ANEMIA

Clinical Findings
➢ From the Greek word “anaimia”
➢ History and physical examination
meaning “without blood”
are important components in
➢ A decrease in the number of
clinical diagnosis
erythrocytes or hemoglobin,
➢ Fatigue and shortness of breath are
resulting in decreased oxygen
the classic symptoms of anemia
delivery to the tissues
➢ History such as:
➢ Anemias can be classified
- Diet
morphologically using RBC indices:
- MCV - Drug ingestion
- MCH - Exposure to chemicals
- Occupation
- MCHC
➢ They can also be classified based - Hobbies
on etiology/cause - Travel
➢ Anemia is suspected when the Hgb - Bleeding disorders
is <12g/dL in men or <11g/dL in - Ethnic group
women - Family history of disease
Note! – 13 g/dL in men and 12g/dL - Jaundice
in women in some books Relative (pseudo) Anemia

➢ RBC mass is normal, but plasma

volume is increased
➢ Secondary to an unrelated
condition and can be transient in
nature
➢ Causes include conditions that
result in hemodilution, such as
pregnancy and volume overload

Absolute Anemia

➢ RBC mass is decreased, but

plasma volume is normal. This is
indicative of a true decrease in
erythrocytes and Hgb
 - Intrinsic/Extrinsic

Anemia of Impaired or Defective

Production

1. Iron Deficiency Anemia (IDA)

➢ Most common form of anemia in
the US
➢ Prevalent in infants and children,
pregnancy, excessive menstrual
flow, elderly with poor diets,
Mechanics Involved Include malabsorption syndromes, chronic
blood loss (GI blood loss,
➢ Decreased delivery of red cells into hookworm infections)
circulation
➢ Laboratory:
- Caused by impaired or
• Decreased in:
defective production
- Microcytic/hypochromic
- Bone marrow fails to respond;
anemia
reticulocytopenia
- Serum iron
➢ Increased loss of red cells from the
- Ferritin
circulation
- Hemoglobin/hematocrit
- Caused by acute bleeding or
- RBC indices
accelerated destruction
- Reticulocyte count
(hemolytic)
• Increased in
- Bone marrow can respond;
- RDW
reticulocytosis
- Total iron binding capacity
Causes of Anemia fall into 3 (TIBC)
categories: ➢ Note! – smear shows
ovalocytes/pencil forms
1. Impaired Red Cell Production
- Aplastic anemia
- Iron deficiency anemia
- Sideroblastic anemia
- Anemia of chronic disease
- Megaloblastic anemia
2. Blood Loss
- Acute
Clinical symptom: - fatigue, dizziness,
- Chronic
pica, stomatitis, (cracks in the corners of
3. Accelerated Red Cell
mouth), glossitis (sore tongue) and
Destruction (Hemolysis)
koilonychias (spooning of the nails)
- Inherited defects
- Acquired disorders
 2. Anemia of Chronic Disease
(ACD)
➢ Due to an inability to use available
iron for Hgb production
➢ Impaired release of storage iron
associated with increased hepcidin
levels
➢ HEPCIDIN – liver hormone and a
positive acute phase reactant. It
plays a major role in body iron
regulation by influencing intestinal
iron absorption and release of
storage iron from macrophages
➢ Inflammation and infections
causes hepcidin levels to increase;
this decreases release of iron from
stores
➢ Anemia of chronic disease is
second only to iron deficiency as a
common cause of anemia

