Eight patients with pernicious anemia in relapse responded hematologically. Two patients with mild neurologic involvement were relieved by therapy with B12 alone. Consideration of the quantities of the crystalline vitamin required to promote maximal erythropoiesis in pernicious anemia indicates that less than about 0.75 µg. daily in doses at intervals of several days will not suffice to establish and maintain blood values as high as does adequate treatment with liver extract. Parenteral daily doses of 1.0 µg. promoted good erythropoiesis in one patient, although it appears that the maximum rate of hemopoiesis may require the initial average daily dose of approximately 3.0 µg. The reticulocyte count is an unreliable quantitative criterion of activity or adequacy of therapy. It is suggested that hemopoietic factors in addition to PGA and B12 may be required by some patients to obtain maximal erythrocyte levels. Vitamin B12, as well as PGA, effects a reduction in the fecal urobilinogen output of patients with pernicious anemia. The significance of this finding is discussed. No change in urinary excretion of pteroylglutamate or of porphyrin was detected in patients treated with vitamin B12.

scholarly journals Microspectrophotometric Determination of Desoxyribosenucleic Acid in Megaloblasts of Pernicious Anemia

Blood ◽  
1951 ◽  
Vol 6 (4) ◽  
pp. 344-349 ◽  
Author(s):  
EDWARD H. REISNER ◽  
ROY KORSON
Keyword(s):  
Bone Marrow ◽  
Folic Acid ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Blood Cells ◽  
Nuclear Dna ◽  
Liver Extract ◽  
Megaloblastic Anemia ◽  
Gradual Loss

Abstract 1. In 9 patients with various types of megaloblastic anemia responding to treatment with vitamin B12, folic acid or liver extract, no significant deviations from the normal amounts of total or polymerized DNA were observed in the nuclei of red blood cells in marrow smears. 2. During the maturation of megaloblasts in the bone marrow there is a gradual loss of nuclear DNA. 3. This pattern is quantitatively and qualitatively similar for normal marrow and for that of pernicious anemia in relapse and after treatment.

scholarly journals Erythrokinetics in Pernicious Anemia

Blood ◽  
1956 ◽  
Vol 11 (9) ◽  
pp. 807-820 ◽  
Author(s):  
CLEMENT A. FINCH ◽  
DANIEL H. COLEMAN ◽  
ARNO G. MOTULSKY ◽  
DENNIS M. DONOHUE ◽  
ROBERT H. REIFF
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Reticulocyte Count ◽  
Red Cells ◽  
Red Cell ◽  
Erythropoietic Activity ◽  
Ineffective Erythropoiesis ◽  
Quantitative Measurements ◽  
Marrow Activity ◽  
Made In

Abstract Quantitative measurements of the erythropoietic activity of the marrow, of circulating red cell production and destruction have been made in patients with pernicious anemia in relapse and during response to vitamin B12 therapy. Total erythropoietic marrow activity as reflected by turnover of heme components proceeds at a rate of approximately 3 times normal. The delivery of viable red cells to the circulating blood, however, does not increase above normal. This would indicate that the greater portion of marrow activity is ineffective in terms of blood production. This marrow dysfunction coupled with an increased rate of cell destruction of approximately 3 times normal is responsible for the anemia. Total erythropoiesis is somewhat less, and effective erythropoiesis considerably less, than that which may be expected of the normal marrow under the sustained stimulus of anemia. The reticulocyte count is shown to be an unreliable index of blood production in untreated pernicious anemia due to loss of reticulum from cytoplasma of many red cells before their delivery into circulation. During the response to vitamin B12 the ineffective erythropoiesis is converted to effective erythropoiesis, whereas total erythropoiesis remains unchanged. The rate of blood production during recovery is 3 to 4 times normal.

scholarly journals Visual Impairment due to Optic Neuropathy in Pernicious Anemia: Report of a Case and Review of the Literature

