By Tiffany Shaw MBChB II 2002 Approach to Anaemia 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)

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

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 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)

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 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.

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 U + E Creatinine LFT 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: Blood loss Increased demand Inadequate intake 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 a and b depending on which chain is deficient Lack of a chain = a thalasaemia Lack of b chain = b thalasaema

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

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: Hereditary type (X-linked) Alcohol Radiation therapy Lead poisoning

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

Haemolytic Anaemia Common types: Autoimmune Alloimmune G-6PD deficiency Pyruvate kinase deficiency Hereditary spherocytosis Thalasaemia (discussed before) 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: Idiopathic c.t. disorder (SLE) CLL Drug induced (methyl dopa) Cold Type Causes: Idiopathic Infection (e.g. glandular fever, Mycoplasma infection) Lymphoma

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

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: 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.

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)

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: Inadequate intake Malabsorption (coeliac disease, bowel resection) Drug induced (anti-convulsant)

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