Case Presentation: A 51-year-old African American Female with PMHx of sickle cell trait, vitiligo (developed 5 years ago), T2DM, HTN, unspecified seizure disorder who presented with altered mental status and found to have severe pancytopenia. She presented hemodynamically stable with a physical exam notable for: pale conjunctiva and diffuse skin hypopigmentation consistent with vitiligo. Medications: Keppra 500 mg, Amlodipine 5 mg. No pertinent family history. Admission labs were notable for: Hgb 2.2 w/ MCV 93.4 & RDW 19.2, WBC 0.8 w/ ANC 0.5, Abs Lymphocyte Count 0.3, Plts 47. B12: 66, Folate 5.77. LDH >4,000, Haptoglobin <8, Reticulocyte Count: 2.4 (Ret Index 0.14). TIBC 252, Ferritin 429, Iron 187, Iron Sat 66%. PT 15.0. INR 1.2. aPTT 23.1. Hep C Ab non-reactive. HIV p24 Ag and Ab nonreactive. Direct Coombs test negative. Her blood smear showed: many tear drop cells, mildly hypochromic RBCs, decreased platelets with normal morphology & no clumping, 1-4 schistocytes per high powered field, multiple hypersegmented neutrophils. Given the history of vitiligo, evaluation for autoimmune etiologies of her severe B12 deficiency revealed Intrinsic Factor Blocking Ab positive and Parietal Cell Ab positive. She was diagnosed with intramedullary hemolysis in the setting of severe B12 deficiency due to a new diagnosis of pernicious anemia. She received four units of blood transfusions and daily B12 injections for a week, folate and pyridoxine. At her outpatient hematology appointment, she had a positive Romberg test and referred interval improvement of distal upper and lower extremity paresthesias; concerning for additional finding of subacute combined degeneration. Repeat testing one-month post-admission shows resolving pancytopenia and will now transition to monthly B12 injections.
Discussion: An estimated 1.5% of patients with B12 deficiency present with hemolytic anemia. Intramedullary hemolytic anemia due to B12 deficiency is a consequence of ineffective RBC maturation due to defective DNA formation in the absence of adequate B12 levels. Decreased B12 levels are also associated with hyper-homocysteinemia, resulting in a pro-oxidant state contributing to endothelial damage and a pseudo-microangiopathic state. Studies have shown that B12 replacement results in the return to normal homocysteine levels and resolved hemolysis. This case highlights the importance of keeping a broad differential diagnosis when faced with hemolytic anemia and not overlooking Vitamin B12 Deficiency as a cause, even when the patient resides in a resource rich nation. Additionally, pernicious anemia should be high in the differential for patients with a history of autoimmune disease presenting with severe vitamin B12 deficiency.
Conclusions: Vitamin B12 deficiency is an important, yet rare, cause of Coombs negative hemolytic anemia with severe pancytopenia.