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APLASTIC ANEMIA And Pancytopea

Aplastic anemia is a bone marrow failure syndrome characterized by
peripheral pancytopenia and marrow hypoplasia.
Bone marrow failure is a term with a larger meaning, referring to
disorders of the hematopoietic stem cell which involves either one cell
line or all of the myeloid cell lines
epidemiology
annual incidence in Europe and US - 2 cases per million population, but 4
cases in Bangkok 6 in Thailand and 14 in Japan.
no racial predisposition exists in the United States; however, prevalence
is increased in the Far East.
The male -to -female ratio is approximately 1:1.
Aplastic anemia occurs in all age groups.
a small peak in incidence in childhood.
a peak incidence in people aged 2 0-25 years, and a peak in people older
than 60 years
Etiology
Congenital/inherited (20%)
Patients usually have dysmorphic features or physical stigmata.
Occasionally, marrow failure may be the initial presenting feature.
 Fanconi anemia
 Dyskeratosis congenita
 Shwachman -Diamond syndrome
 Fami lial aplastic anemia
Acquired:
Drugs
- Cytotoxic dr ugs - Antibiotics - Chloramphenicol -
Anti -inflammatory - Anti -convulsant - Sulphonamides

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- 2-3 months usually between exposure and the development of aplastic

anemia
Radiations
Chemicals e.g., Benzene and pesticides, chloramphenicol,
phenylbutazone, and gold,
Viruses:
 Hepatitis A, Non -A and Non -B
 Herpes simplex
 E-B virus
 Parvovirus: Transient
Important clinically in patients with hemolytic anemias
5-10% of cases of AA in the West and 10 -20% in the Far East.
2-3 months between exposure to the virus and the development of AA.
Immune: SLE, RA (rheumatoid arthritis)
Pregnancy
Idiopathic: 75%
PNH
Pathogenesis
Potential mechanisms:
 Absent or defective stem cells (stem cell failure).
 Abn ormal marrow micro -environment.
 Inhibition by an abnormal clone of hemopoietic cells.
 Abnormal regulatory cells or factors.
 Immune mediated suppression of hematopoiesis.
 It is believed that genetic factors play a role.
 There is a higher incidence with HLA (11) histo comp.
 Antigen. Immune mechanism is involved

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The latest theory is:

there is an intrinsic derangement of hemopoietic pro liferative capacity,
which is consistent with life.
the immune mechanism attempt to destroy the abnormal cells (self
cure) and the clinical course and complications depend on the balance.
If the immune mechanism is strong, there will be severe pancytopenia.
If not, there will be myelodysplasia.
Forms of disease:
Inevitable :
dose related e.g. cytotoxic drugs, ionizing radiation. The timing, duration
of aplasia and recovery depend on the dose. Recovery is usual except
with whole body irradiation.
Idiosyncratic :
unpredictable to drugs e.g., anti -inflammatory antibiotics, anti -epileptic,
these agents usually do not produce marrow failure i n the majority of
persons exposed to these agents.
Common Traits To All Various Causes
Aplasia due to any cause may recover after immunosuppressive therapy
indicating that immune mechanisms are involved.
Transition to a clonal disorder of hemopoiesis can occur in any patient
who has recovered bone marrow function, suggesting that fragility of
the hemopoietic system is common to all forms of aplasia
Clinical Features
anemia  pallor and/or signs of congestive heart failure, such as
shortness of breath.
thrombocytopenia  bruising (eg, ecchymoses, petechiae) on the skin,
gum blee ding, or nosebleeds.
neutropenia  fever, cellulitis, pneumonia, or sepsis

