Pernicious anemia: Pathophysiology and diagnostic difficulties

Abstract

Pernicious anemia (PA) is the most common cause of vitamin B12 (cobalamin) deficiency anemia in the world. It is an autoimmune disease, comprising of salient features of autoimmune chronic atrophic gastritis (CAG) and cobalamin deficiency (CD).Although the anemia was first described as pernicious, it may well be controlled with vitamin B12 replacement. The onset and progression of PA is often insidious. Alternatively, patients may have no anemic symptoms since they become acclimatized to the subtle nature of the disease. Oftentimes, there is a possibility that the underlying disease may be missed unless a full blood count (FBC) is investigated, leading to hindrance in the treatment journey. Diagnostic challenges remain tangible for many practicing clinicians, since there is lack of reliable cobalamin assays to diagnose CD as well as clinical mimics, which simulate many other hematological conditions, such as myelodysplastic syndrome, acute leukemia, sideroblastic anemias, bone marrow failure states, thrombotic microangiopathy, and thromboembolism. Moreover, prompt recognition of the symptoms of CD is also vital, because some neurologic sequalae may become irreversible despite replenishing cobalamin. Herein, we discuss a literature review on the pathophysiology, challenging clinical presentations and diagnostic difficulties of PA.Since the cobalamin replacement therapy for PA is straightforward, it will not be discussed in this review.

Characterization of Gastric Tissue-Resident T Cells in Autoimmune and Helicobacter pylori-Associated Gastritis

“…Autoimmune gastritis, also known as type A gastritis, is characterized by the destruction of oxyntic glands in the stomach, followed by the emergence of atrophic and metaplastic mucosa [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. A significant reduction in the gastric glands results in vitamin B12 and iron malabsorption, leading to pernicious anemia and iron deficiency anemia.…”

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

“…Conversely, macrocytosis is often the first presentation of PA for months or years before anemia sets up. While anemic patients may present symptoms related to anemia itself, such as weakness, reduced mental concentration, headache, palpitations, or, rarely, cardiological chest pain, patients presenting with non-anemic macrocytosis may present with neurological symptoms [46]. Other important hematological manifestations of PA and vitamin B 12 deficiency are hyperhomocysteinemiarelated thrombosis [47][48][49] and bone marrow failure with pancytopenia, whose differentiation from other causes of bone marrow failure may be challenging since morphological changes in hematopoietic cells and the bone marrow are often overlapping and not characteristic for PA [46,50].…”

“…Neurological symptoms may be reversible with vitamin B 12 treatment if recognized in a timely manner. Therefore, it is important to pay attention and intercept initial signs before neurological lesions become irreversible [46]. In this context, it should be kept in mind that copper deficiency may mimic clinical/hematological presentation of vitamin B 12 deficiency and should be accurately excluded, in particular in non-responders to cobalamin supplementation [61,62].…”

“Listen to Your Immune System When It’s Calling for You”: Monitoring Autoimmune Diseases Using the iShU App

“…Pernicious Anemia is megaloblastic anemia (i.e., deficiency of vitamin B12) caused by the lack of intrinsic factors and characterized by the inflammation of the stomach [ 49 ]. Even if this disease is gastric, symptoms may also appear at intestinal, hematological, neurological, cardiac, and urinary levels.…”

“…Even if this disease is gastric, symptoms may also appear at intestinal, hematological, neurological, cardiac, and urinary levels. Some of the clinical findings are low-grade fever, lethargy, fatigue, headache, faintness, tachycardia, abdominal bloating, weight loss, diarrhea, ataxia, paresthesia, palpitations, edema, urinary retention, memory loss, and psychosis [ 49 , 50 ].…”