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