Approach to anemia

1. Presenters

2. OUTLINES
 Definition, RBC indices and classification anemia
 Approach to patients with anemia and
investigations
 Iron deficiency anemia

3. Definition and classification
anemia
 Anemia definitions — Anemia is defined as a reduction in
one or more of the RBC measurements:
 hemoglobin concentration,
 hematocrit,
 RBC count.
 Anemia is defined as values that are more than two
standard deviations (SD) below the mean, with the
following cutoffs:
 Females – Hemoglobin <11.9 g/dL (119 g/L) or hematocrit
<35 percent
 Males – Hemoglobin <13.6 g/dL (136 g/L) or hematocrit
<40 percent

4. Definition cont’d
 WHO criteria for anemia;
 adult males is hemoglobin <13 and in
 adult females is hemoglobin <12 g/dL
 These "normal" ranges may not apply to certain populations
 Athlete
 Smoking and high altitude
 pregnancy
 African-Americans
 Presence of chronic disease
 Older adults

5. Red blood cell indices
 MCV – is the average volume (size) of the patient's RBCs. It
can be measured or calculated (MCV in femtoliters [fL] = 10 x
HCT [in percent] ÷ RBC [in millions/microL]).
 MCH – Mean corpuscular hemoglobin (MCH) is the average
hemoglobin content in a RBC.
 It is calculated (MCH in picograms [pg]/cell = hemoglobin x 10 ÷
RBC
 MCHC –is the average hemoglobin concentration per RBC.
 MCHC in grams [g]/dL = hemoglobin X 100 ÷ HCT .
 RDW – Red cell distribution width (RDW) is a measure of the
variation in RBC size, which is reflected in the degree of
anisocytosis on the peripheral blood smear.
 RDW = [standard deviation/MCV] x 100).

7. Classification of anemia
 A kinetic approach, addressing the mechanism(s)
responsible for the fall in hemoglobin concentration
 A morphologic approach categorizing anemias via
alterations in RBC size (MCV and reticulocyte
response

8. 1) Kinetic approach
 Kinetic approach — Anemia can be caused by
three independent mechanisms:
 decreased RBC production,
 increased RBC destruction, and
 blood loss.
 Occasional patients may have two (or all three) of
these mechanisms operating at the same time. As
examples:

9. Decreased RBC production — Anemia will ultimately
result if the rate of RBC production is less than that of
RBC destruction
 This can occur either due to
 reduced effective production of red cells, or
 the destruction of RBC precursors within the bone
marrow (ineffective erythropoiesis).

10.  Reduced effective production of red cells
Hemoglobin synthesis: Iron deficiency,
thalassemia, anemia of chronic disease
DNA synthesis: megaloblastic anemia
Stem cell: aplastic anemia, myeloproliferative
leukemia
Bone marrow infiltration: carcinoma,
lymphoma

11.  Presence of ineffective erythropoiesis — cxzed
by intense erythroid hyperplasia within the bone
marrow along with a relative reduction in reticulocyte
production (eg, a reduced reticulocyte production
index).
 Megaloblastic anemia
 Alpha and beta thalassemia
 The myelodysplastic syndrome
 Sideroblastic anemias

12. Increased destruction of circulating RBCs
 A RBC life span below 100 days is the operational
definition of hemolysis .
 It could result from intravascular or extravascular
hemolysis .

13. Intravascular hemolysis
 Microangiopathic hemolytic anemia
 Clostridial sepsis
 Paroxysmal nocturnal hemoglobinuria
 Cold agglutinin disease
 Paroxysmal cold hemoglobinuria
Extravascular hemolysis
 Enzyme deficiencies (eg, G6PD or pyruvate kinase deficiencies)
 Hemoglobinopathies (eg, sickle cell disease, thalassemias, unstable
hemoglobins)
 Membrane defects (eg, hereditary spherocytosis, elliptocytosis)
 Liver disease
 hypersplenism

14.  Blood loss — Blood loss is the most common cause
of anemia.
 Obvious bleeding (eg, trauma, melena, hematemesis,
severe menometrorrhagia)
 Occult bleeding (eg, slowly bleeding ulcer or
carcinoma)

15. 2) Morphologic approach
 Morphologic approach — The causes of anemia
can also be classified according to measurement of
RBC size,
 The normal RBC has a volume of 80 to 96
femtoliters and a diameter of approximately 7 to 8
microns, equal to that of the nucleus of a small
lymphocyte.
 Thus, RBCs larger than the nucleus of a small
lymphocyte on a peripheral smear are considered
large or macrocytic, while those that appear smaller
are considered small or microcytic

16.  Macrocytic anemia — Anemia is considered
"macrocytic" when the MCV exceeds 100 fL Causes
include the following
 Marked reticulocytosis ,an increased MCV.
 Abnormal nucleic acid metabolism of erythroid precursors
(eg, folate or cobalamin deficiency and drugs interfering
with nucleic acid synthesis.
 Abnormal RBC maturation (eg, myelodysplastic syndrome,
acute leukemia).
 Other common causes include alcohol abuse, liver
disease, and hypothyroidism.

