Approach to Anaemia
Jameela Sathar MD, MRCP, FRCPath
Basic morphology workshop
24-25 Feb 2025
Approach to anaemia
1. Establish the presence of anaemia
2. Establish the type of anaemia
3. Establish the cause of anaemia
4. Treat the cause and the anaemia
5. Monitor response to treatment
Step 1 : Establish the presence of
anaemia
Know what’s normal and abnormal
Malaysian Normal Range Study
Ambayya A. et al. Plos One 2014
Malaysian normal range
Reference interval
Mean Median
Mean ± 1.96 SD
** ferritin <12 excluded Ambayya A. et al. Plos One 2014
RET-He
Defining anaemia
Hb <13
Natvig H. Acta Med Scand 1967; Ambayya A. et al. Plos One 2014; M. Munoz. BJA 2015; Spahn D, et al. Anesthesiology 2020; Auerbach M. Mayo Clin Proc. 2021
Step 2 : Establish the type of
anaemia
Types of anaemia
Microcytic Normocytic Macrocytic
MCV <80 MCV 80 - 100 MCV >100
Types of anaemia
Microcytic Normocytic Macrocytic
MCV <80 MCV 80 - 100 MCV >100
Iron deficiency
Thalassaemia
Anaemia of inflammation
Sideroblastic anaemia
Chronic blood loss
Types of anaemia
Microcytic Normocytic Macrocytic
MCV <80 MCV 80 - 100 MCV >100
Haemolytic anaemias
Anaemia of inflammation
Combined haematinic deficiency
Acute blood loss
Bone marrow disorders
Types of anaemia
Microcytic Normocytic Macrocytic
MCV <80 MCV 80 - 100 MCV >100
B12 / folate deficiency
MDS
Hypothyroidism
Alcohol, Liver disease
Haemolysis
Types of anaemia
Microcytic Normocytic Macrocytic
MCV <80 MCV 80 - 100 MCV >100
Iron deficiency Haemolytic anaemias B12 / folate deficiency
Thalassaemia Anaemia of inflammation (AI) MDS
Anaemia of inflammation Combined haematinic deficiency Hypothyroidism
Sideroblastic anaemia Acute blood loss Alcohol, Liver disease
Chronic blood loss Bone marrow disorders Haemolysis
Investigation by RBC size (MCV)
Low MCV Normal MCV High MCV
Microcytic Normocytic Macrocytic
Investigation by RBC size (MCV)
Low MCV Normal MCV High MCV
Microcytic Normocytic Macrocytic
Ferritin
Low Normal / High
Hb analysis
Iron deficiency Thalassaemia
Investigation by RBC size (MCV)
Low MCV Normal MCV High MCV
Microcytic Normocytic Macrocytic
Reticulocyte count
Increased Not increased
Haemolysis Marrow
or Blood loss hypoplasia,
Leukaemia,
Infiltration, AI
Investigation by RBC size (MCV)
Low MCV Normal MCV High MCV
Microcytic Normocytic Macrocytic
Serum folate,
Vitamin B12
Folate B12 deficiency
deficiency
Investigation by RBC size (MCV)
Low MCV Normal MCV High MCV
Microcytic Normocytic Macrocytic
Ferritin Reticulocyte count Serum folate,
Vitamin B12
Low Normal / High Increased Not increased
Hb analysis
Iron deficiency Thalassaemia Haemolysis Marrow Folate B12 deficiency
or Blood loss hypoplasia, deficiency
Leukaemia,
Infiltration, AI
Defining iron deficiency
Iron deficiency Ferritin (ug/L)
Mild 70 - 100
Moderate 30 - 69
Severe <30
Ambayya A. et al. Plos One 2014; Spahn D, et al. Anesthesiology 2020; Auerbach M. Mayo Clin Proc. 2021
Defining iron deficiency
Iron deficiency Ferritin (ug/L) RET-He (pg)
Mild 70 - 100 >26 - 30
Moderate 30 - 69 21 - 26
Severe <30 <21
Ambayya A. et al. Plos One 2014; Spahn D, et al. Anesthesiology 2020; Auerbach M. Mayo Clin Proc. 2021
Defining iron deficiency
Iron deficiency Ferritin (ug/L) RET-He (pg) TSAT(%)
Mild 70 - 100 >26 - 30 >25 - 30
Moderate 30 - 69 21 - 26 20 - 25
Severe <30 <21 <20
Ambayya A. et al. Plos One 2014; Spahn D, et al. Anesthesiology 2020; Auerbach M. Mayo Clin Proc. 2021
