A 50-year-old man with no prior history presented with one month of progressively worsening shortness of breath, now occurring with minimal exertion. He endorsed nausea and bilious vomiting, but denied hemoptysis, hematemesis, hematochezia, or melena. He denied recent illness or sick contacts as well easy bleeding or bruising. He denied taking any medications, alcohol or using illicit drugs.
Vital signs were a temperature 98.6 F, blood pressure 131/69, and pulse 97. Exam revealed pale conjunctivae, no scleral icterus and no lymphadenopathy. No murmur was present. There was no hepatosplenomegaly. Neurological exam was unremarkable.
Laboratory tests revealed a leukocyte count of 3.0, hemoglobin of 4.4, and platelets of 41,000. Mean corpuscular volume (MCV) was 115 fL. Hemolysis was demonstrated by bilirubin 2.1, lactate dehydrogenase 4848, and haptoglobin 7. Corrected reticulocyte count was calculated as less than one percent and bone marrow biopsy demonstrated a hypercellular marrow with no evidence of lymphoproliferative process or acute leukemia. HIV and hepatitis panels were negative. Vitamin b12 and methylmalonic acid were found be 59 and 7443 respectively with a normal folate level of 15.6. Esophagogastroduodenoscopy revealed a gastric pH of 8 but was otherwise unremarkable. Antibodies to intrinsic factor and parietal cells returned positive. The diagnosis of vitamin b12 deficiency secondary to pernicious anemia was made and the patient was treated with intramuscular injections of vitamin b12.
Pancytopenia is a common medical condition encountered by internists. One retrospective study of patients with anemia secondary to b12 deficiency identified 17.3% of patients presented with pancytopenia. It is therefore important to include vitamin b12 deficiency in the differential diagnosis for pancytopenia.
Pancytopenia may be due to increased cell destruction is subdivided into intramedullary, intravascular, and extravascular destruction. Pancytopenia may also be due to decreased cell production due to marrow infiltration, hyperplastic or hypoplastic marrow. Vitamin b12 deficiency may manifest as either increased cell destruction secondary to intramedullary destruction (ineffective hematopoiesis) or as decreased blood cell production secondary to hyperplastic bone marrow.
The classic hematological characteristics of b12 deficiency are macrocytic anemia with hypersegmented neutrophils on peripheral blood smear. Additional diagnostic criteria for pernicious anemia include low vitamin b12 level, gastric atrophy, and autoantibodies to either parietal cells or intrinsic factor. Vitamin b12 is a coenzyme for the transfer of the methyl group from N5-methyltetrahydrofolate to form tetrahydrofolate, the active form of folate used by thymidylate synthetase in the synthesis of the nucleic acid thymidine. Though cytoplasmic growth is unaffected in the vitamin b12 deficient state, nucleic DNA synthesis is inhibited and the results in macrocytosis and pancytopenia on laboratory tests. In addition, the thymidine precursor uridine is incorporated into DNA in place of thymidine and the erroneous DNA leads to cell death perpetuating the pancytopenia and producing the characteristic hemolytic pattern of haptoglobin, bilirubin, and lactate dehydrogenase.
An approach to pancytopenia with an understanding of the underlying pathophysiology of vitamin b12 deficiency is important to the diagnosis and treatment of pernicious anemia.
To cite this abstract:Marshall A, White M, Niyogi A. Pernicious Anemia Presenting As Pancytopenia. Abstract published at Hospital Medicine 2015, March 29-April 1, National Harbor, Md. Abstract 611. Journal of Hospital Medicine. 2015; 10 (suppl 2). https://www.shmabstracts.com/abstract/pernicious-anemia-presenting-as-pancytopenia/. Accessed July 23, 2019.