Mudhir S Shekha Aplastic anemia Aplastic anemia was first described by Paul Ehrlich in 1888 from an autopsy of a young pregnant woman Aplastic anemia an unusual hematologic disease is either ID: 908907
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Slide1
Clinical Hematological
Assist Prof. Dr.
Mudhir
S.
Shekha
Slide2Aplastic anemia
Aplastic anemia
was first described by Paul Ehrlich in 1888 from an
autopsy
of a young pregnant woman. Aplastic anemia, an unusual hematologic disease, is either
acquired
or
congenital
in etiology.
Aplastic anemia is one of a group of disorders, known as
hypoproliferative
disorders (
Pancytopenia
), that are characterized by
reduced
growth
or
production
of blood cells. The other anemias in this category include those caused by
deficiencies of erythropoietin
Slide3Etiologic Classification of Aplastic Anemia
1.
Cytotoxic
drugs, organic solvents ( benzene ), fumes, (
lindane
, glue vapors), radiation.
2.
Idiosyncratic
drug reactions: • Chloramphenicol, • Gold, •
Phenylbutazone
,
Indomethacine
, • Sulfa, • Anti-epileptic drugs, • Arsenicals.
3.
Viral
Infections: • Parvovirus B 19 – pure red cell aplasia, • Hepatitis: Non-A, non-B, non-C • HIV, • EBV
4.
Immune
disorders: • Eosinophilic fasciitis, • SLE, • GVH
5.
Miscellaneous
: • Paroxysmal Nocturnal Hemoglobinuria (PNH) , survival of a more adaptive stem cell population. •
Thymoma
and
Thymic
Carcinoma – mostly pure Red Cell aplasia.’ • Pregnancy, most likely immune.
Slide4Pathogenesis Potential mechanisms:
Absent or
defective stem
cells (stem cell failure).
Abnormal
marrow micro-environment
.
Inhibition by an
abnormal clone of
hemopoietic
cells.
Immune mediated
suppression of hematopoiesis
.
It is believed that
genetic factors
play a role. There is a higher incidence with
HLA (11)
histo
-compatibility Antigen. Immune mechanism is involved.
The latest theory is: there is an
intrinsic derangement of
hemopoietic
proliferative capacity
, which is consistent with life. The immune mechanism autoreactive T cells 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.
Slide5Fanconi
anemia
Slide6Phases of Aplastic Anemia
Phase 1
:
Onset
of Disease After an
initiating
event (e.g., viral infection), the
hematopoietic
compartment is
destroyed
by the
immune
system.
Small numbers of surviving stem cells support adequate hematopoiesis for some time, but eventually the circulating cell counts become very low and clinical symptoms appear.
Slide7Phases of Aplastic Anemia
Phase 2
:
Recovery
Either a
partial
response or a
complete
response can occur, at least initially,
without
increased numbers of stem cells
.
In a minority of patients, the primitive-cell compartment appears to repopulate over time by the process of self-renewal of stem cells.
Phase 3
: Late Disease Years after recovery, blood
counts
may
fall
as a
relapse of pancytopenia
occurs, or an abnormal clone of stem cells may emerge, leading to a new diagnosis of
PNH
,
MDS
, or AML.
Slide8Clinical Features
Signs & symptoms of :
Anemia
Bleeding:
Ecchymoses
,Bleeding gums, Epistaxis
Infections: Fever, Mouth ulcers
Slide9Fanconi
anemia
Fanconi
anemia
(FA) is a rare genetic disease resulting in impaired response to DNA damage &
result of a genetic defect in a cluster of proteins responsible
for DNA repair. This is the
most common inherited form of
aplastic
anemia
Slide10Diagnosis of Aplastic AnemiaA diagnosis of severe aplastic anemia is made when at least
two
of the
three
peripheral blood values
fall below
critical levels:
granulocytes
less than 0.5 × 109/L,
platelets
less than 20 × 109/L, or
reticulocytes
less than 1.0% in the presence of anemia.
The bone marrow is either significantly or moderately
hypo-cellular
, with less than
30% of residual hematopoietic cells
.
Most severely affected patients have neutrophil counts less than 2.0 × 109/L, platelet counts less than 20 × 109/L, or reticulocyte counts less than 0.6%.
Red blood cells usually are
normochromic
and
normocytic
. In some cases, there may be varying degrees of
anisocytosis
and
poikilocytosis
or
macrocytosis
. The red cell distribution width (
RDW
) is
normal
in
nontransfused
patients.
Leukopenia
with a significant
decrease
in
granulocytes
and a relative
lymphocytosis
are noticeable.
Thrombocytopenia
is typically present.
Slide11Serum iron
usually is
increased
; this is a valuable early sign of
erythroid hypoplasia
and reflects the decreased plasma iron turnover. In addition, the erythrocyte use of iron is decreased. Both effective and total erythropoiesis are decreased in aplastic anemia.
