Anemia, Aplastic

KEY FEATURES

Essentials of Diagnosis

• Pancytopenia

• No abnormal hematopoietic cells seen in blood or bone marrow

• Hypocellular bone marrow

General Considerations

• In aplastic anemia

  • Bone marrow failure

  • Arises from suppression of and/or injury to the hematopoietic stem cell

• Bone marrow

  • Becomes hypoplastic

  • Fails to produce mature blood cells

  • Pancytopenia develops

Causes of aplastic anemia (Table 15-10)

• Idiopathic (probably autoimmune)

• In some cases of idiopathic aplastic anemia, defects have been identified in

  • Maintenance of the hematopoietic stem cell telomere length (dyskeratosis congenita)

  • DNA repair pathways (ie, Fanconi anemia)

    • Likely linked to initiation of marrow failure

    • May be associated with progression to myelodysplasia, paroxysmal nocturnal hemoglobinuria, or acute myeloid leukemia

• Complex detrimental immune response to viruses

CLINICAL FINDINGS

Symptoms and Signs

• From anemia

  • Weakness

  • Pallor

  • Fatigue

• From neutropenia, vulnerability to infections

  • Bacterial

  • Fungal

• From thrombocytopenia, bleeding

  • Mucosal and skin

  • Petechiae and purpura

• The following should not be present

  • Hepatosplenomegaly

  • Lymphadenopathy

  • Bone tenderness

Differential Diagnosis

• Acute leukemia

• Hypocellular hairy cell leukemia

• Hypocellular forms of myelodysplasia

• Bone marrow infiltrative process (eg, tumor, infection, granulomatous disease)

• Hypersplenism

• Systemic lupus erythematosus

• Nutritional deficiency (eg, vitamin B₁₂ or folate)

• Immune thrombocytopenia

DIAGNOSIS

Laboratory Tests

• Pancytopenia, although in early disease only one or two cell lines may be reduced

• Anemia

  • May be severe

  • Reticulocytopenia is always present

• Red blood cell morphology is unremarkable, but there may be mild macrocytosis (increased MCV)

• Neutrophils and platelets reduced in number, no immature or abnormal forms seen

• Severe aplastic anemia defined by neutrophils < 500/mcL (0.5 × 10⁹/L), platelets < 20,000/mcL (20 × 10⁹/L), reticulocytes < 1%, and bone marrow cellularity < 20%

Diagnostic Procedures

• Bone marrow aspirate and bone marrow biopsy

  • Appear hypocellular

  • Scant amounts of morphologically normal hematopoietic progenitors

TREATMENT

Medications

• For mild idiopathic aplastic anemia, provide supportive care, including

  • Erythropoietic growth factors (epoetin, darbepoetin, or biosimilars) or myeloid growth factors (filgrastim or ...