Today’s Quranic verse

And hold fast, all together, by the rope which God (stretches out for
you), and be not divided among yourselves; and remember with
gratitude God's favour on you; for ye were enemies and He joined
your hearts in love, so that by His Grace, ye became brethren; and
ye were on the brink of the pit of Fire, and He saved you from it.
Thus doth God make His Signs clear to you: That ye may be
guided. [003:103]
No one can make you feel inferior
without your consent
 Steps in Erythropoisis
Early Intermediate Late

Proerythroblast Polychromatophilic Reticulocyte

(Pronormoblast) Normoblast

Basophilic Orthochromatophilic Erythrocyte

Normoblast Normoblast
 C.B.C
• Haemoglobin - 15±2.5, 14 ±2.5 - g/dl

• PCV - 0.47 ±0.07, 0.42 ±0.05 - l/l (%)

– Haematocrit, effective RBC volume – better

• RBC count - 5.5 ±1, 4.8 ± 1 x1012/l

• MCHC - Hb/PCV - 30-36 - g/dl

– Hb synthesis within RBC

• MCH - Hb/RBC - 29.5 ± 2.5 pg/l

– Average Hb in RBC

• MCV - PCV/RBC 85 ± 8 – fl

• RDW (Red Cell Distribution Width )-13 ± 1.5

 Red Blood Cell Disorders

Anemias
• Anemia of Blood Loss: (Acute vs. Chronic)
• Anemia of ↓ Erythropoiesis
• Hemolytic Anemia: (Congenital/Acquired)

Polycythemia
 Anemias
• An (without) -emia (blood):

Reduction below normal in hemoglobin or red blood

cell number (for age & sex).

Hb (g/dL)

Male Female
13-17 12-15
(15±2) (13.5 ± 1.5)
Anemias Anemia

HYPOXIA REDISTRIBUTION
2,3 DPG

COMPENSATORY
MECHANISMS

C.O. PLASMA
PATHOPHYSIOLOGY
OF ANEMAIS
Anemias TIREDNESS
LASSITUDE
EASY
FATIGUABILITY

MUSCLE GIS
CNS WEAKNESS

CLINICAL FEATURES

CRS GUS
PALLOR
Anemias

Classification

Etiological Morphological
Anemias
ETIOLOGIC
Classification
I

BLOOD LOSS
II (Haemorrhagic) III

IMPAIRED
INCREASED
RED CELL
RED CELL
FORMATION
DESTRUCTION
(↓Erythropoiesis)
(Haemolytic)
(Dyshaemopoietic)
Anemias
ETIOLOGIC
Classification
I
ACUTE CHRONIC

BLOOD
II LOSS III
IMPAIRED
RED CELL HEMOLYTIC
FORMATION ANEMIAS

NON RBC RBC ENVIRONMENT

DEFICIENCY ABNORMALITIES ABNORMALITIES
DEFICIENCY
 DEFICIENCY ANEMIAS
ANEMIAS DUE TO DEFICIENCY OF SUBSTANCES
ESSENTIAL FOR ERYTHROPOIESIS

IRON FOLIC ACID/VITAMIN B12

DEFICIENCY DEFICIENCY
MEGALOBLASTIC ANEMAIS
ANEMAIS
MICROCYTIC HYPOCHROMIC
ANEMIAS
 NON DEFICIENCY ANEMIAS

ANEMIAS NOT DUE TO DEFICIENCY OF SUBSTANCES

ESSENTIAL FOR ERYTHROPOIESIS

ACD ANEMIA
ANEMIA OF OF
CHRONIC BONE MARROW
DISORDERS INFILTRATION
INFECTION COLLAGEN DISEASES (myelophthisic)
RENAL FAILURE, LIVER FAILURE
MALIGNANCY
APLASTIC LEUKEMIAS,LYMPHOMAS
MYELOMA,MYELOFIBROSIS

ANEMIA
OTHERS
 OTHER
NON DEFICIENCY ANEMIAS

SIDEROBLASTIC CONGENITAL
DYSERYTHROPOITC
ANEMIAS ANEMIAS
Anemias
MORPHOLOGIC
Classification

