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Pseudo-thrombotic Microangiopathy Related to Cobalamin Deficiency
The American Journal of Medicine (2006) 119, e3
CLINICAL COMMUNICATION TO THE EDITOR Pseudo-thrombotic Microangiopathy Related to Cobalamin Deficiency To the Editor: Several life-threatening hematologic manifestations have been reported in cobalamin (vitamin B12) deficiency.1,2 These manifestations include documented symptomatic pancytopenia, severe anemia with hemoglobin levels less than 6 g/dL, and hemolytic anemia in at least 10% of the patients. In rare cases, pseudo-thrombotic microangiopathy (Moschkowitz’s syndrome) may be present.1,3 However, to date, this latter disorder has not been well documented and, in practice, is often misdiagnosed. We reported 6 new cases of well-documented pseudo-thrombotic microangiopathy related to cobalamin deficiency. These cases were extracted from a cohort study of more than 250 patients with established cobalamin deficiency. Details of this cohort have been published elsewhere.3 The median age of the 6 patients was 77 years (range, 47-89 years); the male to female ratio was 1 to 5e. The main clinical characteristics included asthenia and dyspnea related to anemia (n ⫽ 6), jaundice related to hemolysis (n ⫽ 5), mild peripheral sensitive neuropathy (n ⫽ 3), impairment of mental status related to low cerebral flow (n ⫽ 1), and peripheral infiltrated cutaneous purpura (n ⫽ 1). The mean serum vitamin B12 and total homocysteine levels were 52 pg/mL (range, 12-74 pg/ mL) and 16.2 mol/L (range, 13-22 mol/L) (RIA Bayer Corp, New York; EIA, Abbott, Rungis, France), respectively. Evidence of anti-intrinsic factor antibodies was found in 4 patients (leading to the diagnosis of pernicious anemia). Bloodcount abnormalities included hemolytic anemia, thrombopenia, and a high number of schizocytes in all patients. The mean hemoglobin level was 68 g/L (range, 51-100 g/L), and the mean erythrocyte cell volume was 113 fL (range, 112-124 fL). The mean number of schizocytes was classified as ⫹⫹/⫹⫹⫹ (range, 0 to ⫹⫹⫹). Evidence of medullar regeneration with a high reticulocyte count (⬎120,000/mm3) was found in 2 patients. The mean platelet count was 70 ⫻ 109/L (range, 25-110/ *Previous communication at the 51st French Congress of Internal Medicine, Tours, December 9-11, 2004. Requests for reprints should be addressed to Emmanuel Andrès, MD, Service de Médecine Interne, Diabète et Maladies Métaboliques, Clinique Médicale B, Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 1 porte de l’Hôpital, 67091 Strasbourg Cedex, France.
0002-9343/$ -see front matter © 2006 Elsevier Inc. All rights reserved.
L), and the mean white cell count was 4.2 ⫻ 109/L (range, 2.6-6.4/L). Bone marrow examination confirmed the diagnosis of cobalamin deficiency with typical features of megaloblastic anemia in 3 of 3 patients. Correction of the hematologic abnormalities was achieved in the six patients, equally well in patients treated with either intramuscular (n ⫽ 4) or oral crystalline cyanocobalamin (n ⫽ 2) (Vitamine B12 Mille Delagrange Synthelabo, Meudon-la-Forêt, France and Vitamine B12 Aguettan, Lyon, France, respectively). The present data confirmed that well-documented pseudo-thrombotic microangiopathy may be found in cobalamin deficiency, as reported in “old” textbooks. In our cohort, the frequency of this manifestation was 2.4%. In recent years, it is noteworthy that several patients with pseudo-thrombotic microangiopathy have been misdiagnosed and treated with aggressive therapies including steroids, polyvalent immunoglobulins, and plasmapheresis.4,5 In 2 patients, pseudo-thrombotic microangiopathy was related to food-cobalamin malabsorption.3 To date, only cases of pernicious anemia have been reported. This mechanism of food-cobalamin malabsorption may explain the efficacy of oral crystalline cyanocobalamin we observed.6 Emmanuel Andrès, MD,a Stéphane Affenberger, MD,a Laure Federici, MD,a Anne Sophie Korganow, MD, PhDb a
Departments of Internal Medicine, Diabetes and Metabolic Disorders; b Internal Medicine and Immunology; Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
doi:10.1016/j.amjmed.2006.02.001
References 1. Stabler SP, Allen RH, Savage DG, Lindenbaum J. Clinical spectrum and diagnosis of cobalamin deficiency. Blood. 1990;76(5):871-881. 2. Andrès E, Loukili NH, Noel E, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171(3):251-260. 3. Andrès E, Affenberger S, Vinzio S, et al. Food-cobalamin malabsorption in elderly patients: clinical manifestations and treatment. Am J Med. 2005;118(10):1154-1159. 4. Blanc PL, Legrand E, Marc JM. Faux Moskowitz, vrai Biermer. Rev Med Interne. 1999;20(11):1046-1047. 5. Jubault V, De Lacroix-Szmania I, Zittoun J, et al. Hémolyse et schizocytose, malabsorption et piège à folates: à propos de particularités sémiologiques mal connues des carences en vitamine B12. Rev Med Interne. 1998;19(12):921-923. 6. Andrès E, Kurtz JE, Perrin AE, et al. Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption. Am J Med. 2001;111(12):126-129.
