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Anemia:
 By definition, a patient has anemia whenever the hemoglobin
(Hb) level or number of circulating red cells is significantly
reduced.
 The red blood cell is ideally suited to the task of oxygen
delivery.
 It is essentially a dedicated container for hemoglobin, the
protein responsible for oxygen transport.
 The most sensitive indicator of anemia would be a direct
measure of the level of oxygen delivered to peripheral
tissues.
Definition:
I. A significant deficit in the mass of circulating red blood cells
with resultant reduction in oxygen carrying capacity of blood.
II. exact cutoffs vary from source to source.
III. WHO criteria for anemia:
 Men: Hb < 13.5 g/dL
 Women: Hb < 12 g/dL
IV. Revised WHO/National Cancer Institute:
 Men: Hb < 14 g/dL
 Women: Hb < 12 g/dL
V. American Society of Hematology:
 Men: Hb < 13.5 g/dL
 Women: Hb < 12 g/dL
Values intended for
evaluation of anemia in
patients with malignancy &
chemotherapy
complications.
Clinical presentation:
 Presentation is usually based on nature of patients’ illness:
 Severe hemorrhage will produce acute blood loss anemia.
 Chronic blood loss can be expected to result in iron deficiency anemia (IDA).
 Whereas a patient with collagen vascular disease likely to present with
autoimmune hemolytic anemia.
 Patients report of reduced stamina, tachycardia, and dyspnea upon
exertion.
 When Hb falls <70 g/L:
 Exercise capacity marked reduced.
 Any exertion will be associated with dyspnea.
 Pounding head-ache.
 Rapid exhaustion.
 Palpitations.
Clinical features:
 Asymptomatic.
 Mild anemia often asymptomatic.
 Exertional dyspnea & fatigue.
 Pallor (e.g. on mucous membranes, conjunctivae)
 Jaundice (in hemolytic anemia)
 Worsening of angina pectoralis
 Muscle cramps.
 Features of hyperdynamic state:
 Palpitations
 Bounding pulses
 Flow murmur
 Pulsatile sound in the ear.
NB: Pulse acceleration is often the first
sign of hemodynamically relevant blood
loss
Laboratory tests:
I. Full blood count (FBC)
A. Red blood cell count
1. Hemoglobin (Hb)
2. Hematocrit (Hct)
B. Red blood cell indices
1. Mean cell volume (MCV)
2. Mean cell hemoglobin
(MCH)
3. Mean cell hemoglobin
concentration (MCHC)
C. White blood cell count
1. Cell differential
2. Nuclear segmentation of
neutrophils
D. Platelet count
E. Cell morphology
1. Cell size
2. Hb content
3. Anisocytosis
4. Poikilocytosis
5. Polychromasia
II. Reticulocyte count
III. Iron supply studies
A. Serum iron
B. Total iron-binding capacity
C. Serum ferritin, marrow iron
stain
IV. Marrow examination
A. Aspirate
B. Biopsy
RBC indices:
I. Mean cell / corpuscular volume (MCV):
a. A laboratory value that measures the average size &
volume of a RBC.
b. Calculation done by ‘multiplying the percent
hematocrit by ten divided by the erythrocyte count’.
c. Normally, values ought to be between 80-100 fL.
d. Value obtained assists in classification of anemia as
either:
a. Microcytic anemia – MCV below normal range
b. Normocytic anemia – MCV between normal range
c. Macrocytic anemia – MCV value above normal range.
Normal values for red-cell
indices:
Mean cell volume (MCV) 90 (+/-) 9 fL
Mean cell hemoglobin (MCH) 32 (+/-) 2 pg
Mean cell hemoglobin
concentration (MCHC)
33 (+/-) 3 %
• MCH is sensitive to defects in Hb production (hypochromia).
• Measurement errors can also be encountered.
• This can be a result of distortions in red cell shape, RBC agglutination, or
presence of very high numbers of WBCs.
• Inspection of peripheral blood film can provide important information as to the
passage & nature of an erythropoietic defect.
