eMedicine Specialties > Hematology > Red Blood Cells and Disorders

Myelophthisic Anemia

Author: Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Coauthor(s): Ulrich Woermann, MD, Consulting Staff, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland
Contributor Information and Disclosures

Updated: Jan 4, 2008

Introduction

Background

Infiltrating lesions caused by nonhematopoietic cells invading bone marrow can result in varying degrees of cytopenia, including anemia, thrombocytopenia, neutropenia, and pancytopenia. Bone marrow failure resulting from secondary infiltration is a possible cause of lack of blood cell production (as differentiated from a primary cause of failure). Manifestations range from a leukoerythroblastic picture^1,2 to the presence of a few teardrop-shaped red blood cells and early myeloid precursor cells in the peripheral blood smear.

Pathophysiology

Myelophthisis is a form of bone marrow failure that results from the destruction of bone marrow precursor cells and their stroma, which nurture these cells to maturation and differentiation.

Generally, a form of fibrosis occurs secondary to injury by nonhematopoietic cells or pathogens. This fibrosis destroys the normal hematopoietic cells and their supportive stromal cells. The bone marrow becomes infiltrated by collagen, reticulin, and other forms of fibrosis that replace the normal hematopoietic cells.

Frequency

United States

Infiltrative myelopathy occurs in less than 10% of cancer patients with metastatic disease. It most commonly occurs during the advanced stages of cancer, and the outcome depends on the patient's access to medical care.

International

Myelophthisis is observed more frequently in countries where access to medical care is difficult and diseases are allowed to progress to advanced stages.

Mortality/Morbidity

Mortality is dependent on the underlying condition. The leukoerythroblastic blood picture is often associated with imminent death in some extreme cases.

• Patients with varying degrees of cytopenia are at risk for infection or bleeding.
• If patients are symptomatic, treat their anemia with red blood cell transfusions.

Clinical

History

• Focus the history and physical examination on establishing the underlying disease, such as an advanced carcinoma, lymphoma, or granulomatous disease.
• Family history is important for eliciting information in congenital and inherited forms of the disease.

Physical

• Physical findings usually reflect the underlying medical condition, such as metastatic carcinoma, lymphoma, or tuberculosis.
• Anemia may cause skin pallor.
• Severe thrombocytopenia may produce petechiae or ecchymoses.
• Patients with severe neutropenia may become infected and present with fever.

Causes

• The most common causes of extensive bone marrow infiltrative damage or invasion without much structural damage are listed below. The expanding number and volume of pathologic cells and release of suppressive cytokines can eventually lead to bone marrow failure without the characteristic morphologic features of myelophthisis.
• Leukemic cells, such as in chronic leukemias in which the expanding cells are mature and coexist peacefully with the normal bone marrow cells, show no evidence of myelophthisis, and marrow damage does not occur.
• In both agnogenic and secondary myelofibrotic disorders, megakaryocytes release platelet-derived growth factors, which are fibroblastic stimulants for growth and proliferation. This leads to the consequences of bone marrow space reduction and to disruption of normal bone marrow architecture.
  • Agnogenic myeloid metaplasia is a stem cell abnormality associated with myeloproliferative diseases. It is related to an abnormal stem cell clone that stimulates increased myelofibrosis and damage. It progresses to acute leukemia and is associated with extramedullary hematopoiesis in the liver and spleen, causing hypertrophy of these organs.
  • Secondary myelofibrosis is due to implantation or invasion by malignant cancer cells that have metastasized because of implantation of blood-borne tumor cells from a distant cancer. The most common sources are cancers of the lung, breast, and prostate⁶ and sarcomas.
• Nonmalignant causes of myelophthisis include (1) inflammatory cells, miliary tuberculosis, and fungal infections; (2) sarcoidosis; (3) macrophage proliferation in storage diseases such as Gaucher disease; (4) necrosis in sickle cell disease and septicemia; and (5) bone disease in congenital osteopetrosis.

• Search for CME/CE on This Topic »

• Anemia, Chronic (Emergency Medicine)
• Macrocytosis (Hematology)