Generalized Bone Marrow Hypoplasia
Generalized bone marrow hypoplasia may result from radiation, toxic, or infectious insults to the bone marrow. Common toxins include estrogen, chloramphenicol,
phenylbutazone, antifungals, and chemotherapeutic drugs. Infectious diseases resulting in bone marrow hypoplasia include feline leukemia and chronic Ehrlichiosis. Generalized bone marrow hypoplasia may also result from the crowding out of normal bone marrow precursors by neoplastic
cells, a process termed myelopthisis. The most common neoplastic causes are the hematopoietic and lymphoid neoplasms including lymphosarcoma, granulocytic leukemia,
and lymphoid leukemias. Myelofibrosis, the replacement of marrow spaces by connective/scar tissue, usually represents the endpoint of previous severe marrow injury
(as in the case of estrogen toxicity and ionizing radiation) or it may occur spontaneously. Peripheral blood features of myelofibrosis
usually include severe nonregenerative anemia, severe leukopenia, and a variable platelet response. Confirmation of the diagnosis
depends on marrow core biopsy with a demonstration of connective tissue filling the marrow space.
Normal to Hypercellular Bone Marrow
Iron deficiency anemia results from chronic blood loss. In young animals, parasitic infection is the primary ruleout for iron deficiency anemia,
while in older animals, gastrointestinal masses or ulcers are generally implicated. Chronic blood loss leads to depletion
of bone marrow iron stores over time, resulting in inability to form hemoglobin. Nuclear maturation of RBC precursors is normal
however. Precursors continue to divide, getting smaller in size because they never acquire a complete amount of hemoglobin.
This results in a hypercellular bone marrow with a build up of metarubricytes. Diagnosis is based on the presence of microcytic,
hypochromic anemia, thrombocytosis, source of blood loss, and a bone marrow smear containing no stainable iron. Low serum
iron is not diagnostic as it may rapidly decrease with inflammatory disease as a result of tissue sequestration. Treatment
is aimed at removal of the source of blood loss. Ferrous sulfate may be administered at a dose of 100-300 mg per day in dogs
and 50-100 mg per day in cats if needed. Note that this dose refers to ferrous sulfate, not elemental iron. Reticulocytosis
should develop within 3-4 days of supplementation.
Myelodysplasia refers to a poorly understood group of diseases characterized by non-regenerative anemia or pancytopenia and prominent dysplastic
changes in the bone marrow. Abnormal erythrocytes are generally unable to completely differentiate and early cell death results.
Myelodysplasia may result from idiopathic (primary), neoplastic, toxic, immune-mediated, or infectious (FeLV) causes. The
myelodysplasias tend to carry a very guarded prognosis, with treatment aimed at immunosuppression, chemotherapy, and/or erythropoietin
depending on the suspected cause.
General Comments on the Treatment of Non-Regenerative Anemias
Treatment of decreased production anemia is best aimed at identifying and eliminating any underlying disease processes or
myelosuppressive drugs. Once this is done, clinical experience suggests that the most important thing we can do for patient
is to buy time for the bone marrow to repopulate with normal precursor cells. Blood transfusions should be provided as needed
until the patient is able to mount a regenerative response of their own. Most patients with non-regenerative anemia require
transfusions every 4-6 weeks until their disease is well controlled. Broad-spectrum antibiotics are indicated in the event
of severe neutropenia to prevent secondary infections. Immunosuppressive agents may be indicated if an immune-mediated disease
(eg. red cell aplasia) is identified or strongly suspected. Myeloproliferative diseases and myelodysplasia tend to carry a
poor prognosis, but other forms of decreased production anemia may respond well if the underlying disease or insult is eliminated
and adequate time is provided for recovery.
A variety of diseases, both immunologic and non-immunologic in nature, may result in anemia and/or hemolysis in veterinary
patients. Successful management relies upon accurate diagnosis and treatment of the underlying disease process. Simple test
to help classify a patient's anemia as blood loss, hemolysis, or decreased production may facilitate correct diagnosis. Initiation
of immunosuppressive therapy prior to performing a methodical search for infectious, neoplastic, or other causes of anemia
may result in therapeutic "missteps" and treatment failure.
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