Assessment of hemolytic and hemorrhagic anemias in preclinical safety assessment studies.

Abstract

The general characteristics of anemia and the distinguishing features of hemolytic, hemorrhagic, hypoproliferative, maturation abnormality, and iron-deficiency anemias are described. Hemolytic anemias are differentiated initially from hemorrhagic anemias by excluding hemorrhage on clinical, necropsy, or histologic examination. Next, they are distinguished from the remaining types of anemia on the basis of higher reticulocyte counts or, in some instances, by the very rapid rate of decline of the PCV. Hemolytic anemias are distinguished from each other on the basis of incidence and the presence or absence of a dose-response (idiosyncratic vs toxic) and by the cause of hemolysis (oxidative, nonoxidative, or immune-mediated). Hemorrhagic anemias are subclassified on the basis of single- and multiple-site hemorrhage. The causes of multiple-site hemorrhage (hemostasis dysfunction) are established by first- and second-line tests, the type of bleeding, clinical data, and the information gained from an evaluation of the structure, activity, and metabolism of the compound.