Synonyms and related keywords:
pancytopenia, stem cell defect,
hypoplastic anemia, aplastic anemia,
single cytopenias, acquired bone marrow
failure, inherited bone marrow failure
Author:
Emmanuel C Besa, MD,
Professor, Department of Medicine,
Division of Hematologic Malignancies,
Thomas Jefferson University, Jefferson
Medical College
Coauthor(s):
Ulrich Woermann, MD,
Consulting Staff, Division of
Instructional Media, Institute for
Medical Education, University of Bern,
Switzerland
Editor(s): Thomas H Davis,
MD, Fellowship Program
Director, Associate Professor,
Department of Internal Medicine, Section
of Hematology/Oncology, Dartmouth
Medical School; Francisco
Talavera, PharmD, PhD, Senior
Pharmacy Editor, eMedicine; Marc
Jeffrey Kahn, MD, Program
Director, Associate Professor,
Department of Internal Medicine, Tulane
University School of Medicine;
Rajalaxmi McKenna, MD, FACP,
Southwest Medical Consultants, SC,
Department of Medicine, Good Samaritan
Hospital, Advocate Health Systems; and
Michael E Zevitz, MD,
Clinical Assistant Professor, Department
of Medicine, Rosalind Franklin
University of Medicine and Science
Background: Disorders of the
hematopoietic stem cell involve either one cell
line or all of the myeloid cell lines (ie,
erythroid for red cells, myeloid for white blood
cells, megakaryocytic for platelets). The
lymphoid cells, which primarily are involved in
lymphoproliferative disorders, usually are
spared. This article describes a group of
diseases that result in bone marrow failure.
Other causes may include
Myeloproliferative Disease or
Myelodysplastic Syndrome.
Pathophysiology: Bone marrow
failure can be inherited or acquired. It can
involve just 1 cell line or all 3 cell lines.
The pathophysiology of these defects includes
the following mechanisms of action: (1) a
decrease in or damage to the hematopoietic stem
cells and their microenvironment, resulting in
hypoplastic or aplastic bone marrow; (2)
maturation defects, eg, vitamin B-12 or folate
deficiency; and (3) differentiation defects, eg,
myelodysplasia.
Generally, hematopoietic stem cells are
damaged by a congenital defect or exposure to a
noxious substance or factor. Pathophysiologic
mechanisms are (1) an acquired stem cell injury
from viruses, toxins, and chemicals that leads
to a quantitative or qualitative abnormality;
(2) abnormal humoral or cellular control of
hematopoiesis; (3) an abnormal or hostile marrow
microenvironment; (4) immunologic suppression of
hematopoiesis (ie, mediated by antibodies, T
cells [or cellularly], or lymphokines); and (5)
mutations in genes, causing inherited bone
marrow failure syndromes. Identification of
these relevant mutations has led to progress in
defining the precise functions of the
corresponding proteins in normal cells.
Frequency:
In the US: The
prevalence of bone marrow failure resulting
from hypoplastic or aplastic anemia is low
in the United States and Europe (2-6 cases
per million persons) compared to the
prevalence of bone marrow failure resulting
from acute myelogenous leukemia and multiple
myeloma (27-35 cases per million persons).
The frequency of myelodysplasia, on the
other hand, has increased from 143 cases
reported in 1973 to about 15,000 cases
annually in United States. This is an
underestimation of the actual prevalence,
which is believed to be about 35,000-55,000
new cases a year.
Internationally: Bone
marrow failure occurs more frequently in the
East than in the West. In Japan and the Far
East, the frequency is at least 3 times
higher than in the United States and Europe.
Mexico and Latin America also have high
occurrence rates, which are attributed to
the liberal use of chloramphenicol.
Environmental factors and pervasive use of
insecticides have been implicated as a cause
of this disease. The incidence of
myelodysplasia was recently estimated to be
around 4-5/100,000 population/year in
Germany and Sweden.
