 Bone marrow hypoplasia is a bone marrow failure

syndrome characterized by peripheral pancytopenia

and marrow hypoplasia.

 Paul Ehrlich introduced the concept of aplastic

anemia in 1888 when he studied the case of a
pregnant woman who died of bone marrow failure.

 However, it was not until 1904 that the name

became official of aplastic anemia. Now it is known
as bone marrow hypoplasia
 The theoretical basis of bone marrow failure includes:

 Primary defects or damage to Stem cells.

 Damage to the bone marrow microenvironment.
 It is necessary to distinguish between hereditary
medullary aplasia and acquired bone marrow
hypoplasia.
 Over 80% of cases of aplastic anemia are acquired.

 In acquired bone marrow, clinical and laboratory features

suggest that this is an autoimmune disease.
 Aplasias in the morphological evaluation shows a
severe depletion of hematopoietic elements, with a
large infiltration of fat cells.
 Flow cytometry shows that the population of CD34
cells containing Stem cells and early committed
progenitor cells are substantially reduced.

 In vitro studies suggest colonies loss deep functional

hematopoietic progenitors, which do not respond to
even high levels of hematopoietic growth factors.
 There is little evidence that a defective
microenvironment is a major cause of marrow
failure.

 In patients with severe bone marrow failure,

stromal cells have a normal function, including
production of growth factors.

 A stromal proper function is implicit in the

success of bone marrow transplantation in
marrow failure.
 The etiologic role of immune dysfunction in marrow
aplasia was suggested in 1970, when an autologous
recovery was documented in a patient with aplastic
anemia in whom the bone marrow transplant had failed.

 Mathe proposed that the immunosuppressive regimen

used for transplantation favored the return of normal
marrow function.

 Since then, numerous studies have shown that

approximately 70% of patients with bone marrow
hypoplasia, immunosuppressive therapy improves bone
marrow function.
 The suppression of hematopoiesis is probably
mediated by an increased population of cytotoxic T
lymphocytes and HLA-DR, which are detectable in
blood and in bone marrow of patients with aplastic
failure.

 These cells produce inhibitory cytokines such as

gamma interferon and tumor necrosis factor, which
can suppress the growth of progenitor cells.
 Although the search for
an etiologic agent is
often unhelpful, there
should be a detailed
history of the use of
solvents, exposure to
radiation or drugs such
as Benzene,
Chloramphenicol,
Analgesics, etc.
 The annual incidence of bone marrow failure
according to formal epidemiological studies is 2
cases per million in the general population.

 In some countries (USA, Japan), the incidence

may be as high as 6 cases per million.

 This increased incidence may be related to

environmental factors such as increased
exposure to toxic substances
 The main causes of mortality and morbidity in
marrow failure are severe infections and
excessive bleeding.
 Patients who undergo bone marrow
transplantation have additional risk factors
related to toxicity bone marrow suppression
and graft versus host disease.
 With Immunosuppression, one third of
patients with marrow failure do not respond to
bone marrow transplantation.
Bone marrow transplantion
 In patients who respond to transplantation,
there are risks to be taken into account:
 Relapse of disease, late onset of clonal diseases
such as paroxysmal nocturnal hemoglobinuria,
myelodysplastic syndromes and acute
leukemias.
 Race: No racial predisposition.
 Sex: The male to female ratio in acquired
marrow hypoplasia is approximately 1:1
 Bone marrow hypoplasia can occur in all age groups.
However, there are some stages of life when the
incidence is higher:

 During childhood due to hereditary syndromes

including marrow failure.
 In individuals between 20 and 25 years, perhaps due
to more contact with toxic substances.

 In people over 60, by the presence of

myelodysplastic syndromes unrelated to bone
marrow hypoplasia.
 The clinical presentation of patients with
marrow failure includes those related to
decreased hematopoietic cell production.
 The onset is insidious, and the initial symptom is
associated with anemia or bleeding, although
fever or infections can also occur.

 Anemia can manifest as pallor, headache,

palpitation, dyspnea or fatigue.
 Thrombocytopenia may be
evident: gingival bleeding
(bleeding gums), nose bleeding
(epistaxis) or bleeding on skin
or mucosa (petechiaes).

