IC7 Anaemia & drug induced haematologic disorder

Question 1

What are the 3 pathways that can lead to anaemia?

Answer 1

1. Hypoproliferative
   - Anything that causes you not to produce enough RBC
2. Maturation disorders
   - anything that can affect the maturation of RBC
3. Haemorrhage
   - loss of blood

Question 2

What are the most common causes of anaemia?

Answer 2

1. Iron deficiency
2. Vitamin B12 or Folic acid
3. Inflammation or Chronic disease
4. Drug induced
5. Cancer
6. Renal disease

Question 3

Chronic conditions can cause anaemia.

This is also known as anaemia of inflammation.

What are some chronic conditions that can lead to anaemia?

Answer 3

Chronic conditions that can cause anaemia are:
1. Malignancy
2. HIV infection
3. Inflammatory bowel disease
4. Heart failure
5. Renal insufficiency
6. Chronic obstructive pulmonary disease
7. Rheumatologic disorders
8. Castleman disease

Question 4

What are the lab tests to do for anemia?

Answer 4

1. FBC - the main test to do
2. Reticulocyte count
3. Peripheral smear

Question 5

What to ask pt if low Hgb levels were detected?

Answer 5

1. History of the patient - to sieve out any possible causes
2. Conduct physical examinations for pallor & jaundice.
   (Pallor - pulling down of the eyelid and see how pale it is)
3. Lab test - FBC, reticulocyte count, peripheral smear

Question 6

Under FBC test, there is MCV data. What is MCV?

Answer 6

MCV - Mean corpuscular volume

MCV tells us the size of our red blood cells

Question 7

When MCV is high, what do we look at?

High MCV is aka megaloblastic anaemia.

Answer 7

We look at Vitamin B12 and folate levels.

Vitamin B12 or folate deficiency can result in high MCV.

If patient has high MCV, it is often due to:

1. Normal Vitamin B12 levels + folate deficiency
2. Vitamin B12 deficiency + normal folate levels
   (aka pernicious anaemia)

Pernicious anaemia is a type of megaloblastic anaemia - often due to the body with reduced ability to absorb Vitamin B12.

Question 8

When MCV is low, what do we look at?

Low MCV is aka microcytic anaemia

Answer 8

We look at serum ferritin levels.

If patient has low MCV due to low serum ferritin levels, patient is diagnosed with;
- iron deficiency anaemia.

Question 9

If MCV is low, yet serum ferritin is normal, what else do we look at?

Answer 9

We look at Total Iron Binding Capacity (TIBC).

When serum ferritin does not explain why MCV is low, we look at TIBC.

If patient has low TIBC, it suggest that pt has anaemia due to chronic disease.
Examples of chronic diseases: Malignancy, IBD, HIV infection, etc.

If patient has normal/high TIBC, other testing is required to find out the cause.

Question 10

When MCV is normal, what do we look at?

Answer 10

We look at reticulocyte count when MCV is normal.

If there is high reticulocyte count, it could suggest:

1. Acute blood loss
2. Haemolysis

If reticulocyte count is low,
it tells us that the RBCs are small and there are not enough new RBCs. This could indicate a condition with the bone marrow.

To be sure that it is not the bone marrow, we will look at WBC and platelets after discovering that MCV and reticulocytes are low.

If WBC and platelets are all low as well, it means there is an issue with bone marrow.

If WBC and platelets are normal/high when MCV and reticulocytes are low, it could indicate possible malignancies, chronic infection, chronic renal disease, chronic inflammation.

Question 11

What are common causes of iron deficiency anaemia?

Answer 11

Iron deficiency anaemia is often caused by insufficient iron intake or poor absorption of iron.

Poor iron absorption often results in conditions or medication that reduces gastric acidity.

For example:
1. PPIs
2. H.pylori infection
3. Atrophic gastritis
4. Gastric bypass
5. Other medication that reduces gastric acidity

Question 12

How to treat iron deficient anaemia?

Answer 12

We will give iron supplementation 100-200mg/day for 3-6months

Requiresabout 1000-1500mg of elemental iron for complete supplementation.

Question 13

What is the formula to calculate TSAT?

Answer 13

Serum ferritin ÷ TIBC = TSAT

Question 14

How do we treat Pernicious anaemia?
(Anaemia due to vitamin B12 deficiency)

Answer 14

We will give patient Vitamin B12.