Mortality/Morbidity: Bone
marrow failure resulting in failure to produce
1, 2, or all 3 cell lines of the blood results
in increased morbidity and mortality of the
patients involved.
Morbidity and mortality from
pancytopenia are caused by low levels of
mature blood cells. Severe anemia can cause
high-output cardiac failure and fatigue.
Neutropenia can predispose individuals to
bacterial and fungal infections.
Thrombocytopenia can cause spontaneous
bleeding and hemorrhage.
The severity and extent of cytopenia
determine prognosis. Severe pancytopenia is
a medical emergency, requiring rapid
institution of definitive therapy (ie, early
determination of supportive care and bone
marrow transplant candidates).
Patients with bone marrow failure
present with low blood counts.
Low platelet counts predispose patients
to spontaneous bleeding in the skin and
mucous membranes. Neutropenia places the
patient at risk for serious infections.
Bleeding complications usually are the most
alarming symptom, and infections prompt
individuals to visit the emergency
department.
Weakness and fatigue resulting from
anemia can develop slowly. Months may elapse
before the patient seeks medical help with
these symptoms.
Family and past medical histories can
help distinguish inherited causes from
acquired causes. Inherited bone marrow
failure is usually diagnosed in young adults
but may be missed until their 5th or 6th
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 or acute myelogenous leukemia, or
squamous cell cancer even in the absence of
pancytopenia or a positive family history.
Siblings of a patient with known Fanconi
anemia who developed abnormal blood counts
should be investigated.
Exposure to toxins, drugs, environmental
hazards, and recent viral infections (eg,
hepatitis) should be noted.
Physical: The manifestations
of bone marrow failure relate to the clinical
effects of low blood counts.
Patients with severe anemia may present
with pallor and/or signs of congestive heart
failure, such as shortness of breath.
Bruising (eg, ecchymoses, petechiae) on
the skin, gum bleeding, or nosebleeds
frequently are associated with
thrombocytopenia.
Fever, cellulitis, pneumonia, or sepsis
can be complications of severe neutropenia.
Inherited bone marrow failure includes
Fanconi anemia, which has characteristic
physical developmental anomalies including
absent thumbs, absent radius, microcephaly,
renal anomalies, short stature, and abnormal
skin pigmentation (ie, café-au-lait and
hypopigmented or hyperpigmented spots). As
many as half of patients with Fanconi anemia
may not exhibit obvious developmental or
skin manifestation, and it is increasingly
clear that the diagnosis should be
considered in adults with bone marrow
failure, myelodysplastic syndrome, or early
onset of epithelial cancer.
Causes: The main causes of
bone marrow failure are congenital (ie,
constitutional) in nature, or it may be
acquired. Acquired bone marrow failure syndromes
include single cytopenias and pancytopenias.
Constitutional causes
Constitutional aplastic anemia is
associated with chronic bone marrow
failure, congenital anomalies, familial
incidence, or thrombocytopenia at birth.
Fanconi anemia is characterized by
familial aplastic anemia, chromosomal
breaks, and in some cases, congenital
anomalies of the thumb or kidneys.
Dyskeratosis congenita, another rare
disorder, has a characteristic
dermatologic manifestation of nail
dystrophies and leukoplakia. These
patients develop aplastic anemia in
their second decade of life.
Shwachman-Diamond syndrome consists
of exocrine pancreatic insufficiency and
bone marrow failure. Occasionally,
cartilage and hair hypoplasia can occur,
resulting in short stature and
dysostosis.
Single cytopenias
Pure red cell aplasia may be
secondary, caused by a thymoma. It may
occur transiently, resulting from a
viral infection such as with parvovirus
B19. Pure red cell aplasia also may be
permanent, as a result of viral
hepatitis. Finally, it may be the result
of lymphoproliferative diseases (eg,
lymphomas, chronic lymphocytic leukemia)
or collagen vascular diseases (eg,
systemic lupus erythematosus, refractory
anemia), or it may occur during
pregnancy.
