Agranulocytosis deferiprone

A safe, effective, inexpensive, orally-absorbed iron chelating agent would improve compliance and the quality of life of affected patients. Deferiprone, which is the best of many agents examined, is less effective than desferrioxamine, carries a risk of agranulocytosis and may itself cause tissue fibrosis. It remains under clinical trial but may be too toxic for general use. 

Agranulocytosis is a major limitation to the use of deferiprone and has an estimated frequency of 1.6% (16-21). Moderate leukopenia is more common. 

Oxidation of deferiprone with hypochlorous acid, the major oxidant of neutrophil leukocytes, results in the formation of a chemically reactive species, consistent with the quinone metabolite of deferiprone. Deferiprone-related agranulocytosis presumably results from a T cell-mediated immunological reaction, induced by a reactive metabolite of deferiprone (18). In one case agranulocytosis and systemic vasculitis (with arthritis, palpable purpura of the legs, erythema of the palms and soles, and desquamation of the skin over the distal phalanges) occurred in association with deferiprone (22). 

Loebstein R, Diav-Citrin O, Atanackovic G, Olivieri NF, Koren G. Deferiprone-induced agranulocytosis. A critical review of five rechallenged cases. Clin Drug Invest 1997 13 345-9. 

Castriota-Scanderbeg A, Sacco M. Agranulocytosis, arthritis and systemic vasculitis in a patient receiving the oral iron chelator LI (deferiprone). Br J Haematol 1997 96(2) 254-5. 

Another hypothesis is that agranulocytosis is secondary to immune-mediated damage to myeloid progenitor cells, but there is as yet no conclusive evidence of this. While neutropenia has been reported to recur on rechallenge with deferiprone, it did so at about the same pace as in the original episode, instead of the immediate fall... 

Pontikoglou C, Papadaki HA. Idiosyncratic drug-induced agranulocytosis the paradigm of deferiprone. Hemoglobin 2010 34(3) 291-304. 

Ricchi P, Ammirabile M, Costantini S, Cinque P, Lanza AG, Spasiano A, Di Matola T, Di Costanzo G, Pagano L, Prossomariti L. The impact of previous or concomitant IFN therapy on deferiprone-induced agranulocytosis and neutropenia a retrospective study. Expert Opin Drug Saf 2010 9(6) 875-81. 

Hematologic In a 5-year randomized study in 213 patients with -thalassemia, deferiprone monotherapy 75 mg/kg/day was compared with deferiprone 75 mg/kg/day on 3 days/week alternating with deferoxamine 50 mg/kg/day on 3 days/week [335 ]. While neutropenia was equally frequent in the two groups (11 and 15 patients), there was agranulocytosis in three of the patients who received deferiprone monotherapy and none in the other group. This may be related to the... 

Deferoxamine is the oldest of the chelation therapies, and is administered typically at 40mg/kg body weight, for 8-12 h, 4 days per week. However, some patients do not receive sufficient benefit from deferoxamine and develop cardiac iron overload and failure [S ]. More recently, orally bioavailable chelators, such as deferiprone and deferasirox, have become popular. However, the oral iron chelators have shown side effects that differ from those of deferoxamine. Deferiprone has proven to be more efficacious than deferasirox in several clinical trials, and is now routinely administered when deferoxamine treatment has failed. However, it is associated with agranulocytosis in about 1% of patients through an as yet undetermined mechanism and neutropenia more rarely. Deferiprone has been in use in Europe since 1999 but was not approved in the United States until 2011, due in part to a controversy over its safety [4 ]. 

Deferiprone treatment is known for inducing agranulocytosis and/or neutropenia at rates of 0.2-2.8/100 patient-years [43 ]. A 65-year-old man treated with deferiprone (1000 mg twice a day, 5 days per week) for... 

Huprikar N, Gossweiler M, Callaghan M, Bunge P. Agranulocytosis with deferiprone treatment of superficial siderosis. BMJ Case Rep... 

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