1. By Tiffany Shaw MBChB II 2002
Approach to Anaemia
By Tiffany Shaw
MBChB II
2002

2. Anaemia – Definition Reduced Hb concentration in blood
Compared to normal range for the particular gender + age
NOT reduced red cell count (unlike leucopenia or thrombocytopenia, which is defined by low counts)

3. Depends on cause of anaemia
Symptoms + Signs
Symptoms:
SOB on exertion
Tiredness
Headache
Angina
Signs:
Pallor
Tachycardia
+/- Jaundice
+/- Koilonychia
+/- Splenomegaly
+/- Sore corners of mouth
Depends on cause of anaemia

4. Symptom + Signs
Koilonychia = nail change, usually seen in Fe deficiency. Nails become brittle, spoon shaped, and ridged.
Sore mouth corners = angular cheilosis, seen in Fe, B12, or folate deficiency.
Jaundice = due to increased bilirubin production as a result of increased haemolysis (haemolytic anaemia)

5. Investigation for Suspected Anaemia
Full Blood Count
Hb concentration
Haematocrit
Red cell count
MCV (mean cell volume)
MCH (mean cell haemoglobin)
White cell count
Differential white cell count (neutrophils, lymphocytes, monocytes, eosinophils, basophils)
Platelet count

6. Investigation for Suspected Anaemia
Hb concentration: confirms anaemia + assesses severity
MCV: is this microcytic, normocytic, or macrocytic?
MCH: is this normochromic or hypochromic?
Other cell counts: is this isolated anaemia or pan-cytopenia?
Microcytic = MCV < normal (76)
Normocytic = MCV normal (76 – 96)
Macrocytic = MCV > normal (> 96)

7. Classification Based on MCV
Microcytic ~
Fe deficiency
Thalasaemia
Sideroblastic
Chronic disease
Normocytic ~
Chronic disease
Haemolysis
Marrow disease
Macrocytic ~
B12 deficiency
Folate deficiency
Liver disease
Marrow disease
Haemolysis (MCV pushed up by reticulocytosis)

8. Investigating Microcytic Anaemia
Clue One --- Iron Studies
Serun Iron (free Fe)
Ferritin (stored Fe)
Iron Binding Capacity IBC (transferrin)
NB: Transferrin is the iron binding protein in blood and amount of transferrin reflects capacity to bind Fe.

9. Investigating Microcytic Anaemia
Thalasaemia, Sideroblastic:
Fe Deficiency:
Low serum Fe
Low ferrtin
Increased IBC
NB: Increased IBC kind of reflects body’s attempt to grab more Fe.
Chronic Disease:
Low serum Fe
Normal ferritin
Reduced IBC
NB: Problem here is a block in the utilisation of Fe.
High serum Fe
High ferritin
Normal IBC
NB: There are defects in Hb production, therefore excessive Fe.

10. Investigating Microcytic Anaemia
Clue Two --- Blood Film Exam
Fe deficiency  Microcytes, Target cells, Pencil cells
Chronic disease  Variable, depends on cause
Thalasaemia  Microcytes, Target cells
Sideroblastic  Dimorphic (both normal RBC and microcytic ones), Siderotic granules in RBC

11. Investigating Microcytic Anaemia
Clue Three --- Special Tests
Hb electrophoresis: for thalasaemia
DNA analysis: for hereditary causes (e.g. thalasaemia)
Bone marrow: sideroblastic anaemia shows ringed sideroblasts in marrow

12. Investigating Normocytic Anaemia
Clue one --- Reticulocyte Count
Increased  Haemolysis
Normal or decreased  Chronic disease
Marrow disease

13. Investigating Normocytic Anaemia
Clue Two --- Other Cell Counts
Normal  Chronic disease probably
Abnormal  Marrow disease likely

14. Investigating Normocytic Anaemia
Clue Three --- Special Tests
Bone marrow biopsy for ? marrow diseases
Other tests for ? chronic diseases
U + E
Creatinine
LFT
Thyroid function …etc.