When initiating treatment, we will give Vitamin B12 parenterally.
Oral Vitamin B12 is not enough in initial treatment. It will only be given as maintainence therapy

Dosing:
1) IM 1000mcg Vitamin B12 daily x 1 week
2) Followed by IM 1000mcg Vitamin B12 weekly x 4 weeks
3) Followed by IM 1000mcg Vitamin B12 monthly x lifelong

Question 15

How do we treat folate deficient anaemia?

Answer 15

We will give patients Folic Acid.

Question 16

What is aplastic anaemia?

Answer 16

Aplastic anemia is a condition that occurs when your body stops producing enough new blood cells.

Question 17

How to diagnose a patient with Aplastic Anaemia?

Aplastic anaemia is associated with:
MCV normal, reticulocyte count low, WBC & platelets low

Answer 17

To diagnose a patient with aplastic anaemia, patients must have at least 2 of the following:

WBC ≤3.5 x 10^9/L

Platelet count ≤55 x 10^9/L

Hgb ≤10g/dL & Reticulocyte count ≤30 x10^9/L

Question 18

What is one of the causes of aplastic anaemia that we must know?

Answer 18

Drug-induced aplastic anaemia

Question 19

What are the goals of therapy of aplastic anaemia?

Answer 19

1. To improve peripheral blood count
2. Limit the need for transfusion
3. Minimise risk for infection

Question 20

How do we treat aplastic anaemia?

Rmb goals of therapy:
1. To improve peripheral blood count
2. Limit the need for transfusion
3. Minimise risk for infection

Answer 20

1. 1st thing to do for drug induced aplastic anaemia is to hold off the offending drug
2. Provide transfusion support with erythrocytes & platelets
3. Provide prophylactic antibiotic and antifungal agents when neutrophil counts are <0.5x10^9/L

Question 21

What is drug induced neutropenia?

Answer 21

Drug induced neutropenia is when a drug causes the absolute neutrophil count to be <1500/µL.

Question 22

What is agranulocytosis?

Answer 22

Agranulocytosis - absences of granulocytes.

E.g no neutrophils, no basophils, no eosinophils

Question 23

What are common drug classes that causes agranulocytosis?

Answer 23

1. Anti-thyroid agent - e.g methimazole, PTU, carbimazole
2. Clozapine & other phenothiazines
3. Penicillins

Question 24

What is the main goal of therapy for agranulocytosis?

Answer 24

Improving mortality rate

Question 25

How do we treat agranulocytosis?

Answer 25

1. First thing to do is to stop offending drug
   - Blood cell counts often return back to normal within 2-4 weeks
2. If neutrophil still <0.1 x 10^9/L, use filgrastim (GCSF) SQ 300mcg/day
3. Avoid restarting offending agent
   - Penicillin can be restarted at a lower dosage, once neutropenia has resolved.

Question 26

What is haemolytic anaemia?

Answer 26

Hemolytic anemia is a disorder in which red blood cells are destroyed faster than they can be made.

Question 27

What are the 2 causes of haemolytic anaemia?

Answer 27

1. Metabolic related cause
   - G6PD deficiency*
2. Immune related cause

We will focus on G6PD deficiency haemolytic anaemia.

Question 28

What are the 3 types of G6PD deficiency

Answer 28

Class I, Class II, Class III
(Class I being the most severe, Class III being least severe)

Class I: Class I variants have severe enzyme deficiency, associated with chronic haemolytic anaemia

Class II: Class II variants have severe enzyme deficiency, but there is only intermittent haemolysis - such as exposure to oxidant stress like Fava beans or certain drugs

Class III: Class III variants have moderate enzyme deficiency with intermittent haemolysis, associated with significant oxidant stress.

Question 29

What drugs are associated with Megaloblastic anaemia?

Answer 29

1. Antimetabolites - e.g. methotrexate
2. Co-trimoxazole
3. Phenytoin, phenobarbital

Question 30

What is thrombocytopenia?

Answer 30

It is when platelet count is ≤100 x 10^9

OR

When platelet count reduces by 50%

Question 31

What haem drugs that we have learnt are often associated w thrombocytopenia?

Answer 31

Heparin and GPIIb/IIIa

For heparin induced thrombocytopenia, patient often present with:
1. >50% drop in platelet count
2. The drop occurs either
a. ≤1 day
b. Day 5-10
3. New thrombosis