Polycythemia Rubra Vera With Pernicious Anemia Some Observations on Vitamin B12 Metabolism

Abstract A patient with polycythemia rubra vera developed symptoms and signs of pernicious anemia three years after institution of therapy for the polycythemia. This is the first satisfactorily documented report of this sequence. Strict criteria utilized make both diagnoses unequivocal. Autoantibody studies, the first performed in such a patient, show the presence of parietal cell and intrinsic factor autoantibodies but no antibodies to other tissues. Vitamin B12 requirements have been excessive despite high or high normal serum levels and extreme marrow sensitivity to withdrawal of the Vitamin is evident in the presence of these high serum levels. Studies on Vitamin B12 binding proteins showed an elevation in α binding globulin with reversal of the α to β ratio. It is suggested that this protein is physiologically abnormal. The literature is briefly reviewed regarding the pathogenesis of the two disorders with the conclusion that their appearance in the one patient represents purely a chance phenomenon.

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Chronic Atrophic Gastritis with Negative Intrinsic Factor and Parietal Cell Antibody Presenting as a Severe Hemolytic Anemia

Case Reports in Hematology ◽

10.1155/2020/8697493 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

G. F. Cittolin-Santos ◽

S. Khalil ◽

J. K. Bakos ◽

K. Baker

Keyword(s):

Vitamin B12 ◽

Atrophic Gastritis ◽

Pernicious Anemia ◽

Hemolytic Anemia ◽

Parietal Cell ◽

Intrinsic Factor ◽

Peripheral Blood Smear ◽

Chronic Atrophic Gastritis ◽

Cell Antibody ◽

Parietal Cell Antibody

A 28-year-old Caucasian male with Hashimoto’s disease and vitiligo presented with two weeks of dizziness on exertion following pharyngitis which was treated with prednisone 40 mg by mouth once a day for five days. Initial workup revealed anemia, elevated lactate dehydrogenase (LDH), and low haptoglobin. He underwent workup for causes of hemolytic anemia which was remarkable for a peripheral blood smear with hypersegmented neutrophils and low vitamin B12 levels concerning for pernicious anemia. Parietal cell and intrinsic factor antibodies were negative, and he then underwent an esophagogastroduodenoscopy with biopsy. The biopsy was negative for Helicobacter pylori, and the immunohistochemical stains were suggestive of chronic atrophic gastritis. He was started on vitamin B12 1,000 mcg intramuscular injections daily. His hemoglobin, LDH, and haptoglobin normalized. Given the absence of the parietal cell antibody and intrinsic factor antibody, this is a rare case of seronegative pernicious anemia.

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The Effect of Various Metabolites on the Growth of Marrow Cells in Vitro

Blood ◽

10.1182/blood.v10.7.735.735 ◽

1955 ◽

Vol 10 (7) ◽

pp. 735-752 ◽

Cited By ~ 8

Author(s):

HAROLD T. SWAN ◽

EDWARD H. REISNER ◽

MORRIS SILVERMAN

Keyword(s):

Vitamin B12 ◽

Pernicious Anemia ◽

Folinic Acid ◽

Intrinsic Factor ◽

Suspension Cultures ◽

Normal Serum ◽

Red Cell ◽

Inhibitory Effects ◽

Glass Surfaces

Abstract Marrow was cultured on chick plasma clots, glass surfaces and in suspension and the influence of various metabolites and antimetabolites on the growth and differentiation of red cell precursors was studied. Vitamin B12 appeared to stimulate cell growth in cultures grown on clots and to convert megaloblastic hematopoiesis to normoblastic in cultures grown on glass. In suspension cultures of megaloblastic marrows in pernicious anemia serum significant cell increases were obtained with the addition of folinic acid, but not with vitamin B12. Both vitamin B12 and folinic acid appeared to accelerate the conversion of megaloblasts to normoblasts in differential counts of stained smears of such cultures. No enhancing effect of intrinsic factor upon the activity of B12 in suspension cultures of megaloblasts was observed. The effect of folinic acid could be blocked by colchicine and folinic acid could reverse the inhibitory effects of Amethopterin. These facts indicated that folinic acid acted in suspension cultures by stimulating mitosis. Megaloblasts could be produced from normoblastic marrows by culturing them in pernicious anemia serum, or in normal serum in the presence of Amethopterin.

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The Kinetics of Intravenously Injected Radioactive Vitamin B12: Studies on Normal Subjects and Patients with Chronic Myelocytic Leukemia and Pernicious Anemia

Blood ◽

10.1182/blood.v15.5.646.646 ◽

1960 ◽

Vol 15 (5) ◽

pp. 646-661 ◽

Cited By ~ 16

Author(s):

EUGENE A. BRODY ◽

SOLOMON ESTREN ◽

LOUIS R. WASSERMAN

Keyword(s):

Vitamin B12 ◽

Pernicious Anemia ◽

Total Gastrectomy ◽

Binding Capacity ◽

Intrinsic Factor ◽

Normal Subjects ◽

High Serum ◽

Malabsorption Syndrome ◽

Chronic Myelocytic Leukemia ◽

Myelocytic Leukemia

Abstract 1. Studies of the fate of intravenously injected radioactive vitamin B12 have been performed in patients with normal, low and high serum concentrations of vitamin B12. 2. Abnormal plasma disappearance curves were noted in chronic myelocytic leukemia, pernicious anemia in relapse and in remission, total gastrectomy and malabsorption syndrome. 3. In chronic myelocytic leukemia, the slow clearance of plasma radioactivity may be explained by the increased binding capacity of the plasma proteins for vitamin B12. 4. Plasma clearance of radioactivity is slower than normal in pernicious anemia, even in remission. The failure of the disappearance curve to return to normal in pernicious anemia in complete remission suggests the existence of a plasma "B12-transferase," whose function is to transfer circulating B12 to the tissues. The disappearance curves suggest that the amount of such "B12-transferase" is diminished in pernicious anemia, total gastrectomy and certain Cases of malabsorption syndrome. 5. A relationship between a hypothetical "B12-transferase" and intrinsic factor is discussed.

