ANEMIA

INTERNATIONAL MEDICAL SCHOOL

LECTURER: NAJIHAH MOHD BISRI

Learning outcome

At the end of this chapter, students are expected to

´ Define anemia
´ Explain causes of anemia
´ State symptoms and clinical signs of anemia
´ Elaborate pathophysiology of anemia
´ Explain investigations for anemia
´ Suggest treatment and management for anemia
Anaemia 1- RBC count < normal range men: 4-6 mil/mm3
woman: 4-5 mil/mm3
2- Hb < normal range men: 12-15 g/dL
woman: 13-17 g/dL

Etiology:
1. Blood loss - hemorrhage, heavy menstrual bleeding/ prolonged more than 14 days, GIT : bleeding
peptic ulcer, cancer
2. Decrease RBC production- chronic disease, hepatitis, chronic diabetes, production in hepcidin,
kidney failure(EPO not produce sufficiently), deficiency malnutrition (iron, folate, vit B12
3. Increased demand- does not have enough, happen during pregnancy (fetus require more nutrients
for its development) and breastfeeding
4. Inherited genetic mutation- thalassemia, sickle cell anemia, GGPD, spheroastosis

After 120 days, RBC will damage and will be replaced

General Symptoms
1. weak, exhaustion (fatique)
2. Pale Management and treatment
3. shortness of breathe ( reduce symptoms), (completely treating the disease
4. Dizziness, headache,
5. poor attention, fogginess (blur)
6. Tachycardia (severe anaemia)
7. Palpitation (check on pulse, strong and fast heartbeat)
Investigation
1.
2. Lab investigation (take specimen- blood antigulated blood cell and anti
coagulated serum)
a) CBC (complete blood count)- need blood to measure; RBC, WBC, platelet, HB,
hematocist
b) PBF (peripheral blood film)- observe morphology of the cell
c) Reticulocyte count (immature RBC younger than erythrocyte)- need special
stain that will highligt the cell, related to erythropoiesis count, low low, high
high
- Erythropoiesus rate= low, bone marrow failure, high, compensation
hemolytisease
4 Iron studiens- serum iron
Red Cell Production (Erythropoiesis)
Kidney Bone Marrow Multi-potent
stem cell
Epo
mRNA Erythroid
stem cell
Epo

Oxygen
sensor 3-4
days

Blood vessel Reticulocyte

Peripheral Erythrocyte

blood

RBC survival
100-120 days
 Anemia
´ Understanding anemia
´ Disease - to be treated on its own merits
´ Condition - a secondary manifestation of another disease

´ Causes
´ Decreased production
´ Blood loss
´ Hemolysis
Classification of Anemia

´ Clinical findings
´ Acute
´ Chronic

´ Red cell kinetics

´ Determined by reticulocyte count

´ Red cell size

´ Determined by MCV
Laboratory Evaluation of Anemia

´ Complete blood count

´ Reticulocyte count

´ Peripheral smear

Erythrocyte (RBC)- 120 days

Reticulocyte - 1 day convert to erythrocyte
- Erythropoiesis rate
Reticulocyte Count

´ Relative reticulocyte count

´ Percent of all RBC (normal 0.8-1.5%)

´ Absolute reticulocyte count

´ Relative reticulocyte count x RBC count
´ Normal 50,000-75,000/µl
´ Examples: 6
1.1% x 4.96 x10 = 55,000/µl
6
12.2% x 2.05 x10 = 250,000/µl
 Classification of Anemia Based on RBC
Kinetics and Size
Mean corpuscala volume

MCV
Microcytic Normocytic Macrocytic
(<80 fl) (80-97 fl) (>98 fl)

Retic Low Common Common Common

Count
High Uncommon Common Uncommon
 small cell Sikit less colour

Microcytic Hypochromic Anemia: Diagnosis

´ Mild (MCV > 70 fl) 70 - 79

´ Iron deficiency
´ Thalassemia
´ Lead toxicity
´ Sideroblastic anemia
´ Anemia of chronic disease

