What is Bone Marrow Failure
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What is Bone Marrow Failure

The manifestations of bone marrow failure are secondary to the clinical effects of cytopenia. Patients with severe anemia may present with pallor and/or signs of congestive heart failure, such as shortness of breath.
                      

The bone marrow failure syndromes are a group of disorders than can be either inherited or acquired. These diseases reflect disorders of the hematopoietic stem cell that can involve either one cell line or all of the cell lines (erythroid, myeloid or megakaryocytic). The lymphocytes, which are involved in lymphoproliferative disorders, are usually spared. The pathophysiology of marrow failure involves the following mechanisms:

  • A decrease in or damage to the hematopoietic stem cells or their microenvironment, resulting in hypoplastic or aplastic bone marrow
  • Maturation defects (Vitamin B12 or folate deficiency)
  • Differentiation defects (myelodysplasia)

The prevalence of bone marrow failure secondary to hypoplastic or aplastic anemia is low in the United States and Europe (2 to 6 cases per million persons) compared to the prevalence of bone marrow failure secondary to acute myelogenous leukemia and multiple myeloma (27 to 35 cases per million persons). The frequency of myelodysplasia, on the other hand, has increased from 143 cases reported in 1973 to approximately 15,000 cases annually in the United States. This is likely an underestimation of the actual prevalence, which is believed to be closer to 35,000 to 55,000 new cases a year.

Pancytopenia occurs when red blood cells, white blood cells, and platelets are all affected. The specific causes of marrow failure include:

Aplastic anemia (initially all 3 cell lines may not be affected) is either:

  • Congenital; for example, Fanconi anemia.
  • Acquired: injury from viruses (hepatitis B virus, Epstein-Barr virus, parvovirus), autoimmune, ionizing radiation, antineoplastic agents, poisons (benzene) and drugs (chloramphenicol).

Single-cell line deficiencies are less common, and include:

  • Myelodysplasia: caused by a defect in the differentiation of precursor cells
  • Acute myeloid or lymphoblastic leukemia
  • Infiltration of the marrow (lymphoma, multiple myeloma, carcinoma, hairy cell leukemia)
  • Megaloblastic anemia (vitamin B12 or folate deficiency)
  • Myelofibrosis: fibrosis of the bone marrow associated with radiotherapy, Hodgkin disease, polycythemia vera, and malignant transformation

The history can help distinguish inherited causes from acquired causes. Inherited bone marrow failure is usually diagnosed in young adults but may remain undiagnosed until the fifth or sixth decades of life. These diseases should be considered if any of the following are present: subtle but characteristic physical anomalies, hematologic cytopenias, unexplained macrocytosis, myelodysplastic syndrome, acute myelogenous leukemia, or squamous cell cancer (even in the absence of pancytopenia). Siblings of a patient with Fanconi anemia who develop abnormal blood counts should also be investigated.

Exposure to toxins, drugs, environmental hazards, and recent viral infections (such as hepatitis) should be noted. The manifestations of bone marrow failure are secondary to the clinical effects of cytopenia. Patients with severe anemia may present with pallor and/or signs of congestive heart failure, such as shortness of breath. Bruising (ecchymoses, petechiae), gum bleeding, or nosebleeds suggest thrombocytopenia. Fever, cellulitis, pneumonia, or sepsis suggest neutropenia. The presence of hepatomegaly, splenomegaly, or lymphadenopathy suggests a diagnosis of leukemia or lymphoma.

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Comments (3)

Truly informative article..

Great information here. FB liked.

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