Апластична анемія

True aplastic anemia (most common in adolescents and young adults) is idiopathic in about half of cases. Recognized causes are

• Chemicals (eg, benzene, inorganic arsenic)

• Medications (eg, antineoplastic drugs, antibiotics, nonsteroidal anti-inflammatory drugs, antiseizure medications, acetazolamide, gold salts, penicillamine, quinacrine) or toxins

• Hepatitis (seronegative for hepatitis viruses)

• Pregnancy

• Radiation

• Viruses (Epstein-Barr virus and cytomegalovirus)

• Inherited disorders of bone marrow failure due to genetic mutations (eg, Fanconi anemia, Shwachman-Diamond syndrome, dyskeratosis congenita)

The precise mechanism remains unclear, but in the majority of acquired cases, the mechanism involves an immune attack on the hematopoietic stem cell. Clonal hematopoiesis is frequently present, and there is a risk of progression to a myeloid malignancy.

The onset of aplastic anemia usually is insidious, often occurring over weeks or months after exposure to a virus, medication or toxin (eg, insecticides, benzene), though occasionally it can be acute.

In aplastic anemia, anemia may cause weakness and easy fatigability while severe thrombocytopenia may cause petechiae, ecchymosis, and bleeding from the gums, into the conjunctivae, or other tissues. Agranulocytosis commonly causes life-threatening infections. Splenomegaly is absent unless induced by transfusion hemosiderosis.

Петехії при імунній тромбоцитопенії (ІТП)

Зображення

By permission of the publisher. From Deitcher S. In Atlas of Clinical Hematology. Edited by JO Armitage. Philadelphia, Current Medicine, 2004.

Екхімози при імунній тромбоцитопенії

Зображення

By permission of the publisher. From Deitcher S. In Atlas of Clinical Hematology. Edited by JO Armitage. Philadelphia, Current Medicine, 2004.

• Complete blood count (CBC) and reticulocyte count

• Bone marrow examination with cytogenetic and molecular testing

• Flow cytometry for paroxysmal nocturnal hemoglobinuria (PNH) clone

• Consideration of genetic testing especially in young patients or those with suggestive family history or characteristic dysmorphia

Detection of a PNH clone can exclude an inherited syndrome (1).

Aplastic anemia is suspected in patients, particularly young patients, with pancytopenia. Severe aplastic anemia is defined by a bone marrow with < 25% cellularity (hypocellularity) and the presence of ≥ 2 of the following:

• Absolute neutrophil count < 500/microL (< 0.5 × 10⁹/L)

• Absolute reticulocyte count < 60,000/microL (< 60 × 10⁹/L)

• Platelet count < 20,000/microL (< 20 × 10⁹/L)

Very severe aplastic anemia is defined as absolute neutrophil count < 200/microL (< 0.2 x 10⁹/L).

• Hematopoietic stem cell transplantation

• If transplantation is not an option, immunosuppression with equine antithymocyte globulin and cyclosporine and sometimes eltrombopag

In aplastic anemia, hematopoietic stem cell transplantation can be curative and is the treatment of choice, particularly in younger patients with a matched donor. At diagnosis, siblings are evaluated for HLA (human leukocyte antigen) compatibility.

In those patients unfit for transplant or lacking a donor, immunosuppressive treatment with equine antithymocyte globulin (ATG) combined with cyclosporine produces overall response rates of approximately 60 to 80%. Allergic reactions and serum sickness may occur. Long-term relapse or clonal evolution to myeloid malignancy occurs in up to half of patients.

Eltrombopag, a thrombopoietin receptor agonist, has shown potential efficacy in clinical trials in the upfront and refractory settings with immunosuppression, and haploidentical bone marrow transplants are promising to expand access to hematopoietic stem cell transplantation (1, 2, 3).