Aplastic anemias usually develop when damaged or destroyed stem cells inhibit red blood cell (RBC) production. Less commonly, they develop when damaged bone marrow microvasculature creates an unfavorable environment for cell growth and maturation. About half of such anemias result from drugs (such as chloramphenicol or hair color dye), toxic agents (such as benzene), or radiation. The rest may result from immunologic factors (suspected but unconfirmed), severe disease (especially hepatitis), or preleukemic and neoplastic infiltration of bone marrow.

Idiopathic anemias may be congenital. Two such forms of aplastic anemia have been identified: congenital hypoplastic anemia (such as Blackfan-Diamond anemia) develops between ages 2 and 3 months; Fanconi’s syndrome, between birth and age 10. In the absence of a consistent familial or genetic history of aplastic anemia, researchers suspect that these congenital abnormalities result from an induced change during fetal development.

Life-threatening hemorrhage from the mucous membranes is the most common complication of aplastic or hypoplastic anemias. Immunosuppression can lead to secondary opportunistic infections.

The patient’s history may not help establish the disease onset because the symptoms commonly develop insidiously. The patient may report signs and symptoms of anemia (progressive weakness and fatigue, shortness of breath, and headache) or signs of thrombocytopenia (easy bruising and bleeding, especially from the mucous membranes [nose, gums, rectum, vagina]).

Inspection may reveal pallor if the patient is anemic, and ecchymosis, petechiae, or retinal bleeding if thrombocytopenia is present. You may note weakness and alterations in the level of consciousness if bleeding into the central nervous system has occurred. If the patient has a history of frequent sore throats, cervical lymphadenopathy may be present.

Auscultation may reveal basilar crackles bilaterally, tachycardia, and a gallop murmur if severe anemia results in heart failure.

The patient may also have signs and symptoms of an opportunistic infection (most commonly, a bacterial infection). Fever, oral and rectal ulcers, and sore throat may indicate the presence of an infection without characteristic inflammation.

Confirmation of aplastic anemia requires a series of laboratory tests. (See Key blood test values in aplastic or hypoplastic anemias, page 60.)

Bone marrow biopsies performed at several sites may yield a dry tap or show severely hypocellular or aplastic marrow, with a varying amount of fat, fibrous tissue, or gelatinous replacement; absence of tagged iron (because the iron is deposited in the liver rather than in bone marrow) and megakaryocytes; and depression of erythroid elements.

Differential diagnosis must rule out paroxysmal nocturnal hemoglobinuria and other diseases in which pancytopenia is common.