Amegakaryocytic thrombocytopenic
purpura has been reported to occur as a
result of causes similar to those for
pure red cell aplasia.
Early forms of myelodysplastic
syndrome initially can manifest as a
single cytopenia or, more often, as a
bicytopenia.
Pancytopenia (decrease in all 3 cell
lines)
This is the most common
manifestation of bone marrow failure.
Aplastic or hypoplastic anemia can
be idiopathic in nature, or it can
develop from secondary causes. See
Aplastic Anemia for further
discussion.
Myelodysplastic anemia also can
cause pancytopenia. See
Myelodysplastic Syndrome for further
details.
Myelophthisic anemia may result from
marrow destruction because of tumor
invasion or granulomas.
Laboratory features of bone marrow
failure include a single cytopenia, as in
pure red cell aplasia, and amegakaryocytic
thrombocytopenic purpura or pancytopenia, as
in aplastic anemia.
Peripheral blood findings are as
follows:
Anemia is common, and red cells
appear morphologically normal. The
reticulocyte count usually is less than
1%, indicating a lack of red cell
production. Occasionally, the mean cell
volume is elevated, with macrocytosis.
Platelet counts are lower than
normal, with a paucity of platelets in
the blood smear. Platelet size is
normal, but a low platelet count may
cause greater heterogeneity in size.
Agranulocytosis (ie, decrease in all
granular white blood cells, including
neutrophils, eosinophils, and basophils)
and a decrease in monocytes are
observed. A relative lymphocytosis
occurs (ie, increased percentage)
without an increase in numbers.
The Ham test, or sucrose hemolysis test,
may be positive in a patient with underlying
paroxysmal nocturnal hemoglobinuria, but a
recent transfusion with packed RBCs may
induce a false-negative test result (ie,
testing normal transfused red cells).
Folate, vitamin B-12, and serum
erythropoietin levels usually are increased.
Fanconi anemia should be considered in
all young adults and children with
hypoplastic or aplastic anemia or
cytopenias, unexplained macrocytosis,
myelodysplastic syndrome, acute myelogenous
leukemia, epithelial malignancies, or subtle
but characteristic physical anomalies. The
criterion standard screening test for
Fanconi anemia is based on the
characteristic hypersensitivity of Fanconi
anemia cells to the crosslinking agents (eg,
mitomycin C, diepoxy butane [DEB],
cisplatin). Expose a culture of replicative
cells (ie, phytohemagglutinin
[PHA]–stimulated peripheral blood
lymphocytes or skin fibroblasts) to low
doses of mitomycin C or DEB. Then examine
the cells in metaphase, looking for evidence
of chromosomal breaks and radial
chromosomes.
Mutated genes can be identified by
retroviral complement studies, by direct
sequencing, or by denaturing
high-performance liquid chromatography
(DHLP), which are limited to research
laboratories presently.
Screening for dyskeratosis congenita
(DC) should be considered in children and
adults who have (1) bone marrow failure,
acute myelogenous leukemia, or
myelodysplastic syndrome; (2) negative
mitomycin C and DEB test results, which
rules out Fanconi anemia; and either (3)
hypopigmented macules, reticulated
hypopigmentation, dystrophic nails, or oral
leukoplakia or (4) evidence in the family
history of X-linked or autosomal dominant
forms of DC by genomic DNA sequencing
(DKC1-3).
Diamond-Blackfan anemia (DBA) is a pure
red cell aplasia and usually manifests in
early infancy. Schwachman-Diamond syndrome
is a syndrome of bone marrow failure
(classically neutropenia), exocrine
pancreatic insufficiency, and metaphyseal
dysostosis that also manifests in early
childhood.
Imaging Studies:
Bone marrow activity can be measured by
radiographic methods. Ferrokinetic studies
have been conducted using a radioactive
label, such as iron-59 or indium-111, both
of which are taken up by erythroid cells.
Radioactive iron is no longer available in
the United States.
