Case Presentation: A 33 year-old US born woman with iron deficiency anemia presented after one episode of pre-syncope. She reported 3 weeks of progressive fatigue, shortness of breath, and pain in the chest, back, and hips. She denied abdominal pain, menstrual abnormalities, sick contacts, recent trauma, and blood disorders or malignancy in her family. She did not take any medications or herbal supplements and reported tolerating a normal, unrestricted diet. Her exam was remarkable for tachycardia and mucosal pallor at the conjunctiva and soft palate. Labwork revealed a hemoglobin of 4.5 g/dL, macrocytosis to 114 fL with an RDW of 30.6%, and platelet count of 108,000 per µL. Her RBC count was 1.11 M/µL with a reticulocyte production index of 0.9%. Packed red blood cells were transfused with an appropriate response. Additional work-up was significant for a markedly elevated LDH (7035 U/L) and reduced haptoglobin (<8 mg/dL). A peripheral smear showed schistocytes and anisocytosis, and a direct Coombs test was positive. Pulse dosed steroids were started for suspected autoimmune hemolytic anemia (AIHA). A serum folate level was normal, but a cobalamin level was undetectable. Subsequent methylmalonic acid and homocysteine levels were elevated, so daily intramuscular methylcobalamin was initiated. At the time of discharge, her hemoglobin had improved to 9.1 g/dL and her presenting symptoms had resolved. Serum anti-intrinsic factor and anti-parietal cell antibody assays later returned positive and confirmed a diagnosis of autoimmune pernicious anemia (PA).
Discussion: We present a case of combined AIHA and PA resulting in severe, symptomatic anemia. The prevalence of cobalamin deficiency is <3% in adults 20—39 years old with about 40% attributed to PA, but the incidence of PA with concurrent AIHA is unknown. A previous study of 865 patients with a positive direct Coombs test found PA in 3 lone subjects, and only 23 other case reports of dual-diagnosis have been published since 1951. Some of these reports found transiently positive Coombs tests that resolved after cobalamin supplementation. Conversely, PA can lead to hemolysis in the absence of AIHA less than 2% of the time due to rapid and ineffective erythropoiesis. This can be detected by the reticulocyte production index; if found low, as in our case, there is evidence of lysis within the bone marrow. Although rare, these examples highlight the importance of investigating multiple etiologies of hemolytic anemia, else risking incomplete treatment of the patient.
Conclusions: Cobalamin deficiency caused by autoimmunity often leads to PA and can expeditiously improve with steroids and cobalamin supplementation. PA is often associated with other autoimmune conditions, although concurrent presentation with AIHA is rare. Investigating all potential etiologies for hemolytic anemia minimizes the risk for incomplete treatment and relapse.