Case Presentation: A 65-year-old male presented with a chief complaint of dyspnea beginning 3 months ago. Additionally, he endorsed 15-pound weight loss, fatigue, and decreased appetite during this time. Members of his family noticed yellowing in his eyes. He had no known past medical history. He described his diet as balanced, consisting of meat, eggs, milk, and vegetables. Review of systems was positive for intermittent heart palpitations. Vital signs were blood pressure of 145/88 mmHg, temperature of 99.2º F, respiratory rate of 17/min, and heart rate of 124 beats/min. The patient had scleral icterus on physical examination.
Complete blood count (CBC) was significant for a decreased hemoglobin (Hgb) of 7.1 g/dL, decreased white blood cell (WBC) count of 3.1 10^3/µL, and decreased platelet count of 98 10^3/µL. Reticulocyte index was low at 0.36. Mean corpuscular volume (MCV) was high at 122 fL. Total bilirubin was elevated at 2.3 mg/dl with a predominance indirect bilirubin. Peripheral smear revealed schistocytes and hypersegmented neutrophils. Additional blood work showed an elevated lactate dehydrogenase (LDH) and undetectable haptoglobin. Cobalamin level was found to be significantly decreased at 48 pg/mL. Methylmalonic acid and homocysteine were both elevated. Intrinsic factor antibodies came back positive. Testing for other possible causes of hemolysis was negative.
Low cobalamin coupled with positive intrinsic factor antibodies suggested a diagnosis of pernicious anemia, which was confirmed by endoscopy. It was determined that the hemolysis and thrombocytopenia were both due solely to the cobalamin deficiency, as additional testing was negative. The patient was started on cobalamin replacement therapy. His laboratory abnormalities improved, he experienced improvement of his symptoms, and was discharged.
Discussion: Cobalamin deficiency is relatively common with a prevalence of approximately 15% in patients 60 years and older. With that said, cobalamin deficiency presenting with hemolytic anemia, schistocytes on peripheral smear, and thrombocytopenia is quite uncommon. A study of 201 patients with cobalamin deficiency showed that only 2.5% of those patients presented with pseudothrombotic microangiopathy. This particular presentation can pose a diagnostic challenge for clinicians, as it can mimic a true microangiopathic hemolytic anemia such as TTP. An incorrect diagnosis of TTP, for example, could lead to admission to the intensive care unit and the unnecessary initiation of plasmapheresis. In patients with hemolysis, thrombocytopenia, and macrocytic anemia, cobalamin deficiency should be considered on the differential diagnosis.
Conclusions: Cobalamin deficiency can uncommonly present with hemolytic anemia, schistocytes on peripheral smear, and thrombocytopenia. This presentation, referred to as pseudothrombotic microangiopathy, can resemble a true microangiopathic process such as thrombotic thrombocytopenic purpura (TTP). Correct diagnosis of pseudothrombotic microangiopathy is essential in avoiding mismanagement of the patient and unnecessary treatments.