Microangiopathic Haemolytic Anaemia and Thrombocytopenia Due to Combined Vitamin B12 and Folate Deficiency Masquerading as Thrombotic Thrombocytopenic Purpura

Abstract

Vitamin B12 defi ciency and folate defi ciency are common causes of macrocytic anaemia and both are important for many cellular processes. These defi ciencies could be due to inadequate dietary intake, impaired absorption or drug ingestion. We present an interesting case of pancytopenia with microangiopathic haemolytic anaemia (MAHA) and intracranial bleeding (ICB) due to combined vitamin B12 and folate defi ciency, mimicking thrombotic thrombocytopenic purpura (TTP). Case presentationA 47-year-old male was admitted to the haematology ward for fatigue, persistent frontal headache and left upper-quadrant abdominal pain that had lasted one week. He was diagnosed with diffuse large B-cell lymphoma (DLBCL) which was treated with six cycles of dose-adjusted EPOCH-rituximab regimen. An end of treatment positron emission tomography (PET) scan reported no active fl uorodeoxyglucose (FDG) uptake, consistent with disease in remission. He had a history of jejunal resection at the age of 42 for bowel ischaemia with unknown aetiology and defaulted surgical follow-up. He was on treatment for type 2 diabetes mellitus and hypertension.Physical examination revealed scleral icterus, pallor and excess weight. There was an old midline laparotomy scar on the abdomen. Other physical and neurological examination fi ndings were unremarkable. The initial laboratory study (Table 1) showed white blood cell (WBC) count of 3.4 x 109/l, haemoglobin (Hb) of 76g/l platelet count of 67 x 109/l, mean corpuscular volume (MCV) of 91.2fl and reticulocyte count of 10.4%. He had indirect hyperbilirubinemia 62μmol/l and markedly raised lactate dehydrogenase (LDH) 9894U/l. Peripheral blood fi lm (PBF) reported anisopoikilocytosis, polychromasia, ovalocytes, spherocytes, numerous teardrop and fragmented red cells, thrombocytopenia (Figure 1) and hypersegmented neutrophils. His Coomb's test was negative, consistent with non-immune haemolytic anaemia. Coagulation profi le, renal, liver and thyroid function tests Vitamin B12 deficiency and folate deficiency are common causes of macrocytic anaemia and both are important for many cellular processes. These de ciencies could be due to inadequate dietary intake, impaired absorption or drug ingestion. We present a case of a 47-year-old male with a history of diffuse large B-cell lymphoma (DLBCL) who was admitted for fatigue, persistent frontal headache and left upper-quadrant abdominal pain. Further investigation showed that he had pancytopenia with microangiopathic haemolytic anaemia (MAHA) and intracranial bleeding (ICB). Serum vitamin B12 and folate were later found to be low and a diagnosis of combined vitamin B12 and folate de ciency mimicking thrombotic thrombocytopenic purpura (TTP) was made. The patient responded well to vitamin B12 and folate replacement.

Anemias e suas correlações clínicas

“…Segundo Lavriša et al, (2022) a Vitamina B12 ou cobalamina tem importante função para manutenção do metabolismo celular, atuando como cofator de processos metabólicos, como na síntese de DNA e no funcionamento mitocondrial. Ademais, a deficiência de ácido fólico, também torna a eritropoiese ineficaz devido à síntese prejudicada do DNA e à maturação celular (LEE et al, 2020). A deficiência dessas vitaminas, geralmente se deve à ingestão dietética inadequada, mas também pode se originar de má absorção intestinal, falhas no metabolismo de folato, aumento das necessidades durante a gravidez ou alcoolismo crônico (NDIAYE et al, 2017).…”

“…Enquanto países subdesenvolvidos, como o Paquistão, e que não apresentam nenhuma lei ou decreto que obrigue a indústria alimentícia a acrescentar ácido fólico em determinados alimentos como farinha e arroz, apresentam maiores níveis de anemia por deficiência de vitamina B9. A Europa, apesar de ser um continente majoritariamente desenvolvido, optou pela fortificação voluntária, apresentando números maiores de casos de anemia em comparação aos países que optaram pela fortificação obrigatória (GODOY e TABARES, 2018; SOOFI et al, 2017).deficiência de folato e na doença renal, mas o ácido metilmalônico não, tornando-se um marcador mais específico de deficiência de vitamina B12(LEE et al, 2020).Em relação ao tratamento, ocorre a administração em pequenas doses de ácido fólico e vitamina B12 todos os dias para enfermos que não possuam deficiência grave ou acometimentos neurológicos. Uma suplementação com altas doses por via oral pode ser absorvida, mesmo na ausência de fator intrínseco.…”

Assessment of clinical spectrum of thrombocytopenia and its association with different disease states reported in Dow Diagnostic Reference and Research Lab (DDRRL)

“…Any sort of interruption in these procedures could result in ineffective haematopoiesis and accumulation of homocysteine. Homocysteine in excessive quantity is a toxic compound which could cause oxidative stress and inflammation in the blood vessels 22 .…”

Adult Vitamin B12 Deficiency-Associated Pseudo-Thrombotic Microangiopathy: A Systematic Review of Case Reports

“…A few patients had a history of gastrectomy and alcoholism as comorbidities. Harada et al [ 26 ] reported a history of gastric cancer, and Lee et al [ 35 ] reported a history of lymphoma.…”

“…Chang et al reported celiac disease as a possible etiology [ 19 ]. One case each of autoimmune gastritis, Helicobacter pylori , and atrophic gastritis etiologies was reported [ 35 , 43 , 51 ]. Other rare etiologies included gastric resection [ 26 ] and bowel resection [ 41 ].…”