PEDBASE.org - The Pediatric Database - Detailed information of APLASTIC ANEMIA

APLASTIC ANEMIA

DEFINITION:

A group of disorders characterized by peripheral blood pancytopenia secondary to an acquired decrease in bone marrow function.

EPIDEMIOLOGY:

incidence: 2-6/million
age of onset:
- any
risk factors:
- see below
- M = F

PATHOGENESIS:

1. Risk Factors

1. Idiopathic

2. Secondary

1. Drugs/Chemicals

1. Regular

benzene, cytotoxic (busulphan, cyclophosphamide, 6-mercaptopurine, methotrexate, nitrogen mustard)

2. Idiosyncratic

anticonvulsants, antibiotics (chloramphenicol,sulfonamides, tetracycline), antirheumatoids (NSAID, gold), quinacrine, cimetidine

2. Infections (Viruses)

EBV (mono)
hepatitis (C > A & B)
HIV
parvovirus

3. Immune Diseases

eosinophilic fascilitis
hypoimmunoglobulinemia

4. Others

paroxysmal nocturnal hemaglobinuria, preleukemia, pregnancy, thymoma, radiation

2. Pathogenesis

exposure to risk factor -> damage to progenitor cells (GM-CFU, E-CFU, E-BFU, GEMM-CFU) +/- more mature progeny
risk factors produce stem cell failure by affecting the stem cells directly or indirectly via the microenvironment thus interfering with hematopoiesis

3. Prognostic Factors

of severe aplastic anemia:
- WBC less than 5
- PLT less than 20,000
- reticulocytes less than 1%
- hypocellular bone marrow
67% mortality within 6 months of onset
major cause of death - infection > bleeding

CLINICAL FEATURES:

1. Thrombocytopenia

1. Bleeding

usually the first clinical manifestation
petechiae, ecchymoses, epistaxis, bleeding from mucous membranes

2. Anemia

pallor, fatigue, tachycardia

3. Neutropenia

increased susceptability to bacterial infections - Pseudomonas, Klebsiella, E. coli, S. aureus, S. epi., Streptococcus
oral ulcerations, febrile neutropenia

4. Complications

leukemia
paroxysmal nocturnal hemoglobinuria

INVESTIGATIONS:

1. Serum

Hb: macrocytic/normocytic, increased HbF, low reticulocytes
increased RBC i antigen, erythropoietin
thrombocytopenia
neutropenia

2. Bone Marrow

scanty, fatty, hypocellular
predominance of lymphocytes, plasma cells, reticulum cells, mast cells
decreased number of progenitor stem cells of erythroid and granulocytic series
giant pronormoblasts (parvovirus replicates only in human erythroid progenitor cells)

MANAGEMENT:

1. Supportive

remove offending agent
avoid bleeding:
- soft toothbrush, avoid trauma, amicar
pipercillin/tobramycin for febrile neutropenia

2. Transfusions

1. PRBC

filtered, washed, target >80 g/L
watch for hemosiderosis with chronic transfusions and treat with iron chelators when ferritin >500 ng/cc

2. Platelets

filtered, irradiated
indicated if bleeding or platelet <20,000

3. Bone Marrow Transplantation

treatment of choice in refractory severe cases
acts to replace stem cells

4. Experimental Therapies

anti-thymocyte globulin, anti-lymphocyte globulin
high-dose dexamethasone
cyclosporine
hematopoietic growth factors (GM-CSF)

INTERNET LINKS:

Aplastic Anemia Association of Canada
Aplastic Anemia Foundation of America

Pediatric Database - APLASTIC ANEMIA

Pediatric Organization - Pedbase [at] Gmail.com