Classification of Anemia

Iin Novita Nurhidayati Mahmuda

Fakultas Kedokteran UMS
RS PKU Muhammadiyah Surakarta
Definition of anemia
 Anemia: A reduction in
– red cell mass
– O2-carrying capacity
 It is expressed in terms of reduction
in the concentration of Hb (or RBC or
Hct%) compared to values obtained
from a reference population.
(2 SD below normal)
 Definition of anemia
 Hb level of a patient which is below the normal
ranges of that age and sex.
For adults:
 WHO criteria define anemia as hemoglobin level
lower than 12 g/dL in women and 13 g/dL in men
 But: The reference values for red cells ,Hb or Hct may difer
according to
– sex/age
– Race
– Altitude
– Socioeconomical changes
– Study/reference etc
 Measurements of Anemia
 Hemoglobin = grams of hemoglobin per 100 mL of whole
blood (g/dL)
 Hematocrit = percent of a sample of whole blood occupied
by intact red blood cells
 RBC = millions of red blood cells per microL of whole blood
 MCV = Mean corpuscular volume
– If > 100 → Macrocytic anemia
– If 80 – 100 → Normocytic anemia
– If < 80 → Microcytic anemia
 RDW = Red blood cell distribution width
– = (Standard deviation of red cell volume ÷ mean cell volume) × 100
– Normal value is 11-15%
– If elevated, suggests large variability in sizes of RBCs
Special Considerations in
Determining Anemia
 Acute Bleed
 Drop in Hgb or Hct may not be shown until 36 to 48
hours after acute bleed (even though patient may
be hypotensive)
 Pregnancy
 In third trimester, RBC and plasma volume are
expanded by 25 and 50%, respectively.
 Labs will show reductions in Hgb, Hct, and RBC
count, often to anemic levels, but according to RBC
mass, they are actually polycythemic
 Volume Depletion
 Patient’s who are severely volume depleted may not
show anemia until after rehydrated
RBC Life Cycle
 In the bone marrow, erythropoietin enhances
the growth of differentiation of burst forming
units-erythroid (BFU-E) and colony forming
units-erythroid (CFU-E) into reticulocytes.
 Reticulocyte spends three days maturing in the
marrow, and then one day maturing in the
peripheral blood.
 A mature Red Blood Cell circulates in the
peripheral blood for 100 to 120 days.
 Under steady state conditions, the rate of RBC
production equals the rate of RBC loss.
Normal Peripheral Smear
!!!!!

 A normal Hb in a patient in whom an

elevated Hb level is expected may
represent anemia .(eg:COPD + Hb:N)
!!!!

 Anemia is rarely a disease by itself,

 It is mostly a manifestation or
consequence of an underlying
(genetic or acquired) disease.
 The finding of anemia has to start
attempts to disclose an underlying
disease .
– What is the cause of anemia ?
Anemia leads to two
symptom complexes;
 Tissue hypoxia
– Fatigue,dyspnea on exertion etc
 Compensatory attempts
– Tachycardia,hyperventilation etc
 The amount of O2 necessary to support life
is : 250 ml/min

 O2 carrying capacity of normal blood:1.34

ml/g-Hb (200 ml/L-blood)
 Cardiac output: 5000 ml/min

 O2 delivery to tissues : 1000 ml/min

 Reduced levels of Hb results with
reduced oxygen delivery to tissues ,
leading to tissue hypoxia.
 The symptoms and findings of anemia
concern many different systems/organs
due to the widespread nature of hypoxia.
 The most pronounced effects and
symptoms derive from
– skeletal muscles, heart,and central nervous
system
(due to their greater oxygen demand and compensatory actions).

 What is the mechanism underlying

compensatory mechanisms ?
 Compensating mechanisms in
anemia:
 The release of oxygen to the tissues is
increased (reduced oxygen affinity of Hb)
 Compensating mechanisms in
anemia

 The rate of blood circulation and cardiac

output increases.
 An increase in plasma volume maintains
total blood volume in normal or near
normal ranges.
 Redistribution of blood flow.
 Different patients may have different severity of
symptoms even for the same level of Hb.
 The severity of the symptoms of anemia are
related to;
– The severity of anemia
– The age,CVS,pulmonary status etc of the patient
– The rate of the development of anemia
 Gradual or
 Rapid onset
 Clinical symptoms and findings
of anemia (1)

 The symptoms and findings are related

to anemia itself or to the underlying
disease that causes anemia .
 The symptoms and findings related to
anemia itself will be mentioned during
this course.
Clinical symptoms and findings of
anemia (2)

