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  • Blood as a Target Organ

  • Hematopoiesis

  • Toxicology of the Erythron

    • The Erythrocyte

    • Alterations in Red Cell Production

    • Alterations in the Respiratory

      • Function of Hemoglobin

      • Homotropic Effects

      • Heterotropic Effects

    • Alterations in Erythrocyte

      • Survival

      • Nonimmune Hemolytic Anemia

      • Immune Hemolytic Anemia

  • Toxicology of the Leukon

    • Components of Blood Leukocytes

    • Evaluation of Granulocytes

    • Toxic Effects on Granulocytes

      • Effects on Proliferation and Kinetics

      • Effects on Function

      • Idiosyncratic Toxic Neutropenia

      • Mechanisms of Toxic Neutropenia

  • Leukemogenesis as a Toxic Response

    • Human Leukemias

    • Mechanisms of Toxic

      • Leukemogenesis

    • Leukemogenic Agents

  • Toxicology of Platelets and Hemostasis

    • Toxic Effects on Platelets

      • The Thrombocyte

      • Thrombocytopenia

      • Toxic Effects on Platelet Function

  • Toxic Effects on Fibrin Clot

    • Frmation

    • Coagulation

    • Decreased Synthesis of Coagulation Proteins

    • Increased Clearance of Coagulation Factors

  • Toxicology of Chemicals Used to Modulate Hemostasis

    • Oral Anticoagulants

    • Heparin

    • Fibrinolytic Drugs

    • Inhibitors of Fibrinolysis

  • Risk Assessment

    • Preclinical Risk Assessment

      • Animal Models and Hematologic Monitoring

      • In Vitro Bone Marrow Assays

    • Clinical Trials and Risk Assessment

Blood as a Target Organ

Hematotoxicology is the study of adverse effects of drugs, nontherapeutic chemicals, and other chemicals in our environment on blood and blood-forming tissues. This subspecialty draws on the discipline of hematology and the principles of toxicology. Scientific understanding of the former began with the contributions of Leeuwenhoek and others in the 17th century with the microscopic examination of blood. Hematology was later recognized as an applied laboratory science but limited to quantitation of formed elements of the blood and the study of their morphology, along with that of bone marrow, spleen, and lymphoid tissues. It is now a diverse medical specialty, which—perhaps more than any other discipline—has made tremendous contributions to molecular medicine.

The vital functions that blood cells perform, together with the susceptibility of this highly proliferative tissue to intoxication, make the hematopoietic system unique as a target organ. Accordingly, it ranks with liver and kidney as among the most important considerations in the risk assessment of individual patient populations exposed to potential toxicants in the environment, workplace, and medicine cabinet.

The delivery of oxygen to tissues throughout the body, maintenance of vascular integrity, and provision of the many affector and effector immune functions necessary for host defense require a prodigious proliferative and regenerative capacity. Each of the various blood cells (erythrocytes, granulocytes, and platelets) is produced at a rate of approximately one to three million/s in a healthy adult and several times that rate in conditions where demand for these cells is high, as in hemolytic anemia or suppurative inflammation (Kaushansky, 2006). As with intestinal mucosa and gonads, this characteristic makes hematopoietic tissue a particularly sensitive target for cytoreductive or antimitotic agents, such as those used to treat cancer, infection, and immune-mediated disorders. This tissue is also susceptible to secondary effects of toxic agents that affect the supply of nutrients, such as iron; the clearance of toxins and metabolites, such as urea; or the production of vital growth factors, such as erythropoietin and granulocyte colony-stimulating factor (G-CSF).


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