Mechanism of ranitidine associated anemia.
Ranitidine, an H2 receptor antagonist, has been associated with hematotoxicity. The mechanism(s) underlying the toxicity is not well understood. The authors studied the mechanism of anemia in a patient with ranitidine associated anemia and thrombocytopenia. Clinical evaluation suggested drug-induced Coombs' positive reticulocytopenic hemolysis. In vitro, with the patient off ranitidine, the authors were able to induce Coombs' positivity by incubating patient's red cells with ranitidine and his serum. This process was inhibited by prior exposure of his red cells to histamine. In vitro studies using clonal assays for hematopoietic progenitors revealed that while the patient's serum or ranitidine alone did not affect the patient's or normal bone marrow hematopoiesis, the simultaneous presence of both agents significantly suppressed both patient's and normal erythroid progenitor (BFU-E) colony development. This suppressive effect was prevented by the prior exposure of marrow to histamine and was not observed when the patient's serum was heat inactivated. These studies suggest that the anemia may have resulted from complement-dependent autoimmune destruction/inhibition of progenitor/mature erythroid cells by a process critically dependent on the presence of ranitidine and possibly acting at or near the histamine receptor.
Pixley
J S
JS
Veterans Administration Medical Center, University of Nevada School of Medicine, Reno 89520.
MacKintosh
F R
FR
Sahr
E A
EA
Zanjani
E D
ED
D000740:Anemia / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D003298:Coombs Test; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011899:Ranitidine / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D013921:Thrombocytopenia / Q000139:chemically induced
D006632:Histamine; D011899:Ranitidine