Blood ◽  
1959 ◽  
Vol 14 (4) ◽  
pp. 378-385 ◽  
Author(s):  
HENRY E. HAMILTON ◽  
PHILIP P. ELLIS ◽  
RAYMOND F. SHEETS
Keyword(s):  
Optic Nerve ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Optic Neuropathy ◽  
Optic Atrophy ◽  
Liver Extract ◽  
Review Of The Literature ◽  
Inadequate Information ◽  
Vitamin B12 Absorption ◽  
Optic Nerve Disorders

Abstract 1. A man with optic nerve involvement and pernicious anemia regained normal vision after treatment with vitamin B12. 2. In a search of the literature we found 28 cases with both pernicious anemia and optic neuropathy. The hematologic, neurologic and ophthalmologic findings were analyzed in these cases. In each case, the diagnosis of pernicious anemia was established. Optic atrophy associated with pernicious anemia may be part of the pathologic process of pernicious anemia. If the patient is treated early with vitamin B12 or liver extract, optic nerve function returns. Sixteen other cases with optic atrophy and possible pernicious anemia in the literature had inadequate information to substantiate the diagnosis. 3. The use of a cobalt60-labelled vitamin B12 absorption test may be helpful in optic nerve disorders of obscure etiology.

scholarly journals STUDIES ON THE RELATIONSHIPS OF VITAMIN B12, FOLIC ACID, THYMINE, URACIL, AND METHYL GROUP DONORS IN PERSONS WITH PERNICIOUS ANEMIA AND RELATED MEGALOBLASTIC ANEMIAS

Blood ◽  
1950 ◽  
Vol 5 (8) ◽  
pp. 695-717 ◽  
Author(s):  
RICHARD W. VILTER ◽  
DANIEL HORRIGAN ◽  
JOHN F. MUELLER ◽  
THOMAS JARROLD ◽  
CARL F. VILTER ◽  
...  
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Liver Extract ◽  
Megaloblastic Anemia ◽  
Complete Response ◽  
Mass Action ◽  
Folic Acid Deficiency ◽  
Human Beings ◽  
Combined System

Abstract 1. Patients with pernicious anemia who are maintained on folic acid, 30 mg. three times a week, for two to three years may have a hematologic relapse which will remit satisfactorily if refined liver extract is given, or partially if the dose of folic acid is increased to 50 mg. daily, or if thymine is given. 2. The hematologic remission succeeding the increased dosage of folic acid is followed within several months by a second relapse. At this time the response of these patients to liver extract or vitamin B12 is retarded. Recovery occurs after two to four months. 3. These experiments suggest that folic acid exerts its effect by "mass action" in pernicious anemia and that it is essential to the formation of thymine and other pyrimidines and purines or facilitates the utilization of these substances. 4. Posterolateral column disease or peripheral neuritis occurred in every person with pernicious anemia who received increasing doses of folic acid to maintain an hematologic remission. This observation suggests that folic acid, by pushing a chemical reaction through to completion in the face of a serious deficiency of vitamin B12, depleted the supply of this factor even more and led to the development of combined system disease. 5. Uracil produced a hematologic response in 2 of 3 persons with pernicious anemia in relapse when given in doses of 15-30 grams daily. The data suggest that uracil may be a precursor of thymine. 6. A patient with pernicious anemia of pregnancy failed to respond to uracil, 30 grams daily, but did respond partially when choline, 3 grams, and methionine, 6 grams were given. Thymine induced a complete response. The partial response to methionine and choline and the better response to thymine suggest that choline and methionine supplied methyl groups for the formation of thymine, but that activating substances for the methylating process were missing. 7. Reference is made to a patient previously reported from this laboratory who had liver extract and vitamin B12-refractory megaloblastic anemia but who responded to folic acid and on a second relapse to thymine. Studies on the output of folic acid in the urine of this patient did not support the possibility of folic acid deficiency, and the suggestion was made that another substance, possibly the "Wills’ factor," was deficient, and that this factor together with folic acid activated the formation of thymine. These two factors correspond to the activators of the transmethylation reaction mentioned in the preceding paragraph. 8. These studies on human beings and similar ones in bacterial metabolism suggest that folic acid, liver extract and vitamin B12 are essential to the formation of nucleic acid and nucleoprotein through a chemical chain reaction. The suggestion is made that the megaloblast common to pernicious anemia and related macrocytic anemias is a primitive erythroblast with an abnormality in the metabolism of nucleoprotein. The so-called maturation arrest in all marrow elements occurs because of this abnormality which may be induced by a deficiency of vitamin B12, folic acid, the "Wills’ factor," and probably other chemical activators of this reaction.

