Challenging clinical presentations of pernicious anemia

Discov Med. 2017 Sep;24(131):107-115.


Pernicious anemia (PA) is an autoimmune disease of multifactorial etiologies characterized by autoimmune chronic atrophic gastritis, cobalamin deficiency (CD) due to defective absorption of dietary cobalamin from the terminal ileum, and by the presence of intrinsic factor and parietal cell antibodies. PA is a very common cause of CD-related anemia worldwide. Despite advances in the understanding molecular biology and pathophysiology of PA, the diagnosis of PA remains challenging in many circumstances for many clinicians because of its diverse clinical manifestations and the limitations of currently available diagnostic tools. Diagnostic dilemmas could occur when patients with PA present with spuriously normal or high cobalamin levels, normocytic or microcytic anemia, non-anemic macrocytosis, autoimmune hemolytic anemia, pseudo-thrombotic microangiopathy, hyperhomocysteinemia-associated thromboembolism, pseudoleu-kemia, bone marrow failure, bone marrow ring sideroblasts, and neurologic manifestations without anemia or macrocytosis. Herein, we provide an overview of the challenging clinical presentations of PA, diagnostic approach, and management.

Publication types

  • Review

MeSH terms

  • Anemia, Pernicious* / blood
  • Anemia, Pernicious* / diagnosis
  • Anemia, Pernicious* / genetics
  • Anemia, Pernicious* / immunology
  • Animals
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Autoimmune Diseases* / blood
  • Autoimmune Diseases* / diagnosis
  • Autoimmune Diseases* / genetics
  • Autoimmune Diseases* / immunology
  • Gastritis, Atrophic* / blood
  • Gastritis, Atrophic* / diagnosis
  • Gastritis, Atrophic* / genetics
  • Gastritis, Atrophic* / immunology
  • Humans
  • Vitamin B 12 Deficiency* / blood
  • Vitamin B 12 Deficiency* / diagnosis
  • Vitamin B 12 Deficiency* / genetics
  • Vitamin B 12 Deficiency* / immunology


  • Autoantibodies