Case Presentation: A 52-year-old African American male with a past medical history of gastric ulcer presented to the emergency department with progressively worsening exertional dyspnea and fatigue over the past two months. Physical examination was significant for a heart rate of 105 bpm and icteric sclera. Pinprick and vibratory sensations over bilateral lower extremity were normal. Initial laboratory analysis revealed a hemoglobin of 3.9 g/dl, platelet count of 54 X 103/ml, and white blood cell count of 5.8 X 103/ml, with a mean corpuscular volume (MCV) of 110 fL. Peripheral smear revealed schistocytosis, teardrop cells, and anisopoikilocytosis. No hypersegmented neutrophils were seen. PT/INR and aPTT were normal. Total bilirubin was 2.8 mg/dl with a direct component of 0.9 mg/dl, lactate dehydrogenase (LDH) was 6,975 IU/L and haptoglobin levels (< 8 mg/dl) were undetectable. Abdominal ultrasound showed no hepatosplenomegaly and normal biliary ducts. Additional labs revealed a corrected reticulocyte count of 0.4 %, and direct coombs was negative. D-dimer, fibrinogen levels, ADAMTS13 levels, hemoglobin electrophoresis, and serum Immuno-electrophoresis were normal. However, vitamin B12 level was low (< 150 pg/ml) with elevated methylmalonic acid levels of 3853 mmol/L (MMA) and normal folate levels. The anti-intrinsic factor antibody was positive, and the diagnosis of pernicious anemia was made. The patient was transfused three units of pack red blood cells and started on 1000 mcg of intramuscular B12 injection daily. LDH, haptoglobin, hemoglobin, platelet count, and reticulocyte count all improved with high dose vitamin B12 therapy.

Discussion: Our patient presented with symptomatic anemia, thrombocytopenia, schistocytes, elevated LDH, low haptoglobin, and indirect hyperbilirubinemia concerning for microangiopathic hemolytic anemia (MAHA). However, ADAMTS13 levels, coagulation profile, and fibrinogen levels were normal, ruling out disseminated intravascular coagulopathy (DIC) and thrombotic thrombocytopenic purpura (TTP). The patient’s inadequate bone marrow response, signified by a low reticulocyte count, along with the low vitamin B12 levels and elevated MMA, confirmed vitamin B12 deficiency as the cause for his anemia. Intramedullary hemolysis resulting in pseudo-thrombotic microangiopathy may occur in 2.5 percent of patients with severe vitamin B12 deficiency and can mimic TTP. Pernicious anemia is the most common cause of severe B12 deficiency. It occurs due to an autoimmune response against the gastric mucosa, resulting in the formation of autoantibodies to intrinsic factor secreted by parietal cells. Lifelong treatment with parenteral or oral B12 supplementation is indicated, and initiation of treatment results in a marked improvement in markers of hemolysis and cell counts.

Conclusions: Intramedullary hemolysis is an uncommon presentation of severe vitamin B12 deficiency. Due to the starkly differing management strategies, differentiation between MAHA and vitamin B12 deficiency is of utmost importance. Therefore, physicians should always include B12 deficiency as a differential for a patient presenting with features of MAHA and an inadequate bone marrow response.