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Usefulness of oral cyanocobalamin therapy in severe hematologic manifestations related to vitamin B₁₂ deficiency

Professor of Internal Medicine Université Louis Pasteur Strasbourg, France Clinical Specialist of Internal Medicine Department of Internal Medicine Diabetes and Metabolic Disorders Hôpitaux Universitaires de Strasbourg 1 place de l'Hôpital 67 091 Strasbourg cedex, France fax 3-33-88-11-62-62 emmanuel.andres{at}chru-strasbourg.fr

Esther Noel, MD

Assistant, Internal Medicine Université Louis Pasteur Clinical Specialist of Internal Medicine Department of Internal Medicine Diabetes and Metabolic Disorders Hôpitaux Universitaires de Strasbourg

Claudia Coca, MD

Clinical Specialist of Internal Medicine Department of Internal Medicine Diabetes and Metabolic Disorders Hôpitaux Universitaires de Strasbourg

Helen Fothergill, MD

Clinical Specialist of Internal Medicine Department of Internal Medicine Diabetes and Metabolic Disorders Hôpitaux Universitaires de Strasbourg

Florence Caro-Sampara, MD

Clinical Specialist of Internal Medicine Department of Internal Medicine Diabetes and Metabolic Disorders Hôpitaux Universitaires de Strasbourg

Frédéric Maloisel, MD

Clinical Specialist of Internal Medicine Department of Hematology Hôpitaux Universitaires de Strasbourg

Jean-Frédéric Blicklé, MD

Professor of Internal Medicine Université Louis Pasteur Clinical Specialist of Internal Medicine Department of Internal Medicine Diabetes and Metabolic Disorders Hôpitaux Universitaires de Strasbourg

Published Online, April 30, 2004. www.theannals.com, DOI 10.1345/aph.1D636

Case Reports. Six cases were extracted from a cohort of >200 patients with established B₁₂ deficiencies according to predetermined inclusion criteria.⁴ The median age was 79 years (range 67–81); the male/female ratio was 1/5. Clinical features included peripheral neuropathy (reflex loss) in 3 patients, combined with medullar sclerosis in one patient and memory loss in another. All 6 patients had severe hematologic abnormalities. Baseline hematologic parameters for the patients are reported in Table 1. Patients 4 and 5 had severe thrombotic microangiopathy syndrome. Evidence of megaloblastosis was observed in all 5 patients who underwent a bone marrow examination.

All the patients had an established cobalamin deficiency with a mean ± SD serum cobalamin level of 93.8 ± 30.4 pg/mL. In 5 cases, the diagnosis of pernicious anemia was established by the presence of anti-intrinsic factor antibodies; diagnosis of food–cobalamin malabsorption was documented for patient 3 according to the established criteria.⁴ Patients 1 and 6 also had iron and folate deficiencies. Each patient was treated with oral crystalline cyanocobalamin 1000 µg/day. Three patients (2, 3, 4) were also initially treated with blood transfusion (between 2 and 4 units) and 2 patients (1, 6) with iron and folate supplementation.

After one month of treatment, serum cobalamin levels (mean increase of 135 pg/mL) were normalized in all patients. After 3 months, blood count abnormalities were corrected in all 6 patients. All patients had increased hemoglobin levels (mean increase 4.2 g/dL) and decreased mean erythrocyte corpuscular volumes (mean decrease 11.2 fL). Platelet counts returned to normal in all patients with thrombopenia. Clinical manifestations were improved in 3 patients with combined medullar sclerosis and peripheral neuropathy.

Discussion. These 6 cases illustrate that the administration of oral crystalline cyanocobalamin 1000 µg/day is an effective treatment of vitamin B₁₂ deficiency, even in cases of severe hematologic manifestations.^1-3 In fact, we reported a correction of the hematologic abnormalities during the first 3 months of therapy, even in severe anemia (hemoglobin <8 g/dL) and thrombotic microangiopathy syndrome related to cobalamin deficiency. However, 3 patients also required blood transfusions. In our elderly patients, the benefits of oral administration of cyanocobalamin are multiple: painful intramuscular injections are avoided, there is no risk of hemorrhage as with intramuscular administration, and cost of therapy is decreased.

References

1. Andrès E, Kurtz JE, Perrin AE, Maloisel F, Demangeat C, Goichot B, et al. Oral cobalamin therapy for the treatment of patients with food–cobalamin malabsorption. Am J Med 2001;111:126-9.[CrossRef][Medline]
2. Andrès E, Kaltenbach G, Noel E, Noblet-Dick M, Perrin AE, Vogel T, et al. Efficacy of short-term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food–cobalamin malabsorption. A study of 30 patients. Clin Lab Haematol 2003;25:161-6.[CrossRef][Medline]
3. Lane LA, Rojas-Fernandez C. Treatment of vitamin B₁₂-deficiency anemia: oral versus parenteral therapy. Ann Pharmacother 2002;36:1268-72. DOI 10.1345/aph.1A122[Abstract]
4. Andrès E, Goichot B, Schlienger JL. Food–cobalamin malabsorption: a usual cause of vitamin B₁₂ deficiency. Arch Intern Med 2000;160:2061-2.[Free Full Text]

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