 Fatigue, weakness
– Tiredness, lassitude, reduced exercise
tolerence
– Generalized muscular weakness
 Pallor /skin or mucous membranes
– Skin color may change due to other
reasons;
eg :Blood flow of skin, subcutaneous fluid ,
pigment changes
Pallor (paleness):
 Look at
– Mucous membranes of mouth and pharynx
– Conjunctivae,lips, nail beds,palms
 Creases of the palms lose their pink colour when the
Hb < 7g/dL
 In pernicious anemia there is a lemon yellow pallor.
 Pallor + mild scleral icterus suggests hemolytic
anemia.
 Pallor+ petechiae suggests severe bone marrow
failure
 Some other skin/mucosal changes
– Premature graying of hair:pern.anemia
– Hair loss and fragility + spooning of the nails:iron
deficiency
– Chronic leg ulcers:Sickle cell or other hemolytic
anemia
– Glossitis/burning sense :Pern. anemia, iron deficiency(rare)
– Chelitis(angular stomatitis):iron def.
– Siideropenic dysphagia: iron def.
– Painful ulcerative mouth lesions: aplastic anemia/leukemia
 Clinical symptoms and findings of
anemia (3)
Cardiovascular System(1)

 Palpitation and dyspnea (during activity)

 Angina pectoris
 Claudicatio intermittans
 Murmurs: Mid systolic (rarely diastolic) ,
mainly pulmonary valvular or apical
or over major peripheral arteries
or jugulary veins
Clinical symptoms and findings of
anemia (3)
Cardiovascular System(2)

 High output state: Collapsing

pulse, high pulse pressure
 Cardiomegaly
 Congestive failure
 Ischemic ECG changes
 Clinical symptoms and findings of
anemia (4)
Central nervous system

 Headache
 Faintness
 Giddiness
 Tinnitus
 Decreased concentration ability
 Drowsiness,decreased muscle strength
 Clouding of consciousness
 Symptoms are more prominent in older patients
 Paresthesias:Vitamin B12 deficiency (or other).
Clinical symptoms and findings of
anemia (5)

Reproductive system
 Menstrual changes:
– Amenorrhea ,
– Menorrhagia(mostly a cause of anemia)
 Loss of libido
 Clinical symptoms and findings of
anemia (6)
Gastrointestinal system
(these symptoms may indicate underlying disorder
that might indeed be a cause of anemia)
 Anorexia
These should remind GIS disease as a
 Flatulence cause of anemia
 Nausea (eg:a bleeding lesion-ulcer/malignancy etc)
 Constipation

 Weight loss
 Clinical symptoms and findings of
anemia (7)

 Ocular Fundi:
– Pale and
sometimes
– Hemorrhages
– Papillaedema
 Clinical symptoms and findings of
anemia (8)

 Renal Changes
– Slight proteinuria
– Concentrating defects
– Further reduction of renal function in patients
with previous renal impairment
(Renal failure itself is a cause of anemia!!!!)
 Pyrexia: Due to a hypermetabolic state or
other underlying disease (which may be a cause
of anemia)
 Some Other examples for history
and physical examination

 The duration of symptoms (acute/insidious)

 Bleeding ? Nose/skin/urine/mens/stool etc
 Family history
– Anemia, gall stones and splenectomy
– Bleeding disorder
 Occupation, hobbies,dietary history,alcohol or drug
use,travel history etc (toxic/infectious contacts)
 Ask for skin and hair/nail changes
Some Other examples for history
and physical examination

 Pain / mass / fever/systemic overview for an

underlying disease
– Renal/endocrine/liver disease or
– Chronic infection/malignancy/imflamatory condition
 Parasitis
 Pregnancies
 Paresthesias ,walking difficulty
 Sternal or other bone tenderness
 Splenomegaly, hepatomegaly
 Lymphadenomegaly
Diagnosis and investigation:

 Is the patient anemic?

 What is the type of anemia?
 What is the cause of anemia?
Classification of anemia

 Morphologic
– Normocytic: MCV= 80-100fL
– Macrocytic: MCV > 100 fL
– Microcytic : MCV < 80 fL
 Pathogenic (underlying mechanism)
– Blood loss (bleeding)
– Decreased RBC production
– Increased RBC destruction/pooling
Normocytic Anemias
 Acute post-  Endocrin diseases
hemorrhagic anemia  Renal failure
 Hemolytic anemia  Liver disease
(except thalassemia  Chronic disease anemia
and some other Hb
disorders)  Protein malnutrition
 Hypovitaminosis C
 Aplastic anemia
 Pure red cell aplasia
 Bone marrow
infiltration
Microcytic anemias

 Iron deficiency anemia

 Thalassemia
 Sideroblastic anemia
 Lead poisoning
 Anemia of chronic diseases
(some cases)
Macrocytic anemias

 Megaloblastic

 Non-megaloblastic
Megaloblastic Macrocytic
Anemias
 Vit B12 deficiency
 Folic acid deficiency
 Other.
Non-megaloblastic
Macrocytic Anemias
 Anemia of acute
bleeding  Alcoholism
 Myelodysplastic  Hypothyroidism
syndromes
 Liver disease
 Pathogenic classification
(Causes of anemia)
 Relative (increased plasma volume)
 Decreased RBC production
 Blood loss
– Anemia due to acute bleeding
 Increased RBC destruction
 Pathogenic classification
(Causes of anemia)
 Decreased RBC production
– Decreased Hb production
– Defective DNA synthesis
– Stem cell defects
 Pluripotent stem cell
 Erythroid stem cell(progenitors)
– Other less defined reasons
 Blood loss
– Anemia due to acute bleeding
 Increased RBC destruction
 Relative(increased plasma volume)
Decreased Hb production