I
NORMOCYTIC
NORMOCHROMIC
II III
MICROCYTIC MACROCYTIC
HYPOCHROMIC ACD ANEMIAS

Iron Deficiency Megaloblastic

Thalassemias
 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
 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
 Causes of Iron Deficiency
Iron deficiency is a symptom, not a disease

• Increased iron • Inadequate iron supply

requirements – Insufficient dietary iron (malnutrition)
– Blood loss
– Impaired iron absorption
• Gastrointestinal tract
• Gastric surgery
• Genitourinary tract
• Intestinal malabsorption
• Blood donation
• Celiac disease
• Worm infestation
– Pregnancy and lactation
 Systemic Manifestations of Iron
Deficiency
• Behavioral and neuropsychiatric • Esophageal webs and strictures
manifestations

• Pica (pagophagia)

• Angular stomatitis
• Koilonychia
• Glossitis
 Lab Findings

Hb low
MCV low
Serum iron low
TIBC high
Ferritin low
BM iron absent

Peripheral smear: Microcytic hypochromic

 Hypochromic Microcytic RBC

Smear
Microcytic / Hypochromic RBCs,
Anisocytosis, Poikilocytosis
 Macrocytic Anaemias

Defition:- Anaemias with MCV >95 fl

Classification:-

A. Megalo-blastic
B. Non-megalo-blastic
 Megaloblastic anemia

• Vitamin B12/Folic acid deficiency

• Second most common type of anemia.
• Multi System disease – All organs with increased cell division.
• Macrocytic anemia, pancytopenia.

• Pernicious anaemia –
– autoimmune, Gastric atrophy, VitB12 def.
 Enteric Processing & Absorption
of Cobalamin

Stomach Food-Cbl
H + Peptic
digestion
Cbl + R-binder

R-Cbl
Duodenum
Pancreatic
enzymes R-Cbl Cbl-TC complex
IF + Cb OH -

Cbl-IF
Distal ileum IF receptor Cbl + TC
Cbl-IF
 Vitamin B12 Deficiency
Mechanisms
• Malnutrition
• Intragastric events
– Inadequate dissociation of cobalamin from food protein
– Total or partial gastrectomy
– Absent intrinsic factor secretion
• Proximal small intestine
– Impaired transfer of cobalamin from R protein to intrinsic factor
– Usurpation of luminal cobalamin
• Bacterial overgrowth
• Diphylobothrium latum (fish tapeworm)
• Distal small intestine
– Disease of the terminal ileum
 Megaloblastic Anemia-Pathogenesis

Decreased Vit B12 / Folate

Decreased DNA Synthesis

Delayed maturation of erythroblasts (Nucleus)

Increased cell size (macrocytes)

Normal Hb content (Normochromia)

Decreased RBC number & Decreased WBC number (pancytopenia)

Anemia & Pancytopenia.

 Pernicious Anemia
• Most common cause of vitamin B12 deficiency
• Occurs in all ages and ethnic backgrounds
• Autoimmune destruction of gastric mucosa→ chronic Atrophic gastritis →↓ IF

• Associated with other autoimmune diseases

– Screen for thyroid disease every 1-2 years

• Pernicious anemia is a systemic disease

– Gastrointestinal tract involvement
– Neurologic involvement (sub-acute combined degeneration of spinal cord)

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

– Specific but not sensitive
• Anti-parietal cell antibodies (~90% positive)
– Sensitive but not specific
• Schilling test
Macrocytes & Macropoly & Megaloblast
 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
 Anemia of Chronic Disease

• Associated conditions Prevalence

– Infection 20-95%
• Viral, bacterial, TB, parasitic, fungal
– Autoimmune disease 8-17%
• RA, SLE, sarcoidosis, IBD, vasculitis
– 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
Cytokines
(IL-1, TNF, IL-4)

Disturbed iron metabolism Decreased RBC Inadequate Epo

Diversion of iron from precursors response
circulation to the RE system

Normch/normocy, Hypoch/microcy, ↓ serum iron, ↓/N TIBC, ↑/N S.Ferritin, ↑ Storage iron
 Aplastic Anemia
• Suppression of multipotent myeloid stem cells
• Anemia, thrombocytopenia, neutropenia
• Etiology: idiopathic (65%), irradiation, myelotoxic drugs, chemicals,
viruses
• Idiosyncratic reaction: chloramphenicol, sulfonamides

