Information about Pernicious Anemia

Classification & external resources

ICD-10	D51.0
ICD-9	281.0
DiseasesDB	9870
MedlinePlus	000569
eMedicine	med/1799
MeSH	D000752

Pernicious anemia (also known as Biermer's anaemia or Addison's anaemia or Addison-Biermer anaemia) is a form of megaloblastic anaemia due to vitamin B₁₂ deficiency dependent on impaired absorption of vitamin B₁₂ in the setting of atrophic gastritis, and more specifically of loss of gastric parietal cells. While the term "pernicious anaemia" is sometimes also incorrectly used to indicate megaloblastic anaemia due to any cause of vitamin B₁₂ deficiency, its proper usage refers to that caused by atrophic gastritis and parietal cell loss only.

Mechanisms & manifestations

Pathophysiology

Vitamin B₁₂ cannot be produced by the human body, and must therefore be obtained from diet. Normally, dietary vitamin B₁₂ can only be absorbed by the ileum when it is bound by the intrinsic factor produced by parietal cells of the gastric mucosa. In pernicious anaemia, this process is impaired because of loss of parietal cells, resulting in insufficient absorption of the vitamin, which over a prolonged period of time ultimately leads to vitamin B₁₂ deficiency and thus megaloblastic anaemia.

Presentation

: : The presentation of pernicious anaemia resembles that of any other form of anaemia, but is often accompanied by the manifestations of vitamin B₁₂ deficiency (notably neurological abnormalities such as peripheral neuropathy), as well as by other manifestations of autoimmune atrophic gastritis.

Causes

Most commonly, the cause for impaired binding of vitamin B₁₂ by intrinsic factor is autoimmune atrophic gastritis, in which autoantibodies are directed against parietal cells (resulting in their loss) as well as against the intrinsic factor itself (rendering it unable to bind vitamin B₁₂). Less frequently, loss of parietal cells may simply be part of a widespread atrophic gastritis of non-autoimmune origin, such as that frequently occurring in elderly people affected with long-standing chronic gastritis of any cause (including Helicobacter pylori infection). Note that forms of vitamin B₁₂ deficiency other than pernicious anaemia must be considered in the differential diagnosis of megaloblastic anaemia.

Diagnosis

A diagnosis of pernicious anaemia first requires demonstration of megaloblastic anaemia (through a full blood count) and of its direct cause, vitamin B₁₂ deficiency (by measuring B₁₂ levels in serum). A Schillings test can then be used to distinguish pernicious anemia from other causes of vitamin B₁₂ deficiency (notably malabsorption. A diagnosis of atrophic gastritis should be confirmed by gastroscopy with biopsies. Approximately 90% of individuals with pernicious anemia have antibodies for parietal cells, however only 50% of individuals with these antibodies have pernicious anaemia.

Treatment

: Being a manifestation of vitamin B₁₂ deficiency, pernicious anaemia is treated by administering vitamin B₁₂ supplements. Note that if oral tablets are chosen for this purposes, much higher doses are given than normally required in order to overcome the impaired absorption that characterises pernicious anaemia. If oral tablets are not sufficient, vitamin B₁₂ can also be administered via injection. Often the patient can learn to do this at home.

History

The treatment for pernicious anemia was first devised by George Whipple who bled dogs to make them anemic and then fed them various substances to see what (if anything) would make them healthy again. He discovered that ingesting large amounts of liver seemed to cure the disease. George Minot and William Murphy then set about to chemically isolate the curative substance and ultimately were able to isolate the vitamin B₁₂ from the liver. For this, all three shared the 1934 Nobel Prize in Medicine. As a result, pernicious anemia is now treated with either vitamin B₁₂ injections, or large oral doses of vitamin B₁₂, typically between 2 and 4 mg daily.

Famous sufferers

• Inez Milholland, American Suffragette.
• Alexander Graham Bell, Scottish scientist and inventor.
• Annie Oakley.
• Norman Warne, Editor/Publisher & fiance of Beatrix Potter.
• Yoon Eun Hye, A South Korean actress

External links

• The Pernicious Anaemia Society, a UK-based charitable organisation which operates a forum where you can discuss Pernicious Anaemia with other sufferers around the world.
• Parietal cell antibody
• Antibody to GPC

•  • [ e] Pathology: hematology (primarily /, /)
WBCs	hematological malignancy (Lymphoma, leukemia) -cytosis (Agranulocytosis, Leukocytosis, Lymphocytosis, Monocytosis) • -penia (Lymphopenia, Neutropenia)
RBCs/anemia/ hemoglobinopathy	nutritional anemia: Iron deficiency anemia, Plummer-Vinson syndrome, Megaloblastic anemia (Pernicious anemia) hereditary hemolytic anemia: G6PD Deficiency, Thalassemia, Sickle-cell disease/trait, Hereditary spherocytosis, Hereditary elliptocytosis, Hereditary stomatocytosis acquired hemolytic anemia: Warm autoimmune hemolytic anemia, HUS, MAHA, PNH aplastic anemia: Acquired PRCA, Diamond-Blackfan anemia, Fanconi anemia • Sideroblastic anemia • Hemochromatosis
Coagulation/platelets	coagulopathy: DIC • Hemophilia (A, B, C, XIII) • Von Willebrand disease Purpura: Henoch-Schnlein, ITP, TTP primary hypercoagulable state: Protein C deficiency - Protein S deficiency - Antithrombin III deficiency other hemorrhagic conditions: Bernard-Soulier syndrome - Glanzmann's thrombasthenia - Grey platelet syndrome
Histiocytosis	WHO-I Langerhans cell histiocytosis - non-Langerhans-cell histiocytosis/WHO-II (Juvenile xanthogranuloma, Hemophagocytic lymphohistiocytosis) - malignant histiocytic disorders/WHO-III (Acute monocytic leukemia, Malignant histiocytosis, Erdheim-Chester disease)
Other	Asplenia/hyposplenism - Methemoglobinemia