CLINICAL COMMUNICATION TO THE EDITOR Pseudo-thrombotic Microangiopathy Related to Cobalamin Deficiency To the Editor: Several life-threatening hematologic manifestations have been reported in cobalamin (vitamin B12) deficiency.1,2 These manifestations include documented symptomatic pancytopenia, severe anemia with hemoglobin levels less than 6 g/dL, and hemolytic anemia in at least 10% of the patients. In rare cases, pseudo-thrombotic microangiopathy (Moschkowitz’s syndrome) may be present.1,3 However, to date, this latter disorder has not been well documented and, in practice, is often misdiagnosed. We reported 6 new cases of well-documented pseudo-thrombotic microangiopathy related to cobalamin deficiency. These cases were extracted from a cohort study of more than 250 patients with established cobalamin deficiency. Details of this cohort have been published elsewhere.3 The median age of the 6 patients was 77 years (range, 47-89 years); the male to female ratio was 1 to 5e. The main clinical characteristics included asthenia and dyspnea related to anemia (n ⫽ 6), jaundice related to hemolysis (n ⫽ 5), mild peripheral sensitive neuropathy (n ⫽ 3), impairment of mental status related to low cerebral flow (n ⫽ 1), and peripheral infiltrated cutaneous purpura (n ⫽ 1). The mean serum vitamin B12 and total homocysteine levels were 52 pg/mL (range, 12-74 pg/ mL) and 16.2 mol/L (range, 13-22 mol/L) (RIA Bayer Corp, New York; EIA, Abbott, Rungis, France), respectively. Evidence of anti-intrinsic factor antibodies was found in 4 patients (leading to the diagnosis of pernicious anemia). Bloodcount abnormalities included hemolytic anemia, thrombopenia, and a high number of schizocytes in all patients. The mean hemoglobin level was 68 g/L (range, 51-100 g/L), and the mean erythrocyte cell volume was 113 fL (range, 112-124 fL). The mean number of schizocytes was classified as ⫹⫹/⫹⫹⫹ (range, 0 to ⫹⫹⫹). Evidence of medullar regeneration with a high reticulocyte count (⬎120,000/mm3) was found in 2 patients. The mean platelet count was 70 ⫻ 109/L (range, 25-110/ *Previous communication at the 51st French Congress of Internal Medicine, Tours, December 9-11, 2004. Requests for reprints should be addressed to Emmanuel Andrès, MD, Service de Médecine Interne, Diabète et Maladies Métaboliques, Clinique Médicale B, Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 1 porte de l’Hôpital, 67091 Strasbourg Cedex, France.
0002-9343/$ -see front matter © 2006 Elsevier Inc. All rights reserved.
L), and the mean white cell count was 4.2 ⫻ 109/L (range, 2.6-6.4/L). Bone marrow examination confirmed the diagnosis of cobalamin deficiency with typical features of megaloblastic anemia in 3 of 3 patients. Correction of the hematologic abnormalities was achieved in the six patients, equally well in patients treated with either intramuscular (n ⫽ 4) or oral crystalline cyanocobalamin (n ⫽ 2) (Vitamine B12 Mille Delagrange Synthelabo, Meudon-la-Forêt, France and Vitamine B12 Aguettan, Lyon, France, respectively). The present data confirmed that well-documented pseudo-thrombotic microangiopathy may be found in cobalamin deficiency, as reported in “old” textbooks. In our cohort, the frequency of this manifestation was 2.4%. In recent years, it is noteworthy that several patients with pseudo-thrombotic microangiopathy have been misdiagnosed and treated with aggressive therapies including steroids, polyvalent immunoglobulins, and plasmapheresis.4,5 In 2 patients, pseudo-thrombotic microangiopathy was related to food-cobalamin malabsorption.3 To date, only cases of pernicious anemia have been reported. This mechanism of food-cobalamin malabsorption may explain the efficacy of oral crystalline cyanocobalamin we observed.6 Emmanuel Andrès, MD,a Stéphane Affenberger, MD,a Laure Federici, MD,a Anne Sophie Korganow, MD, PhDb a
Departments of Internal Medicine, Diabetes and Metabolic Disorders; b Internal Medicine and Immunology; Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
doi:10.1016/j.amjmed.2006.02.001
References 1. Stabler SP, Allen RH, Savage DG, Lindenbaum J. Clinical spectrum and diagnosis of cobalamin deficiency. Blood. 1990;76(5):871-881. 2. Andrès E, Loukili NH, Noel E, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171(3):251-260. 3. Andrès E, Affenberger S, Vinzio S, et al. Food-cobalamin malabsorption in elderly patients: clinical manifestations and treatment. Am J Med. 2005;118(10):1154-1159. 4. Blanc PL, Legrand E, Marc JM. Faux Moskowitz, vrai Biermer. Rev Med Interne. 1999;20(11):1046-1047. 5. Jubault V, De Lacroix-Szmania I, Zittoun J, et al. Hémolyse et schizocytose, malabsorption et piège à folates: à propos de particularités sémiologiques mal connues des carences en vitamine B12. Rev Med Interne. 1998;19(12):921-923. 6. Andrès E, Kurtz JE, Perrin AE, et al. Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption. Am J Med. 2001;111(12):126-129.