Magnetic resonance imaging (MRI) can be
used to differentiate densities and
intensity signals of bone marrow fat cells
from densities and intensity signals of
hematopoietic cells.
Positron emission tomography (PET)
scanning with radiolabeled oxygen can
measure the metabolic activity difference
between hypoplastic marrow and cellular
marrow.
Procedures:
Bone marrow
An aspirate and biopsy should be
performed to assess the cellularity and
morphology of the residual cells. In
general, the marrow is replaced with fat
cells and stromal cells are replaced
with lymphocytes, with very few
hematopoietic cells. Occasionally,
localized pockets of marrow are present
(ie, from a sampling error), which can
be misleading. To evaluate cellularity,
the core biopsy specimen should be at
least 1 cm long.
Residual erythroid cells may show
evidence of dysplasia with
nuclear-cytoplasmic maturation
dissociation, which in the absence of a
folate or vitamin B-12 deficiency,
commonly is described as megaloblastoid
features.
Histologic Findings: Bone
marrow studies provide information to
definitively diagnose failure, and the status of
precursor cells of each cell line can be
examined. Pure red cell aplasia
characteristically affects erythroid progenitor
cells; amegakaryocytic thrombocytopenia lacks
megakaryocytes. A finding of hypoplastic bone
marrow differentiates aplastic anemia from
aleukemic leukemia, which produces blast cells
in the marrow.
If clinically indicated, initiate a
blood transfusion using specific cells, such
as packed red cells for anemia and platelets
for thrombocytopenia. Clinical indications
for red cell transfusions are symptoms
secondary to anemia and bleeding from
thrombocytopenia. Supportive care gives only
temporary relief of symptoms and does not
treat the primary disease.
Infections resulting in neutropenia
should be treated as emergencies. Institute
intravenous antibiotics that cover all
possible organisms before culture results
are available.
Bone marrow transplantation (BMT)
candidates are patients who are younger than
55 years who have severe disease and a
matched related donor. With current BMT
regimens, most patients with severe aplastic
anemia have a 60-70% long-term survival
rate. Survival rates of higher than 80% are
reported for patients in more favorable
subgroups. Using matched unrelated donors
still is experimental (11-20% survival
rates). Inherited bone marrow failure,
similar to Fanconi anemia, carries a median
survival of 30 years, but survival is
extraordinarily variable. Those with a
matched sibling are excellent candidates for
hematopoietic stem cell transplantation
(HSCT). A caveat is their extraordinary
sensitivity to chemotherapeutic agents and
radiation used in conditioning regimens,
which must both be reduced to avoid fatal
toxicities. Consider saving cord blood from
healthy siblings when identified.
Patients with severe aplastic anemia who
receive antithymocyte globulin (ATG) or
antilymphocyte globulin (ALG) but do not
receive BMT have a 41% response rate and a
1-year survival rate of 55%. The addition of
androgens increases response rates to 70%,
with a 1-year survival rate of 76%. Although
their roles are unknown, ATG or ALG should
be given with corticosteroids to prevent
serum sickness.
High-dose corticosteroids, using
methylprednisolone (20 mg/kg/d with rapid
taper), have been used in countries where
ATG or ALG is expensive; response rates are
38%. Cyclosporine therapy at 200-400 mg/d
(maintain serum trough levels at 100-250
ng/mL) has a reported 85% hematologic
remission rate.
Androgens were used in the past, but
most are masculinizing and poorly tolerated
by females and children. Danazol is a
nonmasculinizing androgen that may be
useful. The response rate is limited to
approximately 45%, and results may require
6-10 months of therapy. Hematopoietic growth
factors, such as granulocyte
colony-stimulating factor (G-CSF) and
granulocyte-macrophage colony-stimulating
factor (GM-CSF), may be useful in patients
with neutropenia who have infections,
without requiring a WBC transfusion.
Surgical Care: Splenectomy
is no longer performed.
Consultations:
Hematologists should manage these
patients.