´ Severe (MCV < 70 fl) 50 - 69

´ Iron deficiency
´ Thalassemia
Iron Deficiency Anemia

´ A world-wide problem
´ 3% of toddlers age 1-2 years
´ 2-5% of women of child bearing age

´ Iron metabolism

´ Iron stores

´ Laboratory findings of iron deficiency

´ Causes of iron deficiency

´ Treatment
 Body Iron Distribution and Storage
Duodenum Dietary iron
(average, 1 - 2 mg
Utilization Utilization
per day)

Plasma
transferrin (TIBC)
(3 mg)
Bone
Muscle marrow
(myoglobin) Circulating (300 mg)
(300 mg) erythrocytes
Storage
iron (hemoglobin)
(Ferritin) (1,800 mg)

Sloughed mucosal cells

Desquamation/Menstruation
Other blood loss
(average, 1 - 2 mg per day) Reticuloendothelial
Liver
(1,000 mg) macrophages
Iron loss (600 mg)
 Major Iron Compartments
´ Metabolic
´ Hemoglobin 1800-2500 mg
´ Myoglobin 300-500 mg

´ Storage
´ Iron storage 0-1000 mg

´ Transit
´ Serum iron 3 mg

´ Total 3000-4000 mg
 Development of Iron Deficiency
Bone marrow Blood/ serum iron Symptoms
Iron status Ferritin BM iron Fe/TIBC Anemia

Depleted stores Low Absent Normal Absent

Liver start to release stored iron

Compromised delivery Low Absent Low/High Absent

Iron deficiency anemia Low Absent Low/High Present

Ferritin: The Best
Marker for
Iron Deficiency
Ferritin
µg/l

Bone Marrow Iron Stores

 Causes of Iron Deficiency
Iron deficiency is a symptom, not a disease
´ Increased iron ´ Inadequate iron supply
requirements ´ Insufficient dietary iron
´ Blood loss ´ Impaired iron absorption
´ Gastrointestinal tract ´ Gastric surgery
´ Genitourinary tract ´ Intestinal malabsorption
´ Blood donation ´ Celiac disease

´ Pregnancy and lactation

Systemic Manifestations of Iron Deficiency

´ Behavioral and ´ Esophageal webs and

neuropsychiatric strictures
manifestations
Changes in eating behaviour
´ Pica (pagophagia)

´ Angular
Inflammatin tepi stomatitis
bibir
Stomatitis
Koilonicya
´ Koilonychia - Spoon-like finger

Glossitis
- Red beefy
tongue,
thick
´ Glossitis tongue
Treatment with Oral Iron: General Principles

´ Ferrous salts are absorbed better than ferric

´ All ferrous salts are absorbed to the same extent

´ Ascorbic acid increases absorption and toxicity

´ Iron is absorbed best on an empty stomach

´ Iron should not be given with antacids

´ Iron polysaccharide complex (Niferex) seems to be better tolerated than iron

salts
Use of Parenteral Iron

´ Agents available
´ Iron dextran (total dose replacement, 1/300 anaphylaxis)
´ Iron polysaccharide (125 mg/d max, ~1/1000 anaphylaxis)
´ Indications
´ Malabsorption
´ Iron-limited response to erythropoietin
´ Toxicity/noncompliance with oral iron
´ Response
´ Maximal increase in hemoglobin synthesis
´ Rapid increase in iron stores
Thalassemia: Impaired Globin Gene
Production
Hgb A tetramer

a globin b globin

b globin a globin
 Globin Chain Synthesis

t
rio en
on ain

pe opm
d
mp ch

b lt
en
a cluster - chromosome 16

Hg adu
ve
e
co bin

am

De
o

of
bn
Gl
z a2 a1

%
Hg
Gobo 1
z2e2 Gower 1

z2g2 Portland Embryonic

a2e2 Gower II

a2g2 F Fetal < 1%

a2d2 A2 1.5-3.5%
Adult
a2b2 A > 95%

e Gg Ag d b
b cluster - chromosome 11
Thalassemia

´ Decreased production of normal globin chains

´ a thalassemia - deficiency of a gene(s)