3. Sideroblastic Anemia
➢ Caused by blocks in the
protoporphyrin pathway resulting in
defective Hgb synthesis and iron
overload
➢ Excess iron accumulates in the
mitochondrial region of the
immature erythrocytes in the bone
marrow and encircles the nucleus; Two types of Sideroblastic Anemia
cells are called Ringed
1. Primary
Sideroblasts
- Irreversible; cause of the
➢ Excess iron accumulates in the
block’s unknown
mitochondrial region of the mature
- Two RBC populations
erythrocytes in the circulation; cells
(dimorphic) are seen
are calles Siderocytes; inclusions
- One of the myelodysplastic
are sideotic granules
syndromes – refractory
(Pappenheimer bodies on Wright’s
anemia with ringed
stained smear)
sideroblasts
➢ Siderocytes are best demonstrated
using Perl’s Prussian blue stain
 2. Secondary ➢ Hematologic findings are
- Reversible; causes include insignificant
alcohol, anti-tuberculosis
Myelophythisic (Marrow Replacement
drugs, chloramphenicol
Anemia)
Laboratory: microcytic/hypochromic
➢ Hypoproliferative anemia caused
anemia with increased ferritin and serum
by replacement of bone marrow
iron, TIBC is decreased
hematopoietic cells by malignant
Lead Poisoning cells or fibrotic tissue
➢ Associated with cancers (breast,
➢ Multiple blocks in the
prostate, lung, melanoma) with
protoporphyrin pathway affect
bone metastasis
heme synthesis
➢ Seen mostly in children exposed to
4. Megaloblastic Anemia
lead-based paint
➢ Defective DNA synthesis causes
➢ Clinical symptoms: abdominal
abnormal nuclear maturation; RNA
pain, muscle weakness, and a gum
synthesis is normal, so the
lead line that forms from blue/black
cytoplasm is not affected
deposits of lead sulfate
➢ The nucleus matures slower that
➢ Laboratory:
the cytoplasm (asynchronism)
normocytic/normochromic anemia
➢ Megaloblastic maturation is seen
with characteristic coarse
caused by either a:
basophilic stippling
- Vit. B12 deficiency
- Folic acid deficiency
➢ Laboratory:
- Pancytopenia
- Macrocytic/normochromic
anemia with oval macrocytes
and teardrops
- Hypersegmented neutrophils
Porphyrias ➢ Inclusions include:
- Howell-Jolly Bodies
➢ These are a group of inherited
- Nucleated RBCs
disorders characterized by a block
- Pappenheimer Bodies
in protoporphyrin pathway of heme
- Cabot Rings
synthesis. Heme precursors before
➢ Elevated LD, bilirubin, and iron
the block accumulate in the
levels due to destruction of
tissues, and large amounts are
fragile,megaloblastic cells in the
excreted in the urine and/or feces
blood and bone marrow
➢ Clinical symptoms:
photosensitivity, abdominal pains,
CNS disorders
Vitamin B12 Deficiency (cobalamin) methotrexate. Folic acid has low
body stores.
➢ Intrinsic factor is secreted by
paritela cells and is needed to bind Non – Megaloblastic Anemias
vitamin B12 for absorption into the
➢ Include alcoholism liver disease
intestine
and conditions that cause
- Pernicious Anemia – caused
accelerated erythropoiesis
by deficiency of intrinsic
➢ The erythrocyte are round, not oval
factor, antibodies to intrinsic
as seen in megaloblastic anemia
factor, or antibodies to
parietal cells
5. Aplastic Anemia
- Prevalent in older adults of
➢ Bone marrow failure causes
English, Irish, and
pancytopenia
Scandinavian descent
➢ Laboratory: decrease in Hgb/Hct
- Characterized by
and reticulocytes;
achlorhydria and atrophy of
normocytic/normochromic
gastric parietal cells
anemia; no response to
- Other causes of vit.B12
erythropoietin
deficiency include
➢ Most commonly affects people
malabsorption syndrome,
around the age of 50 and above. It
Diphyllobothrium latum
can occur in children.
tapeworm infection, total
➢ Patients have a poor prognosis with
gastrectomy, intestinal blind
complications that include
loops and total vegetarian
bleeding, infection and iron
diet.
overload due to frequent
- Clinical symptopms:
transfusion needs
;jaundice, weakness, and
➢ Treatment includes bone marrow
other CNS problems
transplant and
- Vit.B12 deficiency takes 3-6
immunosuppression
years to develop because oh
high body stores Aplastic Anemia can be Genetic,
Idiopathic, or Acquired
Folic Acid Deficiency
Genetic Aplastic Anemia (Fanconi
➢ Causes a megaloblastic anemia
Anemia)
with a blood picture and clinical
symptoms similar to vit.B12 except ➢ Autosomal recessive trait
that there is NO CNS ➢ Dwarfism, renal disease, mental
INVOLVEMENT retardation
➢ It is associated with poor diet, ➢ Strong association with malignancy
pregnancy, or chemotherapeutic development, especially ALL.
anti-folic acid drugs such as
 Idiopathic Anemia (Primary) Onset of <1 yr of age 5-10 yrs of
hematologi age
➢ 50-70% aplastic anemias have no
c
known cause
abnormalit
Acquired Aplastic Anemia (Secondary) ies
Bone Cellular Hypoplasti
➢ Antibiotics: chloramphenicol and
marrow c to
sulfonamides
biopsy aplastic
➢ Chemicals: Benzene and
Bone Marked Pancytope
herbicides
marrow decrease nia
➢ Viruses: B19 parvovirus secondary
aspirate only in
to hepatitis, measles, CMV and EBV
erythroid
➢ Radiation or chemotherapy
precursors
➢ Myelodysplastic syndrome,
Peripheral Decrease Pancytope
leukemia, solid tumors, PNH
blood in RBC, nia
Diamond – Blackfan Anemia normal
WBC and
➢ True red cell aplasia (leukocytes
Plts
and plts normal in number)
Cytogeneti No Multiple
➢ Rare congenital anemia of unknown
cs associated chromoso
etiology (autosomal inheritance)
abnormalit mal
➢ Evident in the first 3 months of life
ies abnormalit
➢ Anemia is severe and erythropoietin
ies in many
resistant
tissues
➢ The reticulocyte count does not rise

