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.

中文翻译：

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恶性贫血：病理生理学和诊断困难

恶性贫血 (PA) 是世界上维生素 B12（钴胺素）缺乏性贫血的最常见原因。它是一种自身免疫性疾病，包括自身免疫性慢性萎缩性胃炎 (CAG) 和钴胺素缺乏症 (CD) 的显着特征。虽然贫血最初被描述为有害，但可以通过补充维生素 B12 来控制。PA 的发生和进展通常是隐匿的。或者，患者可能没有贫血症状，因为他们已经适应了疾病的微妙性质。通常，除非调查全血细胞计数 (FBC)，否则可能会遗漏潜在疾病，从而阻碍治疗过程。对于许多执业临床医生来说，诊断挑战仍然是切实的，由于缺乏可靠的钴胺素检测方法来诊断 CD 以及模拟许多其他血液病的临床模拟物，例如骨髓增生异常综合征、急性白血病、铁粒细胞性贫血、骨髓衰竭状态、血栓性微血管病和血栓栓塞。此外，及时识别 CD 的症状也很重要，因为尽管补充了钴胺素，一些神经系统后遗症可能变得不可逆。在此，我们讨论了关于 PA 的病理生理学、具有挑战性的临床表现和诊断困难的文献综述。由于 PA 的钴胺素替代疗法很简单，因此在本综述中将不讨论。血栓性微血管病和血栓栓塞。此外，及时识别 CD 的症状也很重要，因为尽管补充了钴胺素，一些神经系统后遗症可能变得不可逆。在此，我们讨论了关于 PA 的病理生理学、具有挑战性的临床表现和诊断困难的文献综述。由于 PA 的钴胺素替代疗法很简单，因此在本综述中将不讨论。血栓性微血管病和血栓栓塞。此外，及时识别 CD 的症状也很重要，因为尽管补充了钴胺素，一些神经系统后遗症可能变得不可逆。在此，我们讨论了关于 PA 的病理生理学、具有挑战性的临床表现和诊断困难的文献综述。由于 PA 的钴胺素替代疗法很简单，因此在本综述中将不讨论。