• The blood film is also important in describing variations in cell size
(anisocytosis) & shape (poikilocytosis).
Normal Hb & Hct values:
Age/Sex Hemoglobin, g/L Hematocrit, %
Adolescents 130 40
Adult men 160 (+/-) 20 47 (+/-) 6
Adult women 130 (+/-) 20 40 (+/-) 6
Adult women
(postmenopausal)
140 (+/-) 20 42 (+/-) 6
Pregnancy (3rd
trimester)
120 (+/-) 20 37 (+/-) 6
• Hematocrit – ratio of the volume of red blood cells to the total volume of a
blood sample.
Reticulocyte count:
 An accurate reticulocyte count is key to the initial classification of
any anemia.
 Reticulocytes are newborn RBCs that contain sufficient residual
RNA that can be stained with dye (‘supravital’) & counted as a
percentage of total circulating RBCs.
 Increases in the reticulocyte count provide a reliable measure of the
RBC production response to anemia.
Classifying anemia:
I. Classification of anemia is done according to dysfunction in
erythropoiesis:
A. Failure in RBC production (hypoproliferative).
B. Failure in maturation.
C. Increase in RBC destruction.
Classifying anemia:
Anemia
FBC,
reticulocyte
count
Index < 2
Red cell
morphology
Normocytic
normochromic
Hypoproliferative
Marrow damage
Iron
deficiency
Decreased
stimulation
Micro or
macrocytic
Maturation
disorder
Cytoplasmic
defects
-Iron
deficiency
-Thalassemia
Nuclear defects
-folate deficiency
-VitB12 deficiency
-Drug toxicity
Index > 3
Hemolysis/hemorrhage
-Acute blood loss
-Intravascular
hemolysis
-Metabolic defect
-Membrane
abnormality
-Autoimmune
defect
Classification using MCV:
I. Microcytic anemia (< 80 fL)
 Insufficient Hb production.
II. Normocytic anemia (80-100 fL)
 Decreased blood volume and/or decreased erythropoiesis.
III. Macrocytic anemia (> 100 fL)
 Insufficient nucleus maturation relative to cytoplasm expansion
due to:
 Defective DNA repair.
 Defective DNA synthesis.
Approach:
I. Check FBC to confirm anemia & assess severity.
II. Classify into either microcytic/normocytic/macrocytic
using MCV.
III. Order initial tests to evaluate underlying cause of
anemia.
A. Microcytic anemia
i. rule out IDA.
B. Macrocytic anemia
i. Peripheral blood smear to differentiate megaloblastic anemia from
non-megaloblastic anemia.
a. Megaloblastic anemia – serum B12 & folate levels.
b. Non-megaloblastic anemia – reticulocyte count to differentiate macrocytosis
due to hemolysis/blood loss from macrocytosis due to drugs, alcohol, or
pure red cell aplasia.
Approach:
A. Normocytic anemia
i. Reticulocyte count to assess bone marrow response.
a. Ret. Count > 2% : re-assess history for blood loss, rule out GI bleeding,
LDH, haptoglobin, unconjugated bilirubin to rule out hemolytic anemia.
b. Ret. Count < 2% : obtain iron studies, serum vitB12 & folate levels,
metabolic panel.
I. Consider advanced diagnostics such as bone marrow
aspirate & biopsy as needed.
 Blood for further tests should be drawn before the patient
receives a blood transfusion as blood products can alter
study findings.
Management:
 The management begins at the time of evaluation.
 Identify & treat underlying cause.
 Blood transfusion with RBCs for severe anemia:
 Hb < 7 g/dL
 Hb < 8 g/dL – if patient has pre-existing cardiovascular disease; or is
undergoing cardiac or orthopedic surgery.
 “Shotgun” therapy is never appropriate.
 The selection of the right therapy should be firmly based on the
documented cause or causes of anemia.
 It is important to evaluate a patient’s iron status before & during
therapy.
Management:
 Consider hospital admission or observation in:
 Acutely symptomatic anemia.
 Actively bleeding patient.
