Pernicious anemia is still a neglected disease in many medical contexts and is underdiagnosed in many patients. The nature of pernicious anemia is related to the important role of cobalamin, which, when deficient, can lead to various dysfunctions and thus to clinical presentations of this condition, but what is pernicious anemia?
What is pernicious anemia?
Pernicious anemia is an autoimmune disease, probably much more common than currently diagnosed. It is linked to autoimmune gastritis, however, are not synonymous. Since pernicious anemia occurs at a stage after autoimmune gastritis, when gastric intrinsic factor deficiency and consequent vitamin B 12 deficiency may occur.
Nature is related to the important role of cobalamin (Vitamin B12), which, when deficient, can lead to several dysfunctions ranging from hematopoiesis to neurological, psychiatric and obstetric abnormalities. The pathogenesis has not yet been clarified, but is probably linked to autoimmune destruction of gastric glands due to selfreactive T lymphocytes in genetically predisposed individuals.
Pathogenesis of pernicious anemia
In pernicious anemia, the gastric oxinic mucosa is destroyed with the loss of parietal cells, resulting in deficiency of intrinsic factor and hydrochloric acid, impairing the absorption of vitamin B12 and other micronutrients. Typically, it is associated with the presence of autoantibodies against intrinsic factor and parietal cells, thus corroborating the autoimmune origin of this condition. These autoantibodies are released from plasma cells activated by self-reactive CD4+ T lymphocytes. It is considered the final stage of autoimmune gastritis and is characterized by the absence of Helicobacter pylori (H. pylori) in histology.
Clinical manifestations
Clinical manifestations are varied and may involve many organs and systems, requiring a global medical approach for their identification and management. The main presentations are hematological and neurological consequences of vitamin B12 deficiency, and both require several years for its development. Vitamin B12 deficiency impairs hematopoiesis due to the fundamental role of vitamin B12 in DNA synthesis. Macrocytic anemia is the hallmark of pernicious anemia.
However, this characteristic is not always present in the diagnosis, since almost 30% of patients do not have macrocytosis, but nor noromocitic anemia. This usually occurs in the case of concomitant iron deficiency and/or other diseases that cause microcytosis.
On the other hand, macrocytosis is usually the first presentation for months or years before anemia is established. While anemic patients may present with symptoms related to anemia itself, such as weakness, reduced mental concentration, headache, palpitations, or, rarely, cardiac chest pain, patients with non-anemic macrocytosis may present with neurological symptoms.
Other important hematological manifestations of vitamin B12 deficiency are thrombosis related to hyperhomocysteinemia and bone marrow failure with pancytopenia, whose differentiation from other causes of bone marrow failure can be challenging, since morphological changes in hematopoietic cells and bone marrow often overlap and are not characteristic.
Clinical practice
Optimal clinical management of pernicious anemia requires continuous crosstalk and practice among various medical specialties, so as not to lose the overall view of this complex disease and ensure the best possible care and outcome to the patient. In addition, annually scheduled clinical and biochemical monitoring is essential for diagnosing new micronutrient deficiencies in a timely manner, and regular endoscopic surveillance is necessary for early detection of gastric neoplastic complications.
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Article: Pernicious anemia – Esposito G, Dottori L, Pivetta G, Ligato I, Dilaghi E, Lahner E. Pernicious Anemia: The Hematological Presentation of a Multifaceted Disorder Caused by Cobalamin Deficiency. Nutrients. 2022; 14(8):1672. https://doi.org/10.3390/nu14081672