Lab Diamond Fanconi

Blood Loss Anemia
Features Blackfan Anemia
Anemia Acute Blood Loss Anemia
Hematolog Congenital Congenital
➢ Characterized by a sudden loss of
ic pure red aplastic
blood resulting from trauma or
classificati cell aplasia anemia
other severe forms of injury
on
➢ Clinical symptoms: hypovolemia,
Brown skin Uncommo Common
rapid pulse, low blood pressure,
pigmentati n
pallor.
on
➢ Laboratory:
Thumb Uncommo Common
- Normocytic, normochromic
abnormalit n
anemia
ies
- Initially normal reticulocyte
Renal Uncommo Common
count, Hgb/Hct
abnormalit n
ies
 - In a few hrs, increase in Plt
count
- Leukocytosis w/ a left shift
- Drop in Hgb, Hct, and RBC
- Reticulocytosis in 3-5 days

Chronic Blood Loss Anemia

➢ Characterized by a gradular, long

term loss of blood; often caused by
gastrointestinal bleeding Hereditary Elliptocytosis (ovalocytes)
➢ Laboratory:
➢ Autosomal dominant
- Initially
➢ Most persons asymptomatic due to
normocytic/normochromic
normal erythrocyte life span
anemia that over time causes
➢ 25% ovalocytes on peripheral blood
a decrease in Hgb/Hct
smear
- Gradual loss of iron causes
➢ Membrane defects is caused by
microcytic/hypochromic
polarization of cholesterol at the
anemia
ends of the cell rather than around
Hemolysis pallor area
Hemolytic Anemias Due to Intrinsic Hereditary Stomatocytosis
Defects
➢ Autosomal dominant; variable
➢ All cause a degree of anemia
normocytic/normochromic ➢ Up to 50% stomatocytes on the
anemia blood smear
➢ Usually hereditary w/ ➢ Membrane defect due to abnormal
reticulocytosis due to accelerated permeability both to sodium and
destruction potassium
➢ Causes erythrocyte swelling
Hereditary Spherocytosis
Hereditary Acanthocytosis
➢ Most common membrane defect
(abetalipoproteinemia)
➢ Autosomal dominant
➢ Characterized by splenomegaly ➢ Autosomal recessive
➢ Increased, permeability of the ➢ Mild anemia associated with
membrane to sodium steatorrhea
➢ Neurological and retinal
abnormalities of erythrocytes are
acanthocytes
➢ Increased cholesterol lecithin
ration in the membrane due to
 abnormal lipid concentrations;
absence of serum beta-lipoprotein
needed for transport