 Patients requiring blood transfusion.
 Bone marrow transplantation may be indicated in certain
cases (e.g. aplastic anemia).

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Anemia Diagnosis and Classification

  • 2. Anemia:  By definition, a patient has anemia whenever the hemoglobin (Hb) level or number of circulating red cells is significantly reduced.  The red blood cell is ideally suited to the task of oxygen delivery.  It is essentially a dedicated container for hemoglobin, the protein responsible for oxygen transport.  The most sensitive indicator of anemia would be a direct measure of the level of oxygen delivered to peripheral tissues.
  • 3. Definition: I. A significant deficit in the mass of circulating red blood cells with resultant reduction in oxygen carrying capacity of blood. II. exact cutoffs vary from source to source. III. WHO criteria for anemia:  Men: Hb < 13.5 g/dL  Women: Hb < 12 g/dL IV. Revised WHO/National Cancer Institute:  Men: Hb < 14 g/dL  Women: Hb < 12 g/dL V. American Society of Hematology:  Men: Hb < 13.5 g/dL  Women: Hb < 12 g/dL Values intended for evaluation of anemia in patients with malignancy & chemotherapy complications.
  • 4. Clinical presentation:  Presentation is usually based on nature of patients’ illness:  Severe hemorrhage will produce acute blood loss anemia.  Chronic blood loss can be expected to result in iron deficiency anemia (IDA).  Whereas a patient with collagen vascular disease likely to present with autoimmune hemolytic anemia.  Patients report of reduced stamina, tachycardia, and dyspnea upon exertion.  When Hb falls <70 g/L:  Exercise capacity marked reduced.  Any exertion will be associated with dyspnea.  Pounding head-ache.  Rapid exhaustion.  Palpitations.
  • 5. Clinical features:  Asymptomatic.  Mild anemia often asymptomatic.  Exertional dyspnea & fatigue.  Pallor (e.g. on mucous membranes, conjunctivae)  Jaundice (in hemolytic anemia)  Worsening of angina pectoralis  Muscle cramps.  Features of hyperdynamic state:  Palpitations  Bounding pulses  Flow murmur  Pulsatile sound in the ear. NB: Pulse acceleration is often the first sign of hemodynamically relevant blood loss
  • 6. Laboratory tests: I. Full blood count (FBC) A. Red blood cell count 1. Hemoglobin (Hb) 2. Hematocrit (Hct) B. Red blood cell indices 1. Mean cell volume (MCV) 2. Mean cell hemoglobin (MCH) 3. Mean cell hemoglobin concentration (MCHC) C. White blood cell count 1. Cell differential 2. Nuclear segmentation of neutrophils D. Platelet count E. Cell morphology 1. Cell size 2. Hb content 3. Anisocytosis 4. Poikilocytosis 5. Polychromasia II. Reticulocyte count III. Iron supply studies A. Serum iron B. Total iron-binding capacity C. Serum ferritin, marrow iron stain IV. Marrow examination A. Aspirate B. Biopsy
  • 7. RBC indices: I. Mean cell / corpuscular volume (MCV): a. A laboratory value that measures the average size & volume of a RBC. b. Calculation done by ‘multiplying the percent hematocrit by ten divided by the erythrocyte count’. c. Normally, values ought to be between 80-100 fL. d. Value obtained assists in classification of anemia as either: a. Microcytic anemia – MCV below normal range b. Normocytic anemia – MCV between normal range c. Macrocytic anemia – MCV value above normal range.
  • 8. Normal values for red-cell indices: Mean cell volume (MCV) 90 (+/-) 9 fL Mean cell hemoglobin (MCH) 32 (+/-) 2 pg Mean cell hemoglobin concentration (MCHC) 33 (+/-) 3 % • MCH is sensitive to defects in Hb production (hypochromia). • Measurement errors can also be encountered. • This can be a result of distortions in red cell shape, RBC agglutination, or presence of very high numbers of WBCs. • Inspection of peripheral blood film can provide important information as to the passage & nature of an erythropoietic defect. • The blood film is also important in describing variations in cell size (anisocytosis) & shape (poikilocytosis).
