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Myelophthisic anemia is a normocytic-normochromic anemia that occurs when normal marrow space is infiltrated and replaced by nonhematopoietic or abnormal cells. Causes include tumors, granulomatous disorders, and lipid storage diseases. Marrow fibrosis often occurs. Splenomegaly may develop. Characteristic changes in peripheral blood include anisocytosis, poikilocytosis, and excessive numbers of RBC and WBC precursors. Diagnosis usually requires bone marrow biopsy. Treatment is supportive and includes measures directed at the underlying disorder.
Descriptive terms used in this anemia can be confusing. Myelofibrosis, which is replacement of marrow by fibrous tissue bands, may be idiopathic (primary) or secondary. True myelofibrosis is a stem cell defect in which the fibrosis is secondary to other hematopoietic intramedullary events. Myelosclerosis is new bone formation that sometimes accompanies myelofibrosis. Myeloid metaplasia refers to extramedullary hematopoiesis in the liver, spleen, or lymph nodes that may accompany myelophthisis due to any cause. An old term, agnogenic myeloid metaplasia, indicates primary myelofibrosis with or without myeloid metaplasia.
Etiology
The most common cause is replacement of bone marrow by metastatic cancer (most often, breast or prostate; less often, kidney, lung, adrenal, or thyroid); extramedullary hematopoiesis tends to be modest. Other causes include myeloproliferative disorders (especially late-stage or spent polycythemia vera), granulomatous diseases, and (lipid) storage diseases. Myelofibrosis can occur in all of these.
Factors that may contribute to decreased RBC production include a decreased amount of functioning hematopoietic tissue, disordered metabolism related to the underlying disorder, and, in some cases, erythrophagocytosis. Extramedullary hematopoiesis or disruption of the marrow sinusoids causes release of immature cells. Abnormally shaped RBCs often result in increased RBC destruction.
Symptoms and Signs
Myeloid metaplasia may result in splenomegaly, particularly in patients with storage diseases. In severe cases, symptoms of anemia and of the underlying disorder may be present. Massive splenomegaly can cause abdominal pressure, early satiety, and left upper quadrant abdominal pain; hepatomegaly may be present. Hepatosplenomegaly is rare with myelofibrosis from malignant tumors.
Diagnosis
Myelophthisic anemia is suspected in patients with normocytic anemia, particularly when splenomegaly or a potential underlying disorder is present. If it is suspected, a peripheral smear should be obtained, because a leukoerythroblastic pattern (immature myeloid cells and nucleated RBCs, such as normoblasts in the smear) suggests myelophthisic anemia. Anemia, usually moderately severe, is characteristically normocytic but may be slightly macrocytic. RBC morphology may show extreme variation (anisocytosis and poikilocytosis) in size and shape. The WBC count may vary. The platelet count is often low, and platelets are often large and bizarre in shape. Reticulocytosis often occurs; it may be caused by premature release of reticulocytes from the marrow or extramedullary sites and thus does not always indicate increased blood regeneration.
Although examination of peripheral blood can be suggestive, diagnosis usually requires bone marrow examination. Indications include a leukoerythroblastic pattern and unexplained splenomegaly.The marrow may be difficult to aspirate; marrow trephine biopsy is usually required. Findings vary according to the underlying disorder. Erythropoiesis is normal or increased in some cases. However, the life span of RBCs is often reduced. Hematopoiesis may be present in the spleen and liver.
X-rays, if obtained incidentally, may disclose bony lesions (myelosclerosis) characteristic of long-standing myelofibrosis or other osseous changes (ie, osteoblastic or lytic lesions of a tumor), suggesting the cause of anemia.
Treatment
The underlying disorder is treated. In idiopathic cases, management is supportive. Erythropoietin (20,000 to 40,000 units sc once/wk or twice/wk) and corticosteroids (eg, prednisone 10 to 30 mg po once/day) have been used, but only modest responses have been observed. Hydroxyurea (500 mg po once/day or once every other day) decreases spleen size and normalizes RBC values in many patients, but the response requires 6 to 12 mo of treatment. Thalidomide (50 to 100 mg po once/day in the evening) may provide modest responses, but it increases the risk of thrombosis and causes fatigue, which can be severe.
Key Points
Last full review/revision May 2013 by Alan E. Lichtin, MD
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