Case Presentation: A 44-year-old man with a history of hypertension presented with progressive weakness and dizziness occurring over the past few months. His physical exam was unrevealing. Initial laboratory results were significant for pancytopenia (WBC count: 2.38 K/mcL, hemoglobin: 3.40 g/dL, platelet count: 89 K/mcL) and markers of hemolysis showing a lactate dehydrogenase above 2,500 U/L, undetectable haptoglobin below 10 mg/dL, and elevated direct bilirubin of 0.5 mg/dL. Two units of packed red blood cells were immediately ordered and hematology was consulted. Further laboratory work up was significant for a vitamin B12 < 150 pg/mL, folate > 20.0 ng/mL, PT of 15.7 seconds, INR 1.3, a normal PTT, D-dimer of 14.74 mcg/mL, a normal fibrinogen, a peripheral smear with pancytopenia and prominent hypersegmented neutrophils, homocysteine > 250 mcmol/L, methylmalonic acid of 46 nmol/mL, and a positive intrinsic factor blocking antibody. This confirmed the diagnosis of severe pernicious anemia presenting as pseudo-thrombotic thrombocytopenic purpura (TTP). After cobalamin replacement with monthly injections, the patient’s hemoglobin, lactate dehydrogenase, and haptoglobin normalized in the outpatient setting.
Discussion: This case illustrates an unusual presentation of a fatal yet easily treatable illness. Vitamin B12 or cobalamin deficiency is a relatively common pathology that can be caused by decreased intake, decreased absorption, or medications. It typically presents as mild anemia and fatigue; however, severe deficiency can present as glossitis, neuropathy, weakness, cognitive slowing, or ataxia [1]. Pernicious anemia, an autoimmune condition that prevents vitamin B12 absorption due to autoantibodies to intrinsic factor and parietal cells, commonly presents with neurologic symptoms. Early recognition is crucial as these neurologic deficits can become irreversible if treatment is delayed [2, 3]. Pernicious anemia rarely causes hemolytic anemia, thus can be an easily missed diagnosis during laboratory work up [4]. Pseudo-TTP occurs in 2.5-10% of patients with B12 deficiency [5]. Unlike true TTP, which involves ADAMTS13 deficiency and platelet microthrombi, pseudo-TTP results from ineffective erythropoiesis and intramedullary hemolysis.
Conclusions: Recognizing this distinction is critical, as pseudo-TTP resolves with intramuscular cobalamin replacement, while misdiagnosis as TTP may lead to unnecessary and risky plasma exchange therapy. Clinicians should maintain a high index of suspicion for B12 deficiency in patients with hemolytic anemia, pancytopenia, and macrocytosis, even when laboratory findings initially suggest microangiopathic hemolysis. This is especially true in the presence of comorbid autoimmune disorders, in younger patients, and in those with long-standing helicobacter pylori infection [6].