Case Presentation: A 49-year-old woman presented with a 2-week history of malaise, nausea, emesis, and lightheadedness. She reports she last felt normal 3 months prior when she started noting progressive weakness. There was associated shortness of breath, diaphoresis, and lightheadedness started on the day of presentation.
Hemoglobin returned at a level of 3.8 g/dL, hematocrit of 11.7%, mean corpuscular volume 103 fL, and platelets of 128 K/uL. Manual smear revealed schistocytes with tear drop cells, fragmented cells, and spherocytes. Other lab data included elevated total bilirubin of 2 mg/DL, indirect bilirubin of 1.6 mg/dL, haptoglobin of <30, LDH of 6150, AST of 54 U/L, B12 of <60pg/ml, folate of 4.5 ng/m, and methylmalonic 1.12 umol/L. Direct Coombs test was negative and ADAMTS13 of 71%.
She was diagnosed with hemolytic anemia and pancytopenia secondary to B12 deficiency and treated with daily IV B12 injection. Hemoglobin and platelets improved after several days of therapy. Subsequent work up also found positive intrinsic factor blocking antibodies and IgG gastric parietal cell antibodies, which are diagnostic of pernicious anemia.
Discussion: While B12 deficiency is a well-known cause of anemia, often presenting with macrocytic anemia and elevated methylmalonic acid (MMA), hemolytic anemia is not a classical presentation of this deficiency. By itself, Cobalamin or vitamin B12, is a water-soluble vitamin that is naturally present in meat, dairy products, and fish. B12 functions as a cofactor for both methionine synthase, a universal methyl donor, and L-methyl malonyl-CoA mutase, an enzyme essential for hemoglobin synthesis. As a result, B12 deficiency has two major effects on the hematopoiesis, leading to both megaloblastic changes and ineffective erythropoiesis. Absence of B12 leads to an abnormal dissociation between the maturation of cytoplasm to immature nuclei as the result of slower nuclear division. The ineffective erythropoiesis leads to intramedullary hemolysis within the bone marrow, prior to release into the blood stream. The lysis of these cells leads to elevated lactate dehydrogenase, decrease haptoglobin, and elevated bilirubin. Hemolytic anemia and thrombocytopenia can be reversed with B12 replacement.
Pernicious anemia is an autoimmune gastritis characterized by destruction of parietal cells and blocking of uptake of Vitamin B12 mediated by intrinsic factor. Prevalence of pernicious anemia ranged from 50 to 4000 cases per 100,000 patients. Diagnostically, anti-parietal cell antibodies have high sensitivity and are present in 85% of affected patients; however, it has relatively low specificity as they can be found in up to 10% of healthy individuals. In comparison, anti-intrinsic factor antibody has a relatively lower sensitivity of 50% but very high specificity which can confirm a pernicious anemia diagnosis. In conjunction, these two tests provide both a sensitive screening test and a specific confirmation test.
Conclusions: This case highlights the evaluation of macrocytic anemia – a common finding in hospitalized patients. Uniquely though, this case describes a life-threatening complication of hemolytic anemia secondary to B12 deficiency.