L06 - Classification and Lab Dx of Anemia

Question 1

Define Anaemia? Is it a disease?

Answer 1

Clinical condition: haemoglobin (Hb) 血紅素 concentration in red blood cell falls below the reference interval*

Specific for age, sex, race, altitude

Not a disease, But a manifestation/sign of the underlying disease

Question 2

What are the 2 determinants of Hb conc.? What variation of these determinants = anemia?

Answer 2

Hb (gram) ÷ Volume of blood (dL / L)

1) Reduced mass of Hb/ normal plasma volume
2) Normal mass of Hb/ Reduced plasma volume

Question 3

Factors that influence normal Hb concentration?

Answer 3

• Age: newborn = 19g/dL, Child = 10g/dL, Adult = 15g/dL
• Sex: lower Hb conc. in female
• Race
• Altitude: Higher alt = higher Hb conc.

Question 4

Principle mechanism of anemia?

Answer 4

upset of the dynamic balance between normal red cell production and loss

Question 5

Describe breakdown of RBC?

Answer 5

In tissue macrophages:

1) Heme > Iron and Biliverdin > Transferrin-Iron and Bilirubin into blood stream
2) Globulin > Amino acids

Unconjugated bilirubin > transformed into bilirubin glucuronides by liver to be excreted > excreted as stercobilinogen in feces or urobilinogen in urine

Breakdown products recycled or excreted

Question 6

Classify anemia under 4 pathological classes?

Answer 6

• Production defect – bone marrow failure
• Destruction – haemolysis, blood loss
• Sequestration – hypersplenism
• Dilution – increase in plasma volume relative to red cell mass

Question 7

Subclassification of anaemia caused by production defect?

Answer 7

1) Inadequate red cell production - upstream stem cell failure or stimulation failure or failure of maturation
2) Ineffective red cell production - Failure of maturation

Question 8

List causes of inadequate RBC production.

Answer 8

a) Bone marrow defect:
i) Haematopoietic stem cells (e.g. aplastic anaemia)
ii) Production site defect (e.g. marrow infiltrative lesions)

b) Lack of humoural stimulation / erythropoietin (e.g. chronic renal failure)

c) Iron metabolism problem:
i) Iron deficiency anaemia
ii) Inability to use iron (sideroblastic anaemia)

Question 9

List causes of ineffective RBC production.

Answer 9

A) Vit B12 metabolism problem

i) dietary B12 deficiency
ii) Inability to use Vitamin B12 (e.g. congenital transcobalamin II deficiency)

B) Involving globin metabolism: quantitative abnormality (Thalassaemia)

C) Myelodysplastic syndrome: common myeloid progenitor mutation with premature apoptosis

C) Megaloblastic anaemia: impaired nucleotide synthesis with abnormal maturation

Question 10

Normal life span of RBC? Factors that influence life span?

Answer 10

Normal lifespan of red cells = 100-120 days – depends on:

• Membrane integrity
• Normal Haemoglobin structure
• Adequate supply of ATP (glycolysis and unloading)
• Adequate supply of reducing power (oxidative damadge)

Question 11

What are the different root causes of increased red cell destruction?

Answer 11

Haemolysis:

1) Intrinsic/ intracorpuscular defect
2) Extrinsic/ extracorpuscular defect: Immune/ Non-immune haemolysis
3) Interaction between intra- and extracorpuscular factors

Question 12

List some Intrinsic/ intracorpuscular defect of RBC?

Answer 12

– Red cell membrane defect
– Red cell enzyme defect (G6PD)
– Haemoglobin defect

Question 13

List some Extrinsic/ extracorpuscular, Immune haemolysis defect of RBC?

Answer 13

Immune haemolysis (antibody-mediated):

1) Alloimmune (e.g. haemolytic transfusion reaction, haemolytic disease of the newborn)
2) Autoimmune (autoimmune haemolytic anaemia)
3) Drug-induced immune haemolysis

Question 14

List some Extrinsic/ extracorpuscular, Non- immune haemolysis defect of RBC?

Answer 14

1) Mechanical damage (e.g. microangiopathic haemolytic anaemia, artificial heart valves)
2) Toxin
3) Infection (e.g. malaria – blackwater fever)
4) Burn

Question 15

List one haemolytic disease due to Interaction between intracorpuscular and extracorpuscular factors ?

Answer 15

paroxysmal nocturnal haemoglobinuria

Question 16

List some causes of RBC sequestration?

Answer 16

hypersplenism/splenomegaly from trapping / pooling of red cells, white cells, platelets:

1) Portal hypertension (e.g. due to liver cirrhosis, Hep B)
2) Haematological diseases (e.g. sickle cell anemia)
3) Uncommon: Chronic infections, Storage diseases

Question 17

List some causes of Haemodilution?

Answer 17

• Pregnancy
• Fluid resuscitation after acute blood loss

Both increase plasma volume

Question 18

Clinical features of anaemia?

Answer 18

Low Hb concentration → impaired O2 transport → tissue hypoxaemia → body compensation / decompensation
• Pallor
• Fatigue (tissue hypoxia)

Cardiopulmonary compensation:
• Palpitation
• Shortness of breath

Question 19

Central and periphery pallor are both accurate in accessing the lack of O2 transport in anaemia. T or F?

Answer 19

False

Periphery = subject to temp change, not accurate

Central = accurate

Question 20

What does the severity of anemic symptoms/ symptomatology depend on?

Answer 20

1) Extent to which haemoglobin concentration is lowered
2) Rate / rapidity of onset (e.g. acute =no time to compensate)
3) Adequacy of cardiopulmonary compensation (e.g. elderly = more severe)

Question 21

Initial investigations techniques used to help guide Dx of anaemia?