 Neutropenia may manifest as

acute opportunistic infections,
recurrent infections or sores in
mouth or pharynx.
 Patients present data of anemia such as pallor,
tachycardia, asthenia, headache, etc.
 Signs like thrombocytopenia with petechiae,
ecchymosis, gingival bleeding, epistaxis.
 Some patients may have physical data of an
infection such as fever, pain at venipuncture sites,
rattles, etc.

 No adenopathies.
 No Spleno or Hepatomegaly
 CONGENITAL OR HEREDITARY: 20%
a) Fanconi Anemia
b) Diamond-Blackfan syndrome
 ACQUIRED: 80%
a) Idiopathic
b) Immune
c) Infectious:
Hepatitis virus, Epstein Barr virus, HIV,
Parvovirus.
Collagenopathies.
Radiation, chemotherapy and pesticides.
Drugs.
 Blood count (including blood smear and
reticulocytes)
The presence of neutropenia and severe
pancytopenia with very low reticulocyte count is
essential for the diagnosis of bone marrow
failure.
The presence of blasts completely rule out the
possibility of a bone marrow hypoplasia.
BONE MARROW ASPIRATION AND BIOPSY
Normal bone Hypocelular Aplastic bone
bone marrow marrow
marrow
Other causes of pancytopenia:
 Acute leukemia.
 Myelodysplastic syndrome.
 Megaloblastic anemia.
 Metastatic infiltration of
bone marrow.
 Slight.
 Moderate.
 Severe (survival 3-6 months):

a) Total neutrophils <500 / mm3.

b) Platelets <20,000 / mm3.
c) Reticulocytes <1.0%.
 TRANSFUSIONS:
Its use must be strictly controlled.
    
For patients who are to be transplanted, limit
further administration of blood.

It is important to avoid as much as possible

transfusions between members of the same
family to avoid sensitization.
Due to the pre-transplant
immunosuppression,
assessing the use of
leukoreduced blood to
prevent alloimmunization
is very important, and even
the use of irradiated
blood to reduce the risk of
infection with CMV.
Through it, all the blood will
  irradiated and be pure, ridding the
  any possible problems receiver
 INFECTION CONTROL:

Infections are the leading cause of death in the

marrow aplasia.
It must be used a prophylactic scheme of broad
spectrum antibiotics, including antifungals.
Administration of leukocyte concentrates
(neutrophils) is controversial.
 TREATMENT
 CORTICOSTEROIDS:
 Prednisone, 1-2 mg/Kg.
 The amount of Prednisone must be
reduced according with the clinical and
laboratorial results.
 The main purpose of using steroids, is
keeping alive the patient until the
transplant is performed.
 BONE MARROW TRANSPLANTATION:
1) HLA-matched family donor
2) Donor unfamiliar with certain HLA compatibility

A greater HLA compatibility, greater chance of

success in transplantation.
In some places an effectiveness of between 60-
80% is achieved.
Processing
Female 28 years old with a history of chronic exposure to paints
and solvents (manual development activities in ceramics), who
started his current condition 8 weeks ago with fatigue, weakness,
dizziness, headache and pallor of integuments. Then she began to
notice the presence of petechiaes and ecchymoses on the arms and
legs, and bleeding gums and epistaxis without cause. She has had
several bacterial infections of the upper respiratory tract, which
have been resolved with not specified antibiotics. Yesterday was
hospitalized with a serious data of pneumonia and
gastrointestinal bleeding. The blood count shows Hb. 6 g., 1,200
leukocytes xmm3, neutrophils 10%, platelets 5,000 xmm3.
reticulocytes 0.5%. At the P.E. the patient is pale and bleeding,
no visceromegaly or lymphadenopathy.
The bone marrow study shows:
…………………………………………………

The patient died today despite all the

  resuscitation efforts.

What is your clinical diagnosis of first impression?

What hematologic disease should be considered as a
differential diagnosis?
What findings would expect to find in bone marrow in
either case?
What was the prognosis from the beginning of this
patient?
  What was the most suitable treatment?