´ b thalassemia - deficiency of b gene(s)
Alpha Thalassemia: Clinical Features
alpha globin- 2 globin chain/Hb, 2 gene 2 gene

´ Absence of 1-2 alpha chains X

a2 a1 a2 a1 X
a2 a1
´ Common a2 a1 XX
a2 a1 X
a2 a1
´ Asymptomatic
´ Does not require therapy RBC have 3 mutation
Anisocytosis- Unequal size RBC
´ Absence of 3 alpha chains
(Hgb H disease)
X
a2 a1
Poikilocytosis- abnormall shape of RBC
(takde biconcave)

´ Microcytic anemia (Hgb 7-10)

X X
a2 a1 These 2 cells come to spleen,
macrophages in it will destroy them.
Result in mass destruction —>
´ Splenomegaly splenomegaly, reticulocyte count
increase
´ Absence of 4 alpha chains
´ Hydrops fetalis (non-viable) XX
a2 a1

X X
a2 a1
 Alpha Thalassemia: Laboratory Findings
Normal size: 80-100
size Hemoglobin
a Chains Hgb (g/dl) MCV (fl) Analysis

aa/aa Normal Normal Normal

aa/-a 12-14 75-85 Normal
a-/a- or 11-13 70-75 Normal with Hgb Barts (g4);
--/aa Hgb H (b4) - small
--/-a 7-10 50-60 Normal with Hgb Barts (g4);
Hgb H (b4) - large
--/-- - - Not viable
 Beta Thalassemia
Beta require only 2 genes

Clinical Hgb
Syndrome Genotype Hgb (g/dl) Analysis
Minor (Trait) b/b+ or b/b° 10-13 ­ Hgb A2, ­ Hgb F

Intermedia b+/b+ 7-10 ­ Hgb A2, ­­ Hgb F

Mutated
Major (Cooleys) b+/b° or b°/b° <7 ­ Hgb A2, ­­­ Hgb F
Missing
 Beta Thalassemia: Clinical Manifestations

´ Skeletal
Frontal expansion
´ Osteoporosis due to bone marrow
expansion BM is doing compensation,
keep to erytropoiesis

´ Pneumatization of the sinuses is

delayed by expanded hematopoiesis
Sinus at the face expanding due to haemopoiesis

´ Dilated cardiomyopathy secondary to

Not hv enough RBC, so always in hypoxia
severe anemia
Heart need to compensate in hypoxia

´ Growth and development delayed

Splinomegaly due to mass destruction of normal RBC
´ Hepatomegaly due to extramedullary
Jaundice can be seen in severe thalassemia
hematopoiesis erythropoiesis happen outside of bone marrow, liver
 Due to gene mutation

Approach to Beta Thalassemia

The management as it cannot be cure

´ b thalassemia trait
´ Screening/counseling

´ b thalassemia intermedia/major
´ Screening/counseling
protect the liver from
´ RBC transfusion therapy (+ chelation therapy)
´ Agents to increase hemoglobin F (hydroxyurea)
´ Bone marrow transplantation

Not having children instead, adopt kid

Normal size

Normocytic Anemia with Low Reticulocyte

Normochromic

Count BM damage, decrease in erythropoiesis

´ Decreased stimulation of RBC production in bone marrow

Not enough stimulation by erytropoietin
´ Anemia of chronic disease
´ Chronic renal insufficiency
Disease

´ Isolated decrease in RBC precursors (red cell aplasia)

´ Bone marrow damage
´ Fibrosis
´ Stem cell damage
´ Infiltration with tumor/infection
´ Disorder of hematopoeisis
´ Myelodysplasia/sideroblastic anemia
cause rbc decrease bu tmorphology it has normal cell
 Have chronic disease first, the get anaemia

Anemia of Chronic Disease

´ Associated conditions
´ Infection
´ Viral, bacterial, TB, parasitic, fungal
Prevalence During chronic disease, it secretes interleukin that
stimulate production of hepcidin, hepcidin ause iron
20-95% lock in cell it lead to decresae in plasma iron. No
iron in bone marrow, it will decrease haemoglobin
synthesis and causing anemia.