JUVENILE PERNICIOUS ANEMIA

PEDIATRICS ◽  
1951 ◽  
Vol 8 (1) ◽  
pp. 88-106
Author(s):  
EDWARD H. REISNER ◽  
JAMES A. WOLFF ◽  
R. JAMES MCKAY ◽  
EUGENIA F. DOYLE
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Gastric Juice ◽  
Liver Extract ◽  
Macrocytic Anemia ◽  
Intrinsic Factor ◽  
The Other ◽  
Free Hydrochloric Acid ◽  
Laboratory Findings ◽  
Gastric Contents

Histories have been presented of two pairs of sibling children with recurrent macrocytic anemia with megaloblastic bone marrow responding specifically to liver extract and vitamin B12. The clinical features and laboratory findings were similar to those of adult pernicious anemia in every respect except for the inconstant presence of histamine refractory achlorhydria. All the patients responded to vitamin B12 given parenterally, but in three to whom it was given by mouth no response was obtained. Two of these subsequently responded to oral B12 when it was accompanied by normal gastric juice. The other two developed histamine refractory achlorhydria while in hematologic remission. This is interpreted as proof that the anemia was due to deficient intrinsic factor in the gastric juice. Three patients showed evidence of disease of the spinal cord, in two of whom the symptoms were severe. These symptoms were compatible with a diagnosis of dorsolateral sclerosis, and improved with antipernicious anemia therapy. In one of these patients, treated with folic acid, the neurologic lesions were aggravated severely. Pernicious anemia due to the absence of gastric juice intrinsic factor occurs in children. The presence of free hydrochloric acid in the gastric contents does not preclude the possibility of the disease.

scholarly journals The Effects of Combined Folic Acid and Liver Extract Therapy

Blood ◽  
1951 ◽  
Vol 6 (12) ◽  
pp. 1213-1233 ◽  
Author(s):  
ROBERT B. CHODOS ◽  
JOSEPH F. ROSS
Keyword(s):  
Nervous System ◽  
Folic Acid ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Liver Extract ◽  
Macrocytic Anemia ◽  
Subacute Combined Degeneration ◽  
Acid Therapy ◽  
System Disease ◽  
Gastro Intestinal Tract

Abstract 1. Folic acid, when administered alone, did not prevent the development or progression of subacute combined degeneration in 12 of 22 patients receiving this agent for from twelve to twenty-five months. 2. One patient with total gastrectomy and a macrocytic anemia developed subacute combined degeneration after five months of folic acid therapy. 3. Neurologic disease did not develop in 6 pernicious anemia patients treated with folic acid and liver extract for three and one-half to thirty-nine months. 4. In 10 pernicious anemia patients with good nutrition, neurologic relapses did not progress when liver extract or vitamin B12 therapy was instituted, even though folic acid therapy was continued. In 2 patients with abnormal nutrition and complicating organic abnormalities, nervous system disease progressed after institution of liver extract therapy. 5. Our observations are best explained by the theory that the hematologic and neurologic manifestations of pernicious anemia and other macrocytic anemias associated with gastro-intestinal tract pathology and inadequate nutrition are due to a deficiency of more than one substance. The administration of folic acid may improve the hematologic status but induce a deficiency of another substance or substances, e.g., vitamin B12, which are essential for the maintenance of a normal blood picture and the integrity of the central nervous system. This deficiency will eventually result in the development of a suboptimal blood picture or subacute combined degeneration of the spinal cord, or both. 6. The hematologic status of patients with pernicious anemia is not maintained in a more satisfactory state by supplementation of liver extract or vitamin B12 therapy with folic acid. 7. Folic acid therapy did not produce neurologic disease in patients with iron deficiency anemia who had free gastric hydrochloric acid in their gastric secretions and presumably sufficient intrinsic factor. It did not influence response to ferrous sulfate therapy. 8. Patients with sprue, nutritional macrocytic anemia and other macrocytic anemias associated with gastro-intestinal tract pathology who are treated with folic acid should also be given supplemental liver extract or vitamin B12 to insure against the development of nervous system disease.

