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• W2045378154 abstract "Macrocytosis is detected in up to 10% of patients seen by primary care physicians. Main etiologies have been previously described and include folic acid or vitamin B12 deficiency, alcohol abuse, hypothyroidism, myelodysplastic syndrome, reticulocytosis, and medications use, particularly antiretroviral drugs for HIV infection, hydroxyurea, or tyrosine kinase inhibitors 1. The level of increase of the erythrocyte mean corpuscular volume (MCV) can help to predict the macrocytosis etiology 2. To our knowledge, there is no published series of patients displaying extreme macrocytosis (MCV ≥130°fL). Using a clinical data warehouse 3, we conducted a retrospective monocentric study over the last 12 years: our objective was to report on the main etiologies of MCV ≥130°fL and to propose an algorithm for the diagnostic strategy. In this study, 269,965 patients had at least one complete blood count and 24,464 patients (9.8%) displayed at least one MCV > 98°fL. Among these patients with macrocytosis, 109 patients (0.4%) presented with a MCV ≥ 130°fL. They consisted of 43 women (39%) and 66 men (61%); median age at presentation was 56 years (interquartile range: 28 years). The number of patients remained constant, with approximately 10 patients identified per year. Seventy-three patients (67%) displayed anemia and a moderate negative significant correlation between MCV and hemoglobin level was found (r = −0.41, p < 0.001). Thirty-seven patients (34%) were daily alcohol drinkers which is, however, an insufficient etiology to raise alone a MCV above 130°fL. Four single main etiologies were reported to explain extreme macrocytosis in 94% of our patients: antiretroviral therapy for HIV infection, hydroxyurea treatment, vitamin B12, and folic acid deficiencies. All patients with folic acid or vitamin B12 deficiency had a macrocytic anemia, whereas 50% of patients receiving antiretroviral drugs or hydroxyurea did not display anemia. Forty out of 41 HIV-infected patients (37%) were treated with highly active antiretroviral therapy (HAART). They consisted of 36 patients receiving zidovudine and four receiving lamivudine (3TC) associated with stavudine (d4T) as part of their therapeutic regimen. One patient was free of antiretroviral treatment but previous therapy was unknown. Twenty-three patients (21%) were treated by hydroxyurea. Most of them were followed-up for a myeloproliferative disorder: nine essential thrombocythemia and eight polycythemia vera. Four patients were treated for secondary polycythemia related to hypoxic cardiac malformation and two patients had sickle cell disease. Thirty-seven patients (34%) displayed macrocytic anemia, due to isolated folic acid deficiency (n = 17), isolated vitamin B12 deficiency (n = 17), or both deficiencies (n = 3). There are many etiologies of vitamin B12 deficiency but pernicious anemia was associated with more profound vitamin B12 deficiency in our study (n = 7). Patients with folic acid deficiency were more frequently alcohol consumers (82% vs 35%; p = 0.04) and presented higher liver dysfunction such as elevated aspartate aminotransferase (p = 0.03) and prolonged prothrombin time (p = 0.04). A bone marrow aspiration was performed among nine patients and confirmed a macrocytic anemia related to vitamin B12 or folic acid deficiency for seven patients. A myelodysplastic syndrome was diagnosed in a HIV-infected patient and in another patient without treatment or deficiency. Macrocytosis is commonly used to assess therapeutic adherence among patients treated by HAART. Myelodysplastic syndrome is rare among HIV-infected patients but the relationship between HIV infection, long-term effects of HAART, and myelodysplastic syndrome with complex karyotype, including Chromosome 5 and 7 abnormalities, is currently more studied 4. Hydroxyurea is widely used as a first line agent for myeloproliferative disorders but also for sickle cell anemia and of secondary erythrocytosis in cyanotic congenital heart malformation 5, because of systemic antioxidant properties including increased hemoglobin F synthesis and oxygen delivery. On the other side, considering that macrocytes are also potentially exposed to oxidative stress, it has recently been showed that macrocytosis might indicate a poor prognosis in cardiovascular diseases 6. From our results, we propose a diagnostic algorithm for patients presenting with extreme MCV. It begins with a careful questioning on drug history, focusing on HAART, and hydroxyurea treatment. Blood smear review and serum assays for vitamin B12 and folic acid will lead to the diagnosis in 94% of cases before performing complementary blood tests and bone marrow aspiration looking for a myelodysplastic syndrome (Table 1). Virginie Planche1 Sophie Georgin-Lavialle2 Paul Avillach3,4 Brigitte Ranque2 Juliette Pavie5 Thibaut Caruba6 Luc Darnige1 Jacques Pouchot2* 1Service d'Hématologie Biologique, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France 2Service de Médecine Interne, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France 3Service de santé publique et Informatique médicale, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France 4INSERM UMR S 872 eq22, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France 5Service d'Immunologie clinique et, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France 6Service de Pharmacie, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France" @default.
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• W2045378154 date "2014-04-18" @default.
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• W2045378154 title "Etiologies and diagnostic work-up of extreme macrocytosis defined by an erythrocyte mean corpuscular volume over 130°fL: A study of 109 patients" @default.
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• W2045378154 doi "https://doi.org/10.1002/ajh.23718" @default.
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