15. Investigating Macrocytic Anaemia
Clue One --- Reticulocyte Count
Increased  Haemolysis
Normal or decreased  B12 deficiency
Folate deficiency
Liver disease
Marrow disease

16. Investigating Macrocytic Anaemia
Clue Two --- B12 / Folate Level
Low  Deficiency
Normal  Liver disease
Marrow disease
NB: For B12, folate, and Fe deficiency, further investigations must be made to determine the cause of deficiency, so that appropriate therapy can be instituted.

17. Investigating Macrocytic Anaemia
Clue Three --- Other Cell Counts
Normal  liver disease probably (confirm with LFT, liver u/s…etc.)
Abnormal  probably marrow disease (confirm with marrow biopsy…etc.)

18. Fe Deficiency Physiology:
Source of Fe = both in animal + vegetable products
Animal Fe more easily absorbed
Site of absorption = proximal jejunum
Vit C enhances absorption
Daily loss = urine, skin, faeces, hair, menstrual blood loss

19. Fe Deficiency Findings associated with Fe deficiency:
Anaemia (microcytic)
Koilonychia
Angular cheilosis
Glossitis
Hair thinning
Abnormal Fe studies (see before)

20. Fe Deficiency Causes: Blood loss Increased demand Inadequate intake
Malabsorption
Menorrhagia
GI bleed
Haematuria …etc..
Pregnancy
Growth
Gastrectomy
Coeliac disease

21. Fe Deficiency Mx: Treat underlying cause if possible (e.g. bleed)
Oral Fe replacement – Ferrous sulphate best, gluconate second
Taken before meals TDS
Continue for 4-6/12
Reticulocytosis typically begins 7 days after Rx
Fe replacement IV or IM if oral not possible

22. Thalasaemia Hereditary anaemia
Impaired production of components of the globin
Classified into a and b depending on which chain is deficient
Lack of a chain = a thalasaemia
Lack of b chain = b thalasaema

23. Thalasaemia a Impaired production of a chain in the globin.
Severity depends on number of genes deleted
4/4 = hydrops fetalis (intrauterine death)
3/4 = haemoglobin H disease (severe anaemia)
1- 2/4 = a trait (mild anaemia) b
Impaired production of b chain in the globin
Major = complete failure of production (severe anaemia)
Intermedia = partial failure (moderate anaemia)
Minor = asymptomatic or mild anaemia

24. Thalasaemia Diagnosis: Microcytic anaemia Blood film examination
Hb electrophoresis
DNA analysis
Associated findings:
Usual signs of anaemia
Failure to thrive
Hepatosplenomegaly
Expansion of the skull
High serum + storage Fe

25. Thalasaemia Mx: Transfusion (packed red cells) prn
Iron chelation therapy with DFX
Splenectomy prn
Bone marrow transplantation (definitive Rx)
Genetic counseling

26. Sideroblastic Anaemia
Defect of haem synthesis
Increased Fe present as granules arranged in a ring around nucleus of developing RBC in marrow (ringed sideroblasts)
Peripheral blood shows microcytic hypochromic RBC
May be hereditary or acquired

27. Sideroblastic Anaemia
Causes:
Hereditary type (X-linked)
Alcohol
Radiation therapy
Lead poisoning

28. Sideroblastic Anaemia
Mx:
Transfusion prn
Iron chelation therapy
Some benefit from Vit B6 (esp the hereditary type)

29. Haemolytic Anaemia Common types: Autoimmune Alloimmune
G-6PD deficiency
Pyruvate kinase deficiency
Hereditary spherocytosis
Thalasaemia (discussed before)
Sickle cell anaemia
Normocytic
Microcytic

30. Autoimmune Autoantibodies against self RBC
Divided into warm + cold types, depending on which temperatures antibodies work best under
May be idiopathic or secondary to other conditions
+ve for direct Coomb’s test

31. Autoimmune Warm Type Max at 37 degrees Ig G
Get microcytosis + spherocytosis
Splenomegaly common
Cold Type
Max at 4 degrees
Ig M