´ Autoimmune disease 8-17% Normal condition:

- No interleukin
´ RA, SLE, sarcoidosis, IBD, vasculitis - Hepcidin X
- Iron is unlock in cell
´ Cancer 30-77%
´ Chronic solid organ rejection 8-70%
´ Characteristics
´ WBC and platelet counts are normal
´ Anemia of variable severity (mild-severe)
´ Low erythropoietin level
´ Low reticulocyte count
 Anemia of Chronic Disease: Pathogenesis
-ACD Stem cells,
-IL myeloid precersor cell
Cytokines - decrease RBC precusors So many cell one of it pronormoblast
-normoblast
(IL-1, TNF, IL-4) - authonomoblast
Tumor nucrosis factor - reticulocyte
- Erythrocyte
IL cause pronomoblast to decrease, so all the
cell after thta will decrease in number

Disturbed iron metabolism Decreased RBC Inadequate Epo

Diversion of iron from response
circulation to the RE system precursors
pronomoblast Cause erythropoietin is
Iron is not in the circulation, because lock in not sensitive
the cells.

Cells involve is enterocyte, liver, and

macrophages
 Iron Transfer Between Cells and Tissues:
Impaired in Anemia of Chronic Disease

X X
Supposedly
macrophages will
release iron Blocked in
Anemia of chronic disease

Hentze, et.al, Cell 2004;117:285

 Iron Transfer Between Cells and Tissues:
Mediated by Hepcidin
All the iron we eat will be
trapped as it will release
Hepcidin
into plasma
Iron overload
Anemia of chronic disease IL
Iron deficiency
Increased iron demand
(hemolysis)

Hentze, et.al, Cell 2004;117:285

 ACD- Symptoms
General:
- Pale (pallor)
- Weakness
etc

Specific:
No specific symptoms in ACD
- Either mild or severe symptoms

-Investigation-

Genereal
1. Physical examination- pallor at skin
2. CDC- RBC low, Hb low, Hct(haematocrit) low
3. Reticulocyte- Decrease
4. PBF- Normocytic normochromic

Specific
5. iron study- iron plasma is low, TIBC low, no iron in circulation
6. Measure plasma erythropoientin- not being produce enough
7. Hepcidin increase
Anemia of Chronic Disease
Treat the disease first, then treat the anaemia

Hb below 7 mg/dl, then need to do blood transfusion

´ Treatment options
´ Underlying condition
´ RBC transfusion
´ Erythropoietic agent Give erythropoientin

´ Iron supplement not usually indicated

Iron is there but not be released
- Iron overload cause toxicity
 Anemia of Chronic Renal Disease failure to produce erythropoientin
´ Characteristics
´ Widespread - 8% of US population has increased creatinine
´ 23% of patients with chronic renal disease have Hct ≤ 30%
´ Long-term anemia is a risk for LVH Left ventricular hypertrophy
= Work hard because to compensate the hypoxia

´ Risk factor for mortality

Normocytic normochromic

´ Etiology
´ Insufficient production of erythropoietin
Erythropoietin low, erythropoiesis rate low

Anaemia Kidney Disease(AKD) Non-renal mechanism that produce EPO:

Pathophysiology - Uterus, brain (cannot increase EPO to normal level)
- Kidney damage
- Less [EPO]
- Erythropoiesis in BM low
- Reduce in reticulocyte
- Reduce in RBC number
Pure Red Cell Aplasia