  • 9. Normal Hb & Hct values: Age/Sex Hemoglobin, g/L Hematocrit, % Adolescents 130 40 Adult men 160 (+/-) 20 47 (+/-) 6 Adult women 130 (+/-) 20 40 (+/-) 6 Adult women (postmenopausal) 140 (+/-) 20 42 (+/-) 6 Pregnancy (3rd trimester) 120 (+/-) 20 37 (+/-) 6 • Hematocrit – ratio of the volume of red blood cells to the total volume of a blood sample.
  • 10. Reticulocyte count:  An accurate reticulocyte count is key to the initial classification of any anemia.  Reticulocytes are newborn RBCs that contain sufficient residual RNA that can be stained with dye (‘supravital’) & counted as a percentage of total circulating RBCs.  Increases in the reticulocyte count provide a reliable measure of the RBC production response to anemia.
  • 11. Classifying anemia: I. Classification of anemia is done according to dysfunction in erythropoiesis: A. Failure in RBC production (hypoproliferative). B. Failure in maturation. C. Increase in RBC destruction.
  • 12. Classifying anemia: Anemia FBC, reticulocyte count Index < 2 Red cell morphology Normocytic normochromic Hypoproliferative Marrow damage Iron deficiency Decreased stimulation Micro or macrocytic Maturation disorder Cytoplasmic defects -Iron deficiency -Thalassemia Nuclear defects -folate deficiency -VitB12 deficiency -Drug toxicity Index > 3 Hemolysis/hemorrhage -Acute blood loss -Intravascular hemolysis -Metabolic defect -Membrane abnormality -Autoimmune defect
  • 13. Classification using MCV: I. Microcytic anemia (< 80 fL)  Insufficient Hb production. II. Normocytic anemia (80-100 fL)  Decreased blood volume and/or decreased erythropoiesis. III. Macrocytic anemia (> 100 fL)  Insufficient nucleus maturation relative to cytoplasm expansion due to:  Defective DNA repair.  Defective DNA synthesis.
  • 14. Approach: I. Check FBC to confirm anemia & assess severity. II. Classify into either microcytic/normocytic/macrocytic using MCV. III. Order initial tests to evaluate underlying cause of anemia. A. Microcytic anemia i. rule out IDA. B. Macrocytic anemia i. Peripheral blood smear to differentiate megaloblastic anemia from non-megaloblastic anemia. a. Megaloblastic anemia – serum B12 & folate levels. b. Non-megaloblastic anemia – reticulocyte count to differentiate macrocytosis due to hemolysis/blood loss from macrocytosis due to drugs, alcohol, or pure red cell aplasia.
  • 15. Approach: A. Normocytic anemia i. Reticulocyte count to assess bone marrow response. a. Ret. Count > 2% : re-assess history for blood loss, rule out GI bleeding, LDH, haptoglobin, unconjugated bilirubin to rule out hemolytic anemia. b. Ret. Count < 2% : obtain iron studies, serum vitB12 & folate levels, metabolic panel. I. Consider advanced diagnostics such as bone marrow aspirate & biopsy as needed.  Blood for further tests should be drawn before the patient receives a blood transfusion as blood products can alter study findings.
  • 16. Management:  The management begins at the time of evaluation.  Identify & treat underlying cause.  Blood transfusion with RBCs for severe anemia:  Hb < 7 g/dL  Hb < 8 g/dL – if patient has pre-existing cardiovascular disease; or is undergoing cardiac or orthopedic surgery.  “Shotgun” therapy is never appropriate.  The selection of the right therapy should be firmly based on the documented cause or causes of anemia.  It is important to evaluate a patient’s iron status before & during therapy.
  • 17. Management:  Consider hospital admission or observation in:  Acutely symptomatic anemia.  Actively bleeding patient.  Patients requiring blood transfusion.  Bone marrow transplantation may be indicated in certain cases (e.g. aplastic anemia).