Primary Bone Marrow Diseases
Primary bone marrow disease or failure from any cause can lead to nonregenerative anemia and pancytopenia. With diffuse marrow involvement, granulocytes are affected first, followed by platelets and finally RBCs.
Aplastic anemia has been reported in dogs, cats, ruminants, horses, and pigs with pancytopenia and a hypoplastic marrow, replaced by fat. Most cases are idiopathic, but reported causes include infection (feline leukemia virus, Ehrlichia, parvovirus), drug therapy (methimazole, chemotherapeutic agents, antibiotics [trimethoprim-sulfa, chloramphemicol], fenbendazole), toxin ingestion (estrogen), and total body irradiation (see Table: Toxic Causes of Anemia and Infectious Causes of Anemia). There may also be an immune-mediated component to this disease. Diagnosis is confirmed by bone marrow aspiration and core biopsy. Treatment consists of eliminating the underlying cause and providing supportive measures such as broad-spectrum antibiotics and transfusions. Immunosuppressive agents such as prednisone, cyclosporine, mycophenolate, or azathioprine may be considered. Recombinant human erythropoietin and granulocyte colony-stimulating factor (5 mcg/kg/day, PO) can be used until the marrow recovers. If the disease is idiopathic or if marrow recovery is unlikely (eg, phenylbutazone toxicity in dogs), bone marrow transplantation is beneficial if a suitable donor is available (investigational and limited availability).
In pure red cell aplasia (PRCA), only the erythroid line is affected. It is characterized by a nonregenerative anemia with severe depletion of red cell precursors in the bone marrow. It has been reported in dogs and cats and may be primary or secondary. Primary cases are most commonly immune mediated and may respond to immunosuppressive therapy. Supportive care, including transfusion, may be indicated when anemia is severe. Feline leukemia–positive cats can have PRCA. Recombinant human erythropoietin has been reported to cause PRCA in dogs and horses. Discontinuation of therapy may eventually lead to RBC recovery in some animals.
Primary leukemias are uncommon to rare in domestic species but have been reported in dogs, cats, cattle, goats, sheep, pigs, and horses. Retroviruses are a cause in some cattle, cats, primates, and chickens. Leukemias can develop in myeloid or lymphoid cell lines and are further classified as acute or chronic. Most affected animals have nonregenerative anemia, neutropenia, and thrombocytopenia, with circulating blasts usually present. Acute leukemias, characterized by infiltration of the marrow with blasts, generally respond poorly to chemotherapy. In animals that do respond, remission times are usually short. In acute lymphoblastic leukemia in dogs, the response rate to chemotherapy is ~30%, with a median survival of 4 mo. Acute myeloblastic leukemias are less common and even less responsive to treatment than acute lymphoblastic leukemia. In acute leukemias, the cell lineage is often difficult to identify morphologically, so cytochemical stains or immunologic evaluation of cell surface markers may be necessary for definitive diagnosis. Chronic leukemias, characterized by an overproduction of one hematopoietic cell line, are less likely to cause anemia and more responsive to treatment.
Myelodysplasia (myelodysplastic syndrome, MDS) is considered a preleukemic syndrome characterized by ineffective hematopoiesis, resulting in a nonregenerative anemia or other cytopenias. MDS has been described in dogs, cats, and people. The disease can be primary or secondary and is commonly seen in cats with feline leukemia. Primary syndromes probably arise from mutations in stem cells. Secondary syndromes are caused by other neoplasia or drug therapy. Some cats and dogs respond to treatment with recombinant human erythropoietin and prednisone. Supportive care with transfusions may be helpful. Survival is variable because MDS can progress to leukemia; many animals are euthanized or die of sepsis, bleeding, or anemia.
Myelofibrosis causes bone marrow failure secondary to replacement of normal marrow elements with fibrous tissue. It has been seen in dogs, cats, people, and goats. It can be a primary disorder or secondary to malignancies, immune-mediated hemolytic anemia, whole body irradiation, and congenital anemias (eg, pyruvate kinase deficiency). Diagnosis can be made by bone marrow biopsy. Treatment varies with the underlying cause but usually consists of immunosuppressive therapy.
Bone marrow aspiration and biopsy are techniques used to evaluate the bone marrow in domestic animal species. The basic technique involves introducing a hollow needle into the bone marrow to obtain a sample for evaluation. Bone marrow aspiration provides a sample for cytologic evaluation, and bone marrow biopsy provides a sample for histopathologic evaluation.
Specific clinical indications to evaluate bone marrow include but are not limited to investigation of nonregenerative anemia, thrombocytopenia, leukopenia, bicytopenia, pancytopenia, abnormal circulating cells of any type, monoclonal gammopathy, suspected osteomyelitis, suspected bone neoplasia, infectious disease affecting the bone, and clinical staging of neoplastic processes such as lymphoma and mast cell disease.
The conventional anatomic sites used for bone marrow aspiration include the iliac crest, the trochanteric fossa of the femur, the tibial crest, and the greater tubercle of the humerus. Some clinicians have also used the rib (costochondral junction) or sternabrae. The humerus is the most common site for bone marrow biopsy.
For bone marrow aspiration, cats and dogs generally require sedation, although some cats may require general anesthesia. General anesthesia is required for bone marrow biopsy. The animal is positioned in lateral recumbency when using the trochanteric fossa or the greater tubercle, and in sternal recumbency when using the iliac crest. The area to be accessed is shaved and aseptically prepared. The site, including the periosteum, is infiltrated with local anesthetic. A #11 scalpel blade is then used to make a stab incision through the skin.
The equipment used for these procedures may differ slightly. Most bone marrow aspiration needles (eg, Rosenthal, Illinois) are very similar and have a removable stylet. With the stylet in place, the needle is advanced with a back and forth screw-like motion until the needle is well seated in the bone. The stylet is then removed, and a syringe (6−12 mL) attached for aspiration. If the animal feels any discomfort, this is when it will occur. Only a small sample is required, ie, enough to fill the syringe hub, which should be put onto slides for cytologic evaluation. The needle can then be removed.
Bone marrow biopsy generally requires a Jamshidi needle, which is rigid and hollow with a stylet. The Jamshidi needle has a cutting edge at its end, designed to obtain a core marrow sample (although it can also be used to obtain a bone marrow aspirate). The needle is driven into the bone with a back and forth, screw-like motion. Once the needle is well seated, the cap is unscrewed and the stylet removed. An aspirate can be obtained similar to the technique described above. To obtain a core sample for histopathology, the needle is advanced further (about ¼ in.) into the marrow and twisted in one direction. The needle is then moved in a wide, circular motion to try to dislodge a core sample. The needle is removed by twisting in the opposite direction in which it was advanced. A blunt stylet is then passed retrograde to remove the core sample. The core can be gently rolled onto a slide for cytology and then placed into formalin for histopathology.