Approach to Anemia

By Umair Ansari
 What is Anemia?
Anemia: Reduction in the circulating red blood
cell mass
Signs and symptoms Hypoxia
1) Weakness, fatigue and dyspnea
2) Pale Conjuntiva and Skin
3) Headache and Lightheadedness
4) Angina (especially with a preexisting
cornoray artery disease)
 Measuring Anemia
Hemoglobin (Hb), Hematoctrit (Hct) and RBC
Count are used as surrogates for RBC mass
which is difficult to measure

Anemia is defined as Hb <13.5 g/dL in males

(13.5-17.5) and < 12.5g/dL in females (12.5-
16)
 Classifying Anemia

Microcytic Normocytic Macrocytic

<80 m3 80-100 m3 >80 m3

Extravascular Intravascular
Iron Deficiency Megaloblastic
Hemolysis Hemolysis

Paroxysmal
Anemia of Chronic Hereditary
Nocturnal Folate deficiency
Disease Spherocytosis
Hemoglobinuria

Sideroblastic
Sickle Cell Anemia G6PD Deficiency
Anemia

Immune
Thalassemia
Hemolytic Anemia

Microangiopathic
Hemolytic Anemia

Malaria
Normal Blood Smear
Microcytic Anemia
Duodenum The Story of Iron

DMT1 Receptors
Enterocytes
Ferroportin

Stored in
macrophages

Transferrin Iron

Ferritin

Erythroid precursor Cells

Stored in macrophages
+ transferred to erythroid
Precursor cells
TIBC: Total Amount of Transferrin present in Blood (Normal = 300 ug/dL)

Serum Iron: Total Amount of Fe bound to Transferrin (Normal = 100 ug/DL)

Percentage saturation: percentage of transferrin molecules that are bound
By Iron (Normal = 33%)

Serum Ferritin: Reflects Iron stores in macrophages and the liver

1) Iron Deficiency Anemia
 Malnourished
Children

Adults with
Hookworm peptic
Infestation ulcer
disease
Decreased
absorption,
intake or
Blood Loss
Pregnancy/
Gastrectomy
Menorrhagia

Colon
polyps/
carcinoma
Decreased Iron
absorbed/
Ingested

Decreased
Serum Iron and
Saturation

Decreased
Ferritin

Compensatory
rise in TIBC
Microcytic, hypochromic RBCs of Iron
Deficiency Anemia
Koilonychia
Esophageal Web
2) Anemia Of Chronic Disease
 Chronic
Inflammation or
Cancer

Hepcidin Released
from Liver

Sequesters Iron to
prevent bacteria
from accessing it

Increases Ferritin

Decreases TIBC,
serum Iron and
saturation
3) Sideroblastic Anemia
In the Mitochondria 4) Isoniazid Tx
Succinyl CoA

ALA Synthetase (Vit B6) 1)Congenital

Absence
2) Alcohol Aminolevulinic
Acid

ALA Dehydratase 3) LEAD

Porphobillinogen

Additional Gets trapped in the

reactions Mitochondria and
Forms RINGS around
the nucleus

Protophyrin
+ Fe Ferrochelatase

Heme
Ringed Sideroblasts
4) Thalassemia
Chromosome 16 Chromosome 11

1) Asymptomatic 1) Microcytic
Hypochromic
2) Mild Anemia with Anemia with
Increased RBC Target Cells
Count Increased
HbA2 and HbF
3) Increased HB Barts
Severe Anemia
Hb H increases 2) Alpha Tetramers
Accumulate
4) Incompatible with Extravascular
Life ( Hydrops Fetalis) hemolysis
Hb Barts Increases
Microcytic
hypochromic
Anemia and
Increased
HbA2 and HbF
Hemoglobin H
Hydrops Fetalis
Target Cells
Crew cut appearence
Chipmunk Facies
Macrocytic Anemia
1) Folate Deficiency Anemia
 Homocysteine Methionine
Increased levels will
Increase the risk of Homocysteine
methyl transferase
Stroke, DVT etc (N5-methyl THF and
Cystathione Vit B12)

Alpha keto butyrate

Propinyl CoA

Increased levels will cause Methylmalonyl CoA

Subacute Combined Methyl Malonyl CoA Mutase
Degeneration of the (Vit B12)

Spinal cord Succinyl CoA

 Poor diet in
the elderly
and
alcoholics

Decreased
absorption
or intake
Folate Increased
antagonists demand in
pregnancy,
that inhibit cancer and
dihydrofolate hemolytic
reductase anemia
 Decreased Folate
intake

Impaired division Impaired division

and enlargement of granulocytic
of RBC precursors precursors

Hyper-segmented
Macrocytic
Neutrophils >5
Anemia
lobes

Decreased serum folate, increased serum homocysteine, Normal Methylmalonic Acid

2) Vitamin B12 deficiency or
Megaloblastic Anemia
 Dietary
deficiency
in Vegans

Destruction of
terminal ileum Decreased Autoimmune
by Crohns destruction
disease absorption of Parietal
Diphylbothrium
Latum or intake cells

Pancreatic
Insuffeciency
 Macrocytic RBCs with hypersegmented
neutrophils
Glossitis
Subacute degeneration of the spinal cord

Decreased Vit B12, Increased serum Homocysteine, Increased Serum Methylmalonic Acid
Hypersegmented Neutrophils
Glossitis
Normocytic Anemia
 Types