´ Normocytic anemia with reticulocyte count < 0.5%

´ Absent erythroid precursors in marrow

´ Caused by parvovirus B19

´ Clinical setting
´ Immunocompetent patients with chronic hemolysis
´ Immunodeficient patients with persistent viremia
 GENERAL SYMPTOMS Investigation
1. Pale 1. Physical examination- Pallor at skin
2. Weakness 2. CBC- RBC low, WBC N, Platelet N, Hb low, Hct low
3. Headache/dizziness 3. Retic count- Low
4. Cardiomegaly (LVH) 4. PBF- Normocytic normochromic (normal size + colour)

*No specific symptoms Specific

5. Plasma EPO- low
6. Kidney function test- GFR low, plasma creatine high, plasma urea high, urine albumin high, FEME infection

Kidney anaemia is terminal illness

Management and treatment

1. Treat underlying dis kidney first
2. Beta blockers to reduce tachycardia
3. Iron supplement + vitamin C, folate, vit B12
4. Recombinant EPO (if not well treated)
5. Blood transfusion BT
Pure Red Cell Aplasia: Parvovirus B19 in an
Immunocompetent Host
 Pure Red Cell Aplasia: Parvovirus B19 in an
Immunodeficient Host

Treatment with
IVIG
Macrocytic Anemia with Low Reticulocyte
Count
´ Megaloblastic anemia Megaloblastic
- Blast (immature)
´ Vitamin B12 deficiency - normoblast
- myloblast
- lymphoblast
´ Folate deficiency

´ Nonmegaloblastic macrocytic anemia

´ Liver disease
´ Hypothyroidism
´ Drug-induced (DNA synthesis block)
´ Myelodysplastic syndrome
 Folate and Cobalamin Daily Requirements
Normal daily requirement for B12 & folate

Diet

Vitamin B12
(Cobalamin) Folate
Source Animal products Widespread
Body stores 5 mg 5 mg
Daily requirement 2-5 µg 50-200 µg
Daily intake 10-20 µg 400-800 µg
Dietary deficiency Rare Common
Cofactor Activities of Folate and Cobalamin
Inside BM during production of RBC

Methionine
synthetase
Homocysteine Methionine

CH3-Cobalamin Cobalamin
THF THF-CH3

MMA-CoA
mutase
Methylmalonic acid (MMA) Succinyl-CoA

Adenosyl- Cobalamin
Cobalamin
Metabolic Testing for the Diagnosis of
Vitamin B12 and Folate Deficiency

Vitamin B12 Folate Deficiency

Deficiency
Methylmalonic acid Increased Normal

Homocysteine Increased Increased

 Enteric Processing and Absorption of
Cobalamin
Stomach Food-Cbl
H + Peptic
digestion
Cbl + R-binder

R-Cbl
Duodenum
Pancreatic Cobalamin will absorb to bloodstream
Cobalamin w/o protein but will bind
to instrinsic factor that produce enzymes R-Cbl Cbl-TC complex
IF + Cb OH - Cobalamin with R protein
by parietal cell that only located in
stomach

Complex cobalamin instrinsic factor Cbl-IF

Distal ileum IF receptor Cbl + TC
Cbl-IF The cell in ileum wall there
is instrinsic factor
receptor,
B12 absorb in ileum
Vitamin B12 Deficiency: Common
Mechanisms
Inside stomach
´ Intragastric events
´ Inadequate dissociation of cobalamin from food protein
´ Total or partial gastrectomy Removal of stomach
´ Absent intrinsic factor secretion Attack by auto-antibody