scholarly journals The Effect of Transfusions of Erythrocytes on Untreated Pernicious Anemia

Blood ◽  
1956 ◽  
Vol 11 (7) ◽  
pp. 632-640 ◽  
Author(s):  
JAMES D. MASON ◽  
BYRD S. LEAVELL
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Clinical Condition ◽  
Reticulocyte Count ◽  
Subjective Improvement ◽  
Basic Change ◽  
Platelet Counts ◽  
Peripheral Leukocyte ◽  
The Absolute ◽  
Significant Change

Abstract 1. Three patients with untreated pernicious anemia were transfused with packed erythrocytes to produce a normal hematocrit before they were treated with vitamin B12. One patient with untreated pernicious anemia was transfused with 250 cc. plasma prior to therapy with vitamin B12. No significant changes were noted in this patient who received plasma. 2. Following erythrocyte transfusions the bone marrows of these patients were considered to show the megaloblastic type of maturation with a reduction in percentage of the early megaloblasts (Stages I and II). The ME ratio of the marrows increased. A decrease in the absolute reticulocyte count occurred. No change occurred in the peripheral leukocyte and platelet counts and there was no significant change in the clinical condition of the patients. 3. After therapy with vitamin B12, at a time when the hematocrits were normal, the bone marrows became normoblastic, a small but definite reticulocytosis occurred, the leukocyte and platelet counts returned to normal, and there was subjective improvement in the condition of the patient. 4. It is concluded that in these three patients with untreated pernicious anemia multiple transfusions of packed erythrocytes decreased erythropoiesis but did not cause any basic change in the type of erythrocyte maturation.

scholarly journals PERNICIOUS ANEMIA IN CHILDHOOD REPORT OF CASE IN SIX YEAR OLD GIRL RESPONDING TO REFINED LIVER EXTRACT, FOLIC ACID AND VITAMIN B12 IN SUCCESSIVE RELAPSES

Blood ◽  
1949 ◽  
Vol 4 (12) ◽  
pp. 1361-1366 ◽  
Author(s):  
R. WENDELL DAVIS ◽  
RICHARD M. CHRISTIAN ◽  
DONALD M. ERVIN ◽  
LAWRENCE E. YOUNG
Keyword(s):  
Folic Acid ◽  
Hydrochloric Acid ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Gastric Juice ◽  
Liver Extract ◽  
Megaloblastic Anemia ◽  
Free Hydrochloric Acid ◽  
Neurologic Complications ◽  
Hematologic Response

Abstract A case of megaloblastic anemia without specific neurologic complications in a 6 year old girl is presented as an example of pernicious anemia in childhood despite the fact that a small amount of free hydrochloric acid was present in the gastric juice after injection of histamine. Prompt hematologic response was obtained following administration of refined liver extract, folic acid and vitamin B12 in successive relapses.

A case report on Subacute Combined Degeneration of spinal cord in children – A rare neurological manifestation in Vitamin B12 deficiencies

2017 ◽  
Vol 6 (12) ◽  
pp. 5562
Author(s):  
Tiana Mary Alexander ◽  
Vineeta Pande ◽  
Sharad Agarkhedkar ◽  
Dnyaneshwar Upase
Keyword(s):  
Spinal Cord ◽  
Case Report ◽  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Chronic Diarrhea ◽  
Megaloblastic Anemia ◽  
Vegetarian Diet ◽  
Malabsorption Syndrome ◽  
Subacute Combined Degeneration ◽  
B12 Deficiency

Megaloblastic anemia is a common feature between 6 months – 2 years and rarely occurs after 5 years of age, especially in a child consuming non-vegetarian diet. B12 deficiency may occur after 5 years of age because of chronic diarrhea, malabsorption syndrome, or intestinal surgical causes. Pernicious anemia causes B12 deficiency, but nutritional B12 deficiency with subacute combined degeneration causing ataxia is rare.

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