G6PD (Glucose 6 Phosphate

Dehydrogenase) Deficiency

➢ Sex-linked enzyme defect

➢ Most common enzyme deficiency in
the hexose monophosphate shunt
Paroxysmal Nocturnal Hemoglobinuria
➢ Reduced glutathione levels are not
(PNH)
maintained because of decreased
NADPH (Nicotinamide adenine ➢ Acquired membrane defect in
dinucleotide phosphate) generation which the red cell membrane has
➢ Result in oxidation of Hgb to an increased sensitivity for
methemoglobin (Fe3+) complement binding as compared
➢ Denatures to form Heinz bodies to normal RBCs
➢ Etiology unknown
Pyruvate Kinase (PK) Deficiency
➢ All cells are abnormally sensitive to
➢ Autosomal recessive lysis by complement
➢ Most common enzyme deficiency in ➢ Ham’s and Sugar water tests used
Embden Meyerhof Pathway in diagnosis, flow cytometry is the
➢ Lack of ATP causes impairment of standard method
the cation pump that controls
Hemolytic Anemias Due to Extrinsic
intracellular sodium and potassium
Immune Defects
levels
➢ Decreased erythrocyte ➢ All cause a
deformability reduces their life normocytic/normochromic anemia
span due to defects extrinsic to RBC
➢ Severe hemolytic anemia with ➢ All are required disorders that
reticulocytosis and echinocytosis cause accelerated destruction with
reticulocytosis

Warm Autoimmune Hemolytic Anemia

(WATHA)

➢ RBCs are coated with IgG or

complement
➢ Macrophages phagocytize these
RBCs, or they may remove the
antibody or complement from the
RBCs surface, causing membrane
loss and spherocytes
 Cold Autoimmune Hemolytic Anemia intravascular hemolysis that is
(CAIHA or cold hemagglutinin disease) complement induced:
a. Usually, IgM antibodies
➢ RBCs are coated with IgM and
b. Can trigger DIC due to release
complement at temperature below
of tissue factor from lysed
37c
RBCs
➢ RBCs are lysed by complement or
➢ Laboratory: positive DAT, increased
phagocytized by macrophages
plasma Hgb
➢ Antibody is usually anti-I but can be
anti-I Hemolytic Disease of the Newborn
(HDN)
Paroxysmal Cold Hemoglobinuria
(PCH) ➢ RH negative woman is exposed to
Rh antigen from fetus and forms IgG
➢ An IgB biphasis Donath-
antibodies
Landsteiner antibody with P
➢ These antibodies will cross the
specific fixes complement to RBCs
placenta and detroy RBCs of the
in the cold (< 20c); the
next fetus that is Rh positive
complement-coated RBCs lyse
when warmed to 37c
➢ Laboratory: variable anemia
following hemolytic process;
increased bilirubin and plasma
Hgb, decreased haptoglobin; DAT
may be positive, Donath-
Landsteiner test positive

Hemolytic Transfusion Reaction ➢ Laboratory: severe anemia, nRBCs,

➢ Recipient has antibodies to positive DAT; very high bilirubin
antigens on donor RBCs levels cause kernicterus leading to
➢ Donor cells are destroyed by ABO brain damage
incompatibility causes and ➢ Exchange transfusions in utero or
immediate reaction with massive shortly after birth
 ➢ No longer a common problem with
the use of Rh immunoglobin
(RhoGam)
➢ May be due to ABO incompatibility

Hemolysis Anemia Due to Extrinsic

Non – Immune Defects

➢ All cause a
normocytic/normochromic anemia
caused by trauma to the RBC
➢ All are acquired disorders that
cause intravascular hemolysis with
schistomacytes and
thrombocytopenia

Microangiopathic Hemolytic Anemias Other causes

(MAHAs)
➢ Mechanical trauma, caused by
➢ Group of disorders characterized by prosthetic heart valves (Waring
RBC fragmentation, hemolysis and blender syndrome), chemicals,
anemia drugs and snake venom, damage
➢ Term that is used to describe the the RBCs through various
anemia that results from physical mechanisms
damage to the red cells following ➢ Thermal burns (3rd degree) cause
the occlusion of arterioles and direct damage to the RBC
capillaries as a result of fibrin membrane, producing acute
deposition or platelet aggregation hemolysis, which is characterized
by severe anemia with many
Disseminated Intravascular
schistocytes and micro-
Coagulation (DIC)
spherocytes.
➢ Systemic clotting is initiated by the
activation of the coagulation
cascade due to toxins or conditions
that trigger release of procoagulant
(tissue factor). Multiple organ
failure can occur due to clotting
➢ FIBRIN is deposited in small
vessels, causing RBC
fragmentation
 Key Laboratory Findings:

Anemia Laboratory
Findings
Normocytic / Normochromic
Antibody ↑ bilirubin, ↓
mediated haptoglobin, + DAT

PCH + Donath
Landsteiner
Antibody
Cold IgM Ab, + Cold
Agglutinin agglutinin
Disease
Warm
autoimmune IgG Ab

Hemolytic IgG Ab
Anemia

Anemia Laboratory Findings

Macrocytic
Vit. B12 ↓ Vit. B12, Retics,
Deficiency Pancytopenia, Oval
macrocytes
Hypersegmentation
Polys
Schilling test corrected
with intrinsic factor
(IF), anti-IF
Folate ↓ folate levels, Anti-IF,
Deficiency ↓ Retics, Oval
-Dietary macrocytes,
-Increased Hypersegmentation
need polys
Liver ↑ liver enzymes, target
Disease / cells, round
Alcoholism macrocytes
 3. Hgb E is the third most
common

Sickle Cell Disease (Hgb SS)

➢ Sickle cell disease is caused when

valine replaces glutamic acid at
position 6 on both beta chains. It
results in a decrease in Hgb
solubility and function.
➢ Defect is inherited from both
parents
➢ Characterized with the production
of:
1. Hb S
HEMOGLOBINOPATHIES 2. Anemia
THALASSEMIA 3. Acute and chronic tissues
damage secondary to the
Hemoglobinopathies blockage of blood flow
➢ A group of inherited disorders produced by abnormally
causing structurally abnormal shaped RBCs.
globin chain synthesis due to amino
acid substitution (qualitative
defect)
➢ Changes in RBC deformability and
electrophoretic mobility can occur
➢ Homozygous/disease conditions
(both globin chain affected) are
more serious than
heterozygous/trait conditions (only
globin chain affected)
➢ Target cells are associated with the
Sickle Cell Disease (Hgb SS)
hemoglobinopathies
➢ Hgb electrophoresis, isoelectric • Most common form of
focusing and/or DNA hemoglobinopathies
➢ (PCR) analysis may be used to • No Hgb A is produced, and
confirm the diagnosis approximately 80% Hgb S and 20%
➢ The amino acid substitution Hgb F (the compensatory
causing formation of: hemoglobin) are seen. Hgb A2 is
1. Hgb S is the most common variable.
2. Hgb C the second most • Hgb S is deoxygenated, it becomes
common polymerized and produces sickling.
• When sickled cells receive oxygen, • All organs are affected, with
they return to their normal shape. kidney failure being a common
The repeated cycle of sickling and outcome; hyposplenism and joint
unsickling lead to RBCs becoming swelling may also occur.
permanently damaged. This process
Sickle Cell Disease (Hgb SS)
ends in hemolysis.
• The membrane of a sickle cell has an Clinical findings:
excessive increase of ionized
• SS homozygotes have a severe
calcium.
hemolytic anemia
Sickle Cell Disease (Hgb SS) • Found most commonly in
persons of African ancestry
• Polymerization of Hgb S occurs
• Apparent immunity to
under reduced oxygen and
Plasmodium falciparum
promoted by the following:
• The median age at death is 42
➢ 1. Low Oxygen Tension
years for men and 48 for women
➢ 2. Increased 2,3 DPG
(Diphosphoglycerate) Sickle Cell Trait (Hgb As)
➢ 3. High Cellular Concentration of
Hemoglobin • Sickle Cell Trait is caused when
➢ 4. Cell Water Loss valine replaces glutamic acid at
➢ 5. Hgb C, Hgb O-Arab position 6 on one beta chain
• Sickle cell is retarded by: • Defect is inherited from one
➢ 1. Hgb A parent (Hgb S).
➢ 2. Hgb F (at least 30%) • One normal beta chain can
➢ 3. Hgb J produce some Hgb A
➢ 4. Alpha Thalassemia • Approximately 60% Hgb A and
40% Hgb S produced, with normal
Sickle Cell Disease (Hgb SS) amounts of Hgb A2 and F.
Clinical findings: • This heterozygous trait is the most
common hemoglobinopathy in
• Erythrocytes become rigid and the US
trapped in capillaries; blood flow • The PBS of a patient shows
restriction causes lack of oxygen normal RBC morphology with few
to the tissues, resulting in tissue target cells.
necrosis • Positive hemoglobin solubility
• Vacoocclusion: The adherence of screening test
sickled erythrocytes to the • Apparent immunity to
vascular endothelium and causes Plasmodium falciparum
painful crises. It develops
between the ages of 12 months
