Clinical Hematological

Assist Prof. Dr. 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 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
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.
 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.
Fanconi anemia
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.
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.
Clinical Features
• Signs & symptoms of :
• Anemia
• Bleeding: Ecchymoses ,Bleeding gums,
Epistaxis
• Infections: Fever, Mouth ulcers
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
• Diagnosis of Aplastic Anemia
• A 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.
• 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.
• 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)
BM Aspiration BM Biopsy
 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
 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
The haemolytic anaemias are a heterogeneous group of disorders
which can be classified into

haemolytic anaemias

Congenital Acquired
• Haemoglobinopathies • Autoimmune
— sickle cell disease • Non-immune
— thalassaemia
• membrane defects — Microangiopathic
— spherocytosis haemolytic anaemia
— elliptocytosis — Prosthetic heart valve
• red cell enzyme defects — Drug or toxin induced.
— glucose 6-phosphate dehydrogenase
deficiency
Causes
Intrinsic 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
Diagnosis
1. Peripheral blood smear microscopy
schistocytes, spherocytes, Reticulocytes,
Bite cells (Heinz body)
2. Increased LDH.
3. Increased indirect bilirubin (unconjugated ).
4. Increased reticulocyte count
5. Decreased haptoglobin.
6. Haemosiderin can be detected in urine.
7. direct Coombs test is positive autoimmune
hemolytic anemia
8. Haemaglobinuria PNH
 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 membrane
• Results in splenic hemolysis
• TreatmentSplenectomy (non-hereditary spherocytosis) and
Partial splenectomy, Cholecystectomy
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
 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.