´ Proximal small intestine

´ Impaired transfer of cobalamin from R protein to intrinsic factor
´ Usurpation of luminal cobalamin
´ Bacterial overgrowth
´ Diphylobothrium latum (fish tapeworm)
Ileum
´ Distal small intestine
´ Disease of the terminal ileum
 Pernicious Anemia
Cause by autoimmune disease, autoantibody attack the
´ Most common cause of vitamin B12 deficiency
´ Occurs in all ages and ethnic backgrounds
´ Associated with other autoimmune diseases
´ Screen for thyroid disease every 1-2 years
´ Pernicious anemia is a systemic disease
´ Gastrointestinal tract involvement
´ Neurologic involvement
Related to thyroid disease
Pathophysiology
- Auto-antobody damaging IF/parietal cell
- cause no IF in duodenum
- no complex cobalamin- intrinsic factor complex
- IF receptor do not allow absorbtion
- Cause reduce CBL in plasma
- Staganant growth (terbantut sebab no mature
because stop at erytrocyte
- Reduce reticulocyte
- Reduce RBC
Pronomoblast- has nucleus & DNA, not mature
othonormoblast- “
nomoblast- “
retic- degrade of DNA + nucleus
erythrocyte- no nucleus, no DNA
Pernicious Anemia: Laboratory Diagnosis Specific investigation

´ Anti-intrinsic factor antibodies (~60% positive)

´ Specific but not sensitive
´ Anti-parietal cell antibodies (~90% positive)
´ Sensitive but not specific
´ Schilling test Masuk exam

´ Procedure
´ Administer IM vitamin B12 to prevent incorporation of radioactive cobalamin
´ Provide PO radiolabeled cobalamin ± Intrinsic factor
´ Measure urinary excretion of radioactivity
´ Difficult to administer
Interpretation of Schilling test

Cobalamin Cobalamin + IF Interpretation

Normal Normal Dietary insufficiency

Abnormal Normal Intrinsic factor deficiency

(Gastrectomy, PA)
Abnormal Abnormal Small bowel abnormality
(terminal ileum disease)
Treatment of Vitamin B12 Deficiency

Outside the intestine

´ Parenteral cobalamin
´ 1 mg/day x 7 days
´ 1 mg/week x 4 weeks
´ 1 mg/month for life
Text
´ Oral cobalamin If no absorption issue
´ 1 mg/day for life
Kat nasal byk blood vessel. Go to blood vessel
´ Nasal cobalamin gel
´ 500 µg/week

´ Iron supplementation often needed

Folate Deficiency

´ Minimum daily folate requirement is 50 µg

´ Usual dietary folate 50-500 µg
´ Absorption in small intestine
´ Causes of folate deficiency
´ Dietary (90%)
´ Alcohol abuse
´ Pregnancy

´ Malabsorption
´ Drug-induced
´ Treatment - oral folic acid supplementation
 Normocytic Anemia with High Reticulocyte
Count Reticulocyte high, there is compensation happen

´ General principles No disease, the blood cell is normal, boconcave

´ Bleeding may have similar lab findings as hemolysis

Found a lot of microcyte
´ High reticulocyte count may lead to macrocytosis
´ Clinical manifestations of long term hemolysis
If have bleeding, no cholelithiasis
´ Cholelithiasis (Gallstone), high bilirubin content in the blood
´ Risk of aplastic crisis (parvovirus B19) RBC not being produce enough
´ Risk of pulmonary hypertension
´ Classification
sickle anaemia
´ Hereditary vs. acquired
Tyep of haemolysis ´ Extravascular vs. intravascular
´ Immune vs. nonimmune
Hemolytic Anemia with Extravascular
Hemolysis
´ Extravascular (reticuloendothelial system)
´ Hereditary
´ Hemoglobinopathies (sickle cell anemia) Homeo- structure of haemoglobin is not normal due to gene mutation

´ Enzymopathies (G6PD deficiency) Not being produce properly

´ Membrane defects (hereditary spherocytosis) Involve in material for RBC production

´ Acquired Autoimmune haemolytic anaemia, not related to gene

mutation

´ Immune mediated
´ Autoimmune hemolytic anemia

´ Nonimmune mediated
´ Spur cell hemolytic anemia
 Sickle Cell Disease
Glutamate

´ Mutation in beta globin (b6 Glu Val)

Molecule structure of haemoglobin is abnormal because different amino acid in the structure.

