Case Presentation: A 47-year-old male with no past medical history was admitted with acute generalized weakness of one-week duration associated with bloating, nausea, and dark yellowish discoloration of urine. He also reported poor appetite and weight loss for one month. Physical examination was significant only for conjunctival pallor, vital signs were stable. Initial investigations revealed severe anemia with hemoglobin 5.0 g/dL, mean corpuscular volume 86.2 fl, leukopenia (1.85×109/L), and thrombocytopenia (67×109/L), following which he received two units PRBC transfusion which improved the hemoglobin level. Further workup showed normal iron studies, LDH >2500 U/L, haptoglobin < 10 mg/dL, absolute reticulocyte count 21.2x109/L, total bilirubin 1.9 mg/dl, direct bilirubin 0.4 mg/dl. Direct Coombs test, HIV antigen test, hepatitis panel, and ANCA panel were negative. Peripheral smear showed marked anisopoikilocytosis including hypochromic microcytes, schistocytes, teardrop cells, and atypical plasmacytoid lymphocytes. CT chest/abdomen/pelvis showed borderline splenomegaly, otherwise normal imaging. The clinical picture was concerning for thrombotic thrombocytopenic purpura versus malignancy and he underwent a bone marrow biopsy. Additionally, he was found to have low vitamin B12 levels < 150 pg/mL with normal folate levels, and was started on daily vitamin B12 injections. The deficiency was likely nutritional considering the patient’s strict vegetarian diet. Over the next three days, the patient had significant symptomatic improvement and hemoglobin remained stable. The patient was discharged home on vitamin B12 injections and pending bone marrow biopsy results. At the two-week follow-up, the patient remained asymptomatic and his pancytopenia had resolved. Bone marrow biopsy results came back normal supporting the diagnosis of vitamin B12 deficiency-induced pseudo-TMA.
Discussion: Vitamin B12 deficiency usually presents with macrocytic anemia with or without neurologic involvement. It can rarely present with anemia, thrombocytopenia, and schistocytosis, an entity known as pseudo-thrombotic microangiopathy which is seen in roughly 2.5% of the cases (1). It is postulated to be due to decreased activity of enzymes involved in DNA synthesis of rapid turnover cells resulting in ineffective erythropoiesis (2). Early differentiation of pseudo-TMA from true TMA is important as the management of these two conditions is entirely different and also to limit invasive workup. Markedly elevated LDH with a relatively normal unconjugated bilirubin, relatively higher platelet count, and lower reticulocyte count are clues to identifying pseudo-TMA (3). Our case was unusual due to the presence of leukopenia and the absence of macrocytosis, which is atypical in vitamin B12 deficiency. Another unique feature was the presence of plasmacytoid lymphocytes on peripheral smear, as they have never been previously reported in literature in association with pseudo-TMA. These cells are the intermediate-stage cells between B-lymphocytes and plasma cells, usually reactive, seen in infectious processes and lymphoproliferative disorders, thus contributing to the diagnostic dilemma necessitating bone marrow biopsy (4).
Conclusions: Our case reports a hitherto undescribed association of plasmacytoid lymphocytes in pseudo-TMA. It also highlights the importance of early diagnosis of pseudo-TMA for timely initiation of vitamin B12 supplementation without the need for invasive workup