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On the Nature of Castle’s Hemopoietic Factor

Blood ◽

10.1182/blood.v6.12.1234.1234 ◽

1951 ◽

Vol 6 (12) ◽

pp. 1234-1239 ◽

Cited By ~ 30

Author(s):

SHEILA T. CALLENDER ◽

L. G. LAJTHA

Keyword(s):

Vitamin B12 ◽

Gastric Juice ◽

Intrinsic Factor ◽

Normal Serum ◽

Relationship Of ◽

The Relationship

Abstract 1. Normal gastric juice (intrinsic factor) and vitamin B12 together form a thermolabile hemopoietic factor which ripens megaloblasts in vitro, both gastric juice and B12 alone being inactive. 2. The hemopoietic factor in normal serum which ripens megaloblasts in vitro also appears to be thermolabile, heating to 56 C. for 2 hours destroying some of its activity. 3. The relationship of these factors is discussed and an extra-gastric as well as a gastric source of intrinsic factor is postulated.

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Blocking and Binding Antibodies to Intrinsic Factor and Parietal Cell Antibody in Pernicious Anemia

Gastroenterology ◽

10.1016/s0016-5085(19)34006-5 ◽

1968 ◽

Vol 55 (5) ◽

pp. 575-583 ◽

Cited By ~ 50

Author(s):

I. Michael Samloff ◽

Martin S. Kleinman ◽

Michael D. Turner ◽

Michael V. Sobel ◽

Graham H. Jeffries

Keyword(s):

Pernicious Anemia ◽

Parietal Cell ◽

Intrinsic Factor ◽

Cell Antibody ◽

Parietal Cell Antibody

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Absorption of Liver-bound Vitamin B12 in Relation to Intrinsic Factor

Blood ◽

10.1182/blood.v32.2.313.313 ◽

1968 ◽

Vol 32 (2) ◽

pp. 313-323 ◽

Cited By ~ 9

Author(s):

KUNIO OKUDA ◽

ISAO TAKARA ◽

TERUMI FUJII

Keyword(s):

Vitamin B12 ◽

Pernicious Anemia ◽

Rat Liver ◽

Intrinsic Factor ◽

In Vitro Digestion ◽

Enhanced Absorption ◽

Biochemical Studies ◽

Peptide Complexes ◽

Liver Powder

Abstract Rat liver containing radioactive native B12 was prepared by repeated injections of 57Co-OH-B12, and absorption of liver B12 was measured in patients with pernicious anemia and in subjects without stomach, using physiologic doses. It was found that absorption of liver B12 was very poor, not superior to that of free OH-B12, and coadministration of IFC markedly enhanced absorption. In vitro digestion of rat liver with several enzymes, as determined from liberation of dialyzable radioactivity, suggested its easy digestibility. Biochemical studies of the dialyzable products of liver containing 57Co-B12 failed to demonstrate any detectable quantities of radioactivity other than free 57Co-OH-B12. A study in which cow liver powder mixed with a small quantity of 57Co-CN-B12 was fed to humans and digestion of liver was estimated from the reduction in absorption of radioactivity, indicated that most of the extractable liver B12 was liberated free in the intestine. Thus, no evidence has been obtained for the production of B12-peptide complexes from liver by digestion that require no IF for absorption.

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Vitamin B12 Malabsorption Due to Intrinsic Factor Deficiency in Indian Subjects

Blood ◽

10.1182/blood.v40.5.747.747 ◽

1972 ◽

Vol 40 (5) ◽

pp. 747-753 ◽

Cited By ~ 3

Author(s):

H. G. Desai ◽

F. P. Antia

Keyword(s):

Vitamin B12 ◽

Pernicious Anemia ◽

Indian Population ◽

Intrinsic Factor ◽

Subacute Combined Degeneration ◽

Factor Deficiency ◽

Vitamin B12 Absorption ◽

Intrinsic Factor Deficiency ◽

Intrinsic Factor Antibody ◽

Vitamin B12 Malabsorption

Abstract Sixteen patients (from Bombay) with severe vitamin B12 malabsorption due to intrinsic factor deficiency, presenting as subacute combined degeneration of the cord (7), tropical sprue (3), anemia (2), thyrotoxicosis (2), diabetes mellitus (1), and pain in the abdomen (1), are reported. The difficulties of establishing a definite diagnosis of pernicious anemia in Indian population are described. The lower incidence of circulating intrinsic factor antibody (IFA) in Indian patients with histamine-fast achlorhydria and poor vitamin B12 absorption is emphasized. The necessity of separating atrophic gastritis, with severely impaired vitamm B12 absorption, from pernicious anemia on the basis of absence or presence of IFA in serum and/or gastric juice cannot be overemphasized.

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