Anaemia

• Defined as a low Hb concentration and can be due to a low red cell mass or an increase circulating volume
• Defined as <13.5g/dL in men and <11.5g/dL in women

Symptoms

• Fatigue
• Dyspnoea
• Faintness
• Palpitations
• Headache
• Tinnitus
• Anorexia
• Angina (if there is pre-existing coronary artery disease)

Signs

• Pallor
• Signs of a hyperdynamic circulation – tachycardia, flow murmur, cardiac enlargement (Hb <8g/dL)
• Later heart failure can develop

Types of anaemia

• Based on MCV (normally 76-96 femtolitres)
  • Low MCV (microcytic)
    • Iron-deficiency
    • Thalassaemia
    • Sideroblastic anaemia
    • In the last two conditions there is an accumulation of iron so tests will show ­ iron, ­ ferritin and a low TIBC
  • Normal MCV (normocytic anaemia)
    • Acute blood loss
    • Anaemia of chronic disease (may be ¯ MCV)
    • Bone marrow failure
    • Renal failure
    • Hypothyroidism (or may be ­ MCV)
    • Haemolysis (or may be ­ MCV)
    • Pregnancy
    • If both WCC and platelets are reduced suspect BM failure
  • High MCV (macrocytic anaemia)
    • B12 or folate deficiency
    • Alcohol excess or liver disease
    • Reticulocytosis (e.g. with haemolysis)
    • Cytotoxics e.g. hyroxycarbamide
    • Myelodysplastic syndromes
    • Marrow infiltration
    • Hypothyroidism
    • Antifolate drugs e.g. phenytoin

Haemolytic anaemias

• May be normocytic or macrocytic (if there are lots of young RBCs and reticulocytes)
• Suspect if there is;
  • Reticulocytosis
  • Mild macrocytosis
  • ¯ haptoglobin
  • ­ bilirubin
  • ­ urobilinogen

Iron deficiency

• Common – seen in 14% of menstruating women

Causes;

• Blood loss – menorrhagia or GI bleeding
• Poor diet in babies and young children
• Malabsorption e.g. Coeliac disease
• In the tropics Hookworm

Signs;

• Koilonychia
• Atrophic glossitis
• Angular cheilosis
• Post-cricoid webs (Plummer-Vinson syndrome)

Tests

• Microcytic, hypochromic anaemia with anisocytosis and poikilocytosis
• ¯MCV, ¯MCH, ¯MCHC (Mean cell Hb concentration), ¯ ferritin

Treatment

• Treat cause
• Give ferrous sulphate SE – nausea, abdo discomfort, constipation, diarrhoea, black stools

Anaemia of chronic disease

• Associated with many diseases including;
  • Chronic infection e.g. TB, osteomyolitis
  • Vasculitis
  • Rheumatoid arthritis
  • Malignancy
  • Renal failure
  • There is cytokine driven inhibition of erythrocyte production

Investigations

• Mild normocytic anaemia
• Ferritin normal or ­

Sideroblastic anaemia

• Characterised by ineffective erythopoiesis due to disordered haem synthesis, leasing to increased iron absorption, iron loading (bone marrow) and occasionally haemosiderosis (endocrine, liver and cardiac damage due to iron deposition)
• May be congenital (X-linked mutation of ALA-synthase enzyme gene)
• Or acquired – myelodysplasia
• Can also follow;
  • Chemotherapy
  • Irradiation
  • Alcohol excess
  • Lead excess
  • Anti-TB drugs
  • Myeloproliferative disease
• Hypochromic RBCs are seen in the blood film with ring sideroblasts in the marrow (erythroid precursors with iron deposited in the mitochondria in a ring around the nucleus)

Treatment

• Remove cause
• Pyridoxine (Vitamin B6) may be helpful in genetic cause as it is a co-factor for ALA synthase

Macrocytic anaemia

• Common (MCV >96fL), seen in alcohol excess without accompanying anaemia
• A megaloblast is a cell in which nuclear maturation is delayed compared with the cytoplasm
• This occurs in folate and VitB12 deficiency as they are both required for DNA synthesis