Defining folate / B12 deficiency
Normal Low Deficiency
Serum folate >6.0 3.0 - 6.0 <3.0
(ng/mL)
B12 >300 200 - 300 <200
(ng/L)
Ensuring meaningful results
• Serum ferritin, iron, TIBC, folate and B12 testing
• Following an overnight fast
• Avoid iron or folate supplements 12 hours prior
• Test in the morning
Step 3 : Establish the cause of
anaemia
Cause of anaemia
Blood loss Destruction of RBCs Reduced production
Haemorrhage Haemolysis Ineffective erythropoeisis
Cause of anaemia
Blood loss Destruction of RBCs Reduced production
Haemorrhage Haemolysis Ineffective erythropoeisis
Heavy menstrual bleeding
Peptic ulcer disease
Haemorrhoids
GI malignancy
Cause of anaemia
Blood loss Destruction of RBCs Reduced production
Haemorrhage Haemolysis Ineffective erythropoeisis
Autoimmune
Haemoglobinopathy
G6PD deficiency
Drugs
Valve haemolysis
Cause of anaemia
Blood loss Destruction of RBCs Reduced production
Haemorrhage Haemolysis Ineffective erythropoeisis
Vitamin B12 / folate deficiency
MDS
Hypothyroidism
Renal failure
Anaemia of inflammation
Bone marrow disorder
Cause of anaemia
Blood loss Destruction of RBCs Reduced production
Haemorrhage Haemolysis Ineffective erythropoeisis
Heavy menstrual bleeding Autoimmune Vitamin B12 / folate deficiency
Peptic ulcer disease Haemoglobinopathy MDS
Haemorrhoids G6PD deficiency Hypothyroidism
GI malignancy Drugs Renal failure
Valve haemolysis Anaemia of inflammation
Bone marrow disorder
CAUSE Iron Deficiency Folate Deficiency Vitamin B12 Deficiency
Poor dietary intake,
Poor diet, alcoholism, Vegan diet, malnutrition,
Inadequate Intake vegetarian/vegan diet,
malnutrition inadequate intake
malnutrition
Increased Pregnancy, infancy, Pregnancy, haemolysis, Combination of increased
Demand adolescence rapid cell turnover demand and poor diet
Coeliac disease, IBD, Pernicious anaemia, IBD,
Malabsorption gastric bypass, Coeliac disease, IBD gastric surgery, pancreatic
Helicobacter pylori insufficiency
GI bleeding, heavy
Chronic haemolysis,
Blood Loss menses, postpartum
dialysis
Parasitic infections
haemorrhage
NSAIDs, anticoagulants Methotrexate, Metformin, PPIs, H2
Drug-Induced (causing blood loss) trimethoprim, phenytoin blockers
Functional iron
Autoimmune disorders,
Other Causes deficiency (chronic Liver disease
bacterial overgrowth
inflammation, CKD)
Step 4 : Treat the cause and the
anaemia
Stop the Correct Treat the
bleeding the underlying
or anaemia cause
hemolysis
Step 5 : Monitor response to
treatment
Monitor response based on FBC
• Hb
• Reticulocyte count
• Immature reticulocyte fraction (IRF)
• RET-He
Case 1
Case 1
Hb 5.2
MCV 57.2
RDW 23.4
45-year-old woman
Heavy menstrual bleeding x 3 months
RET-He
15.0
Case 1
Heavy menstrual bleeding
Menarche Perimenopausal
Case 2
Case 2
Hb 11.6
MCV 91.1
54 | Male
Underlying neuroendocrine tumour stomach grade 2
Underwent gastrectomy & splenectomy
Case 2
Chong SL 2019
Case 2 – BMAT: Severe aplastic anaemia
Case 3
Case 3
• 61-year-old man
• Referred for pancytopenia
• c/o:
• Syncopal attacks x 1 week
• 6 months of:
• Lethargy, SOB
• Yellow discoloration eyes and body
• Abdominal pain, loose stool
• LOW, LOA
Case 3 – history & exam
• Social history • Clinical examination
• Retired • Pale+ Jaundice+
• Smoker • Liver & Spleen 2 fb
• Alcohol 1 beer/day • Neurology: normal
Case 3
Hb 6.0
MCV 109.0
WBC 1.4
Plt 24
Case 3
Lab investigations
• Total bil 63.1 • Vitamin B12 <30 (243 – 894) pg/mL
