Case Presentation: A 77-year-old female with a history of hypertension and osteoporosis presented to the emergency department with dizziness, fatigue, decreased oral intake, and weakness for a few weeks. She also reported blurry vision and paresthesias in her lower extremities. Physical examination including a neurological examination was normal. Laboratory tests revealed a severe macrocytic anemia and thrombocytopenia. Hemoglobin was 6.4 gm/dL (11.5 – 15.1 gm/dL), mean corpuscular volume was 124.7 FL (82 – 97 FL), and platelets were 102,000/CUMM (150,000 – 450,000 /CUMM). Further work-up was remarkable for a low vitamin B12 of 107 pg/ml (180 – 914 pg/mL) and ongoing non-immune hemolysis. Total bilirubin was 1.74 mg/dL (< 1.50 mg/dL), Indirect bilirubin was increased at 1.31 mg/dL (0 - 0.8 mg/dL), LDH was also increased at 1,433 unit/L (140 - 271 unit/L), haptoglobin was low at <30 mg/dL (44 - 215 mg/dL), and direct antiglobulin test was negative. Reticulocyte production index (RPI) was calculated to be 1.11%. Peripheral blood smear revealed macrocytosis, schistocytes, cigar cells, helmet cells, teardrop cells, and very few platelets. Initially there was concern for thrombotic thrombocytopenic purpura (TTP) however reticulocytopenia, evident by the RPI, reflecting ineffective erythropoiesis was more consistent with the diagnosis of pseudo-thrombotic microangiopathy (TMA) secondary to severe B12 deficiency than TTP. Endoscopy was performed which revealed atrophic gastritis and intestinal metaplasia. Intramuscular vitamin B12 (1000 mcg daily) was started and over the next week, the patient’s hemoglobin and platelets continued to improve. The patient was discharged in a stable condition with outpatient follow up with hematology for weekly vitamin B12 intramuscular injections. The patient’s intrinsic factor antibody later came back positive and gastrin level was elevated at 902 pg/mL (0 - 115 mg/mL), consistent with pernicious anemia.
Discussion: Vitamin B12 deficiency is usually associated with megaloblastic anemia. Pseudo-TMA secondary to severe vitamin B12 deficiency is an uncommon presentation that can mimic TMA present in TTP. Our patient presenting with thrombocytopenia, hemolytic anemia, and schistocytes raises concern for TTP however reticulocytopenia was not consistent with TTP. Low vitamin B12 level and further antibody testing subsequently confirmed pernicious anemia as the etiology of this patient’s TMA. Advanced pernicious anemia can lead to ineffective erythropoiesis which results in the production of poorly formed red blood cells that are more prone to lysis. This is known as intramedullary hemolysis and results in a severe anemia, thrombocytopenia, and fragile red blood cells that are easily sheared resulting in the production of schistocytes.
Conclusions: Although rare, vitamin B12 deficiency should be considered as an etiology in patients presenting with TMA in order to avoid misdiagnosis as TTP and prevent the initiation of aggressive and incorrect management such as plasmapheresis. Reticulocytopenia in the setting of hemolysis should alert physicians to consider other diagnoses.