title: Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone.
abstract: Drug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4'-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging -2.64 g/dL (range -6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference -1.46 g/dL; 95% confidence interval -1.76, -1.15). Hemoglobin concentrations were decreased by ≥ 40% versus pretreatment in 24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin was -1.83 g/dL (range +0.90 to -5.20 g/dL); 1 in 200 (0.5%) required blood transfusion. All children eventually recovered. All the G6PD-deficient children had the G6PD A- variant, ie, mutations V68M and N126D. Drug-induced acute hemolytic anemia in G6PD A- subjects can be life-threatening, depending on the nature and dosage of the drug trigger. Therefore, contrary to current perception, in clinical terms the A- type of G6PD deficiency cannot be regarded as mild. This study is registered at http://www.clinicaltrials.gov as NCT00344006 and NCT00371735.
authors.affiliation: GlaxoSmithKline, Brentford, TW8 9GS, London, United Kingdom. allan.pamba@GSK.com
authors.forename: Allan
authors.initials: A
authors.lastname: Pamba
authors.forename: Naomi D
authors.initials: ND
authors.lastname: Richardson
authors.forename: Nick
authors.initials: N
authors.lastname: Carter
authors.forename: Stephan
authors.initials: S
authors.lastname: Duparc
authors.forename: Zul
authors.initials: Z
authors.lastname: Premji
authors.forename: Alfred B
authors.initials: AB
authors.lastname: Tiono
authors.forename: Lucio
authors.initials: L
authors.lastname: Luzzatto
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000349:Africa; D000743:Anemia, Hemolytic / Q000139:chemically induced* / Q000209:etiology / Q000628:therapy; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D017326:Clinical Trials, Phase III as Topic; D003622:Dapsone / Q000009:adverse effects* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications* / Q000235:genetics; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy; D008297:Male; D015337:Multicenter Studies as Topic; D010084:Oxidation-Reduction; D002727:Proguanil / Q000009:adverse effects / Q000031:analogs & derivatives*; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D016037:Single-Blind Method
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D006454:Hemoglobins; C519882:chloroguanil, dapsone drug combination; D003622:Dapsone; D002727:Proguanil