Background

Neutropenia results either from enhanced peripheral neutrophil destruction or decreased neutrophil production. Patients with severe neutropenia are at risk of developing life-threatening infections. Severe neutropenia may be a consequence of drug interactions. Since the first description of drug-dependent neutropenia (DDN), many other drugs have been identified to be involved in the mechanism of neutropenia.

Methods

Here we report a case of metamizole induced neutropenia in a 24-year old woman suffering from epilepsy and sepsis. She had been taking metamizole for three days prior to hospital admission.

A white cell differential revealed neutropenia. A bone marrow revealed increased granulopoiesis but was otherwise unremarkable, a finding which is compatible with peripheral consumption of neutrophils. Metamizole was stopped, and she was put on broad-spectrum antibiotic treatment and granulocyte colony stimulating factor (G-CSF). She recovered quickly.

Serum was analyzed in a granulocyte immune fluorescence test (GIFT) and a granulocyte agglutination test (GAT). Antibody reactivity was also evaluated in a flow-cytometry based GIFT (flowGIFT).

Results

In GIFT, the patient's serum gave positive reactions with all test cells only in the presence of metamizole. Similarly, analysis of serum with isolated granulocytes in flowGIFT, showed binding of anti-granulocytes antibodies to isolated neutrophils only in the presence of metamizole. In both assays, antibody binding was not dependent on the metamizole concentration (0.25 and 0.5 mg/mL). The patient's drug-dependent anti-neutrophil antibodies were non-reactive in GAT with all test cells.

Conclusion

Analysis indicated that neutropenia in this patient was induced by metamizole-dependent antibodies. In the clinic, DDN is under-recognized and the frequency of drug-dependent antibodies in patients with metamizole-induced neutropenia has not been systematically studied. To make a better understanding of the mechanism behind this severe side-effect of metamizole therapy, more awareness and adequate laboratory assays are required.

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