and 6 years.
 Hgb C Disease/ Hgb CC from the other parent are
inherited
• HgbC disease is caused when
• Seen in African, Mediterranean
lysine replaces glutamic acid at
and Middle Eastern populations;
position 6 on both beta chains.
symptoms less severe than sickle
• Defect is inherited from both
cell anemia but more severe than
parents
Hgb C disease
• Occurs in the African-American
• No Hgb A is produced
and African Populations
approximately 50% Hgb S and
• No HgbA is produced;
50% Hgb C are produced.
approximately 90% Hgb C 2%
Compensatory, Hgb F may be
HgbA2 and 7% HgbF are
elevated up to 7%.
produced.
• Infection with S. pneumoniae is
• Hgb C does not alter RBC shape
common
to the extent that Hgb S does (no
vasoocclusive) Laboratory:
• Mild anemia may be present
• 1. Moderate to severe normocytic
• No specific treatment is required
/ normochromic anemia with
unless it leads to gallbladder
target cells.
disease due to hemolysis
• 2. Characterized by SC crystals
Hgb C Disease/ Hgb CC appear as "hand in glove" or
"Washington monument"
Laboratory:
• 3. May see rare sickle cells or C
• Normochromic/normocytic crystals
anemia with target cells. • 4. Positive hemoglobin solubility
• characterized by intracellular screening test.
rodlike C crystals.
OTHER
• HgbC migrates with hemoglobins
A2, E and O on alkaline HEMOGLOBINOPATHIES
electrophoresis; can differentiate
Hemoglobin E
hemoglobins using acid
electrophoresis. • Caused when lysine replaces
• Negative in hemoglobin solubility glutamic acid at position 26 on
test. the beta chain.
• Found more commonly in
Hgb SC Disease
Southeast Asian, African and
• Hgb SC disease is double African*American population
heterozygous condition where an • Hgb F migrates with hemoglobins
abnormal sickle gene from one A2, C, and 0 on alkaline
parent and an abnormal C gene electrophoresis.
 Hemoglobin D THALASSEMIAS
• Caused when glycine replaces • Group of inherited disorders
glutamic acid at position 121 on causing decreased rate of
the beta chain commonly Middle synthesis of a structurally normal
Eastern and Indian populations. globin chain (quantitative defect)
• Both homozygous and • Characterized by
heterozygous conditions are microcytic/hypochromic RBCS
asymptomatic. and target cells.
• Hgb D migrates with Hgb S and • Autosomal inherited (dominant or
Hgb G during alkaline recessive)
electrophoresis. • Globin structural genes are
Variants: located on Chromosomes 11 and
16
• 1. Hb D-Punjad • Alpha chain and Zeta chain is in
• 2. Hb D-Los Angeles chromosome 16
Hemoglobin C-Harlem (Hgb C- • Non-alpha chains are in
Georgetown) chromosome 11.
• Classified according to the globin
• Substitution of valine for glutamic chain affected / Found in
acid at the 6 the position of beta Mediterranean (beta), Asian
chain, identical with Hgb S (alpha), and African (alpha and
• Hgb C-Harlem migrates with Hb C beta) population
on cellulose acetate • Severity varies from no clinical
electrophoresis at alkaline pH. abnormalities to transfusion-
• Positive in Hemoglobin solubility dependent to fatal
test.
Thalassemia major:
Hemoglobin O-Arab
• Severe anemia; either no alpha or
• Substitution of lysine for glutamic no beta chains produced
acid at the 121st amino acid
position. Thalassemia minor/trait:
• Inherited with Hgb S • Mild anemia; sufficient alpha and
• Rare disorder in Kenya, Egypt and beta chains produced to make
Israel. normal hemoglobins A1, A2, and
• Migrates with Hgb A2, Hgb C and E but may be in abnormal
Hgb E
• No clinical symptoms
• No Treatment
 BETA-THALASSEMIAS ➢ Heinz bodies
➢ Increased serum iron
• Decrease or absent production of
➢ Increased bilirubin reflect the
Beta Chains
hemolysis
• Increase Hgb A2 and F, Hgb A
decrease or absent Minor/Heterozygous
• Microcytic and hypochromic
• Decreased rate of synthesis of
anemia
one of the beta chains; other beta
Major/Homozygous (Cooley Anemia) chain normal