´ Inherited as autosomal recessive

´ Gene occurs in 8% of African-Americans (Sickle cell trait)

Sickle Cell Trait

People with sickle cell will not get malaria

´ Protection against malaria

´ Genitourinary complications
´ Hyposthenuria
´ Painless hematuria
´ UTI during pregnancy

There is obstruction on the blood vessel

Sickle cell trait areas shown in
´ Vaso-occlusive complications
orange stripes
´ Splenic infarction with hypoxia
´ Sudden death during extreme
exertion
´ Rhabdomyalysis
Pathophysiology of
Sickle Cell Disease

Normal

Sickle cell
Much longer that Sickle is not elastic so obstruct the
cause obstruction to
blood vessel cannot be in hypoxia condition, need enough oxygen throughout their life

Due to hypoxia, the RBC will change the structure to sickle cell,
cannot return to biconcave shape.
Sickle Cell Anemia: Clinical Presentations
In hypoxia condition, the Hb will crystalized
(become keras and RBC will follow the shape into
sickle

General Investigation
1. CBC - RBC low, Hb low, Hct low
2. PBF - normocyte, sickle cell
3. RBC count - erythropoiesis increase to compensate haemolyzed RBC
´ Chronic hemolytic anemia 4. Measure valine (check possible or not
Hv symptoms of jaundice that lead 5. Level of bilirubin - increase
to choleltiatis 6. Haemoglobin analysis - haemoglobin S (the one that mutated)
7. Splenomegaly- found jaundice cus present of bilirubin. Mass haemoglobin obstruction.

´ Susceptible to infection Management & Treatment

Blood circulation is not good, prone to get the disease 1. Blood transfusion (Hb below 7 g/gL)
2. Relief pain - anelgesic
´ S. pneumoniae 3. Supplement - iron, vit C, folate, B12
4. O2 therapy- to reduce hypoxia
´ Osteomyelitis 5. Stem cell/ Bone marrow transplant- to
reduce
6. UV treatment - Uv will break the bilirubin
´ Staphylococcal infections 7. Hydration - give a lot of water

Text
´ Vaso-occlusion
 Sickle
Normal
- Biconcave
-Biconcave
- Hypoxia
- Hypoxia
- Hb S —> Crystal
- Biconcave +
- Change structure of Hb
elastic
- RBC take place of crystalized Hb S
- Haemolysis in spleen to destroy the sickle cell
Glucose-6-Phosphate Dehydrogenase
Deficiency
They will burst in the blood vessel cus membrane is fragile
´ G-6-PD - reduces NADP/oxidizes glucose-6-phosphate
´ Detoxifies free radicals and peroxides
´ Sex-linked disorder
Oxidative stress- free radical peroxide is too high in
blood, can cause infection, or drug, attack RBC
´ Effects > 200 million people Common in Malaysia membrane cause it to be fragile
Every newborn need to screen for this enzyme
´ Hemolytic anemia occurs in the presence of stress (infection or drugs)
´ African form - mild hemolysis
´ Mediterranean form - more severe
´ Unique sensitivity to fava beans
 A part of glucolysis process

Antioxidant is to neutralze H2O2 to water (not harm)

Glutatione is substance that neutralize G6PD

Require to reduce glutatione

Cause oxidant increase

 Investigation
Hb analysis tak payah buat sebab the shape normal just. the enzyme G6PD