 Iron deficiency anemia

 Thalassemia
 Sideroblastic anemia
 Lead poisoning
Defective DNA synthesis

 Vit B12 deficiency

 Folic acid deficiency
 Other.
Pluripotent stem cell defects

 Aplastic anemia
 Leukemia or myelodysplastic syndromes

Defective erythroid stem cell

 Pure red cell aplasia
 Anemia of chronic renal failure
 Endocrin disease anemia
 Congenital dyserythropoetic anemias
Decreased RBC production due to
multipl or undefined mechanisms

 Anemia of chronic diseases

 Bone marrow infiltration
 Anemia due to nutritional defects
Anemias caused by
increased RBC destruction
(hemolytic anemias)
Can be classified as;
 Hemolysis due to intracorpuscular defects
 Hemolysis due to extracorpuscular defects
Or
 Hereditary hemolytic diseases
 Acquired hem. diseases
Or
 Intravascular hemolysis
 Extravascular hemolysis etc.
A Very Simple Classification of Hemolytic Anemias

1- Abnormalities of RBC interior

a. Enzyme defects
b. Hemoglobinopathies & Thalassemia M Hereditary
2-RBC membrane abnormalities
a. Hereditary spherocytosis, elliptocytosis etc
b. Paroxysmal nocturnal hemoglobinuria
c. Spur cell anemia
3- Extrinsic factors
a. Hypersplenism Acquired
b. Antibody : immune hemolysis
c. Traumatic & Microangiopathic hemolysis
d. Infections , toxins , etc
Is the patient anemic ?

 RBC count
 HB level
 Hct level
 Volume status
What is the type of
anemia?
 History and physical exam.
 RBC,HB,Hct ,
 MCV, MCH,RDW
 Red cell morphology ( peripheral smear)
 Reticulocyte count
– Incresed ?
 Other Lab. investigations
Lab. investigation of anemia(1)

 WBC count and differential

 Platelet count and morphology
 ESR
 Biochemistry, special tests and others
 Bone marrow exam.(only when indicated)
 Lab. investigation of anemia(2)

 Serum values of
– Iron
– TIBC
– Ferritin
– Bilirubins
– Proteins / electrophoresis
– LDH
– Vit B12 and /or Folic acid
(None of these tests are routine screening tests)
 Lab. Investigation of Anemia(3)

 Red cell enzymes

 Hb F,A2,Hb electrophoresis
 Coombs tests
 Liver, renal, endocrin functional tests
 Urinalysis
– Hemosiderin
 Occult GIS bleeding / parasites etc
(tests should be chosen individually-do not order routinly )
 Investigation of a microcytic hypochromic anemia

Blood Film

Serum Iron

Serum iron high Serum iron normal/high Serum iron low

Marrow for iron Hemoglobin studies Ferritin level

Low Normal / High

Sideroblastic anemia Thalassemia İron deficiency Anemia of

Abnormal Hb chronic disease
 Investigation of a normocytic, normochromic anemia

Reticulocyte count

Retic. normal / low Retic. high

response to anemia treatment

Bone marrow morphology hemolysis acute blood loss

Normal Abnormal

Hypoplastic infiltration dysplastic

Secondary anemia
eg. Inflammation aplastic anemia leukemia myelodysplasia
liver disease myelofibrosis
Renal failure metastases
endocrine failure
 Macrocytic anemia (MCV: high)

Blood film
Reticulocyte count

Retic. High Retic. Normal/low

Bone marrow
Non-megaloblastic Megaloblastic
Acute blood loss or
Hemolytic anemia normoblastic dysplastic(MDS) folate or B12 levels

Treatment response (Other macrocytic anemias)

folate Vit B12
deficiency deficiency
Reference values (I)

Parameter Female Male

 RBC (x1012/L) 4.8+0.6 5.4+0.9
 Hb (g/dL) 14+2 16+2
 Htc (%) 42+5 47+5
 Reference values (II)

 Ret (% / n) 0.5-2.5 / 50-100x109/L

 MCV (fl) 90+7
 MCH (pg) 29+2
 MCHc (g/dL) 34+2
 RDW (%) 11.5-14.5
BEUTLER andWAALEN BLOOD, 1 MARCH 2006 VOLUME 107, NUMBER 5
Age and blood count changes
age WBC Neutrophyls Eos. Baso Lenfo Mono Hb

12 mo 6-17.5 1.5-8.5 0.05-0.7 0-0.20 4-10.5 0.05-1.1 11.1-14.1

4y 5.5-15 1.5-8.5 0.02- 0-0.20 2-8 0-0.8 11.2-14.3

0.65

6y 5-14.5 1.5-8 0-0.65 0-0.20 1.5-7 0-0.8 11.4-14.5

10 y 4.5-13 1.8-8 0-0.60 0-0.20 1.5-6.5 0-0.8 11.8-15

21 y 4.5-11 1.8-7.7 0-0.45 0-0.20 1-4.8 0-0.8 E: 16

K: 14

WBC: x10E3/mm3 Hb:g/dL