An infectious disease specialist may be
necessary.
In severe cases, early consideration for
BMT should be initiated.
The approach to
bone marrow failure depends on which mechanism
is thought to predominate in the patient. If an
immune mechanism is suspected, an
immunosuppressive agent is used. Hematopoietic
growth factors and androgens also have been
tried in an effort to stimulate hematopoiesis.
Drug Category:
Immunosuppressive agents -- These
are used to manipulate the bone marrow
microenvironment and eliminate any
immune-mediated bone marrow suppression.
Intensive immunosuppression using a combination
of ALG and cyclosporine has resulted in
hematologic remission rates of 70-80% in
patients with aplastic anemia.
Drug
Name
Lymphocyte immune globulin (Atgam) --
Antibody to T cells used as an
immunosuppressive agent. Because it is
extracted from horse serum, serum
sickness may be induced when
administered.
Adult Dose
40
mg/kg/d IV for 4 d; with prednisone at 1
mg/kg during the first 2 wk
C -
Safety for use during pregnancy has not
been established.
Precautions
Administer only via IV to reduce risk of
phlebitis; medical emergency resources
should be immediately available to
manage rash, dyspnea, hypotension, or
anaphylaxis if they develop
Drug Category: Androgens
-- These agents push the resting
hematopoietic stem cells into cycle, making them
more responsive to differentiation by
hematopoietic growth factors. They also
stimulate endogenous secretion of erythropoietin
Drug
Name
Danocrine (Danazol) -- Attenuated
androgen without adverse virilizing and
masculinizing effects. Increases levels
of C4 component of the complement.
Adult Dose
600
mg PO tid
Pediatric Dose
Not
established
Contraindications
Documented hypersensitivity; seizure
disorders; hepatic or renal
insufficiency; lactation; pregnancy;
conditions influenced by edema
Interactions
Decreases insulin requirements and
increases effects of anticoagulants
Pregnancy
X -
Contraindicated in pregnancy
Precautions
Caution in renal, hepatic, or cardiac
insufficiency and in seizure disorders
Drug Category:
Immunosuppressive agents -- These
are used to address the immune mechanisms of
bone marrow failure.
Drug
Name
Cyclosporine A (Sandimmune) -- Cyclic
polypeptide that suppresses some humoral
immunity and, to a greater extent,
cell-mediated immune reactions such as
delayed hypersensitivity, allograft
rejection, experimental allergic
encephalomyelitis, and graft versus host
disease for a variety of organs.
For children and adults, dosing should
be based on ideal body weight.
Adult Dose
12
mg/kg/d PO, increase to 16 mg/kg/d,
adjusting to blood trough levels of
200-400 ng/mL
Pediatric Dose
Administer as in adults
Contraindications
Documented hypersensitivity;
uncontrolled hypertension or
malignancies; concomitant PUVA or UVB
radiation for psoriasis (may increase
risk of cancer)
Interactions
Carbamazepine, phenytoin, isoniazid,
rifampin, and phenobarbital may decrease
concentrations; azithromycin,
itraconazole, nicardipine, ketoconazole,
fluconazole, erythromycin, verapamil,
grapefruit juice, diltiazem,
aminoglycosides, acyclovir, amphotericin
B, and clarithromycin may increase
toxicity; acute renal failure,
rhabdomyolysis, myositis, and myalgias
increase when taken concurrently with
lovastatin
Pregnancy
D -
Unsafe in pregnancy
Precautions
Evaluate renal and liver function often
by measuring BUN, serum creatinine,
serum bilirubin, and liver enzymes; may
increase risk of infection and lymphoma;
reserve IV use only for those who cannot
take PO
Drug
Name
Methylprednisolone (Adlone, Medrol,
Solu-Medrol) -- Decreases inflammation
by suppressing the migration of
polymorphonuclear leukocytes and
reversing increased capillary
permeability.
