Tuesday, July 18, 2017

Danazol: Use in Aplastic Anemia


Availability in Hospital Keningau:

  • Danazol 200 mg Capsule

Aplastic Anemia:

  • Aplastic Anemia (AA) is a rare hematopoietic stem cell disease characterized by the presence of peripheral blood cytopenia and marrow hypoplasia.
  • Immunosupresive therapy (IST) is recommended first line therapy for 
    • non-severe AA patients requiring treatment 
    • severe or very severe AA patients who lack a matched sibling donor (MSD)
    • severe or very severe AA patients aged >35-50 years.
  • The current standard first line IST is horse ATG (antithymocyte globulin) combined with ciclosporin (CSA) and/or corticosteroids.

 Indication for Danazol:

  • It is a synthetic anabolic steroid with unique properties similar to corticosteroids, such as inhibition of interleukin-1 and TNF-α production with reduced virilising and toxic effects. 
  • Danazol is not indicated for treatment of aplastic anemia based on FUKKM
  • However, it has been employed for the treatment of AA patients having no stem cell donor and those refractory to IST.
  • is an alternative to AA patients with short telomeres: (< 1% of the age-adjusted telomere length) +/- underlying telomeropathy, or to patients not eligible for immunosuppressive therapy and allogeneic stem cell transplantation 
  • Findings also indicate that danazol is effective for a subset of AA patients, and particularly for female patients with AA refractory to IST.

Mechanism of Action:

  • No clear mechanism of action identified for effectiveness in AA
  • In present study, a beneficial effect of danazol was seen mainly on anemia, and not on thrombocytopenia. All responders showed not only improvement of anemia but also an increase in the number of reticulocytes. 
  • Therefore, administration of danazol appears to stimulate erythropoiesis, rather than inhibit degradation of mature blood cells.

Clinical Outcomes:  

  • There was a difference in the rate of response to danazol between males (17%) and females (75%), which was significant in the result of the chi-square test (P 5 0.03). It is possible that the antagonistic effects of danazol on female hormones may lead to augmentation of hematopoiesisin AA.
  • Danazol has been shown to improve thrombocytopenia in some patients with MDS.
  • Stadtmauer et al.demonstrated that patients with MDS who responded to danazol tended to show higher levels of platelet-associatedI gG or platelet-bindable IgG in plasma, compared to non responders. 

References:

  1. Jaime-Pérez, J. C., Colunga-Pedraza, P. R., Gómez-Ramírez, C. D., Gutiérrez-Aguirre, C. H., Cantú-Rodríguez, O. G., Tarín-Arzaga, L. C., & Gómez-Almaguer, D. (2011). Danazol as first-line therapy for aplastic anemia. Annals of hematology, 90(5), 523-527.
  2. Guidelines for the diagnosis and management of adult aplastic anaemia 2015
  3. Chuhjo, T., Yamazaki, H., Omine, M., & Nakao, S. (2008). Danazol therapy for aplastic anemia refractory to immunosuppressive therapy. American journal of hematology, 83(5 ), 387-389.

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