Chlorpropamide-induced pure white cell aplasia.
We investigated the mechanism for isolated agranulocytosis and marrow pure white cell aplasia in an elderly man receiving 0.5 to 1.0 g per day of chlorpropamide (Chl) without other toxic drug exposure or overt systemic illness. Patient marrow revealed an absence of recognizable granulocytic precursors; megakaryocytes and erythroid precursors were normal. The WBC count was 1800/mm3 on admission with only 2% neutrophils; the absolute neutrophil count first exceeded 500/mm3 on the 17th day following cessation of Chl. A serum Chl level on admission was 100 micrograms/mL (acute phase, AP); no Chl was detected in serum (convalescent phase, CP) assessed on the 22nd hospital day. Antineutrophil antibodies were not detected, and T cell depletion failed to augment patient in vitro granulopoiesis. Patient AP serum produced potent complement-mediated inhibition (87% +/- 7%) of autologous granulocyte progenitors (CFU-GM) with minimal inhibition of erythroid (11% +/- 5%) or multipotent (5% +/- 4%) progenitor cells. Selective inhibition by patient AP serum of CFU-GM (74% +/- 11%) was also seen against two allogeneic marrows. Patient CP serum no longer inhibited (6% +/- 4%) autologous CFU-GM. Addition of Chl (5 to 120 micrograms/mL) to CP serum but not to control serum resulted in potent drug concentration-dependent complement-mediated inhibition of autologous and allogeneic CFU-GM. Inhibition of CFU-GM in the presence of Chl was no longer demonstrable following immunoabsorbent removal of IgG from patient serum. Patient serum in the presence of Chl had limited activity against morphologically recognizable marrow granulocytic precursors in a microimmunofluorescence assay. These results are most consistent with the development of Chl-dependent, selective antibody-mediated immune inhibition of granulopoiesis.
D000368:Aged; D000369:Aged, 80 and over; D000380:Agranulocytosis / Q000139:chemically induced*; D001855:Bone Marrow Diseases / Q000139:chemically induced* / Q000473:pathology; D002747:Chlorpropamide / Q000009:adverse effects* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D008297:Male
D002747:Chlorpropamide