Causes of macrocytosis

• Megaloblastic
  • B12 deficiency
  • Folate deficiency
  • Cytotoxic drugs
• Non-megaloblastic
  • Alcohol
  • Reticulocytosis
  • Liver disease
  • Hypothyroidism
  • Pregnancy
• Other haematological disease
  • Myelodysplasia
  • Myeloma
  • Myeloproliferative disorders
  • Aplastic anaemia

Blood film

• Hypersegmented polymorphs in B12 and folate deficiency
• Target cells in liver disease

Other tests

• LFTs (including ?-GT), TFT, serum B12, folate

BM biopsy

• May show one of 4 states;
  • Megaloblastic
  • Normoblastic marrow (liver disease and hypothyroidism)
  • Abnormal erythopoiesis (sideroblastic anaemia, leukaemia, aplasia)
  • Increased erythopoiesis (haemolysis)

Folate

• Found in vegetables, nuts, yeast and liver
• It is also synthesised by gut bacteria
• Body stores can last for 3-4 months
• Maternal folate deficiency can result in neural tube defects in the fetus
• It is absorbed by the duodenum and proximal jejunum

Causes of folate deficiency

• Poor diet
• Increased demand e.g. pregnancy, increased cell turnover
• Malabsorption e.g. Coeliac disease
• Drugs – alcohol, antiepileptics (phenytoin, sodium valproate), methotrxate, trimethoprim

Treatment

• Folic acid
• Never give with VitB12 unless the patient is known to have normal B12 levels as in low B12 states this may precipitate or worsen subacute combined degeneration of the spinal cord
• In pregnancy give 400?g/d from conception until 12 weeks to prevent spina bifida

B12 deficiency

• Vitamin B12 is found in meat and diary products
• Body stores are sufficient for 4years
• It is protein bound and released upon digestion, it binds to intrinsic factor in the stomach and the complex is absorbed in the terminal ileum
• In B12 deficiency, synthesis of thymidine and hence DNA is impaired so cell production is reduced

Causes of deficiency

• Diet
• Malabsorption
• Affecting the stomach – post gastrectomy, pernicious anaemia
• Terminal ileum – ileal resection, Crohn’s disease, bacterial overgrowth, tropical sprue, tapeworms

Features

• Lemon tinge to skin due to a combination of pallor and mild jaundice (due to haemolysis)
• Glossitis
• Angular stomatitis
• Neuropsychiatric – irritability, depression, psychosis, dementia
• Neurological;
  • Paresthesiae
  • Peripheral neuropathy
  • Subacute degeneration of the spinal cord;
    • There is a combination of dorsal column loss causing sensory and LMN signs and symmetrical corticospinal tract loss causing motor and UMn signs
    • Joint and vibration sense are often affected causing ataxia
    • The classical triad is;
      • Extensor plantars
      • Absent ankle jerks
      • Absent knee jerks
    • Pain and temperature sense remain intact as the spinothalamic tracts are preserved

Pernicious anaemia

• Autoimmune atrophic gastritis leading to achlorhydria and lack of gastric intrinsic factor secretion
• High incidence in blood group A
• Associated with other autoimmune diseases – thyroid disease, vitiligo, Addison’s disease, hypoparathyroidism, carcinoma of the stomach

Tests

• ¯Hb
• ­MCV
• WCC and platelets can be ¯ in severe cases

• ¯ serum B12

• Hypersegmented polymorphs
• Parietal cell autoantibodies
• Intrinsic factor autoantibodies
• Schilling test
  • Determines where the low B12 is due to malabsorption from the terminal ileum or from a lack of intrinsic factor
  • Compare the proportion of an oral dose of radioactive B12 that is absorbed and excreted in the urine with and without intrinsic factor

Treatment

• Hydroxycolbalamin IM
• Supplementation improves peripheral neuropathy but has little effect on cord signs