Myelophthisic anemia is anemia characterized by the presence of immature erythrocytes in the peripheral blood due to the infiltration (crowding out) of the bone marrow by abnormal tissue. It is a hypo-proliferative variant of anemia because it results from inadequate production of red blood cells from the bone marrow.[rx] Hypoproliferative anemia is different from other forms of anemia since the reticulocyte count is usually low compared to anemia caused by increased blood loss or peripheral destruction, wherein the reticulocyte count mostly increases. Other causes of hypo-proliferative anemia include nutritional deficiencies, toxin exposures, endocrine abnormalities, hematologic malignancies, and bone marrow failure syndromes. [rx] This article will be focusing on myelophthisic anemia, and its epidemiology, etiology, pathophysiology, complications, evaluations, and management.
Myelophthisic anemia categorizes under the normocytic variety of anemia characterized by the presence of immature erythrocytes in the peripheral blood due to infiltration of the bone marrow by abnormal tissue. It is also one of the hypo-proliferative anemias because it results from inadequate production of red blood cells from the bone marrow. Normocytic anemia has the mean corpuscular volume (MCV) within the normal range of 80 to 100 fL. Other types of normocytic anemia apart from myelophthisic anemia include aplastic anemia, anemia of chronic disease, and anemia of renal disease.
Causes
Myelophthisic anemia results from fibrosis and crowding out of the normal bone marrow owing to infiltration by non-hematopoietic or abnormal cells such as metastatic cancers or hematologic malignancy, granulomatous lesions, lipid storage diseases, and primary myelofibrosis. Several cases of breast, prostate and hematological cancers have been reported to cause bone marrow infiltration. Khan et al. reported a similar case of lobulated breast cancer infiltrating the bone marrow.[rx] These space-occupying cancers replace hematopoietic stem cells leading to pancytopenia and resulting in extramedullary hematopoiesis.[rx] Fibrosis of the bone marrow can also result from disseminated mycobacterial infection, autoimmune diseases, renal osteodystrophy, hypo, or hyperthyroidism.[rx]
Research has implicated proinflammatory cytokines such as tumor necrosis factor alfa and interleukins in inducing fibroblastic proliferation, thereby leading to marrow fibrosis.[rx]
In myelophthisic anemia, the peripheral blood smear will show characteristic leukoerythroblastic reactions with the presence of immature myeloid and nucleated erythrocytes, including abnormal erythrocytes such as schistocytes, and dacrocytes (teardrop) and anisopoikilocytosis cells. These are secondary to extramedullary hematopoiesis and the disruption of marrow sinusoids. Since there may be a dry tap during bone marrow tap owing to fibrosis, bone marrow biopsy is essential for the diagnosis along with the visualization of underlying etiologies such as metastatic cancer cells or granulomatous lesions.
Diagnosis
Patients with myelophthisic anemia will have a history of underlying malignancy or chronic inflammatory or infectious diseases. Malignancies that have correlations with myelophthisic anemia include prostate, breast, and lung carcinomas. Reports also exist of myelophthisis in a patient with advanced-stage melanoma.[rx] Patients will have symptoms of anemia, including fatigue, weakness, shortness of breath, and exercise intolerance. On physical examination, the patient will have conjunctiva pallor, delayed capillary refill, tachycardia, and splenomegaly. Splenomegaly, as well as hepatomegaly, is found in this type of anemia because of the development of extramedullary hematopoiesis due to the failure of the bone marrow to produce matured erythrocytes. These patients also have increased risks for bleeding tendencies (thrombocytopenia) as well as repeated infections (leukopenia).
To recognize and appropriately diagnose myelophthisic anemia, the combinations of relevant laboratory data, peripheral blood smear, and bone marrow biopsy should be studied. Laboratory data include a complete blood count, which will show the level of white blood cells, hemoglobin, hematocrit, platelets, MCV, reticulocytes counts, and Red cell distribution with (RDW). In myelophthisic anemia, pancytopenia could be found due to infiltration by cancers and also fibrosis. MCV is usually normal in this type of cancer, and reticulocyte counts are low. A peripheral blood smear will show abnormal red blood cells ranging from immature to defective shapes and the size of the cells. Red blood cells will be nucleated, and some will be in teardrop forms. Other cells include giant platelets and immature leucocytes. The presence of these immature cells is called leucoerythroblastic.[rx] Bone marrow biopsy will show signs of infiltration by primary cancer and fibrosis in cases secondary to granulomatous infections, or autoimmune diseases.[rx]
Treatment
The treatment of myelophthisic anemia is variable because it has as its basis the underlying etiology. For patients with malignancies, treating, and getting rid of the malignant tissue either through chemotherapy or radiation will help to eliminate the infiltrating tissue taking the space of hematopoietic cells. Rosner et al. (2013) reported a case report where an advanced staged melanoma causing myelophthisis responded to immune checkpoint inhibition with the anti-programmed cell death-1 inhibitor or PD-1 inhibitor, called pembrolizumab.[rx] They reported a favorable response after using this PD-1 inhibitor. As a result of the reaction of the melanoma to a PD-1 inhibitor, they believe that there is an immunologic compartment within the bone marrow. Other clinicians have also reported that there is an interaction between immune and skeletal systems implicating the pathogenesis behind such an entity.[rx]
Because a patient with myelophthisic anemia has low hemoglobin levels, transfusion of packed red blood cells is also indicated. Even though other cell lines are also low, transfusions of platelets or giving leukocytes stimulating medication are also not indicated unless there is severe concurrent bleeding or infections.
For a patient with myelophthisic anemia following primary myelofibrosis, a study demonstrated survival benefits from the use of ruxolitinib, a Janus kinase inhibitor.[rx]
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