Pernicious anaemia definition
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Understanding Pernicious Anemia: Definition and Key Characteristics
Definition of Pernicious Anemia
Pernicious anemia (PA) is a chronic and complex disorder primarily characterized by a deficiency in vitamin B12 (cobalamin) due to the body's inability to absorb it properly. This condition is often associated with a lack of intrinsic factor, a protein produced by the stomach that is essential for vitamin B12 absorption . The disease typically manifests in middle and later life and is marked by megalocytic normochromic anemia, which involves the presence of abnormally large red blood cells.
Pathophysiology and Causes
Autoimmune Gastritis and Intrinsic Factor Deficiency
The primary cause of pernicious anemia is autoimmune gastritis, which leads to the atrophy of the stomach's mucosal lining. This atrophy results in a deficiency of intrinsic factor, a crucial protein for vitamin B12 absorption . The autoimmune nature of the disease is further evidenced by the presence of antibodies against intrinsic factor and gastric parietal cells in many patients .
Genetic and Autoimmune Factors
Pernicious anemia has a significant autoimmune component and is often associated with other autoimmune disorders such as type 1 diabetes, vitiligo, and autoimmune thyroid diseases . Genetic studies have identified several risk loci associated with the disease, including genes like PTPN22, PNPT1, HLA-DQB1, IL2RA, and AIRE, which highlight the genetic predisposition to PA.
Clinical Presentation and Diagnosis
Hematological and Neurological Symptoms
Patients with pernicious anemia often present with a range of symptoms including unexplained fatigue, memory loss, poor concentration, and paraesthesia (tingling or numbness). The hematological hallmark of PA is megaloblastic anemia, characterized by the presence of large, immature red blood cells and hypersegmented neutrophils in the peripheral blood .
Diagnostic Criteria
The diagnosis of pernicious anemia involves several key criteria:
- Histological evidence of atrophic body gastritis
- Peripheral blood examination showing megaloblastic anemia
- Cobalamin deficiency
- Presence of antibodies to intrinsic factor and gastric parietal cells
Anti-parietal cell antibodies are found in about 90% of patients but are not highly specific, whereas anti-intrinsic factor antibodies, found in about 60% of patients, are highly specific for PA.
Management and Long-term Consequences
Treatment
The primary treatment for pernicious anemia is lifelong vitamin B12 supplementation, which can reverse anemia and neurological symptoms if administered promptly. Monitoring for iron deficiency and other potential complications is also crucial.
Long-term Risks
Patients with pernicious anemia are at an increased risk for gastrointestinal complications, including gastric cancer and type 1 gastric neuroendocrine tumors, due to the chronic atrophic gastritis associated with the disease . Therefore, regular monitoring and endoscopic surveillance are recommended for these patients.
Conclusion
Pernicious anemia is a multifaceted disorder with a complex interplay of autoimmune and genetic factors leading to vitamin B12 deficiency. Early diagnosis and lifelong management with vitamin B12 supplementation are essential to prevent serious long-term complications. Understanding the underlying mechanisms and clinical presentations of PA can aid in timely diagnosis and effective treatment, improving patient outcomes.
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