Adult Dose
Days 1-3: 20 mg/kg/d IV/IM
Days 4-7: 10 mg/kg/d IV/IM
Days 8-11: 5 mg/kg/d IV/IM
Days 12-20: 2 mg/kg/d IV/IM
Days 20-30: 1 mg/kg/d IV/IM
Follow-up maintenance: 0.1-0.2 mg/kg/d
Pediatric Dose
0.5-1.7 mg/kg/d or 5-25 mg/m2
PO/IV/IM q6-12h
Contraindications
Documented hypersensitivity; viral,
fungal, or tubercular skin infections
Interactions
Coadministration with digoxin may
increase digitalis toxicity secondary to
hypokalemia; estrogens may increase
levels; phenobarbital, phenytoin, and
rifampin may decrease levels (adjust
dose); monitor patients for hypokalemia
when taking concurrently with diuretics
Pregnancy
C -
Safety for use during pregnancy has not
been established.
Precautions
Hyperglycemia, edema, osteonecrosis,
peptic ulcer disease, hypokalemia,
osteoporosis, euphoria, psychosis,
growth suppression, myopathy, and
infections are possible complications of
glucocorticoid use
Drug
Name
Prednisone (Deltasone, Orasone,
Sterapred) -- Used as an
immunosuppressant in the treatment of
autoimmune disorders. By reversing
increased capillary permeability and
suppressing PMN activity, may decrease
inflammation.
Adult Dose
5-60 mg/d PO qd or divided bid/qid
Pediatric Dose
4-5
mg/m2/d
Alternatively, administer 1-2 mg/kg PO
qd; taper over 2 wk as symptoms resolve
Contraindications
Documented hypersensitivity; viral,
fungal, or tubercular skin infections
Interactions
Coadministration with estrogens may
decrease prednisone clearance;
concurrent use with digoxin may cause
digitalis toxicity secondary to
hypokalemia; phenobarbital, phenytoin,
and rifampin may increase metabolism of
glucocorticoids (consider increasing
maintenance dose); monitor for
hypokalemia with coadministration of
diuretics
Pregnancy
B -
Usually safe but benefits must outweigh
the risks.
Precautions
Hyperglycemia, edema, osteonecrosis,
peptic ulcer disease, hypokalemia,
osteoporosis, euphoria, psychosis,
growth suppression, myopathy, and
infections are possible complications of
glucocorticoid use
Supportive care is essential for patient
survival. In patients with bone marrow
failure, the resulting cytopenia can lead to
life-threatening symptoms.
Anemia can cause fatigue and can impair
the patient's ability to function in daily
activities. Impaired heart function can be
aggravated into congestive heart failure by
increasing oxygen demands on the heart and
other tissues.
Transfuse packed red cells to
maintain hemoglobin levels of 7-10 g/dL.
Patients with coronary artery disease
may need to be maintained at 10-12 g/dL
if they are symptomatic at lower levels
of hemoglobin.
The benefits of this therapy are
limited to 1 month because the life span
of transfused red blood cells is limited
to the average life span of collected
cells.
Also, each unit of transfused packed
red cells introduces unwanted iron,
which over time, accumulates in the
patient.
Although minimal, the risk of
infection still is present (eg, HIV,
hepatitis C).
Bleeding/hemorrhage resulting from
thrombocytopenia is a major problem and may
be life threatening if it occurs
intracranially.
Platelet transfusions are effective
for stopping acute bleeding.
Unfortunately, the platelet life span is
short; the effects may last 2-4 days.
This treatment temporarily stops
bleeding, but it is not a practical
maintenance therapy. Development of
alloantibodies can make the patient
refractory to platelet transfusions.
Mucosal bleeding from the nose,
gums, or teeth may be easily controlled
by oral aminocaproic acid (Amicar 500-mg
tab or 500 mg/mL elix). The dose of
aminocaproic acid can be as high 6-8
g/d, in divided doses, every 6-8 hours.
