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, and then pancytopenia develops

Causes of aplastic anemia

• "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) or in 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

• Medications

  • Chloramphenicol

  • Gold salts

  • Sulfonamides

  • Phenytoin

  • Carbamazepine

  • Quinacrine

  • Tolbutamide

• Chemotherapy, radiation therapy

• Systemic lupus erythematosus

• Toxins: benzene, toluene, insecticides

• Posthepatitis

• Pregnancy

• Paroxysmal nocturnal hemoglobinuria

• Congenital (rare)

CLINICAL FINDINGS

Symptoms and Signs

• Weakness, pallor, and fatigue from anemia

• Vulnerability to bacterial or fungal infections from neutropenia

• Mucosal and skin bleeding (petechiae and purpura) from thrombocytopenia

• Hepatosplenomegaly, lymphadenopathy, or bone tenderness should not be present

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, with scant amounts of morphologically normal hematopoietic progenitors

TREATMENT

Medications

• Antibiotics to treat infections

• Immunosuppression and hematopoietic stimulation with equine antithymocyte globulin (ATG) plus cyclosporine and eltrombopag for severe idiopathic aplastic anemia in adults aged > 40 or in those without HLA-matched siblings

  • Established regimen is equine ATG (40 mg/kg/d intravenously for 4 days) in combination with cyclosporine (6 mg/kg orally twice daily) and eltrombopag (150 mg orally daily) given in hospital in conjunction with corticosteroids, and transfusion and antibiotic support

  • Corticosteroids are given with ATG (prednisone or methylprednisolone, 1–2 mg/kg/d orally for 1 week followed by taper over ...