Aplastic Anemia

Note the absence of red and white blood cells in this bone marrow biopsy.
90% of area is fat-filled.

This is a hypoproliferative or defective RBC anemia. It is characterized by a stoppage of RBC production and loss of all hemopoietic elements. There is a peripheral pancytopenia and the presence of a hypocellular bone marrow. In all of the aplastic anemias investigated, approximately 60% are idiopathic.

Clinically, aplastic anemia presents with three typical symptoms:

• [1] bleeding due to thrombocytopenia with the platelet count <20,000/μl,>
• [3] infection characterized by granulocytopenia with a neutrophil count <500/μl.>
• [4] Other clinical symptoms include [a] fatigue, [b] weakness, [c] bleeding gums,[d] petechiae, [e] tendency for infections, [f] easily bruised, [g] sleepiness,[h] hepato- and/or [i] splenomegaly as rare occurrences.

Diagnosis of aplastic anemia requires the following parameters be demonstrated.

• [1] Bone marrow with a 30% or more loss of cellularity (see below)
• [2] Granulocyte count less than 500/μL.
• [3] Platelet count less than 20,000/μL.
• [4] Corrected reticulocyte count <1.0%.>60 y/o. Aplastic anemia is classified as being either primary (constitutional) or secondary.

Primary types of aplastic anemias are due to congenital causes which will show up early in life. Two types of congenital aplastic anemia are Fanconi’s anemia (a rare disorder) and familial aplastic anemia (for which is thought to be a variation of Fanconi’s anemia and can manifest at any age). Secondary aplastic anemias make up the majority of these type of disorders. This type of anemia occurs because of exposure to a causative agent.

The following are known to cause secondary aplastic anemia:

[1] Secondary to toxic agent exposure.

• Benzene and benzene-type compounds.
• Insectides: DDT and Lindane.
• Arsenic compounds.
• Certain antibiotics (chloramphenicol, methicillin, sulfonamides,sulfadimethoxine, sulfamethoxypyridazine, penicillin, streptomycin, amphotericin B, cephalosporins, and oxytetracycline.
• Gold compounds used in arthritic treatments.
• Certain drugs (acetazolamide, chlorothiazide, tolbutamide, phenothiazine,phenytoin, phenylbutazone, acetophenetidin, carbamazephine, colchicine, and epinephrine.
• Cytotoxic agents (those used to treat malignancies).

[2] Infections:

• Viral hepatitis (especially type non-a/non-b).
• Measles.
• Flu
• Infectious mononucleosis.
• Epstein-Barr virus.
• Miliary tuberculosis. (Miliary, pronounced "mil-ya-re" occurs when there are many tiny discrete nodules in various organs.)
• Brucellosis.

[3] Other conditions that allow for the manifestation of aplastic anemia are:

• Paroxysmal Nocturnal Hemoglobinuria.
• Pregnancy
• Infectious Mononucleosis
• Radiation
• Pancreatitis

If the aplastic anemia is induced due by chemical exposure (estimated to cause about 33% of these cases), it is thought that it is due to direct injury to the stem cell. Such drugs tend to be metabolized slowly and tends to accumulate in the marrow, thus causing injury.

[1] The first symptoms of chemical/drug injury is neutropenia and/or thrombocytopenia. The body maintains a seven day supply of neutrophils. In this context, the neutrophil becomes a sensitive indicator to bone marrow injury and allows for stoppage of medication before critical damage sets in. Quick withdrawal of the offending drug will permit recovery.

[2] Using chloramphenicol (a potent broad spectrum antibiotic)as an example:

• The first signs of bone marrow suppression is a decrease in the “retic” count.
• This drug suppresses marrow by inhibiting mitochondria synthesis.
• The second sign is an increase in the serum iron.

Anemia then will manifest.

The next sequence of events is neutropenia and thrombocytopenia.

The bone marrow will present early with vacuolated rubriblasts.

Typical findings in the clinical laboratory for aplastic anemia are:

• [1] Hemoglobin = less than 7.0 g/dL
  
• [2] Hematocrit = <24%
• [3] RBC = normochromic, normocytic with tendency to slight macrocytosis.
• [4] Anisocytosis = mild to moderate
• [5] Poikilocytosis = mild to moderate
• [6] NRBC’s are usually present.
• [7] Corrected Retic count = <1.0%
• [8] Thrombocytopenia (up to 50,000/μL)
• [9] Neutropenia (relative count - 0 to 20%) with lymphocytosis (relative count up to 90%) and normal monocyte numbers. The WBC count will probably drop to <1,500>
• [10] Serum iron = 200 to 2,000 μg/dL (N: 60 - 160 μL)
• [11] Bleeding time is increased
• [12] Clot retraction time = increased with poor clot retraction