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jaundice and evidence of clinical hepatitis in subset of patients

adenopathy or organomegaly  should suggest an alter native diagnosis.
In any case of aplastic anemia, look for physical stigmata of inherited
marrow failure syndromes such as
 skin pigmentation,
 short stature,
 microcephaly,
 hy pogonadism,
 mental retardation,
 skeletal anomalies.
investigations
 CBC
 Reticulocyte count
 Blood film.
 B12/folate.
 Liver function tests
 Virology
 Bone marrow aspirate & trephine
 PNH screen.
CBC : Anemia is common, and red cells appear morphologically normal.
The reticulocyte count usually is less than 1%. Thrombocytopenia , with
a paucity of platelets in the blood smear. Agranulocyt osis (ie, decrease
in all granular white blood cells, including neutrophils, eosinophils, and
basophils) and a decrease in monocytes are observed. A relative
lymphocytosis occurs. The degree of cytopenia is useful in assessing the
severity of aplastic anemia
Bone marrow exam : A bone marrow biopsy is performed in addition to
the aspiration. In aplastic anemia, these sp ecimens are hypocellular.
Aspirations alone may appear hypocellular because of technical reasons
(eg, dilution with peripheral blood), or they may appear hypercellular
because of areas of focal residual hematopoiesis.

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A core biopsy provides a better idea of cellularity; the specimen is

considered hypocellular if it is less than 30% cellular in individual s
younger than 60 years or less than 20% in those older than 60 years.
other investigations
 Hemoglobin electrophoresis - may show elevated fetal
hemoglobin.
 Biochemical profile , including evaluation of transaminases,
bilirubin, lactic dehydrogenase, Coombs test, and kidney function,
is useful in evaluating etiology and differential diagnosis.
 Serologic testing for hepatitis EBV, CMV, and HIV
 Autoimmune disease evaluation for evidence of collagen -vascular
disease
 The Ham test or sucrose hemolysis test frequently is performed
for excluding PNH.
 Histocompatibility testing should be conducted early to establish
potential related donors, esp ecially in younger patients
Criteria for diagnosis
1. pan cytopenia - Hb <10g/dL
- ANC <1, 5 G/L
- PL <100 G/L
2. Bone marrow histology and cytology
- decreased marrow cellularity (< 25%)
- increased fat cells component
- no extensive fibrosis
- no malignancy or storage disease
APLASTIC ANEMIA – differential
 Pancytopenia
 Acute Myelogenous Leukemia
 Anemia
 Aplastic Anemia
 Hairy Cell Leukemia
 Paroxysmal Nocturnal Hemoglobinuria

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 Immune pancytopenias in connective tissue disorders (eg,

systemic lupus erythematosus, refractory anemia)

Causes of pancytopenia

1. Failure of production of blood cells
a) bone marrow infiltration
 - acute leukemias
 - hairy cell leukemia
 - multiple myeloma
 - lymphoma
 - myelofibrosis
 - metastatic carcinoma
b) aplastic anemia
2. Ineffective hematopoesis
- m yelodysplastic syndrome
- vit.B12 and folate deficiency
3. Increased destruction of blood cells
- hipersplenism
- autoimmune disorders
- paroxysmal nocturnal hemoglobinuria
4. Myelosuppression after irradiation or antiproliferative drugs

Classification of aplastic anemia

1. Severe apl astic anemia is defined if at last two of the following
criteria are present:
 ANC < 0.5 G/l
 PLT < 20 G/l
 RTC < 1% (20 G/l)
Hypoplastic b one marrow (less than 25 %) on biopsy

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2. Very severe aplastic anemia

- criteria as above but ANC < 0.2 G/l
3. Non -severe aplastic anemia
Aplastic Anemia - Treatment
 Withdrawal of etiological agents.
 Supportive.
 Restoration of marrow act ivity:
 Bone marrow transplant
 Immunosuppressive treatment
- Prednisolone - Antilymphocyte glob.
- Cyclosporin - Anti T cells abs.
- Splenectomy
 Androgens
 Growth factors
 Supportiv care
 Transfusion
 Treatment of anemia
 Treatment of bleeding
 Pr evention and treatment of infection

APLASTIC ANEMIA – complications

 Infections
 Bleeding
 Iron overload
 Complications of BMT
 Graft versus host disease
 Graft failure


رفعت المحاضرة من قبل: Ahmed monther Aljial
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