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Principles of Hematotoxicology: Laboratory Assessment and Interpretation of Data

Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285

The toxicologic evaluation of the hematopoietic system is part of most preclinical and clinical safety studies and has become routine in monitoring a variety of novel and conventional therapies in humans and animals. As with spontaneous disease, iatrogenic blood dyscrasias may be primary but are frequently secondary to other tissue toxicity. The latter tendency makes this easily accessible tissue particularly useful in monitoring for systemic toxicity, while primary hematotoxicity ranks with liver and kidney effects as important and often limiting complications. Although the principles driving the diagnostic approach to spontaneous (clinical) blood disorders generally apply to preclinical and clinical safety studies, there are important differences, particularly regarding control of variables, feasibility of testing, and interpretation of resulting data. The luxury of studying a homogenous population of subjects free of complicating disease under controlled (uniform) laboratory and environmental conditions allows changes to be defined with greater precision and sensitivity. There are generally more options regarding the assays available and frequency of monitoring. Moreover, the hierarchy of tests applied are influenced by regulatory as well as scientific or problem-driven indications. Finally, interpretation of laboratory findings is usually based on the use of subjects as their own controls (pretreatment and sequential monitoring), comparison to a control population and well-defined reference ranges specific for the population under study, and in accordance with the principles of pathology and internal medicine.

Key Words: Hematopathology • blood dyscrasias • preclinical safety assessment • drug-induced • anemia • thrombocytopenia • neutropenia • myelotoxicity

Toxicologic Pathology, Vol. 21, No. 2, 130-134 (1993)
DOI: 10.1177/019262339302100203


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