Destruction of Underproduction
RBCs of RBCs

Increased
Reticulocyte
count
Reticulocytes
Anemia with
Splenomegaly,
Jaundice due to
increased u. Billirubin,
Increased risk of
billirubin gallstones
Hemolysis

Extravascular Intravascular
(within RES) (within vessels)

RBCS enter into the RES

(spleen, liver, Hemoglobobinemia Hemoglobinuria Hemosideriuria Decreased septum Hb
Lymphnodes)

Renal tubular cells pick

up Hb in urine store
Macrophages
the Fe as Hemosiderin
Shed

Consume RBCs and

break down Hemoglobin

Protophyrin
U.Billirubin serum
albumin Liver for
conjugationBile
Predominant Extravascular Hemolysis
1) Hereditary Spherocytosis
Cell
Cell Membrane

cytoskeleton Spectrin, Ankyrin

Or Ban 3
Spherocytes
Howell Jolly Bodies
2) Sickle Cell Anemia
AR Mutation (Valine
replaces glutamic
acid)

Two abnormal Beta

genes (>90% HbS)

Deoxygenation
(Hypoxemia,
dehydration, acidosis)

HbS Polymerizes and

aggregates into
needle like structures
( Sickles)

Cells Sickle and

Unsickle passing
through the
microcirculation

Eventual Membrane
damage
 Both Intravascular and Extravascular
Hemolysis ensues. The RES removes RBCs with
damaged RBC membranes and RBCs with
damaged membranes dehydrate decreased
haptaglobin and target cells
 Signs and Symptoms

Vasocclusive infarcts Renal Papillary Expansion of Acute Chest

Autosplenectomy Pain Crisis
in Bones Necrosis Hematopoiesis Syndrome

Increased risk of
Chest pain, shortness
infection by Gross Hematuria and Crew cut appearance
Dactylitis of breath and lung
encapsulated Proteinuria and Chipmunk Facies
infiltrates
organisms

Increased risk of
Osteomyelitis by
salmonella Typhi

Howell Jolly Bodies

Dactylitis
Sickle Cell Disease
Autosplenectomy
Renal Papillary Necrosis
3) Hemoglobin C
Hemoglobin C crystal
Predominant Intravascular Hemolysis
1) Paroxysmal Nocturnal
Hemoglobinuria (PNH)
Complements Complements

GPI GPI
DAF
C3 Convertase

Complements
Complements
In people of have a congenital absence of GPI
Night time Asleep Deep Shallow breathing
Mild Acidosis Body comes under stress
Activates Complements RBCs are defenseless
Intravascular Hemolysis

Hemoglobinuria (especially
In the morning) and
Hemoglobinemia

Back pain and Anemia

2) G6PD deficiency
Glucose 6 Phosphate 6 phosphogluconate Ribose

NADP NADPH

Oxidized Glutathione Reduced Glutathione Breaks down H2O2

Relieves oxidative stress

Increased Oxidative stress Hb denatures and
condenses to form Heinz Bodies When RBCs
enter the RES the macrophages bite portions off
(the heinz bodies) to form Bite Cells These
bite cells later undergo intravascular hemolysis
Bite Cell
Heinz Bodies
3) Immune Hemolytic Anemia
SLE, CLL, drugs like
Type of antibody
Penicillin and cephalosporin

IgG mediated ( warm) IgM mediated (cold)

(Extravascular Hemolysis) (intravascular hemolysis)

Warm temperature center IgM binds to RBC fixes

of body antibody covered complement in the
RBC consumed by splenic relatively cold temperature
macrophages - Spherocytes of extremities

Drug may attach to RBC Related to infectious

membrane with Ab mononucleosis and
attaching to drug mycoplasma pnemoniae

Drug may induce

production of
autoantibodies
4) Microangiopathic Anemia
 Occurs because of an underlying vascular
pathology, RBCs destroyed as they pass
through the circulation
Iron deficiency anemia occurs with chronic
hemolysis
Occurs with micro thrombi (DIC, HELLP),
prosthetic heart valves and aortic stenosis
Microthrombi produce schistocytes on blood
smear
Schistocytes
5) Malaria
 RBCs rupture as part of the Plasmodium life
cycle Intravascular hemolysis and cyclical
fever.
1) P Falciparum recurrent fever every 36 48
hours or a an almost continuous one.
2) P Malariae Quartan fever Every 3 days
3) P Ovale and Vivax Tertian Fever Every 2
days
Erythrocytes with P. Falciparum
Anemia due to underproduction
1) Parvovirus B19
 Infects progenitor red cells halts
erythropoiesis
Leads to significant anemia in preexisting
marrow stress (sickle cell anemia)
Treatment is supportive
2) Aplastic Anemia
 Drugs or chemicals, viral
infections, autoimmune

Toxins like Benzene

Drugs like chloremphenicol,
Carbamazepine etc Pancytopenia, low reticulocyte
count

Empty bone marrow, fat

replaces normal tissue

Tx is cessation of causative
drugs, supportive care,
transfusions and marrow
stimulating factors like
erythropoietin, GM CSF and G
CSF

In idiopathic cases:
Immunosuppression

Last resort: Bone marrow

transplant
Bone Marrow Biopsy Aplastic
Anemia
 3) Myelophthisic Process
Pathologic Process e.g metastatic cancer that
replaces bone marrow, hematopoiesis is injured,
resulting in pancytopenia
Thank You