Pernicious Anaemia: Mechanisms, Diagnosis, and Management

Abstract

Pernicious anaemia (PA) is an autoimmune disease of multifactorial aetiology involving environmental and immunological factors. It is the most common cause of cobalamin deficiency anaemia worldwide. The disease is a macrocytic anaemia caused by a vitamin B12 deficiency, which, in turn, is the result of intrinsic factor deficiency, a protein that binds avidly to dietary vitamin B12 and promotes its transport to the terminal ileum for absorption. Despite the advances in understanding the pathogenesis and molecular biology, diagnosis of PA is still challenging for clinicians because of its complexity, diverse clinical presentations, and the limitations of the available diagnostic tools for the evaluation of cobalamin status and the presence of chronic autoimmune atrophic gastritis. Asymptomatic autoimmune gastritis, a chronic inflammatory disease of the gastric mucosa, precedes the onset of corpus atrophy by 10–20 years. Diagnostic dilemmas could occur when patients with PA present with spuriously normal or high cobalamin levels, normocytic or microcytic anaemia, nonanaemic macrocytosis, autoimmune haemolytic anaemia, pseudo-thrombotic microangiopathy, hyperhomocysteinemia-associated thromboembolism, pseudoleukemia, bone marrow failure, and neurologic manifestations without anaemia or macrocytosis. Other autoimmune disorders, especially thyroid disease, Type 1 diabetes mellitus, and vitiligo, are also commonly associated with PA. The present review focusses on novel aspects regarding the pathogenesis, clinical presentation, and the diagnostic approach of PA; the true usefulness of serum vitamin B12 levels; and the risk of adenocarcinoma and gastric carcinoids as well as their treatment and monitoring strategies.

How Do Patients Receiving Prescribed B12Injections for the Treatment of PA Perceive Changes in Treatment During the COVID-19 Pandemic? A UK-Based Survey Study

“…In recent weeks, many patients with PA have been moved to alternative treatments which use oral B 12 in tablet form. However, there is a debate that this oral replacement is not effective at managing PA where absorption and neurological manifestations may be an issue (3). Current guidance from the British Society for Hematology is to offer oral B 12 ( cyanocobalamin) as a replacement treatment, however, where possible to continue treating using B 12 injections (4).…”

Pernicious anemia

“…among people over the age of 60 years. 2 PA is slightly more prevalent among females than males. Diagnosing PA can be diffi cult due to its insidious onset, diverse clinical presentations, nonspecific symptom progression, and coexisting comorbidities that can present with similar signs and symptoms, oft en masking the disorder.…”

“…The inflammatory process of autoimmune gastritis, which leads to the destruction of parietal cells and subsequent vitamin B12 deficiency, can cause PA 1. It is found worldwide across all ages but is more common among people over the age of 60 years 2. PA is slightly more prevalent among females than males.…”

“…Additional evaluation with methylmalonic acid (MMA) and homocysteine levels is needed if the patient has a low B12 level. An elevated level of MMA is specific to vitamin B12 deficiency and associated with PA, as the MMA level decreases with vitamin B12 therapy 2. The level of serum total homocysteine is more sensitive and less specific because it is also elevated in folate deficiency 2…”

“…An elevated level of MMA is specifi c to vitamin B12 defi ciency and associated with PA, as the MMA level decreases with vitamin B12 therapy. 2 Th e level of serum total homocysteine is more sensitive and less specifi c because it is also elevated in folate defi ciency. 2 ■ Patient information Th is clinical case report describes the care of a 62-yearold woman who presented for her yearly checkup in early 2022.…”