Case Presentation: A 40 year-old female presented to the Emergency Department with several months of fatigue followed by acute fever and confusion. She denied weight loss, swollen glands, cough, rash, arthralgias, or myalgias. No drug or alcohol use. She was febrile to 102.5F. The remainder of the vital signs were normal, and the neuro exam was non-focal. Confusion fully resolved prior to admission. The remainder of the exam did not reveal lymphadenopathy, focal signs of infection, stigmata of cirrhosis, or petechiae. CBC showed WBC 2.6 x109/L, Hgb 5.5 g/dL, and platelets of 92 x109/L. MCV was 109 fL, and absolute neutrophil count (ANC) was 0.7×109/L. LFTs revealed mild transaminitis, total bilirubin of 2.7 mg/dL (direct bilirubin 0.8 mg/dL), and normal albumin. Fibrinogen was 274 mg/dL and INR was 1.27. Urinalysis and urine drug screen were negative. A CT head and chest X-ray were normal. A CT abdomen and pelvis showed no signs of intra-abdominal infection, cirrhosis, or lymphadenopathy. She was started on empiric cefepime, vancomycin, and acyclovir for neutropenic fever and transfused two units of red blood cells. Further testing included a negative HIV, elevated LDH (3,912 U/L), and undetectable haptoglobin. Uric acid was also elevated. B12 level was 139 pg/mL(low). Pancytopenia was notably present two months prior (WBC 3.6×109/L, Hgb 10.4 g/dL, Plt 132×109/L). Direct Coombs antibody testing was negative. The reticulocyte index was 0.73, suggesting hypoproliferation. Peripheral smear revealed schistocytes and anisopoikilocytosis with hypersegmented neutrophils without peripheral blasts (Figure 1). The patient clinically improved on intramuscular B12 supplementation with normalization of LDH and ANC. Subsequent labs included a negative Parvovirus IgM antibody, and flow cytometry was not suggestive of leukemia/lymphoma. Methylmalonic acid and homocysteine levels were elevated, supporting B12 deficiency. The patient was discharged on oral B12 supplementation. One month post discharge, fatigue fully resolved, and repeat blood counts were nearly normal.

Discussion: B12 deficiency results in ineffective marrow erythropoiesis leading to bone marrow failure (1). Impaired DNA synthesis results in fragile RBC membranes and hemolysis. While not fully clear, there is evidence that hyperhomocysteinemia contributes to endothelial damage and increased RBC fragmentation and schistocytosis. This rare manifestation of B12 deficiency with pancytopenia and hemolysis with schistocytes can mimic the presentation of acute leukemia and thrombotic microangiopathy (2,3). Many patients undergo unnecessary treatment with plasma exchange and bone marrow biopsy prior to confirming the diagnosis of B12 deficiency. Autoimmune hemolytic anemia was unlikely with a negative direct Coombs antibody test. Thrombotic thrombocytopenic purpura (TTP) is also unlikely as the patient has neutropenia, relatively high platelets for TTP, and evidence of pancytopenia two months before admission. Leukemia was less likely given the absence of peripheral blasts and normalization of the ANC after three days of B12 replacement.

Conclusions: When confronted with pancytopenia, hemolytic anemia and schistocytes, clinicians should keep in mind the possibility that B12 deficiency can mimic leukemia, hemolytic anemia and thrombotic microangiopathy.

IMAGE 1: Peripheral Smear in Severe B12 Deficiency