The bone marrow reveals very few early
erythroid
and
myeloid
cells at any stage of differentiation, and
megakaryocytes
are scanty if present at all.
Primitive progenitor
and
stem cells
, which normally constitute approximately
1% of marrow cells
, cannot be identified by their appearance.
If acute exposure to radiation is the inciting agent, the production of new red blood cells (
reticulocyte
count)
falls
, but the
RBC
decline
slowly
because of their long survival.
Slide12Within the first few hours
, there is a
neutrophilic leukocytosis
caused by a
shift
from the
marginal
and probably the
marrow storage pools as well
.
A
decrease
in
lymphocytes
occurs after the
1st day
and is
responsible for early leukopenia
.
After approximately
5 days
,
granulocytes
begin to
decrease
.
The
platelets
decrease
later. Platelets are often the last to return to normal in the
recovery phase
.
X-rays
, computed tomography (
CT
) scans, or
ultrasound
imaging tests:
enlarged lymph nodes
(sign of lymphoma),
kidneys
and
bones
in arms and hands
Vitamin B12
and folate levels: Vitamin deficiency
Viral studies
: viral infections (
Hep
A,B,C, CMV, EBV, HIV, ParvoB19)
Slide13BM Aspiration
BM Biopsy
Slide14Aplastic Anemia
Treatment
Identifying cause
Blood transfusions
Antibiotics
Immunosuppressants
(
neoral
,
sandimmune
)
Corticosteroids (Medrol,
solu-medrol
)
Bone marrow
stimulants
Filgrastim
(
Neupogen
)
Epoetin
alfa
(
Epogen, Procrit)Bone marrow transplantation
Slide15Slide16Hemolytic Anemias???
Destruction of red cells by a disease process either
intrinsic (
intravascular
)
or
extrinsic (
extravascular
)
to the cell
causes:
Shortened
red cell survival
Increased
erythropoiesis
Anaemia if erythropoiesis cannot keep pace with red cell destruction.
signs
of hemolytic
anemias
include:
pallor, fatigue, shortness of breath, and potential for heart failure
Treatment
blood transfusion, steroid, splenectomy
Slide17The haemolytic
anaemias
are a heterogeneous group of disorders which can be classified into
Haemoglobinopathies
— sickle cell disease
—
thalassaemia
membrane defects
— spherocytosis
—
elliptocytosis
red cell enzyme defects
— glucose 6-phosphate dehydrogenase deficiency
Autoimmune
Non-immune
—
Microangiopathic
haemolytic
anaemia
— Prosthetic heart valve
— Drug or toxin induced.
Slide18CausesIntrinsic causes
Defects of red blood cell membrane production
Defects in hemoglobin production
Defective red cell metabolism
Extrinsic causes
Immune-mediated causes
Paroxysmal nocturnal
hemoglobinuria
hypersplenism
burns
Lead poisoning
footstrike
hemolysis
Low-grade hemolytic anemia
Slide19Diagnosis
Peripheral blood smear microscopy
schistocytes
,
spherocytes
, Reticulocytes, Bite cells (Heinz body)
Increased LDH.
Increased indirect bilirubin (
unconjugated
).
Increased reticulocyte count
Decreased
haptoglobin
.
Haemosiderin
can be detected in urine.
direct Coombs test is positive
autoimmune hemolytic anemia
Haemaglobinuria
PNH
Slide20Hereditary Spherocytosis
Minkowski
–
Chauffard
syndrome
is a very
heterogeneous
form of hemolytic anemia transmitted in the majority of cases as an autosomal dominant trait; it is the most common prevalent hereditary hemolytic anemia among people of
Northern European descent
. It is not restricted to any single race. Manifestations of the disorder range from almost-normal carriers of the
trait
to cases of severe hemolytic anemia. Anemia may manifest itself anytime, from early infancy to later life.
HS
characterized
by the production of RBCs that are
sphere-shaped
rupture
why?? Duration Live??
Disorder
of a
structural protein in the cell membraneResults in splenic hemolysisTreatmentSplenectomy (non-hereditary spherocytosis) and Partial splenectomy, Cholecystectomy
Slide21Red Cell Membrane Protein Defects
Membrane loss in hereditary spherocytosis is as a result of
deficiency
or
dysfunction
of one or combined membrane
proteins
based on which the disease can be divided into subsets
Deficiency of
spectrin
Combined deficiency of
spectrin
and
ankyrin
Deficiency of
band 3 protein
Deficiency of
protein 4.2
Deficiency of
Rh complex
Undefined
protein abnormalities
Slide22Slide23Diagnosis
Reticulocyte
count
↓
The reticulocyte count is characteristically low at the onset, but will increase rapidly in the recovery period.
MCHC
↑
Other protein deficiencies cause hereditary
elliptocytosis
,
pyropoikilocytosis
or
stomatocytosis
.
Measuring iron stores is therefore considered part of the diagnostic approach to hereditary spherocytosis.
osmotic fragility test
Raptured increased permeability of the spherocyte membrane to salt and water.
Slide24