Pernicious Anemia: The Hematological Presentation of a Multifaceted Disorder Caused by Cobalamin Deficiency

Abstract

Pernicious anemia is still a neglected disorder in many medical contexts and is underdiagnosed in many patients. Pernicious anemia is linked to but different from autoimmune gastritis. Pernicious anemia occurs in a later stage of autoimmune atrophic gastritis when gastric intrinsic factor deficiency and consequent vitamin B₁₂ deficiency may occur. The multifaceted nature of pernicious anemia is related to the important role of cobalamin, which, when deficient, may lead to several dysfunctions, and thus, the proteiform clinical presentations of pernicious anemia. Indeed, pernicious anemia may lead to potentially serious long-term complications related to micronutrient deficiencies and their consequences and the development of gastric cancer and type 1 gastric neuroendocrine tumors. When not recognized in a timely manner or when pernicious anemia is diagnosed with delay, these complications may be potentially life-threatening and sometimes irreversible. The current review aimed to focus on epidemiology, pathogenesis, and clinical presentations of pernicious anemia in an attempt to look beyond borders of medical specialties. It aimed to focus on micronutrient deficiencies besides the well-known vitamin B₁₂ deficiency, the diagnostic approach for pernicious anemia, its long-term complications and optimal clinical management, and endoscopic surveillance of patients with pernicious anemia.

Keywords: atrophic gastritis; autoimmune gastritis; blue light imaging; cobalamin; gastric cancer; gastric neuroendocrine tumor; intestinal metaplasia; iron deficiency anemia; narrow-band-imaging endoscopy; pernicious anemia; surveillance.

Figure 1

Main clinical consequences in patients with pernicious anemia (PA) related to hypochlorhydria and vitamin B₁₂ deficiency.

Figure 2

Mainstays in the diagnosis of pernicious anemia. When pernicious anemia is suspected, the first step is usually a full blood panel to test for anemia and/or macrocytosis, together with testing for cobalamin deficiency and increased levels of homocysteine and/or methylmalonic acid. Next, the positivity of gastric autoantibodies towards parietal cells and/or intrinsic factor is commonly assessed. In any case, the hematological and/or serological suspicion of pernicious anemia always needs to be confirmed by histological assessment of gastric antral and corpus biopsies obtained during gastroscopy.