Case Description
A 17-year-old male with history of intestinal resection secondary to gastroschisis at birth was referred to the emergency room for shortness of breath, fatigue, and lightheadedness for a week. His history was significant for celiac disease, iron and B12 deficiency with symptomatic anemia in the past, requiring transfusions. It had been at least a year since he had taken his last supplements and he had not adhered to a gluten-free diet. He denied constitutional symptoms, fevers, bleeding, or recurrent illnesses. His physical examination was significant for weight below the third percentile, pallor, mildly icteric sclerae and hepatosplenomegaly. He was alert and oriented with no noticeable neurological deficits.
His complete blood count (CBC) was significant for pancytopenia with a WBC: 2.42 x 10^3/uL, Hb: 5.9 g/dL, MCV: 95.4 fL, Plt: 111 x 10^3/uL and a reticulocytopenia of 0.6%. Review of his peripheral smear was significant for anisocytosis, microcytosis, poikilocytosis and schistocytes. Routine chemistries were suggestive of hemolysis with an elevated LDH of >50 000 U/L, an unconjugated hyperbilirubinemia of 3.7 mg/dL and an undetectable haptoglobin. His synthetic liver function was unremarkable with normal coagulation studies despite a notable transaminitis. A liver ultrasound showed diffuse echogenicity with likely fatty infiltration but no evidence of portal hypertension. He had a negative direct coombs, iron studies were unremarkable and a B12 <109 pg/mL. His renal function was also unremarkable. He was transfused two units of packed red blood cells, which allowed for stabilization of his hemoglobin and he was started on oral iron and B12 supplementation.
The differential included a pancytopenia secondary to B12 deficiency with a superimposed hemolytic process as well as concern for a malignant bone marrow infiltrative process given his pancytopenia and hepatomegaly. Paroxysmal nocturnal hemogobinuria testing was negative. A bone marrow biopsy and aspirate displayed no changes consistent with myelodysplasia or malignancy. There was evidence of erythroid hyperplasia and megaloblastic maturation along with hypersegmented neutrophils consistent with his B12 deficiency as shown in Fig. 1. His liver biopsy showed non-alcoholic steatohepatitis attributed to his uncontrolled celiac disease and the decision was made to convert his oral B12 to an intramuscular formulation.
Repeat B12 and LDH were 525 pg/mL and 503 U/L respectively showing resolution of his symptoms. Despite not being included in the initial differential, a hemolytic anemia in the presence of a progressive thrombocytopenia warrants the consideration of a TMA. However, given the resolution of his symptoms with B12 supplementation the diagnosis of pseudo-TMA secondary to B12 deficiency was made.