General:
1. CBC- RBC low, Hb low, Hct low, platelet normal
Sign + symptoms
2. PBF- normocyte, fragment cell/ schistocyte
1. Pallor
3. Retic count - Increse due to compensation
2. Weaknesses
4. Total bilirubin - high (show symptoms of jaudice)
3. Headache
4. Jaundice Intravascular haemolysis
Specific
5. Dark urine
5. G6PD enzyme spot test- measure the serum (screening)
(fragment will go
6. Serum G6PD
to the kidney and
7. Measure urine haemoglobin/urine bilirubin - hematuria, urine
become darker)
analysis (FEME)
Glucose-6-Phosphate Dehydrogenase
Deficiency: Treatment
´ Hemolytic anemia occurs in the presence of stress (infection or drugs)
´ African form - mild hemolysis
´ Mediterranean form - more severe
´ Unique sensitivity to fava beans
- Stop exposure to cause of oxidative stress (if have medication that
cause stress, stop eat that)
- cannot eat favabean will stimulate production of oxidant
- Blood transfusion if blood Hb < 7 g/dL
- There is jaundice, give UV therapy
- Eat supplement or nutritionist food that high in antioxidant (oranges,
blueberries, papaya, watermelon)
- Too severe, BM transplant
 Hereditary Spherocytosis

´ Autosomal dominant disorder

´ Abnormality in RBC
membrane protein
´ mutation on spectrin and
ankyrin gene
´ Clinical sign and symptoms

Patophysiology:
no ankynin + spectin
b RBC membrane structure
Spherocyte
Destroyed by spleen (extracellular hemolysis) spleenomegaly
Production of bilirubin increase cause jaundice
Laboratory findings
Investigation
1. CBC - RBC low, Hb low, Hct low
2. PBF - spherocytosis (RBC is spherical, not biconcave
3. Retic count - Increase in order to compensate the destroy RBC
4. Total bilirubin - Increase
5. urine test - dipstick, bilirubin increase, Hb absent
6. Analgenic + spectrim
7. Physical examination - jaundice, splenomegaly
(sign and symptoms)
* dont do Hb analysis
 Treatment
Management
1. Uv teraphy- jaundice
2. Blood transfusion - to compensate/replace the destroyed (haemolyzed) RBC
- Hb <7 g/dL
3, Supplement - iron, vit C, folate, B12
4. Splenectomy - to prevent the RBC to be destroyed, spepherocyte RBC have short lifespan, even the shape is not perfect, it is still abel to transport O2
5. If severe, go for BM/stem cell transplant (t wo different procedure) do this when RBC is very low

Exam:
The effect of splenectory long-term and short-term effect
Acquired Hemolytic Diseases

´ Immune mediated hemolytic anemia

´ Non-immune mediated
Autoimmune Hemolytic Anemia

´ Warm antibodies (IgG-mediated)

´ Primary 45%
´ Secondary 40%
´ Lymphoproliferative disease
´ Connective tissue disease
´ Infectious disease
´ Drug-induced 15%

´ Laboratory testing
´ Normocytic/macrocytic anemia
´ Peripheral smear - spherocytosis
Direct Anti-Globulin
antiglobulin testing (Coombs) Testing
+
Anti-C3d
Patients RBCs Anti-IgG

Indirect antiglobulin testing

+ +
Patients serum RBCs Anti-IgG
Treatment of Autoimmune Hemolytic Anemia

´ Treat underlying disease if indicated

´ Prednisone (1 mg/kg/day for two weeks, then taper)

´ Splenectomy

´ Other
´ Immunosuppressive agents (Rituximab)
´ IVIG

´ Similar approach to ITP

Hemolytic Anemia with Intravascular
Hemolysis
´ Mechanical damage (Microangiopathic hemolytic anemia)

´ Chemical damage (Burns)

´ Infection (Malaria or Babesiosis)

´ Transfusion reaction (ABO incompatibility)

Differential Diagnosis of Microangiopathic
Hemolytic Anemia
´ Thrombotic thrombocytopenic purpura (TTP)

´ Hemolytic uremic syndrome (HUS)

´ Disseminated intravascular coagulation (DIC)

´ Vasculitis

´ Malignant hypertension

´ Metastatic neoplasm with vascular invasion

´ Preeclampsia/HELLP syndrome of pregnancy