aplastic anemia
Jump to navigation
Jump to search
Introduction
A group of disorders characterized by hematopoietic failure, peripheral pancytopenia, hypocellular bone marrow & the absence of malignant or myeloproliferative disorders.
Etiology
- acquired
- pharmaceutical agents
- industrial chemicals: benzene, insecticides
- paroxysmal nocturnal hemoglobinuria
- infections
- hepatitis
- non-A, non-B, non-C most common
- hepatitis A
- hepatitis-B is least common
- Epstein-Barr virus
- influenza
- mycobacterial infections
- HIV1 infection
- parvovirus B19 (pure red cell aplasia)
- hepatitis
- ionizing radiation
- pregnancy
- connective tissue disorders
- graft-versus-host disease
- hereditary
- idiopathic (40-70%)
Pathology
- apoptosis
- defect in stem cell population
- autoimmune reaction against stem cell population
- cytokines secreted by T-cells may suppress stem cells
- defect in the marrow environment
- defect in stem cell population
- immune suppression
- hypocellular bone marrow biopsy
- fat:cell ratio 9:1
- residual cells are mostly mononuclear cells, plasma cells, macrophages & stromal non-hematopoietic cells
Genetics
- may be assicated with mutations in the nibrin gene
- in Caucasians, genetic variation in IFN-gamma is associated with risk of aplastic anemia
- other implicated genes: GFI1B, TERT
Clinical manifestations
- weakness
- fatigue
- easy bruising or bleeding
- fever
- infections may be clinically unimpressive, despite severe neutropenia[3] (contrast with acute leukemias)
- lymphadenopathy & splenomegaly are uncommon
Laboratory
- complete blood count (CBC)
- normocytic or macrocytic anemia
- all lines of leukocytes diminished in number (pancytopenia)
- lymphocytosis[3]
- thrombocytopenia
- absolute reticulocyte count is low
- hepatitis serology
- HIV testing
- serum vitamin B12 & serum folate
- aspiration & core biopsy of bone marrow
- bone marrow cellularity < 10%[3]
- cytogenetic analysis of marrow to evaluate possibility of hypoplastic myelodysplasia
- positive direct antiglobilin test (DAT) rules out aplastic anemia[9] (even in patients with CLL, some are known to have positive DAT)
Differential diagnosis
- acute leukemia
- myelodysplasia
- paroxysmal nocturnal hemoglobinuria
- drugs
- infection
Management
- mitigation of potential causes
- allogeneic stem cell transplantation
- HLA matched donor or identical twin
- 66% success rate in young patients
- high mortality in older patients[3]
- treatment of choice for severe aplastic anemia in a patient < 40 years of age with an HLA-identical sibling[3]
- consider for patients < 50 years of age with compatible donor
- radiation of necessary blood products prior to stem cell transplantation may reduce risk of graft vs host disease[3]
- immunosuppressive therapy if > 50 years or without a compatible donor
- antithymocyte globulin & corticosteroids with or without cyclosporine
- 40-80% partial recovery, NOT curative
- 20-30% relapse, generally within 1-2 years
- antithymocyte globulin plus cyclosporine
- eltrombopag added to immunosuppressive therapy is associated with better hematologic response[8]
- complications:
- myelodysplasia
- acute myelocytic leukemia (AML)
- paroxysmal nocturnal hemoglobinuria (PNH)
- 15-20% of patients
- occurs 2-10 years after therapy
- high-dose cyclophosphamide (50 mg/kg)
- potentially curative[5]
- early mortality as high as 15%
- androgens had been used in the past
- hematopoietic growth factors are ineffective[3]
- transfusion
- avoid transfusions if possible
- if transfusion is needed
- select non-related donors
- do NOT use family members as donors
- likely to sensitize patient to minor HLA antigens in donor
- use leukocyte-poor packed RBC
- use single donor platelets
- select non-related donors
- survival is better for those NOT receiving transfusion
- full recovery is uncommon without allogeneic bone marrow transplantation or immunosuppressive therapy
More general terms
More specific terms
Additional terms
- nibrin; Nijmegen breakage syndrome protein 1; cell cycle regulatory protein p95 (NBN, NBS, NBS1, P95)
- pancytopenia
- paroxysmal nocturnal hemoglobinuria (PNH, Marchiafava-Micheli syndrome)
- pharmaceutical agents associated with aplastic anemia
References
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 446-47
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 672
- ↑ 5.0 5.1 Journal Watch 21(21):169, 2001
Brodsky RA et al Durable treatment-free remission after high-dose cyclophosphamide therapy for previously untreated severe aplastic anemia. Ann Intern Med 135:477, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11578150
Abkowitz J. Aplastic anemia: which treatment?. Ann Intern Med 135:524, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11578156 - ↑ Marsh JC, Ball SE, Cavenagh J et al Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 2009 Oct;147(1):43-70. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19673883
- ↑ Tichelli A, Schrezenmeier H, Socie G et al A randomized controlled study in patients with newly diagnosed severe aplastic anemia receiving antithymocyte globulin (ATG), cyclosporine, with or without G-CSF: a study of the SAA Working Party of the European Group for Blood and Marrow Transplantation. Blood. 2011 Apr 28;117(17):4434-41 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21233311
- ↑ 8.0 8.1 Townsley DM, Scheinberg P, Winkler T et al Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med 2017; 376:1540-1550. April 20, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28423296 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1613878
- ↑ 9.0 9.1 Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
Patient information
Aplastic anemia patient information