A population-based case-cohort study of drug-associated agranulocytosis

Background: Agranulocytosis is a life-threatening disorder, often caused by drugs. Incidences or risks of drug-induced agranulocytosis are not well kn own, since it is rare. Methods: To determine the risk of drug-associated agranulocytosis as a reas on for admission to Dutch hospitals, we performed a population-based case-c ohort study. Hospital discharge data came from the Dutch Centre for Health Care Information, Utrecht, which contains data on all general and universit y hospitals in the Netherlands. The reference cohort consisted of all perso ns in the catchment area of the Pharmaco Morbidity Record Linkage System (P HARMO RLS) in the Netherlands, composing a population of approximately 220 000 to 484 000 persons from 1987 through 1990. All admissions during that p eriod with agranulocytosis or related diagnoses were included in the study (n = 923). The potential causes of agranulocytosis were assessed in all cas es classified as probable or possible agranulocytosis. Results: Discharge summaries were received of 753 admissions, of which 678 contained enough information for analysis. Of the 678, 108 were classified as "agranulocytosis probable" eras "agranulocytosispossible." In 75 of thes e 108 cases, agranulocytosis had been the reason for admission. Fifteen pat ients had used methimazole within 10 days before developing agranulocytosis ; 2, carbimazole; 9, sulfasalazine; 8, sulfamethoxazole-trimethoprim; 4, cl omipramine hydrochloride; and 2, dipyrone with analgesics, yielding adjuste d relative risks of agranulocytosis of 114.8 (for thyroid inhibitors combin ed) (95% confidence interval [CI], 60.5-218.6), 74.6 (95% CI, 36.3-167.8), 25.1 (95% CI, 11.2-55.0), 20.0 (95% CI, 6.1-57.6),and 26.4 (95% CI, 4.4-11. 1), respectively. Conclusions: The highest relative risks were found for thyroid inhibitors, sulfamethoxazole-trimethoprim, sulfasalazine, clomipramine, and dipyrone co mbined with analgesics.