• ID bil 47.6 • Folate 13.9 (3.1 – 17.5) ng/mL
• Coombs negative • LDH 2634 (135 – 225) U/L
• Alb 37 • Ferritin 529 (30.7 – 579.2)ug/L
• ALT 23
• Crea 56
Case 3 - BMA
Causes of B12 deficiency
• 48-year-old Indian lady JW
• Turners syndrome with primary
amenorrhoea
• c/o: Exertional dyspnoea &
Bilateral leg swelling x 1 month
• Hb 3.5 MCV 126 MCH 40
• WBC 1.9 Plt 62
G. Kasinathan 2024
Causes of B12 deficiency
• Total 8 PRBCs + 8 PLTS
transfused
• Cause of anaemia not
determined
MCV 124
(4 PRBC + 4 PLTS)
Case 4
Case 4
• 35-years-old lady • Hb 6.7
• NKMI • MCV 92.0
• c/o fever & lethargy x 2 weeks • WBC 4.5
• O/E: Jaundiced • Plt 40
Case 4
Direct Coombs 3+
Chong SL 2019
Case 5
Case 5
• 75-year-old man
• Referred for anaemia
• Hb 10 MCV 100 MCH 30
• WBC 2.9
• Plt 300
Case 5
Chong SL 2019
Case 6
Case 6
• 6-year-old boy • Hb 5.1
• Cough and fever x 3 days • MCV 90.0
• Given antibiotic by GP • WBC 7.6
• Noted jaundice • Plt 244
Case 6
Chong SL 2019
Case 7
Case 7 RCC 6.3
Hb 9.7
MCV 49.0
MCH 15.3
WBC 9.6
Plt 383
RDW-CV 24.7
Form 4 screening
Case 7
Ferritin 11.0
Hb analysis: Hb A2 5.6%
Chong SL 2019
Case 8
Case 8
• 32-year-old stockbroker, male
• Good health
• Petechiae and purpura LL for 1 week
• Hb 11.5 MCV 95 WBC 8.0 Plt 14
• Bilirubin 19
• Commenced prednisolone for ITP
Case 8
Case 8 – a week later …
• Presented to ED with status epilepticus
• Intubated and transferred to ICU
• Hb 9 WBC 13 Plt 14
• Bilirubin 42 ID 38
• LDH 2450
• Hb done a year ago 15.6
Case 8 – 2nd blood film
Case 8 – Plasma exchange
Case 9
Case 9
• 51-year-old lady • Completed 6 cycles of chemoRx
• DM & HT >20 years • 3 cycles of FEC
• Epirubicin
• Left breast CA Stage 2 • Cyclophosphamide
• Left mastectomy performed • 5-fluorouracil
• 3 cycles of Doxetecal
• Currently on tamoxifen
Case 9
Presented with lethargy
Hb 4.8 TW 2.5 Plt 2
Case 9
Case 10
Case 10
Hb 3.5
MCV 120.8
MCH 43.8
MCHC 36.3
63 | Chinese | Male
Presented with lethargy & weakness x 2 weeks
Case 10
Coombs C3d 3+
R. Hamzah 2020
Case 11
Case 11
Hb 7.6
MCV 75.4
MCH 22.8
RDW-CV 18.8
RET-He 22.9
31 | Malay | Female
G3P2@33 weeks
Case 11
R. Hamzah 2020
Case 12
Case 12
Hb 6.5
MCV 79.4
WBC 129.1
Plt 35
55 | man
c/o: fever & lethargy x 3 weeks
O/E: Hepatosplenomegaly & lymphadenopathy
Case 12
R. Hamzah 2022
Case 13
Case 13
Hb 8.3
MCV 52.6
RDW-CV 23.8
RET-He 19.9
WBC 81.0 76 | Male
Plt 225 Lethargy & weight loss
Large spleen
Case 13
BM iron stores
Newly-Diagnosed Haematological Malignancies
• Ampang Hospital
15%
• July to Oct 2023
• Bone Marrow samples
Leukaemia
• n = 55
Lymphoma
• Female = 25 56%
29% Multiple Myeloma
• Male = 30
Nur Aida 2023
Absent iron stores Normal iron stores
Nur Aida 2023
Bone Marrow Iron stores - Results
• 76% had low or absent iron Iron stores in newly-diagnosed hematological
malignancies
stores 50.00 45.45
• Female 19/25 = 76% 45.00
40.00
• Male 23/30 = 77% 35.00 30.91
30.00
25.00
20.00
14.55
15.00
10.00
5.00 1.82 3.64 3.64
0.00
0: Absent 1: Moderate 2: Adequate 3: Good 4: Very good 5:
to severely Suboptimal
reduced
Nur Aida 2023
Take home message
Approach to Anaemia
1. Establish presence of anaemia
– Hb <13
2. Establish type of anaemia
– RBC size
3. Establish cause of anaemia
– Iron deficiency is the leading cause
4. Treat the cause and anaemia
– Blood transfusion does not correct the underlying cause
5. Monitor response to treatment
– IRF, Reticulocyte, RET-He, Hb
Thank you
