PURE RED CELL
APLASIA
By assistant lecture:
Waleed fouad
Definition
• Erythropoietic hypoplasia occurring in
the absence of abnormalities in the
leukopoietic
or
thrombocytopoietic
systems.
• The marrow is normally cellular but
devoid of erythroblasts.
Classification
Congenital (Diamond-Blackfan syndrome)
Acquired:
• Acute
• Chronic
Acquired forms
 Hemolytic Disorders (aplastic crisis)
 Infection parvovirus B19 and others
 Malnutrition
 Drug therapy
 Thymoma
 Immunoglobulin inhibitors (cytotoxic for erythroid
precursors, inhibitor of erythropoietin)
 Idiopathic or unknown orgin
Congenital (diamond-Blackfan syndrome)
Acute Acquired Pure
Red Cell Aplasia
Hemolytic Disorders
• In chronic hemolytic anemias, erythroblasts
may suddenly disappear from the marrow for a
short time.
• Transient
aplastic
crisis
occurs
when
reticulocytes disappear from the peripheral
blood and progressive anemia follows.
• These episodes often are accompanied by a
prodromal illness and usually are followed by
recovery, with return of reticulocytes in 7 to 10
days.
Transient erythroblastopenia
of childhood
• Reported in children in the course of various
infections or in association with malnutrition.
• It occurs most commonly in children between 1
and 4 years of age.
• Often associated with prodromal symptoms,
and is almost always self–limited, with complete
recovery in a few weeks.
• The presence of serum inhibitors of
erythropoiesis has been demonstrated.
Infections
• Acute arrest of erythropoiesis also has been
reported in adults during the course of:
 Respiratory infections.
 Gastroenteritis.
 Primary atypical pneumonia.
 Infectious mononucleosis.
 Mumps.
 Viral hepatitis.
 Parvovirus B19 infection.
Drugs
Aminosalicylic
acid
Phenylbutazone
Aspirin
co–trimoxazole
Sulfonamide
Isoniazid
Colchicines
Azathioprine
Heparin
Butabarbital
Diphenylhydantoin Halothane
Tolbutamide
Chlorpropamide
Aminopyrine
Complete recovery follows withdrawal of the drug.
Chronic Acquired Pure
Red Cell Aplasia
• It occurs in adults.
• A rare disease and only a few hundred
cases have been reported.
• It has been suggested that two forms
may exist:
Those associated with benign thymoma.
Those unassociated with thymic
abnormality.
Benign thymoma associated
cases
• More than 50% of the patients are
females.
• Myasthenia gravis was noted in 14% of
the patients in one series.
• Thymectomy may provide immediate
hematologic improvement in some
patients.
Non Benign thymoma
associated cases
• Noted more often in male patients than in
females (2:1).
• Has been associated with immunologic,
lymphoproliferative, and neoplastic disorders as
well as drug and toxic exposures.
• An etiology cannot be established in many
patients.
• Noted most often in the fifth to seventh
decades of life.
• Antibody-mediated pure red-cell aplasia is a
rare syndrome of anemia associated with a low
reticulocyte count, an absence of erythroblasts
in the bone marrow, resistance to recombinant
human erythropoietin (epoetin) therapy, and
neutralizing antibodies against erythropoietin.
• This syndrome was reported in patients who
had been receiving epoetin administered
subcutaneously.
Pathogenesis of acquired form
Two proposed theories:
• The first is called the "seed or stem cell-deficiency
theory". It proposes that a common stem cell
population is irreversibly altered, rendering it
incapable of proliferation and differentiation.
• The second theory is the "microenvironmental
deficiency theory", which proposes that the stem cell
environment (the marrow) is altered so as to inhibit
erythropoiesis.
Congenital Erythroid
Hypoplasia of Diamond–
Blackfan
• In 1938, Diamond and Blackfan described a
syndrome that they characterized as a slowly
developing
and
progressive
anemia,
beginning early in infancy, in which the
white blood cells and platelets were normal
and only red cell precursors in bone marrow
were deficient.
• 90% of cases are sporadic and are caused by
in utero damage to erythroid stem cells while
10% of patients have a dominant, or more
rarely recessive, familial pattern.
Manifestations
Anemia is the primary problem in PRCA.
The degree of anemia can range from
subclinical to severe according to type:
In acquired acute PRCA:
• Anemia is barely noticeable because the
decrease in the hemoglobin level is gradual and
self-limited.
• Evidence of a recent viral infection:
 Rash, jaundice in viral hepatitis.
 Splenomegaly in infectious mononucleosis.
 Enlarged parotid glands in mumps.
In acquired chronic PRCA:
• Evidence of anemia.
