title: Chemotherapy-induced hemolytic uremic syndrome: description of a potential animal model.
abstract: Hemolytic uremic syndrome (HUS) is an uncommon complication of chemotherapy that contributes to the morbidity of oncology and bone marrow transplant patients. The pathogenesis is not well understood and no established clinical animal model exists. We studied four rhesus monkeys (RM) that developed fatal HUS following high-dose chemotherapy. Microangiopathic hemolytic anemia (pre-Hct 40% and day 5-8 Hct 31% (P < .05), increased BUN (168 mg/dl), creatinine (8.2 mg/dl), and lactate dehydrogenase (1458 IU/L) (mean day 5-8 measurements) were observed. Platelets counts decreased to 39 +/- 15 x 10(9)/l from a mean of 397 +/- 31 x 10(9)/L (P < .0001). vWF, ATIII, thrombin:anti-thrombin complex (T:AT) and prothrombin fragment F1.2 levels were not different from a control group (N = 2). The data presented describe chemotherapy-induced HUS with typical clinical and laboratory features which may provide an animal model for the study of this important syndrome.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Hillyer
authors.forename: A
authors.initials: A
authors.lastname: Duncan
authors.forename: M
authors.initials: M
authors.lastname: Ledford
authors.forename: T J
authors.initials: TJ
authors.lastname: Barrett
authors.forename: S A
authors.initials: SA
authors.lastname: Klumpp
authors.forename: D C
authors.initials: DC
authors.lastname: Anderson
authors.forename: H M
authors.initials: HM
authors.lastname: McClure
authors.forename: E F
authors.initials: EF
authors.lastname: Winton
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000990:Antithrombin III / Q000032:analysis; D001160:Arterioles / Q000473:pathology; D016026:Bone Marrow Transplantation; D016190:Carboplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D003520:Cyclophosphamide / Q000633:toxicity*; D004195:Disease Models, Animal; D006400:Hematocrit; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008253:Macaca mulatta; D009336:Necrosis; D010447:Peptide Hydrolases / Q000032:analysis; D010976:Platelet Count; D012016:Reference Values; D013997:Time Factors; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; C046193:antithrombin III-protease complex; D014841:von Willebrand Factor; D003520:Cyclophosphamide; D000990:Antithrombin III; D003404:Creatinine; D016190:Carboplatin; D007770:L-Lactate Dehydrogenase; D010447:Peptide Hydrolases