Hypotension is the dose-limiting
symptom. Disseminated intravascular
coagulation (DIC) and clots in the
urinary tract are contraindications.
This therapy is useful in the long-term
maintenance of severe thrombocytopenia
in patients with bone marrow failure.
Sepsis, pneumonias, urinary tract
infections, and cellulitis with bacterial
organisms are common complications of
neutropenia. The risk is moderate with
actual or total neutrophil counts of
500-1000, and the risk is high at levels
below 500.
After blood is drawn and other
cultures are taken, broad-spectrum
antibiotics should be started
empirically in the presence of febrile
neutropenia. Coverage for the most
common gram-positive and gram-negative
organisms should be considered. With the
new broad-spectrum antibiotics, a single
antibiotic generally is sufficient. The
choice can be altered later, depending
on the results of sensitivity tests from
positive cultures.
The addition of antifungal agents
should be considered in the presence of
persistent fever despite adequate
antibacterial coverage. Liposomal
amphotericin B is indicated if renal
dysfunction is present because of
toxicity resulting from the drug in
another form.
Complications:
Over time, the transfusion of packed red
cells increases the total iron load to the
patient.
Measure iron stores in the form of
ferritin.
Increased levels of iron are toxic
to various organs, including the heart.
Iron toxicity can cause arrhythmia
by blocking the bundle of His, diabetes
by damaging the islets of Langerhans in
the pancreas, liver cirrhosis, and
bronze color in fair-skinned
individuals.
Administering a chelating agent is
an effective method of removing excess
iron. Chelating agents are composed of
molecules that bind tightly with free
iron and remove the iron by carrying it
as the agent is excreted from the body.
Desferrioxamine is the iron chelator
available in parenteral form. If given
intravenously, its activity is short and
it is excreted rapidly by the kidneys. A
subcutaneous infusion given continuously
by a portable pump for 3-4 hours every
12 hours is the preferred method. It
optimizes the binding of the chelator to
the free iron. As more free iron is
excreted, storage iron is mobilized into
the free form. This treatment can be
performed in an outpatient setting.
Monitoring serum ferritin levels and
measuring total iron urinary excretion can
determine effectiveness of therapy.
Most tissue damage can be reversed with
timely chelation, except for cirrhosis of
the liver (once it has set in).
Prognosis:
The prognosis of bone marrow failure
depends on the duration of the marrow
function abnormality.
Most inherited forms of bone marrow
failure, such as Fanconi anemia, are
associated with transformation into leukemia
several years later.
Viral causes, such as parvoviruses,
usually are self-limiting.
Acquired idiopathic aplastic anemia
usually is permanent and life threatening.
Half the patients die during the first 6
months.
Patient Education:
For excellent patient education
materials, please see eMedicine's
Blood and Lymphatic System Center. For
information specific to anemia, see the
article
Anemia. All these materials may be
printed free of charge.
Caption: Picture 1.
Bone marrow failure. This bone marrow
film at 400 X magnification demonstrates
a complete absence of hemopoietic cells.
Most of the identifiable cells are
lymphocytes or plasma cells.
Photographed by U. Woermann, MD,
Division of Instructional Media,
Institute for Medical Education,
University of Bern, Switzerland
(http://www.aum.iawf.unibe.ch/).
Molldrem JJ, Leifer E, Bahceci E, et al:
Antithymocyte globulin for treatment of the
bone marrow failure associated with
myelodysplastic syndromes. Ann Intern Med
2002 Aug 6; 137(3): 156-63[Medline].
Tichelli A, Gratwohl A, Wursch A, et al:
Late haematological complications in severe
aplastic anaemia. Br J Haematol 1988 Jul;
69(3): 413-8[Medline].
Young NS: Acquired bone marrow failure.
In: Handin RI, Stossel TP, Lux SE, eds.
Blood: Principles and Practice of
Hematology. Philadelphia, Pa: JB Lippincott;
1995:293-365.
NOTE:
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changes drug and treatment therapies
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is constantly changing and human error
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