Aplastic anemia

Question 1

What is Aplastic anemia?

Answer 1

Aplastic anemia is a pancytopenia associated with bone marrow hypoplasia (i.e., the bone marrow is wipped out and replaced by mostly fat) due to autoimmune destruction of the hematopoietic stem cells

Question 2

What are the causes of Aplastic anemia?

Answer 2

• Hereditary ( MC is Fanconi anemia)
• Autoimmune disease
• exposure to radiation
• exposure to toxins (e.g., benzenes, insecticides, cleaning solvents, toluene)
• Viruses (HIV, HBV CMV, Parvovirus B19, Epstein barr virus)
• Side effect of certain medications
  - NSAIDs
  - Antibiotics like: Chloramphepnicol, Sulfonamides
  - Anti-thyroid meds like: Propylthiouracil, Methimazole
  - Anti-seizure meds like: Phenytoin

Cant Make New Blood Cells Properly:
Carbamazepine, Methimazole, NSAIDs, Benzenes, Chloramphepnicol, Propylthiouracil

Question 3

What is Fanconi anemia?

Answer 3

Fanconi anemia is a form of hereditary aplastic anemia. It is autosomal recessive due to a defect in DNA replication and repair, which results in bone marrow failure

Question 4

Fanconi anemia is typical diagnosed in children of what age?

Answer 4

3 -14

Question 5

What are the signs of Fanconi anemia?

Answer 5

• Physical abnormalities in the skeleton & organs:
• Developmental delay
• Microcephaly
• Short stature
• Poor growth
• Absent or hypoplastic thumbs
• Forearm malformations
• Physical abnormalities in the organs (kidney, ear, GI, heart, eye, skin: Cafe - au - lait lesions )

Question 6

What are the symptoms of Fanconi anemia?

Answer 6

• Fatigue
• Malaise
• Pallor
• Mucosal Bleeding, Petechiae, Purpura (due to ↓ Platelet count )
• Recurrent infections (due to ↓ WBC count)

Question 7

What does a CBC look like for a person with Fanconi anemia?

Answer 7

• Pancytopenia with Normocytic or Macrocytic anemia
• ↓ Hb
• ↑ MCV
• ↓ Reticulocyte count (cells are not being produced)

Recall reticulocytes are the precursors of RBCs

Question 8

How do you diagnose Fanconi anemia

Answer 8

A Bone marrow biopsy, which shows:

• Fewer cells than normal with a fat filled marrow
• Normal RBC morphology
• No infiltrative disorders like malignancy or fibrosis

Question 9

How do you treat Aplastic anemia?

Answer 9

Treatment is dependent on age and clinical history:

If the cause was a drug or toxin, remove it

For > 50 y.o:
* Bone marrow stimulants
- Eltombopag (induce platelet proliferation)
- Granulocyte colony stimulating factor: Filgrastim (↑ Hematopoiesis)

• If the cause was an anutoimmune disease, Immunosupressants are used:
  - Antithymocyte globulin (ATG) - kills T cells
  - Cyclosporine
  - Corticosteroids
  - Alemtuzumab
  - Tacrolimus
• Blood transfusions as needed, followed by an Iron chelating agent (Deforoxamine) to prevent iron overload

For < 50 y.o.: Bone marrow transplant i.e., hematopoietic cell transplant