(See also Overview of Decreased Erythropoiesis.)
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. Primary 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.
The most common cause of myelophthisic anemia is
Cancers most often involved include breast or prostate; less often kidney, lung, adrenal, or thyroid cancers are the cause. Extramedullary hematopoiesis tends to be modest.
Other causes include myeloproliferative disorders such as primary myelofibrosis or myelofibrosis evolving from polycythemia vera or essential thrombocythemia, granulomatous diseases, and lipid storage diseases such as Gaucher disease or other causes of marrow fibrosis.
Decreased functional hematopoietic tissue due to bone marrow infiltration is the main cause of anemia.
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, cachexia, portal hypertension, and left upper quadrant abdominal pain; hepatomegaly may be present. Hepatosplenomegaly is rare with myelofibrosis due to malignant tumors.
Myelophthisic anemia is suspected in patients with normocytic anemia, particularly when splenomegaly or a potential underlying cancer is present. If it is suspected, a peripheral smear should be done, because a leukoerythroblastic pattern (immature myeloid and erythroid cells such as myelocytes and metamyelocytes, and normoblasts or other nucleated RBCs) suggests myelophthisic anemia. Extramedullary hematopoiesis or disruption of the marrow sinusoids causes release of immature myeloid cells and nucleated red cells into the periphery. Abnormally shaped RBCs, typically teardrop-shaped (dacrocytes), are also present.
Anemia, usually moderate to severe, is characteristically normocytic but may be slightly macrocytic. RBC morphology may show extreme variation (anisocytosis and poikilocytosis) in size and shape. The white blood cell count may vary. The platelet count is often low, and platelets are often large and bizarre in shape.
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. 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.
The underlying disorder is treated. Management is supportive with transfusions.
Myelophthisic anemia is a normocytic-normochromic anemia that occurs when normal marrow space is infiltrated and replaced by nonhematopoietic or abnormal cells.
The most common cause is replacement of bone marrow by metastatic cancer; other causes include myeloproliferative disorders, granulomatous diseases, and lipid storage diseases.
Suspect myelophthisic anemia in patients with normocytic anemia and characteristic findings on peripheral smear, particularly in those with splenomegaly or a known causative disorder; confirm with bone marrow examination.
Treat the cause and transfuse as needed.