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KEY POINTS

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  • Hematotoxicology is the study of adverse effects of exogenous chemicals on blood and blood-forming tissues.

  • Direct or indirect damage to blood cells and their precursors includes tissue hypoxia, hemorrhage, and infection.

  • Xenobiotic-induced aplastic anemia is a life-threatening disorder characterized by peripheral blood pancytopenia, reticulocytopenia, and bone marrow hypoplasia.

  • Idiosyncratic xenobiotic-induced agranulocytosis may involve a sudden depletion of circulating neutrophils concomitant with exposure that persists as long as the agent or its metabolites are in the circulation.

  • Leukemias are proliferative disorders of hematopoietic tissue that originate from individual bone marrow cells.

  • Xenobiotic-induced thrombocytopenia may result from increased platelet destruction or decreased platelet production, which lead to decreased platelet aggregation and bleeding disorders.

  • Blood coagulation is a complex process involving a number of proteins whose synthesis and function can be altered by many xenobiotics.

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BLOOD AS A TARGET ORGAN

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Hematotoxicology is the study of adverse effects of exogenous chemicals on blood and blood-forming tissues. The delivery of oxygen to tissues throughout the body, maintaining vascular integrity and providing the many affector and effector immune functions necessary for host defense, requires a prodigious proliferative and regenerative capacity. Each of the various blood cells (erythrocytes, granulocytes, and platelets) is produced at a rate of approximately 1–3 million/s in a healthy adult; 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 (EPO) and granulocyte colony-stimulating factor (G-CSF). The consequences of direct or indirect damage to blood cells and their precursors are predictable and potentially life-threatening. They include hypoxia, hemorrhage, and infection.

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Hematotoxicity may be regarded as primary toxicity, where one or more blood components are directly affected, or secondary, where the toxic effect is a consequence of other tissue injury or systemic disturbances. Primary toxicity is regarded as among the serious effects of xenobiotics, particularly drugs. Secondary toxicity is exceedingly common, due to the propensity of blood cells to reflect various local and systemic effects of toxicants on other tissues.

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HEMATOPOIESIS

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The production of blood cells, or hematopoiesis, is a highly regulated sequence of events by which blood cell precursors proliferate and differentiate. The location of hematopoiesis changes throughout one’s life. For instance, fetal hematopoiesis is located in the liver, spleen, bone marrow, thymus, and lymph nodes, while the primary location in adults is the bone marrow of the axial skeleton and proximal limbs. Two types of bone marrow exist: (1) red marrow, which is active in hematopoiesis, and (2) yellow marrow, which is called so because it turns fatty as it ceases participation in hematopoiesis.

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Whereas the ...

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