Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 13-21: Aplastic Anemia + Key Features Download Section PDF Listen +++ +++ 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 or injury to the hematopoietic stem cell Bone marrow becomes hypoplastic, fails to produce mature blood cells, and 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 (PNH), or acute myeloid leukemia Complex detrimental immune response to viruses Drugs Chloramphenicol Phenylbutazone Gold salts Sulfonamides Phenytoin Carbamazepine Quinacrine Tolbutamide Chemotherapy, radiotherapy Systemic lupus erythematosus Toxins: benzene, toluene, insecticides Posthepatitis Pregnancy Paroxysmal nocturnal hemoglobinuria Congenital (rare) + Clinical Findings Download Section PDF Listen +++ +++ 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 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 Download Section PDF Listen +++ +++ 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, platelets < 20,000/mcL, 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 Download Section PDF Listen +++ +++ Medications ++ Antibiotics to treat infections Immunosuppression with equine antithymocyte globulin (ATG) plus cyclosporine for severe aplastic anemia in adults aged > 40 or those without HLA-matched siblings Useful regimen is equine ATG, 40 mg/kg/day intravenously for 4 days, in combination with cyclosporine, 6 mg/kg orally twice 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/day orally for 1 week followed by taper over 2 weeks) to avoid ATG infusion reactions and serum sickness Equine ATG is superior to rabbit ATG Androgens (such as fluoxymesterone, 10–20 mg/day orally in divided doses) Used widely used in the past, with a low response rate May be considered in mild cases Appear to partially correct telomere length maintenance defects Appear to increase the production of endogenous erythropoietin Eltrombopag A thrombopoietin mimetic In combination with ATG plus cyclosporine, tri-lineage hematologic responses are as high as 90% +++ Therapeutic Procedures ++ Supportive care, including erythropoietic (epoetin or darbepoetin) or myeloid (filgrastim or sargramostim) growth factors, only for mild cases Allogeneic bone marrow transplantation is treatment of choice for severe aplastic anemia in adults aged < 40 with HLA-matched siblings Allogeneic transplantation using unrelated donor if immunosuppression is not effective Red blood cell and platelet transfusions as necessary + Outcome Download Section PDF Listen +++ +++ Complications ++ Bacterial infections Bleeding +++ Prognosis ++ Patients with severe aplastic anemia have a rapidly fatal illness if left untreated Allogeneic bone marrow transplantation from an HLA-matched sibling donor produces a survival rate over 80% in recipients under 20 years of age and about 65–70% in those 20–50 years of age Respective survival rates drop 10–15% when the donor is HLA-matched but unrelated Equine ATG-cyclosporine immunosuppressive treatment leads to a response in approximately 70% of patients, including those with hepatitis virus–associated aplastic anemia Up to one-third of patients will relapse with aplastic anemia after ATG-based therapy Factors that predict response to ATG-cyclosporine therapy Age Reticulocyte count Lymphocyte count Age-adjusted telomere length of leukocytes at the time of diagnosis PNH, acute myeloid leukemia, or myelodysplasia develop in as many as 25% of patients treated with immunosuppressive therapy after 10 years of follow-up +++ When to Refer ++ All patients should be referred to hematologist +++ When to Admit ++ Treatment of neutropenic infection Administration of ATG Allogeneic bone marrow transplantation + References Download Section PDF Listen +++ + +Bacigalupo A. How I treat acquired aplastic anemia. Blood. 2017 Mar 16;129(11):1428–36. [PubMed: 28096088] + +Clucas DB et al; Australian Aplastic Anaemia Registry Steering Committee. Revisiting acquired aplastic anaemia: current concepts in diagnosis and management. Intern Med J. 2019 Feb;49(2):152–9. [PubMed: 30324755] + +Kumar R et al. Hematopoietic cell transplantation for aplastic anemia. Curr Opin Hematol. 2017 Nov;24(6):509–14. [PubMed: 28877042] + +Marsh JCW et al. The case for upfront HLA-matched unrelated donor hematopoietic stem cell transplantation as a curative option for adult acquired severe aplastic anemia. Biol Blood Marrow Transplant. 2019 Sep;25(9):e277–84. [PubMed: 31129354] + +Shallis RM et al. Aplastic anemia: etiology, molecular pathogenesis, and emerging concepts. Eur J Haematol. 2018 Dec;101(6):711–20. [PubMed: 30055055] + +Townsley DM et al. Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med. 2017 Apr 20;376(16):1540–50. [PubMed: 28423296]