Autoimmune hemolytic anemia causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Assosciate Editor(s)-In-Chief: Prashanth Saddala M.B.B.S; Shyam Patel [2], Irfan Dotani [3]

Overview

Autoimmune hemolytic anemia is caused by primary and secondary conditions. Secondary conditions that cause autoimmune hemolytic anemia include malignancies, autoimmunity, and medications. Malignancies that cause autoimmune hemolytic anemia include chronic lymphocytic leukemia and non-Hodgkin lymphoma. Autoimmune conditions that cause autoimmune hemolytic anemia include systemic lupus erythematosus, primary biliary cirrhosis, and others. Medications that cause autoimmune hemolytic anemia include methyldopa and fludarabine.

Causes

Primary autoimmune hemolytic anemia

  • In most cases, autoimmune hemolytic anemia is due to a secondary cause, since there must be autoantibody production in response to a stimulus. Primary autoimmune hemolytic anemia can sometimes be caused by infections such as Mycoplasma pneumoniae or Epstein-Barr virus (mononucleosis).

Secondary autoimmune hemolytic anemia

Secondary autoimmune hemolytic anemia is due to an underlying condition, such as malignancy or autoimmune disorders.

  • Malignancy: Blood-related cancers accounts for 50% of cases of secondary autoimmune hemolytic anemia. A variety of malignancies can cause secondary warm autoimmune hemolytic anemia including chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma.[1] Lymphoproliferative disorders are more commonly associated with secondary autoimmune hemolytic anemia compared to myeloproliferative disorders. The premise behind lymphoproliferative disorders causing secondary autoimmune hemolytic anemia is that these conditions cause abnormal immune activation which results in plasma cells producing antibodies, which can then attack normal red blood cells.
    • Chronic lymphocytic leukemia (CLL): Approximately 10-25% of patients with CLL will develop autoimmune hemolytic anemia [1] The presence of autoimmune hemolytic anemia in patients with CLL is an indication for treatment of CLL and suggests a worse prognosis compared to the absence of autoimmune hemolytic anemia. In CLL, the malignant B lymphocytes are not the cells that produce anti-red blood cell antibodies.[2] The mechanism by which CLL triggers autoimmune hemolytic anemia is thought to be related to antigen presentation by CLL cells and/or impaired self-tolerance upon release of cytokines by CLL cells.[3]
    • Non-Hodgkin's lymphoma (NHL): This condition is less commonly associated with autoimmune hemolytic anemia compared to CLL. The frequency of autoimmune hemolytic anemia in non-Hodgkin lymphoma is approximately 2-3%. A variety of NHLs can result in autoimmune hemolytic anemia.
    • Nodular lymphocyte-predominant Hodgkin lymphoma: In rare cares, autoimmune hemolytic anemia can be secondary to Hodgkin lymphoma.[3]
  • Autoimmune disorders[4] : Systemic autoimmune conditions can also cause secondary autoimmune hemolytic anemia. The premise behind autoimmune conditions causing secondary autoimmune hemolytic anemia is failure of self-recognition by the immune system, resulting in aberrant immune activation and production of autoantibodies that attack normal cells, including red blood cells.[4] These conditions include:
  • Medications: There are multiple medications associated with autoimmune hemolytic anemia.
    • Methyldopa: This medication is used for the treatment of hypertension.
    • Fludarabine: This medication is a chemotherapy agent that is approved for the treatment of chronic lymphocytic leukemia.
    • Immunotherapeutic agents: This class of medications includes PD-1 inhibitory antibodies, which are used for treatment of cancer.

References

  1. 1.0 1.1 Berentsen S, Sundic T (2015). "Red blood cell destruction in autoimmune hemolytic anemia: role of complement and potential new targets for therapy". Biomed Res Int. 2015: 363278. doi:10.1155/2015/363278. PMC 4326213. PMID 25705656.
  2. Tandra P, Krishnamurthy J, Bhatt VR, Newman K, Armitage JO, Akhtari M (2013). "Autoimmune cytopenias in chronic lymphocytic leukemia, facts and myths". Mediterr J Hematol Infect Dis. 5 (1): e2013068. doi:10.4084/MJHID.2013.068. PMC 3867225. PMID 24363883.
  3. 3.0 3.1 Salmeron G, Molina TJ, Fieschi C, Zagdanski AM, Brice P, Sibon D (2013). "Autoimmune hemolytic anemia and nodular lymphocyte-predominant hodgkin lymphoma: a rare association". Case Rep Hematol. 2013: 567289. doi:10.1155/2013/567289. PMC 3655493. PMID 23710384.
  4. 4.0 4.1 Berentsen S (2015). "Role of Complement in Autoimmune Hemolytic Anemia". Transfus Med Hemother. 42 (5): 303–10. doi:10.1159/000438964. PMC 4678321. PMID 26696798.

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