• Markedly decreased rate of Laboratory:

synthesis or absence of both beta
• 1. Mild microcytic/hypochromic
chains results in an excess of
anemia with a normal or slightly
alpha chains; no Hgb A can be
elevated RBC count
produced; compensate with up to
• 2. Target cells
90% Hgb F.
• 3. Basophilic stippling
• Excess alpha chains precipitate
• 4. Hgb A is slightly decreased, but
on the RBC membrane, form
HgbA2 is slightly increased to
Heinz bodies, and cause rigidity;
compensate
destroyed in the bone marrow or
removed by the spleen. Alpha-Thalassemia
• Symptomatic by 6 month of age;
➢ Decrease production of alpha
➢ 1. Hepatosplenomegaly –
chains
enlargement
➢ 2. Stunted growth. Note!
➢ 3. Jaundice
➢ A. 1 deleted alpha gene (-a/a a)
➢ 4. Prominent facial bones,
➢ Silent carrier; normal CBC
especially the cheek and jaw
➢ B. 2 deleted alpha genes (- a/- a)
➢ 5. Iron overload from RBC
or (- -/a a)
destruction and multiple
➢ Mild microcytic, hypochromic
transfusion cause organ failure.
anemia
Laboratory: ➢ C. 3 deleted alpha genes (--/- a):
➢ Hemoglobin H disease
➢ Severe microcytic/hypochromic
➢ Chronic hemolytic disease...
anemia
➢ Нb Н (BA)
➢ Target cells
➢ Hb Bart's (Y4) present at birth.
➢ Teardrops,
➢ Hb H inclusions (Heinz
➢ Many nRBCs.
bodies)
➢ Basophilic stippling
➢ D. 4 deleted alpha genes (--/-) - no
➢ Howell-Jolly bodies
life
➢ Pappenheimer bodies.
➢ Hydrops fetalis
➢ Nonviable fetus • Up to 6% Hgb Bart's in newborns
may be helpful in diagnosis;
Silent Carrier
absent by 3 months of age
• One alpha gene is deleted. • Mild microcytic/hypochromic
Patients are asymptomatic and anemia often with a high RBC
are often not diagnosed unless count and target cells
gene analysis is done.
Thalassemia/Hemoglobinopathy
• Borderline low MCV may be the
Interaction
only sign...
• Caused by the inheritance of a
Hgb H Disease
thalassemia gene from one
• Three alpha genes are deleted; parent and a hemoglobin variant
decrease in alpha chains leads to gene from the other parent
beta chain excess. • Severity and symptoms depend
• Hemoglobin H, unstable on the specific interactions
hemoglobin is produced. Heinz • Common interactions include
bodies form and rigid RBCs are HgbS/beta-thalassemia,
destroyed in the spleen. HgbC/beta thalassemia, and
• Distinguishing characteristics HgbE/beta thalassemia.
include:
➢ 1. moderate microcytic
hypochromic anemia
➢ 2. up to 30% Hgb H: the rest is
HbA.

Major (hydrops fetalis)

• All four alpha genes are deleted;

no normal hemoglobins are
produced.
• 80% hemoglobin Bart's
produced; cannot carry oxygen;
incompatible with life; die in utero
or shortly after birth.

Minor/Trait

• Two alpha genes are deleted.

• Patients are usually
asymptomatic and discovered
accidentally.