17.  Microcytic anemia — Anemia is considered
"microcytic" when the MCV is less than 80 fL.
 Reduced iron availability – Severe IDA, AOCD
 Acquired disorders of heme synthesis – Lead
poisoning, acquired sideroblastic anemias
 Reduced globin production – Thalassemia, other
hemoglobinopathies
 Rare congenital disorders including sideroblastic
anemias, porphyria, and defects in iron absorption,
transport, utilization, and recycling

18.  Normocytic anemia, is when mcv 80-100
Normocytic anemia: systemic disease like
anemia of chronic renal disease,
Cardio renal anemia syndrome
 anemia of acute blood loss
hemolysis.

19. Approach to patients with Anemia
 Is the patient anemic?
 What is the type of anemia?
 What is the cause of anemia?

20. The evaluation of the patient with anemia requires a careful
history and physical examination.
The symptoms and findings are related to anemia itself or to the
underlying disease that causes anemia .
The Signs and symptoms of anemia are usually non-specific
So, the clinical diagnosis Made by combination of factors
including: patient history, physical signs and changes in
hematologic profile (investigation).

25. Angular stomatitis
glossitis
Nutritional deficiency anemia

26. Koilonychia - spoon shaped nail

27. Investigation
Initial Testing
1. Complete blood count (CBC)
A. Red blood cell count
 Hemoglobin
 Hematocrit
B. Red blood cell indices
 Mean cell volume (MCV)
 Mean cell hemoglobin (MCH)
 Mean cell hemoglobin concentration (MCHC)
 Red cell distribution width (RDW)
C. White blood cell count
 Cell differential
 Nuclear segmentation of neutrophils
2.Reticulocyte count
3.Peripheral blood smear

30. 2. Reticulocyte count
o Reflects bone marrow response to anemia
o Absolute reticulocyte count(ARC)=reported
reticulocytes (%)xRBC count
o ARC= 25-75,000/µl, ARC>100,000/µl indicates hemolysis
or blood loss
o Corrected reticulocyte count (CRC) =ARC x Pts
Hct/45(normal Hct)
o RPI (reticulocyte production index)

31. 3. Peripheral morphology
1. Size
 Microcytic (MCV<80), normocytic (MCV=80-100), macrocytic(MCV>100)
 Anisocytosis : RBCs with increased variability in size (increased RDW)
2.Colour
 Hypochromic: increase in size of central pallor (normal = less than 1/3 of
RBC diameter)
 Polychromasia: increased reticulocytes (pinkish-blue cells)
 Increased RBC production by the marrow
3. Shape
 Poikilocytosis: increased proportion of RBCs of abnormal shape
4. RBC Inclusions

33. 4) Further investigations: depends on the suspected cause/s of
anemia based on the above tests, the history and physical examination
findings.
➢ Suspected iron deficiency anemia:
✓ Serum ferritin
✓ Total iron binding capacity (TIBC)
✓ Transferrin saturation = 𝐒𝐞𝐫𝐮𝐦 𝐈𝐫𝐨𝐧 𝐓𝐈𝐁𝐂 𝑋 100 %, TIBC = Total Iron
binding capacity
Once iron deficiency is diagnosed:
✓ Stool for occult blood
✓ Stool microscopy for hookworm infestation
✓ Upper GI endoscopy or colonoscopy may be needed based on the clinical
suspicion.

