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Clinical Hematological Assist Prof. Dr. Clinical Hematological Assist Prof. Dr.

Clinical Hematological Assist Prof. Dr. - PowerPoint Presentation

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Clinical Hematological Assist Prof. Dr. - PPT Presentation

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

cells anemia red cell anemia cells cell red aplastic blood immune stem deficiency marrow increased hemolytic disease protein membrane

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Slide1

Clinical Hematological

Assist Prof. Dr.

Mudhir

S.

Shekha

Slide2

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

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

Slide3

Etiologic 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.

Slide4

Pathogenesis 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.

Slide5

Fanconi

anemia

Slide6

Phases 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.

Slide7

Phases 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.

Slide8

Clinical Features

Signs & symptoms of :

Anemia

Bleeding:

Ecchymoses

,Bleeding gums, Epistaxis

Infections: Fever, Mouth ulcers

Slide9

Fanconi

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

Slide10

Diagnosis 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.

Slide11

Serum 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.

Slide12

Within 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)

Slide13

BM Aspiration

BM Biopsy

Slide14

Aplastic 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

Slide15

Slide16

Hemolytic 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

Slide17

The 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.

Slide18

CausesIntrinsic 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

Slide19

Diagnosis

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

Slide20

Hereditary 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 hemolysisTreatmentSplenectomy (non-hereditary spherocytosis) and Partial splenectomy, Cholecystectomy

Slide21

Red 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

Slide22

Slide23

Diagnosis

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