Atypical and Exceptional Hematological Presentations of Vitamin B12 (Cobalamin) Deficiency: A Review of Case Reports and a Practical Diagnostic Approach

Vitamin B12 (cobalamin) deficiency is classically recognized by macrocytic anemia, but a minority of patients present with life-threatening or misleading hematological pictures. In a series of 201 consecutive patients, about 10% had severe manifestations, including symptomatic pancytopenia, pseudo-thrombotic microangiopathy (pseudo-TMA) and hemolytic anemia. Case reports describe further presentations that mimic thrombotic thrombocytopenic purpura (TTP), myelodysplastic syndrome (MDS), acute leukemia, Evans syndrome and immune thrombocytopenia, or that present with venous thrombosis, including cerebral venous sinus thrombosis. The resulting diagnostic errors expose patients to plasma exchange, corticosteroids, marrow-directed work-up and central venous access. Drawing on a targeted narrative review, we summarise reported phenotypes, identify features that may distinguish these presentations from their mimics, and propose a parallel diagnostic approach incorporating serum B12 and, when indicated, methylmalonic acid (MMA), total homocysteine and holotranscobalamin. Testing must not delay emergency treatment for suspected TTP. The evidence consists of isolated observations and one consecutive single-center series, and should be read as a prompt for vigilance rather than as a measure of frequency.