34. ➢ Suspected megaloblastic anemia:
✓ serum vitamin B12 level
✓ serum folate
➢ Suspected hemolytic anemia:
✓ Reticulocyte count or percentage bilirubin (indirect
hyperalbuminemia)
✓ LDH
✓ Coomb’s tes
 Marrow examination
A. Aspirate
 M/E ratioa
 Cell morphology
 Iron stain
B. Biopsy
 Cellularity
 Morphology

36. Iron metabolism
• The iron cycle in humans
• Nutritional iron balance
Iron deficiency
 Introduction
 Stages of iron deficiency
 Causes of iron deficiency
 Clinical presentation
 Laboratory iron studies
 Differential diagnosis
 Management

37. Iron metabolism
 Iron is a critical element in the function of all cells.
 Requirement
 Free iron => toxic. (Why?)
 Roles of iron
 Hemoglobin
 Myoglobin
 Cytochrome
 As a cofactor

38. Iron Homeostasis
Sources of iron (3)
 Dietary sources (2 types)
 1 mg/d is required from the diet in men
 1.4 mg/d in women to maintain homeostasis
 Drugs
 Transfusions

39.  Iron absorbtion => (I=>D)
 Promoters vs Inhibitors
HCP1 Haem carrier protein-1
CYBRD cytochrome-b reductase-1
DMT1 divalent metal transporter 1
HMOX1 haemox reductase 1
FPN ferroportin
HEPH ceruloplasmin
CP hephaestin

40. Regulation of absorbtion
Promoters ( )
 Ascorbic acid (Vit C)
 Citric acid
 Normal stomach acid
 Presence of heme iron
 Fermented foods
 Low body stores
 ed erythropoiesis
 ed demand
Inhibitors ( )
 Phytates & phosphates
 Antacids, Calcium,
Surgery
 Tannins and
tetracyclines
 Oxalates, Gallic and
tannic acid
 High body stores
 ed erythropoiesis
 ed demand
.

41. Body stores
Iron
Blood (66%)
Storage form
(30%)
Skeletal system
(4%)

42. Body iron distribution
Iron content (mg)
Man Woman
Hemoglobin 2500 1700
Myoglobin/enzymes 500 300
Transferin 3 3
Iron stores 600-1000 100-300
Total 3.5 – 5.0gm

43. Excretion (loss from body )
GIT loss, GUT loss, skin
No physiologic mechanism that regulate iron
excretion
Regualtion is
Absorbtion
Utilization

44. External
sources
 Dietary
 Drug
 Transfusion
Stores
Serum (transferin)
Monoferric
Diferric
Loss from
the body

45.  Almost all of the iron transported by transferrin is
delivered to the erythroid
plasma iron level and
the erythroid marrow activity

46. NUTRITIONAL IRON BALANCE
Balance of iron in humans is tightly controlled and
designed to conserve iron for reutilization.
No regulated excretory pathway for iron
gastrointestinal bleeding
 Menses
 other forms of bleeding
 the loss of epithelial cells

47. Iron deficiency anemia(IDA)
 most common nutritional deficiency worldwide
 most common cause of anemia throughout the world
 A million deaths per year. (70% in Africa)

48. Causes of ID
Rapid growth
Pregnancy
Erythropoietin therapy
Blood loss
Menses
Phlebotomy
Inflammation
Malabsorbtion
Inadequte diet

49. Stages of ID
Negative iron balance
 Demand(loss) > absorption
 Mobilization from storage sites
 Serum ferritin
 Stainable iron
 Serum iron
 TIBC
 RBC protoporphyrin
 Red cell morphology and indices

50. Iron-deficient erythropoiesis
 Storage sites are depleted
 Serum ferritin
 Stainable iron
 Serum iron
 TIBC
 RBC protoporphyrin
 Red cell morphology and indices

51. Iron deficiency anemia
 Storage sites are depleted
 Serum ferritin
 Stainable iron
 Serum iron
 TIBC
 RBC protoporphyrin
 Red cell morphology and indices

52. Clinical presentation
History
 Age
 Sex (Pregnancy status and menstrual)
 Intermittent history of blood loss
“Iron deficiency in an adult male or postmenopausal female means
git blood loss until proven otherwise”

53. Physical examination
 Cheilosis (fissures at the corners of the mouth)
 Koilonychia (spooning of the fingernails

54. LABORATORY IRON STUDIES
 Serum Iron (50–150 μg/dL)
 Total Iron-Binding Capacity (300–360 μg/dL)
 Transferrin saturation (25-50%)
 Serum Ferritin
 Evaluation of Bone Marrow Iron Stores
 Red Cell Protoporphyrin Levels
 Serum Levels of Transferrin Receptor Protein

55. Differntial diagnosis
 Thalassemias
 Anemia of inflammation
 Myelodysplastic syndromes

56. Management
 Depends on severity and cause of IDA
I. Red cell transfusion
II. Oral iron therapy