• BM: hypocellular with fat replacement

• No splenomegaly, if + diagnosis, not AA

• No reticulocytosis
• Treatment: stop drug, BMT (< 40 y/o) for idiopathic,
immunosuppression for older patients, w/o donors
Aplastic anemia
HEMOLYTIC ANEMIA
 Hemolytic Anemia with Extravascular
Hemolysis
Hereditary
• Hemoglobinopathies (sickle cell anemia, thalassemia)
• Enzymopathies (G6PD deficiency)
• Membrane defects (hereditary spherocytosis)

Acquired
• Immune mediated
– Autoimmune hemolytic anemia
• Nonimmune mediated
– Spur cell hemolytic anemia

Extravascular (reticuloendothelial system)

 Sickle Cell Anemia
• Most prevalent hemoglobinopathy caused by mutations of the ß-
globin chain → sickle Hb (HbS)
– 8% of American blacks (1:600)
– 30% of African blacks (protective effect of HbS vs. malaria)
– Autosomal recessive
• Single AA substitution in the globin chain (val for glu)
• Normal adult: 96% HbA, 3% HbA2, 1% HbF
• On deoxygenation: HbS polymerize (gelation/crystallization)
– Change in physical state cause RBC distortion “ sickle/crescents”
– Reversible sickling → irreversible sickling despite adequate O2
– RBC hemolysis (anemia), capillary stasis (ischemia/thrombosis)
Target cell
Sickle cells

Anisocytosis/poikilocytosis
Hemolytic Anemia: Sickle Cell Anemia

Clinical: anemia + complications:

– acute chest syndrome, strokes, acute pain crisis, priapism, leg ulcers (vaso-
occlusion),
– Susceptible to infection: S. pneumoniae, Staphylococcal, Salmonella
(osteomyelitis)

Diagnosis:
-Peripheral smear, Lab iron studies & Electrophoresis

Treatment:
– Hydroxyurea
• Increases HbF = retards sickling by inhibiting polymer formation
– RBC transfusions
– RBC exchanges during acute crises
 Hereditary Spherocytosis
• Abnormal RBC skeletal/membrane proteins (ie. Ankyrin)
• RBCs with reduced membrane stability → lose membrane fragments,
assume a “sphere”
• Clinical: anemia, splenomegaly, jaundice

• Lab: ↑ osmotic fragility

– Upon exposure to hypotonic salt solution, spheroidal shape limits
volume of expansion.

• RBCs shortened lifespan

• Treatment: splenectomy to alleviate anemia, continue to have
spherocytes
Hereditary Spherocytosis
Glucose-6-Phosphate Dehydrogenase
Deficiency

• G-6-PD – essential for maintaining glutathione in active form

– Detoxifies free radicals and peroxides
• Sex-linked disorder
• Effects > 200 million people
• Hemolytic anemia occurs in the presence of stress (infection or
drugs- antimalarial, sulphonamide, nitrofurantoin etc)
– African form - mild hemolysis
– Mediterranean form - more severe
Peripheral smear shows Heinz bodies & bite cells
Unique sensitivity to fava beans
 Immunohemolytic Anemias
• Caused by antibodies reacting against normal or altered RBC membranes
- Autoimmune, drug-induced
- Antigen that stimulates antibody or complement-mediated
destruction of RBCs

• Classification:
1. Warm antibody: idiopathic, B-cell Neoplasms (CLL/SLL), SLE,
drugs (aldomet, PCN, Quinidine)
2. Cold antibody: M. pneumoniae. Infectious mono.

