Aplastic Anemia

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Contents 1 More Specific Terms 2 Introduction 3 Etiology 4 Pathology 5 Genetics 6 Clinical-manifestations 7 Laboratory 8 Differential-diagnosis 9 Management 10 More General Terms 11 Additional Terms 12 References

More Specific Terms

• pure red cell aplasia; erythrocyte aplasia

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
• HIV

• ionizing radiation
• pregnancy
• connective tissue disorders
• graft-versus-host disease

• hereditary

• Fanconi's anemia
• dyskeratosis congenita
• Shwachman syndrome

• 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

• immune suppression
• 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
• other implicated genes GFI1B, TERT

Clinical-manifestations

• weakness
• fatigue
• easy bruising or bleeding
• fever
• infections
• lymphadenopathy & splenomegaly are uncommon

Laboratory

• complete blood count ( CBC)

• normocytic or macrocytic anemia
• all lines of leukocytes diminished in number
• lymphocytosis [3]
• thrombocytopenia

• absolute reticulocyte count is low
• aspiration & core biopsy of bone marrow

• cytogenetic analysis of marrow to evaluate possibility of hypoplastic myelodysplasia

Differential-diagnosis

• acute leukemia
• myelodysplasia
• drugs
• infection

• mycobacteria
• cytomegalovirus

Management

• allogeneic bone marrow transplantation

• HLA matched donor or identical twin
• pretreatment with cyclosporine (plus radiation if prior transfusion)
• 66% success rate in young patients
• high mortality in older patients [3]

• immunosuppressive therapy

• antithymocyte globulin & corticosteroids with or without cyclosporine
• 40-80% partial recovery, NOT curative
• 20-30% relapse, generally within 1-2 years
• 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

• success rate < 25%
• not effective in severe aplastic anemia

• 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

• survival is better for those NOT receiving transfusion

• full recovery is uncommon without allogeneic bone marrow transplantation or immunosuppressive therapy

More General Terms

• bone marrow disease
• hypoplastic anemia

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

1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 446-47
3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15 American College of Physicians, Philadelphia 1998, 2006, 2009
4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 672
5. 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: [1]
   - Abkowitz J. Aplastic anemia: which treatment?. Ann Intern Med 135:524, 2001 PMID: [2]
6. National Guideline Clearinghouse Guidelines for the diagnosis and management of aplastic anaemia. British Committee for Standards in Haematology ngc-guideline: [3]

aplastic anemia