(Infograph)

OXILLO, C.J., PENASO, A.M.A. & PAULINO, E.G.

Size: A3
Reference: Rodak, B.F., Fritsma, G.A., & Keohane, E.M. (2012). Hematology: Clinical Principles and
Application-5th edition

Bone marrow failure

Bone marrow failure is the reduction or cessation of blood cell production affecting one or more cell
lines. Pancytopenia—or decreased numbers of circulating red blood cells (RBCs), white blood cells
(WBCs), and platelets—is seen in most cases of bone marrow failure, particularly in severe or advanced
stages

The pathophysiology of bone marrow failure includes:

(1) the destruction of hematopoietic stem cells due to injury by drugs, chemicals, radiation, viruses, or
autoimmune mechanisms;
(2) premature senescence and apoptosis of hematopoietic stem cells due to genetic mutations;
(3) ineffective hematopoiesis due to stem cell mutations or vitamin B12 or folate deficiency;
(4) disruption of the bone marrow microenvironment that supports hematopoiesis;
(5) decreased production of hematopoietic growth factors or related hormones; and
(6) the loss of normal hematopoietic tissue due to infiltration of the marrow space with abnormal cells.

Acquired (80% to 85% of cases)

Acquired aplastic anemia is classified into two major categories: idiopathic and secondary.
o Idiopathic acquired aplastic anemia has no known cause.
o Secondary acquired aplastic anemia is associated with an identified cause.
Approximately 70% of all aplastic anemia cases are idiopathic, whereas 10% to 15% are
secondary.3 Idiopathic and secondary acquired aplastic anemia have similar clinical and laboratory
findings. Patients may initially present with macrocytic or normocytic anemia and reticulocytopenia.
Pancytopenia may develop slowly or progress at a rapid rate, with complete cessation of hematopoiesis.

Inherited (15% to 20% of cases)

In comparison with acquired aplastic anemia, patients with inherited aplastic anemia present at an
earlier age and may have characteristic physical stigmata. The three inherited diseases for which bone
marrow failure and pancytopenia are a consistent feature are Fanconi anemia, dyskeratosis congenita, and
Shwachman-Bodian-Diamond syndrome .

Treatment and Prognosis

In some cases, no treatment of hematologic features is required. However, if needed, treatment
consists of G-CSF for neutropenia, transfusion support for anemia and thrombocytopenia, and enzyme
replacement for pancreatic insufficiency. The risk of AML and MDS is approximately 19% at 20 years and
36% at 30 years.72 Allogeneic bone marrow transplantation is recommended in cases of severe
pancytopenia, AML, or MDS. Unfortunately, despite supportive care and attempted curative therapy, 5-year
overall survival is 60% to 65%, with many deaths occurring from severe infections and malignancy.

Differential Diagnosis
A distinction must be made between acquired aplastic anemia, inherited aplastic anemia, and other
causes of pancytopenia, including PNH, MDS, megaloblastic anemia, and leukemia. The importance of a
correct diagnosis is clear, as diagnostic conclusions dictate therapeutic management and prognosis.