32. Autoimmune Warm Type Causes: Idiopathic c.t. disorder (SLE) CLL
Drug induced (methyl dopa)
Cold Type
Causes:
Idiopathic
Infection (e.g. glandular fever, Mycoplasma infection)
Lymphoma

33. Autoimmune Warm type Mx: Steroids Transfusion prn
Splenectomy if steroids fail
Other immunosuppressives
Cold type
Mx:
Avoid cold environment
Immunosuppressives (chlorambucil, cyclophosphamide)
Transfusion prn

34. Alloimmune Mismatched blood transfusion
Haemolytic disease of the newborn
Post bone marrow transplantation
Post organ transplantation

35. Hereditary Spherocytosis
Hereditary anaemia
Most common one in Caucasian
Autosomal dominant
Defect in RBC membrane
RBC becomes spherical
Therefore destroyed prematurely in spleen
Splenomegaly common

36. Hereditary Spherocytosis
Special test --- Osmotic Fragility Test
Spherical RBC  increased volume : surface area ratio
More prone to lysis by osmosis
Measure degree of lysis of RBC in different concentrations of saline  spherical ones lyse more
Therefore confirm spherocytosis

37. Hereditary Spherocytosis
Mx:
Splenectomy to stop destroying RBC prematurely

38. G-6PD Deficiency
G-6PD = enzyme required to generate ATP to maintain shape of RBC
Deficiency  RBC more susceptible to oxidation stress, e.g. ingestion of certain drugs / fava beans
Haemolysis occurs with such ingestion
Normal at other times

39. 6-GPD Deficiency Mx: Stop offending drugs / fava beans
Transfusion prn during attacks

40. Vit B12 Deficiency Vit B12 ingested Physiology:
Binds to “R protein” in saliva, gastric juice
IF secreted by parietal cells releases Vit B from R protein
Form IF-Vit B12 complex
Complex absorbed in terminal ileum
Transcobolamin in plasma strips off Vit B12 and transport to tissues
Physiology:
Source of B12 = food of animal origin
Storage = in liver, enough for 2 – 4 years
Absorption = in terminal ileum

41. Vit B12 Deficiency Diagnosis: Macrocytic anaemia Low B12 level
Associated findings:
Features of anaemia
Mild jaundice
Glossitis
Angular cheilosis
Neuropathy (often tingling in feet +/- visual or psych disturbance)

42. Vit B12 Deficiency Causes: Inadequate intake (e.g. vegan)
No IF (gastrectomy, pernicious anaemia)
Malabsorption (ileal resection, Crohn’s disease)

43. Vit B12 Deficiency Pernicious Anaemia:
Autoandibodies develop against parietal cells or intrinsic factors
Therefore no IF
Can’t absorb Vit B12
Peak incidence at 60 years old

44. Vit B12 Deficiency Distinguish between no IF & ileal problems:
Hx (e.g. gastrectomy)
Test for autoantibodies against parietal cells or IF
Radioactive Vit B12 study  Give radio-labelled Vit B12 +/- IF. IF corrects gastric problems, but not ileal problems.

45. Vit B12 Deficiency
Mx:
Correct underlying cause if possible (e.g. adequate intake)
IM Vit B12 injection
6 injections to replace deficit (1 every 2 –3 days)
Maintenance (1 injection 3/12)

46. Folate Deficiency Physiology: Source = green vegetables + animal liver
Body store = 4/12 supply
Absorption = through proximal jejunum

47. Folate Deficiency Diagnosis: Macrocytic anaemia Low folate level
Associated findings:
Features of anaemia
Mild jaundice
Glossitis
Angular cheilosis
No neuropathy!!

48. Folate Deficiency Cause: Inadequate intake
Malabsorption (coeliac disease, bowel resection)
Drug induced (anti-convulsant)

49. Folate Deficiency
Mx:
Treat underlying cause if possible (e.g. coeliac disease)
Folate replacement
Oral folate 5 mg OD for 4-6/12