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The hypoproliferative anemias are normochromic, normocytic, or macrocytic and are characterized by a low reticulocyte count. Hypoproliferative anemia is also a prominent feature of hematologic diseases that are described as bone marrow failure states; these include aplastic anemia, myelodysplastic syndrome (MDS), pure red cell aplasia (PRCA), and myelophthisis. Anemia in these disorders is often not a solitary or even the major hematologic finding. More frequent in bone marrow failure is pancytopenia: anemia, leukopenia, and thrombocytopenia. Low blood counts in the marrow failure diseases result from deficient hematopoiesis, as distinguished from blood count depression due to peripheral destruction of red cells (hemolytic anemias), platelets (idiopathic thrombocytopenic purpura [ITP] or due to splenomegaly), and granulocytes (as in the immune leukopenias). Marrow damage and dysfunction also may be secondary to infection, inflammation, or cancer.

Hematopoietic failure syndromes are classified by dominant morphologic features of the bone marrow (Table 11-1). Although practical distinction among these syndromes usually is clear, some processes are so closely related that the diagnosis may be complex. Patients may seem to suffer from two or three related diseases simultaneously, or one diagnosis may appear to evolve into another. Many of these syndromes share an immune-mediated mechanism of marrow destruction and some element of genomic instability resulting in a higher rate of malignant transformation.

TABLE 11-1Differential Diagnosis of Pancytopenia

It is important that the internist and general practitioner recognize the marrow failure syndromes, as their prognosis may be poor if the patient is untreated; effective therapies are often available but sufficiently complicated in their choice and delivery so as to warrant the care of a hematologist or oncologist.



Aplastic anemia is pancytopenia with bone marrow hypocellularity. Acquired aplastic anemia is distinguished from iatrogenic aplasia, marrow hypocellularity after intensive cytotoxic chemotherapy for cancer. Aplastic anemia can also be constitutional: the genetic diseases Fanconi anemia and dyskeratosis congenita, although frequently associated with typical physical anomalies and the development of pancytopenia early in life, can also present as marrow failure in normal-appearing adults. Acquired aplastic anemia is often stereotypical in its manifestations, with the abrupt onset of low blood counts in a previously well young adult; seronegative hepatitis or a course of an incriminated ...

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