Answer 21

1) Complete blood count (CBC):
- Cell count, Hb conc., Red cell indicies, Reticulocyte count, White cell and platelets

2) Examination of peripheral blood smear

> > Provide useful information on possible differential diagnosis, pathogenic mechanism for anaemia

Question 22

List the variation in the size, shape and colour of blood cells seen under peripheral blood smear?

Answer 22

• Size: normocytic, microcytic, macrocytic, dimorphic (2 red cell populations)
• Variation in size = anisocytosis
• Colour (chromia): normochromic, hypochromic, polychromatic (indicates reticulocytosis)
• Variation in shape = poikilocytosis

Question 23

List the RBC indicies obtained in CBC?

Answer 23

• Haemoglobin (HGB)
• Mean cell volume (MCV)
• MCH (follows MCV normally)
• Red cell distribution width (RDW)
• Mean cell haemoglobin concentration (MCHC)

Question 24

Which RBC indicies is the most useful for DDx of anaemia after HGB?

Answer 24

Mean cell volume (MCV)

Question 25

How to guide the DDx of anaemia based on MCV?

Answer 25

Classify into Microcytic, Normocytic, Macrocytic

Question 26

List causes of Microcytic anaemia?

Answer 26

 Iron deficiency
 Thalassaemia
 Anaemia of chronic disease

Question 27

List causes of Normacytic anaemia?

Answer 27

• Renal failure

Anaemia of chronic disease:

• Haemolysis
• Aplastic anaemia/ BM defects
• Myelodysplasia

Question 28

List causes of Macrocytic anaemia?

Answer 28

• Megaloblastic anaemia

Anaemia of chronic disease:

• Severe haemolysis
• Aplastic anaemia/ BM defect
• Myelodysplasia

Question 29

Define RDW and its use in DDx of anaemia?

Answer 29

Reflects differences in red cell sizes

Useful to differentiate between thalassaemia trait and iron deficiency anaemia (both microcytic anaemia)

Question 30

Explain how to use RDW to DDx anaemia?

Answer 30

Microcytic:
• normal RDW, High RBC = thalassaemic trait (genetic defect)

• high RDW, Low RBC = acquired iron deficiency, severe thalassaemia (intermedia or major)

Question 31

Derive MCHC and its use to DDx anaemia?

Answer 31

Derived from Hb, MCV and red cell count

MCHC = Hb / (MCV x RBC)

High value = sensitive indicator of spherocytosis (membranopathy causing loss of central pallor and SA:vol ratio) /agglutination

Fast way to analyze PBS result

Question 32

Appearance of reticulocytes in PBS?

Answer 32

• Large, light-blue staining cells (due to RNA, no nucleus)

* Polychromasia

Question 33

How is reticulocyte count used to guide DDx of anaemia?

Answer 33

Reticulocytosis indicates marrow compensation to hypoxemia, which requires:

1. Functioning marrow
2. Adequate erythropoietin
3. Adequate raw materials (Fe, vitamin B12, folate, normal hemoglobin)

Question 34

Aplastic anaemia can lead to reticulocytosis. T or F?

Answer 34

False

Apalstic anaemia = BM defect

Impossible to make normal marrow compensation to increase reticulocyte count

Question 35

How is WBC count used to guide DDx of anaemia?

Answer 35

• Isolated anaemia = limited defect

- Pancytopenia = generalized defect, more suggestive of BM disorder

Question 36

Appearance of RBC in PBS?

Answer 36

• Biconcave disc with central pallor (pallor too big = hypochromia; too small = hyperchromia)

Diameter of pallor should not exceed 1/3 of total RBC diameter

• Normal, consistent size and shape

Question 37

Give examples and underlying causes of haemotological disease that give rise to abnormal shape RBC. SSS TEAC

Answer 37

 Sickle cell anemia
 Spherocyte (immune-mediated hemolysis, congenital red cell membrane defects)
 Schistocyte (microangiopathic hemolytic anemia)

 Target (beta thalassemia trait, liver disease)
 Elliptocyte (iron deficiency anemia)
 Acanthocyte (severe liver disease)
 Crenated (liver / renal failure)

Question 38

Give examples and underlying causes of haemotological disease that give rise to abnormal disposition of RBC.

Answer 38

 Rouleaux (stacks / aggregations: increased serum proteins (e.g. globulin), plasma cell myeloma)

 Agglutination (e.g. Ab against RBC)

Question 39

Give examples and underlying causes of haemotological disease that give rise to abnormal Inclusion bodies of RBC.

Answer 39

HbH inclusion bodies = a-thalassemia

Howell-Jolly body = hypersplenism, asplenism, severe hemolytic anemias e.g. sickle cell anemia

Pappenheimer body (iron granules) = Sideroblastic anaemia, Thalassemia, Hemolytic anaemia, Post-splenectomy

Basophilic stippling = lead poisoning to bone marrow, megaloblastic anemia

Organism (e.g. malarial parasite)

Question 40

Morphology of RBC from PBS and CBC are enough for DDx of anaemia. T or F?

Answer 40

False

Red cell morphology should not be examined out of clinical context

> > Clinical history, physical examination findings, morphology of other cell lines and other available investigation results need to be taken into account

Question 41

Apart from CBC and PBS, what other investigations are valuable in guiding DDx of anaemia?

Answer 41

1) Iron profile (inadequate RBC production)
2) Total active Vit B12 level (Ineffective RBC production)
3) Markers of haemolysis: LDH, reti count, urine hemosiderin, bilirubin
4) Direct anti-globulin test (DAT)
5) Renal function test (EPO, inadequate stimulation)
6) Hb pattern study