<p>Vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy: a case report and literature review</p>

Abstract

Pseudo-thrombotic microangiopathy (pseudo-TMA) is a recognized, yet uncommon, clinical presentation of vitamin B12 deficiency. Patients with pseudo-TMA present with microangiopathic hemolytic anemia (MAHA), thrombocytopenia and schistocytes. They are often misdiagnosed as thrombotic thrombocytopenia purpura (TTP) and receive unnecessary therapy. Here, we report a case of a 60-year-old male who presented with thrombocytopenia and normocytic normochromic anemia. Anemia work-up was remarkable for severe B12 deficiency (<60 pg/mL) and a positive non-immune hemolysis panel. Peripheral smear was reviewed and showed anisocytes, poikilocytes, schistocytes and hypersegmented neutrophils. Vitamin B12 replacement (1000 mcg IM daily) was started, ADAMTS13 activity was sent and daily plasmapheresis was initiated. Over the next 3 days, the patient’s hemoglobin and platelets were stable and the hemolysis panel showed gradual improvement. On day 4, ADAMTS13 activity results came back normal at 61%. Accordingly, plasmapheresis was discontinued, parenteral B12 replacement was continued and that resulted in gradual improvement and eventually cessation of hemolysis and normalization of hemoglobin and platelets. In this patient, parietal cell autoantibodies were positive and so the diagnosis of pernicious anemia was made. Patients with severe vitamin B12 deficiency may present with features mimicking TTP such as MAHA, thrombocytopenia and schistocytosis. An early and accurate diagnosis of pseudo-TMA has a critical clinical impact with respect to administering the correct treatment with vitamin B12 replacement and avoiding, or shortening the duration of, unnecessary therapy with plasmapheresis.

Chronic Atrophic Gastritis Presenting as Hemolytic Anemia due to Severe Vitamin B12 Deficiency

“…It is speculated that the etiology of dysmorphic red blood cells in severe vitamin B12 deficiency stems from both intramedullary and extramedullary dysfunction. From an extramedullary perspective, research has shown that hyperhomocysteinemia, which occurs in vitamin B12 deficiency, may increase the risk of hemolysis in addition to causing endothelial damage, which further leads to intravascular hemolysis and RBC fragmentation [ 6 ]. Of note, hyperhomocysteinemia can also be caused by hypothyroidism, obesity, diabetes, hyperlipidemia, medications, and more rarely possessing a methylenetetrahydrofolate reductase gene variant [ 7 ].…”

Vitamin B12 Deficiency Presenting With Microangiopathic Hemolytic Anemia

“…Although TTP can be deadly without any proper therapy plan, starting plasmapheresis treatment for TTP and vitamin B12 replacement for cobalamin deficiency might be a plausible choice for pseudo-TMA-suspected cases [ 14 ]. One of the features that assist in primary diagnosis is that pseudo-TMA does not respond to FFP, which was the case in our report [ 1 ].…”

“…Every vitamin is assigned a specific and unique role in the human body, for instance, “vitamin B12" is one of the most vital vitamins with its unique structure and composition of the mineral cobalt and thus the origin of the name cobalamin. It possesses various roles on different levels, including DNA and red blood cell (RBC) synthesis, in addition to several neurologic functions [ 1 ]. The cut-off was defined by the World Health Organization, where cobalamin deficiency was presented as less than 150 pmol/L [ 2 ].…”

“…Usually, cases with pseudo-TMA present with hemolytic anemia, thrombocytopenia, and dysmorphic “fragmented” RBCs. They are often misdiagnosed to have other TMA syndromes and receive unnecessary therapy such as plasmapheresis [ 1 , 2 ]. We herein describe a case of an elderly patient with pseudo-TMA whose lack of vitamin B12 was misdiagnosed with TTP.…”

Suspected Metformin-induced Cobalamin Deficiency Mimicking Thrombotic Thrombocytopenic Purpura

“…This would be reflected by the presence of schistocytes (Figure 1) and bizarre anisopoikilocytosis on the peripheral blood smear (Figure 2). These abnormal blood findings can affect the mean corpuscular volume; however, it has been found to be normal in less than 50% of the patients [9]. Moreover, D-dimer levels can also be elevated in some patients due to activation of the coagulation cascade and co-relate well with the degree of schistocytosis [2].…”