Selective Erythroid Hypoplasia
Anemia of chronic disease, also termed anemia of inflammation, is immune driven. Cytokines and cells of the reticuloendothelial system (RES) induce
changes in iron homeostasis, erythrocyte lifespan, production of erythropoietin, and proliferation of erythroid lines. Iron
is diverted from circulation to storage sites within the RES, limiting availability for erythroid progenitors. Inflammatory
mediators (TNF, IL-1, IFN) suppress activity of erythroid precursors and decrease their responsiveness to erythropoietin.
Release of erythropoietin is also inhibited. Finally, erythrophagocytosis and free radical mediated erythrocyte damage shorten
RBC survival. In contrast to iron deficiency anemia, anemia of chronic disease tends to be normocytic, normochromic, rather
than microcytic, hypochromic. Serum iron tends to be low, but bone marrow iron stores are adequate. Anemia of chronic disease
is generally mild to moderate unless complicated by other factors such as blood loss or hemolysis. Treatment is therefore
directed at correcting the underlying disease. Transfusion may be considered if anemia is associated with clinical signs.
Iron supplementation for anemia of chronic disease is controversial, and indications for its use in veterinary patients with
chronic disease is unclear.
Chronic renal failure is typically associated with mild to moderate anemia. Because of the gradual and chronic nature of this type of anemia, it
tends to be well compensated until very advanced stages. Anemia in renal failure is multifactorial and results from decreased
erythropoietin production by the kidney, impaired responsiveness of bone marrow precursors, shortened RBC lifespan due to
uremia, and GI blood loss resulting from uremic ulcers. Anemia of renal failure is typically well compensated, though transfusions
may be indicated in the event of concurrent losses or surgery. Human recombinant erythropoietin has been used to stimulate
RBC production in veterinary patients with renal failure, but is increasingly being used only as a "last ditch effort" as
antibody production against epogen may lead to antibodies being directed against the patient's own erythropoietin as well.
Canine recombinant erythropoietin has not been associated with antibody production in dogs with renal failure, but is unfortunately
not commercially available. Anabolic steroids (Winstrol-V) have been used in patients with renal failure based on the observations
that they increase RBC mass in healthy animals. A benefit in these cases has not been clearly identified.
Pure red cell aplasia (PRCA) is an immune mediated disease directed against erythrocyte precursors. The anemia is non-regenerative, normocytic-normochromic,
with normal leukocyte and platelet counts. Animals tend to present with marked anemia, as the progression of the disease is
typically slow and there is adequate time to mount a compensatory response. Diagnosis is made on the basis of bone marrow
aspiration or biopsy, with few to no erythroid precursors seen. In cases of non-regenerative immune-mediated
anemia (NRIMA), left shifted erythroid hyperplasia may be seen, with maturation arrest at the level of the metarubricytes or rubricytes.
Some animals with NRIMA will also have immune mediated destruction of mature erythrocytes, resulting in concurrent hemolysis.
Cats with PRCA should always have PCR or IFA performed on the bone marrow to rule out feline leukemia C associated attack
on erythroid progenitors, as this form of PRCA is typically fatal. Treatment for immune-mediated PRCA and NRIMA relies on
immunosuppressive therapies similarly to IMHA. Prednisone (2-4 mg/kg/day) and cyclosporine (5-10 mg/kg/day) is the protocol
most widely used at this time. Periodic transfusions may be needed until regeneration occurs. This may take weeks to several
months. Clinical signs and progression tend to be less severe than IMHA, as the anemia results from decreased production,
rather than hemolysis.
Endocrine diseases such as hypothyroidism and hypoadrenocorticism may also result in a decreased production anemia. Both cortisol and thyroid
hormone have a permissive role in the response of red blood cell precursors to erythropoietin. These anemias are generally
mild unless complicated by concurrent blood loss and resolve with hormone replacement therapy.