There are several known causes of bone marrow necrosis. It may occur as a direct result of compound administration (e.g.,cyclophosphamide) or may be secondary to severe infectious disease states (e.g., septicemia) or tissue ischemia caused by vascular injury, thrombosis, or vascular occlusion. Specific causes of the latter include neoplasia (e.g., tumor emboli, vascular occlusion), disseminated intravascular coagulation (thrombosis), and exposure to endotoxin (vascular injury). Necrosis caused by an obstruction of the blood supply (infarct) generally has well-delineated borders microscopically as a distinguishing feature (Figure 3 and Figure 4).
In a rat study to evaluate the effects of feed restriction on common toxicologic parameters, severe diet restriction (75%reduction) of only two weeks resulted in bone marrow necrosis and degeneration. Specific observations included vacuolated or necrotic-appearing stromal cells, necrosis of hematopoietic cells, remaining hematopoietic tissue <25% of concurrent controls, focal areas of hemorrhage, and readily observed emperipolesis of neutrophils within the megakaryocytes.
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