Hematology 9 Springer-Verlag 1993 Case Report Acute agranulocytosis after prolonged high-dose usage of intravenous dipyrone - a different mechanism of dipyrone toxicity? J. Sabbaga 1, C. Osawa 1, F.H. Pahl 2, E. Vellutini 2, D. Pereira 3, and I. Cecconello 1 i Intensive Care Unit, 2 Neurology, 3 Clinical Pathology, Hospital Alem~o Oswaldo Cruz, Silo Paulo, SP, Brazil Received 7 October 1992/Accepted 16 December 1992 Summary. Two seriously injured trauma patients present- ing with intense and progressive neutropenia are de- scribed. Bone marrow examination in both cases showed virtually absent granulopoiesis but normal erythropoiesis and megakaryopoiesis, allowing the diagnosis of acute agranulocytosis. Discontinuation of only one drug (dipy- rone) with no further treatment was required for normali- zation of blood parameters. The association of dipyrone with neutropenia is still debatable. The recent medical literature on dipyrone generation of agranulocytosis is reviewed. Key words: Agranulocytosis - Dipyrone - Neutropenia - Side effect Introduction Development of neutropenia in critically ill patients usually reflects an increase in peripheral consumption caused by gram-negative bacterial infections. Appropri- ate care of the primary disease results, in general, in nor- malization of leukocyte counts. There are, however, situa- tions in which abrupt a decrease in neutrophil numbers indicates a functional bone marrow failure. Acute agra- nulocytosis is an often fatal disease manifested by virtual absence of granulocytes in the blood, associated with spe- cific marrow granulocytic hypoplasia [12]. The extremely uncommon condition incidence of this was recently determined to be approximately seven per million per year [13]. In this report we describe two seriously injured trauma patients who developed severe selective granulo- cytopenia after several days of intensive care. Both patients were receiving prescription high-dose intrave- nous dipyrone. Correspondence to: J. Sabbaga, Unidade de Terapia Intensiva Hospital Alem~o Oswaldo Cruz, Rua Joao Juli~o 331, 01323 S~o Paulo, SP Brazil I I I I I I I I I I I ~ ~ t ~ l l i I I I I I ~ t l ~ 2 4 6 8 10 14 18 22 26 Days post admission Case reports Case L An 18-year-old Korean man was transferred to our intensive care unit (ICU) 6 h after being involved in a car accident. He ar- rived intubated and artificially ventilated. On admission the patient was found to be in deep coma and to have decerebrate posturing on painful stimulation. His pupils were moderately dilated, presenting prompt reactions to light. ACT scan showed discrete brain swel- ling. The patient was then submitted to intracranial pressure moni- toring and was mechanically hyperventilated while receiving intra- venous phenobarbital for sedation. Antibiotic therapy administered initially as prophylaxis and then for a chest infection consisted of cephalothin from day 1 to day 4, cefotaxime and metronidazole from day 5 to day 13, and pefloxacin from day 14 to day 17. Sixteen days after admission a gradual decrease in the patient's leukocyte count was noted (Fig. 1). Platelet and reticulocyte values were 300000/mm 3 and 1.6% respecitvely. Bone marrow aspiration performed on day 17 revealed an absolute absence of granulocytic 12 10 6 ,_1 Ann Hematol (1993) 66:153-155 Annals of Fig. 1. Leukocyte counts presented by case 1 (• and case 2 (e) during the month in our ICU