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After studying this chapter, you should be able to:

  • Establish a differential diagnosis of pancytopenia.

  • Classify the primary bone marrow disorders that lead to pancytopenia.

  • Explain the pathogenesis of aplastic anemia and the principles underlying its treatment.

It is clear from the information presented in Chapter 2 that the regulated production of circulating blood cells depends on the presence of an adequate number of functional multipotent hematopoietic stem cells. Accordingly, disease processes that either injure stem cells directly or compromise their environmental niche within the bone marrow result in a decrease in the numbers and sometimes the function of circulating blood cells. Thus, these bone marrow disorders often give rise to pancytopenia, a reduction in the numbers of circulating red cells, leukocytes, and platelets.

A variety of disorders can cause pancytopenia (Table 4-1). Because red cells, leukocytes, and platelets are all produced in the bone marrow, it is no surprise that microscopic examination of the marrow by aspiration and biopsy is critical in evaluating patients with pancytopenia. As shown in the italicized portions of Table 4-1, this chapter will cover disorders involving injury to hematopoietic stem cells as well as those characterized by disruption of the marrow microenvironment by infiltrating cells that are extrinsic to the marrow (myelophthisis). Severe pancytopenia is a hallmark of marrow aplasia, whereas more variable degrees of cytopenia are encountered in myelophthisic disorders. Additional causes of pancytopenia listed in Table 4-1 are covered in other chapters of this book.

TABLE 4-1Causes of Pancytopenia



Because over 95% of the cells in the bone marrow are progeny of hematopoietic stem cells, injury to these cells will result in a marked decrease in cellularity. Figure 4-1 compares a low-magnification view of normal bone marrow with that of bone marrow from a patient with severe aplastic anemia. In this specimen (Figure 4-1B), it would be difficult to identify any cells of the erythroid, myeloid, or megakaryocyte lineages. The few cells that can be identified are a mix of lymphocytes, plasma cells, and marrow stroma that includes endothelial cells and fibroblasts.


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