Aplastic Anemia

Aplastic Anemia

ETIOLOGY AND EPIDEMIOLOGY.

Drugs

Chemicals

Toxins

infectious agents

radiation

immune disorders

Mechanism -    direct destruction of hematopoietic progenitors

                        destruction of the marrow and its necessary growth factors,

                        direct or indirect (e.g., virus-related) immune-mediated destruction of marrow elements

careful history of exposure to known risk factors

genetic predisposition to bone marrow failure should always be considered

incidence of acquired aplastic anemia is low

drugs

            antineoplastic agents (e.g., anthracyclines, alkylators, antimetabolites)

            antibiotics (e.g., chloramphenicol).

Insecticides

Anticonvulsants

nonsteroidal anti-inflammatory agents

antihistamines

sedatives

metals).

viruses

            Parvovirus B19 = pure red blood cell (RBC) aplasia,

                        sickle cell disease = transient aplastic crisis

hepatitis virus (both hepatitis B virus and hepatitis C virus

dengue virus

Herpes viruses

Epstein-Barr virus (EBV)

cytomegalovirus (CMV),

HIV

paroxysmal nocturnal hemoglobinuria (PNH)

collagen vascular diseases

bone marrow replacement by leukemic or neuroblastoma malignant cells.

PATHOLOGY AND PATHOGENESIS.

peripheral pancytopenia

hypoplastic or aplastic bone marrow.

             two or more cell components have become seriously compromised

                        an absolute neutrophil count <500/mm3

                        a platelet count <20,000/mm3

                        a reticulocyte count <1% after correction for the hematocrit

bone marrow biopsy = hypocellular.

CLINICAL MANIFESTATIONS, LABORATORY FINDINGS, AND DIFFERENTIAL DIAGNOSIS.

Acquired pancytopenia = anemia, leukopenia, and thrombocytopenia

The pancytopenia = fatigue, cardiac failure, infection, and bleeding

cancer, collagen vascular disorders, PNH, or infections that may respond to specific therapies (e.g., intravenous immune globulin for parvovirus) should be considered in the differential diagnosis.

peripheral blood smear for RBC, leukocyte, and platelet

congenital pancytopenia must always be considered and chromosomal breakage should be evaluated (see earlier).

presence of fetal hemoglobin suggests a congenital pancytopenia

rule out PNH, a Ham's test should be performed.

Bone marrow examination should include both aspiration and a biopsy,

the marrow should be carefully evaluated for cellularity and morphology.

The presence of more than 70% lymphocytes has a poor prognosis.

COMPLICATIONS.

life-threatening bleeding due to thrombocytopenia

infection secondary to protracted neutropenia. =serious bacterial infections , invasive mycoses.

TREATMENT.

supportive care

treat the underlying marrow failure.

antithymocyte globulin (ATG),

corticosteroids

cyclosporine

bone marrow transplantation

hematopoietic colony-stimulating factors

allogeneic bone marrow transplantation = complications of the transplantation, graft versus host disease (which increases with patients' age), and the increased risk for subsequent cancers

androgens, cyclophosphamide, and plasmapheresis.

PROGNOSIS.

severe pancytopenia have an extremely poor prognosis

PANCYTOPENIAS CAUSED BY MARROW REPLACEMENT

before or during malignancy = neuroblastoma or leukemia

consequence of osteoporosis -marble bone disease

myelofibrosis,

myelodysplasia.

collagen vascular disease (e.g., rheumatoid arthritis)

Chromosomal analysis = myelodysplastic syndromes .