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By Tiffany Shaw
MBChB II
2002
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)
Symptoms + Signs
Symptoms:
SOB on exertion Tiredness Headache Angina
Signs:
Pallor Tachycardia +/- Jaundice +/- Koilonychia +/- Splenomegaly +/- Sore corners of mouth
Depends on cause of anaemia
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)
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
Investigation for Suspected Anaemia
1. Hb concentration: confirms anaemia + assesses severity
2. MCV: is this microcytic, normocytic, or macrocytic?
3. MCH: is this normochromic or hypochromic?
4. Other cell counts: is this isolated anaemia or pan-cytopenia?
Microcytic = MCV < normal (76)
Normocytic = MCV normal (76 – 96)
Macrocytic = MCV > normal (> 96)
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)
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.
Investigating Microcytic Anaemia
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.
Thalasaemia, Sideroblastic:
•High serum Fe
•High ferritin
•Normal IBC
NB: There are defects in Hb production, therefore excessive Fe.
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
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
Investigating Normocytic Anaemia
Clue one --- Reticulocyte Count
Increased Haemolysis Normal or decreased Chronic disease
Marrow disease
Investigating Normocytic Anaemia
Clue Two --- Other Cell Counts
Normal Chronic disease probably Abnormal Marrow disease likely
Investigating Normocytic Anaemia
Clue Three --- Special Tests
Bone marrow biopsy for ? marrow diseases Other tests for ? chronic diseases
1. U + E
2. Creatinine
3. LFT
4. Thyroid function …etc.
Investigating Macrocytic Anaemia
Clue One --- Reticulocyte Count
Increased Haemolysis Normal or decreased B12 deficiency
Folate deficiency
Liver disease
Marrow disease
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.
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.)
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
Fe Deficiency
Findings associated with Fe deficiency:
Anaemia (microcytic) Koilonychia Angular cheilosis Glossitis Hair thinning Abnormal Fe studies (see before)
Fe Deficiency
Causes:
1. Blood loss
2. Increased demand
3. Inadequate intake4. Malabsorption
•Menorrhagia
•GI bleed
•Haematuria …etc..
•Pregnancy
•Growth
•Gastrectomy
•Coeliac disease
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
Thalasaemia
Hereditary anaemia Impaired production of components of the
globin Classified into and depending on
which chain is deficient Lack of chain = thalasaemia Lack of chain = thalasaema
Thalasaemia
Impaired production of 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 = trait (mild anaemia)
Impaired production of chain in the globin
Major = complete failure of production (severe anaemia)
Intermedia = partial failure (moderate anaemia)
Minor = asymptomatic or mild anaemia
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
Thalasaemia
Mx:
Transfusion (packed red cells) prn Iron chelation therapy with DFX Splenectomy prn Bone marrow transplantation (definitive Rx) Genetic counseling
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
Sideroblastic Anaemia
Causes:
1. Hereditary type (X-linked)
2. Alcohol
3. Radiation therapy
4. Lead poisoning
Sideroblastic Anaemia
Mx:
Transfusion prn Iron chelation therapy Some benefit from Vit B6 (esp the
hereditary type)
Haemolytic Anaemia
Common types:
1. Autoimmune2. Alloimmune 3. G-6PD deficiency4. Pyruvate kinase deficiency5. Hereditary spherocytosis6. Thalasaemia (discussed before)7. Sickle cell anaemia
Normocytic
Microcytic
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
Autoimmune
Warm Type
Max at 37 degrees Ig G Get microcytosis +
spherocytosis Splenomegaly
common
Cold Type
Max at 4 degrees Ig M
Autoimmune
Warm Type
Causes:
1. Idiopathic
2. c.t. disorder (SLE)
3. CLL
4. Drug induced (methyl dopa)
Cold Type
Causes:
1. Idiopathic
2. Infection (e.g. glandular fever, Mycoplasma infection)
3. Lymphoma
Autoimmune
Warm type
Mx:
1. Steroids2. Transfusion prn3. Splenectomy if steroids
fail4. Other
immunosuppressives
Cold type
Mx:
1. Avoid cold environment
2. Immunosuppressives (chlorambucil, cyclophosphamide)
3. Transfusion prn
Alloimmune
Mismatched blood transfusion Haemolytic disease of the newborn Post bone marrow transplantation Post organ transplantation
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
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
Hereditary Spherocytosis
Mx:
Splenectomy to stop destroying RBC prematurely
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
6-GPD Deficiency
Mx:
Stop offending drugs / fava beans Transfusion prn during attacks
Vit B12 Deficiency
Physiology:
Source of B12 = food of animal origin
Storage = in liver, enough for 2 – 4 years
Absorption = in terminal ileum
1. Vit B12 ingested2. Binds to “R protein” in
saliva, gastric juice3. IF secreted by parietal cells
releases Vit B from R protein
4. Form IF-Vit B12 complex5. Complex absorbed in
terminal ileum6. Transcobolamin in plasma
strips off Vit B12 and transport to tissues
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)
Vit B12 Deficiency
Causes:
Inadequate intake (e.g. vegan) No IF (gastrectomy, pernicious anaemia) Malabsorption (ileal resection, Crohn’s
disease)
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
Vit B12 Deficiency
Distinguish between no IF & ileal problems:
1. Hx (e.g. gastrectomy)2. Test for autoantibodies against parietal
cells or IF3. Radioactive Vit B12 study Give radio-
labelled Vit B12 +/- IF. IF corrects gastric problems, but not ileal problems.
Vit B12 Deficiency
Mx:
1. Correct underlying cause if possible (e.g. adequate intake)
2. IM Vit B12 injection3. 6 injections to replace deficit (1 every 2 –
3 days)4. Maintenance (1 injection 3/12)
Folate Deficiency
Physiology:
Source = green vegetables + animal liver Body store = 4/12 supply Absorption = through proximal jejunum
Folate Deficiency
Diagnosis:
Macrocytic anaemia Low folate level
Associated findings:
Features of anaemia Mild jaundice Glossitis Angular cheilosis No neuropathy!!
Folate Deficiency
Cause:
1. Inadequate intake
2. Malabsorption (coeliac disease, bowel resection)
3. Drug induced (anti-convulsant)
Folate Deficiency
Mx:
1. Treat underlying cause if possible (e.g. coeliac disease)
2. Folate replacement
3. Oral folate 5 mg OD for 4-6/12