Aplastic AnemiaAplastic Anemia

Rakesh Biswas

MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur,

Bhopal, India

Morphologic, Etiologic

Possible causes:

Investigations and treatment

• Definition:

– Pancytopenia with hypocellularity (Aplasia) of Bone Marrow

• One cell line may be affected more than the others

Etiology• Inherited

– Fanconi’s Anemia

• Acquired– Idiopathic (majority)-2/3rd of cases– Drug : Acetazolamide, Carbamazepine, Gold,

Hydantoin, Penicillin, Phenylbutazone,

– Chemical – Radiation exposure – Viral illness

Pathogenesis

• Immune mechanism responsible for most of the cases of Idiopathic acquired aplastic anemia

• Activated Cytotoxic T cells in Blood & Bone marrow Bone marrow failure

Clinical Features

• Signs & symptoms of :

– Anemia:……….

– Bleeding: Ecchymoses ,Bleeding gums, Epistaxis

– Infections: Fever,Mouth ulcers

Diagnosis

• Blood peripheral smear : Pancytopenia and reticulocytopenia

• Bone marrow aspiration & biopsy : Hypocellular / aplastic bone marrow with increased fat spaces

• Tests for underlying cause ( viral titers)

• Other causes of Pancytopenia:– Drugs,– Megaloblastic anemia– Bone Marrow infiltration or Replacement:

Lymphoma, Myeloma,Acute Leukemia, Secondaries

– Hyperspleenisn– SLE– Disseminated TB– PNH– Sepsis

BM Aspiration BM Biopsy

BM biopsyhypocellular ,increased fat spaces

Text book Treatment

• Treatment of underlying cause –if possible• Removal of cause• Supportive care

– Blood & platelet transfusion – Infection: Broad spectrum antibiotics– Asepsis

• Bone Marrow Transplant (SCT) – patient age <40yrs , availability of a HLA-

identical sibling marrow donor

• Immunosuppression:

– Cyclosporine,

– Glucocorticoids : in cong Pure Red Cell Aplasia

– Antilymphocyte or Antithymocyte globulin (ALG / ATG)

– Cyclophosphomide

• Androgens

• Thymectomy : for Adult Pure Red Cell Aplasia

Case History:My first post-Cyclophosphamide white cells appeared 10 days after treatment. I had 6. I ordered them all little party hats,

and got to know them personally:-)

Severe AA (SAA)

Bad prognosis

Two of three peripheral blood criteria:

• Neutrophils < 500 / cmm,

• Platelets < 20,000/cmm,

• Reticulocyte < 0-0.5%

Prognosis

• Improved survival with newer treatment modalities

• Relates to severity

• Evolution to MDS, PNH, AML`

Agranulocytosis

• Leukopenia: Decrease in Total Leukocyte Count

• Neutropenia: Decrease in Neutrophil count < 1500 / micro L

• Agranulocytosis: severe neutropenia < 500 neutrophils / micro L

Causes• Congenital• Drug induced:Chloramphenicol,CBZ, Carbimazole

, Co-trimoxazole, Gold, Phenytoin, Sulfa drugs• Infections:

– Viral-Hepatitis,Influenza,HIV – Bacterial-Typhoid,Miliary TB

• Benign ( familial/racial)• Cyclical• Immune: AI, SLE,Felty’s,

Clinical Features

• Mouth infection,Sore throat ( Mucositis)• Ulcers of : Mouth & throat , Skin, Anus

• Features of Sepsis (Gm +ve &–ve):– Fever +/-– Hypotension,– MODS

• In prolonged neutropenia Fungal infections are likely to develop: Candida (Oral), Aspergillus(Pulm)

Investigations and Treatment

The peripheral blood smear shows a marked decrease or absence of neutrophils.

The bone marrow may show myeloid hypoplasia or absence of myeloid precursors.

In many cases, the bone marrow is cellular with a maturation arrest at the promyelocyte stage.

On occasion, the marrow may be hypercellular.