• Physical findings of underlying thymomas,
however, thymomas are rarely large enough to
be detected during the physical examination.
• Lymphadenopathy and splenomegaly may
indicate the presence of an underlying
lymphoproliferative disorder.
In congenital PRCA:
• Some, but not all cases are associated with
severe anemias.
• Anemia is often not observed during the early
neonatal period, but pallor, weakness, and
dyspnea develop during the first year of life.
• Physical abnormalities involving the head,
upper limbs, thumbs, urogenital system or
cardiovascular system may be detected.
Work up for a case of PRCA
Basic studies include:
• CBC counts.
• Reticulocyte count.
Studies to rule out hemolysis include:
• Lactate dehydrogenase.
• Indirect bilirubin.
• Serum haptoglobin.
In acute PRCA, rule out the
following:
•
•
•
•
•
Parvovirus B19 infection.
Infectious mononucleosis.
Atypical mycoplasmic pneumonia.
Mumps.
Viral hepatitis.
In acquired chronic PRCA, rule out
the following:
•
•
•
•
•
•
HIV infection.
Thymoma.
Chronic active hepatitis.
Systemic lupus erythematosus.
Autoimmune disorders (direct Coombs test).
Collagenvascular disorders.
For congenital PRCA
• Fetal Hgb and erythrocyte adenine
deaminase levels.
• Serum folate and vitamin B12 levels.
• Genetic testing.
• Peripheral smear results Can show
megaloblastic changes.
Bone marrow
• Bone marrow aspiration and biopsy
indicated to confirm the diagnosis.
are
• It usually reveals a selective depletion in RBC
precursors.
• In acute PRCA, bone marrow aspiration and
biopsy performed during the recovery phase
may yield misleading findings that suggest
active erythropoiesis.
• In congenital PRCA, megaloblastosis of
RBC precursors may be observed and
occasionally, a depression in the level of
megakaryocyte and WBC precursors
occurs.
• Findings from biopsy of a thymoma
usually reveal that the tumor is
encapsulated and contains primarily
spindle cells, with or without small
lymphocytes.
TREATMENT
Acute self-limited PRCA:
• Discontinue offending drugs and treatment of
associated infections or other illness.
• Transfusion therapy is not usually indicated
because of the self-limited nature of acute
PRCA.
• Transfusions may be indicated in patients
with hemolytic anemias who develop PRCA.
Acquired chronic PRCA:
• The underlying disorder should be treated.
• Corticosteroids can be effective, but a high dosage is
often required, and the adverse effects frequently
preclude using these agents.
• However, some patients respond to low doses of
corticosteroids.
• Prednisone can induce remission in approximately
45% of cases.
• If the underlying cause of PRCA is
immunological
and
the
response
to
corticosteroids has been inadequate, the next
level of treatment is with cytotoxic or
immunosuppressive drugs.
• Cyclophosphamide,
6-mercaptopurine,
azathioprine, and cyclosporine have all been
used.
• These drugs have been effective at dosages
sufficient to induce leukopenia.
Congenital PRCA
• Treatment is complicated because this condition is a
lifelong disorder, and the consequences of treatment
can have devastating effects on growth and sexual
maturity.
• Transfusion is an integral modality in treating
congenital PRCA.
• With severe anemia, patients can have a lifelong
dependency on transfusions.
• Two units of blood every 2 weeks is usually
sufficient.
• Aggressive chelation using deferrioxamine
infusions are critical to avoid hemosiderosis
because transfusion therapy is usually started
at a young age.
• Corticosteroids are also a principal
therapeutic option, and this therapy is
believed to allow the abnormal stem cells in
patients with congenital PRCA to become
more sensitive to growth factors.
• High doses of prednisone (1-2 mg/kg) are needed
but should not be continued for more than 4-6
weeks.
• If prednisone therapy fails,
methylprednisolone can be tried.
a
high-dose
• The major complications of corticosteroid therapy in
these patients are growth retardation, muscle
weakness, and osteopenia.
• Danazol and other androgens can be used in
refractory cases, but these agents may be
contraindicated in prepubertal children.
• Surgical Care: Surgical care may be
indicated if a thymoma is suspected or if the
patient has significant hypersplenism.
Prognosis
• Prognosis varies widely, depending on:
Etiology.
Underlying disorders.
Clinical course.
• Acute self-limited PRCA usually has
an excellent prognosis.
• Acquired chronic PRCA is associated
with a number of complications.
• Congenital PRCA is usually a lifelong
disorder and is associated with a high
morbidity rate due to the disorder and
the treatment adverse effects.
• Most patients survive through early
adulthood.
THANK YOU