• Lab:
- + DAT detects anti-RBC antibodies
- Microspherocytes on peripheral smear
 Anti-Globulin (Coombs) Testing
Direct antiglobulin testing

+
Anti-C3d
Patients RBCs Anti-IgG

Indirect antiglobulin testing

+ +
Patients serum RBCs Anti-IgG
 Hemolytic Anemia with Intravascular
Hemolysis

• Mechanical damage (Microangiopathic hemolytic anemia)

• Chemical damage (Burns)

• Infection (Malaria or Babesiosis)

• Transfusion reaction (ABO incompatibility)

Thalassemia
 NORMAL INDIVIDUAL
4 α-globin genes 2 β- globin genes
on chromosomes No 16 on chromosomes No 11
( 2 on each chromosome) ( 1 on each chromosome)

2 from the father 1 from the father

& 2 from the mother & 1 from the mother

Net result :-

Normal α / β globin chain ratio is 1/1

 Normal Hemoglobin(s)

α α2β2 β A
α
2
δ
2

A2
Hb%
F A
δ

α γ2
A2

‹1 1.6 - 3.2 97
F Adult
70±20 Negligible 30±20
f
In ant
 Thalassemia

• Decreased production of normal globin

chains
  thalassemia - deficiency of  gene(s)
  thalassemia - deficiency of  gene(s)
 Thalassemia
 thalassemia
Heterozygote  thalassemia Europe – 4-12%
Italian, Sicilian, and Greek 10% Middle East and western Asia - 12-55%
Southeast Asian populations 5% in Southeast Asia –  6-75%
in African and American black populations 1.5% Africa – 11-50%
South America and the Caribbean - 7%

• Imbalance of globin chain production

 - vs. -thalassemia
• anemia due to both decreased production and increased hemolysis
in spleen
• - thalassemia has decreased/absent Hgb A, increased Hgb F, and
increased Hgb A2
• Treatment- hypertransfusion with chelation, splenectomy, bone
marrow transplantation
Father Mother

αα αα

αα/αα
Normal
α-Thalassemia(s)

-α/αα Silent carrier

--/αα α- thal minor

(α-thal trait)

--/-α HbH disease

--/--
Hb. Bart’s
Hydrops fetalis
 Alpha Thalassemia: Clinical
Features
• Absence of 1-2 alpha chains
– Common X
    X
 

– Asymptomatic   XX
 
X
 

– Does not require therapy

• Absence of 3 alpha chains
(Hgb H disease)
X
 

XX
 
– Microcytic anemia (Hgb 7-10)
– Splenomegaly
• Absence of 4 alpha chains XX
 

– Hydrops fetalis (non-viable) XX

 
 β- Thalassemia(s)

β-
thalassemia
major

β-
thalassemia
minor
 Beta Thalassemia

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

Intermedia +/+ 7-10  Hgb A2,  Hgb F

Major (Cooleys) +/° or °/° <7  Hgb A2,  Hgb F

 Beta Thalassemia: Clinical
Manifestations
• Skeletal
– Osteoporosis due to bone marrow expansion (crew cut)
– Pneumatization of the sinuses is delayed by expanded
hematopoiesis

• Dilated cardiomyopathy secondary to severe

anemia

• Growth and development delayed

• Hepatomegaly due to extramedullary

hematopoiesis
Beta Thalassemia

Crew cut appearance

• Skeletal
– Osteoporosis
– Delayed pneumatization of
the sinuses

• Dilated cardiomyopathy
• Growth and development
delayed

• Hepatomegaly
Smear
Microcytic / Hypochromic RBCs,
Anisocytosis, Poikilocytosis, target cells

Thalassemia
 Hemolytic Anemia

• ↑ RBC destruction • Intravascular:

• ↑ erythropoiesis: – hemoglobinemia,
reticulocytosis hemoglobinuria,
hemosiderinuria
• Iron accumulation: – ↓ haptoglobin
hemosiderosis
• Extravascular
• Etiology: – No hemoglobinemia or
– Intravascular: heat, hemoglobinuria
clostridia toxin, trauma
– Normal haptoglobin
complement fixation
– Microspherocytes
– Extravascular (RES)
 Causes of High Hct/polycythemia

• Relative or spurious erythrocytosis

– Hemoconcentration secondary to dehydration
– (diarrhea, diaphoresis, diuretics, deprivation of water, emesis,
ethanol, etc.)
• Absolute erythrocytosis (True ):
– Tissue hypoxia – Smoking (Co), High altitude, Pulmonary disease,
Cardiac shunts, High oxygen-affinity Hb.
– High EPO - Tumors eg. HCC.
– Androgen therapy
– Primary - Polycythemia vera