Anaemia

 

• Definition

  ↓Hb and/or ↓red blood cells.

• Signs and symptoms

  • SOB
  • Fatigue
  • Pallor including of conjunctiva.
  • Angina
  • ↑HR

• Differential diagnosis

  Microcytic (MCV <80 fL)

  • Iron deficiency.
  • Thalassaemia: usually ↓↓MCV but can be normocytic.
  • Sideroblastic anaemia e.g. lead poisoning.
  • Anaemia of chronic disease (although usually normocytic).

  Normocytic (MCV 80-100 fL)

  • Anaemia of chronic disease. Other findings include ↑ferritin, as iron stores are increased in chronic disease and ferritin is an acute phase reactant
  • ↑RBC loss: acute bleeding, haemolytic anaemia. The anaemia of acute bleeding (aka posthaemorrhagic anaemia) may only become apparent after fluid resuscitation.
  • ↓RBC production: bone marrow failure, aplastic anaemia, myelodysplastic syndrome.
  • Haemodilution: pregnancy, fluid overload. Pregnancy can also cause iron-deficiency anaemia (microcytic), or mild macrocytosis in late pregnancy.

  Macrocytic (MCV >100 fL)

  Normoblastic anaemia

  Alcoholic liver disease:

  • Causes macrocytosis but usually without anaemia.
  • Macrocytosis is uncommon in other causes of liver disease.

  The following can all cause macrocytic anaemia, but more commonly cause normocytic anaemia:

  • ↑RBC loss: acute bleeding, haemolytic anaemia. Macrocytosis only occurs when there is a sufficiently large compensatory response causing reticulocytosis.
  • ↓RBC production: bone marrow failure, aplastic anaemia, myelodysplastic syndrome.
  • Late pregnancy (mild).
  • Hypothyroidism

  Megaloblastic anaemia

  • ↓Folate
  • ↓B12

• Investigations

  When anaemia is identified on FBC, consider:

  • Blood film (aka peripheral smear): classic findings include pencil poikilocytes (iron deficiency), hypersegmented neutrophils (megaloblastic), target cells (sickle cell, thalassaemia, iron deficiency, hyposplenism).
  • Reticulocyte count.
  • Haematinics: iron studies (ferritin, iron, TIBC), B12 (serum cobalamin), and folate.

• Iron deficiency anaemia

  Anaemia resulting from low iron stores.

  Iron physiology

  • Dietary iron is absorbed in the duodenum and proximal jejunum via DMT-1. This process is aided by the stomach, where gastric acid and vitamin C help reduction of ferric (Fe3+) to the better-absorbed ferrous (Fe2+).
  • Two-thirds of iron in the body is in circulation within haemoglobin.
  • The rest is stored in the proteins ferritin and haemosiderin, mostly intracellular (esp. liver) but with some ferritin also in plasma. It is transported to developing RBCs by transferrin.
  • Regulated by hepcidin from liver, which leads to ↓duodenal absorption.

  Causes

  • Bleeding: GI (ulcer, tumour), uterine (menses, fibroid).
  • Malabsorption: gastrectomy, gastritis, coeliac.
  • ↓Intake

  Presentation

  Signs and symptoms are usually absent or non-specific e.g. fatigue, pallor. Specific features include:

  • Signs: angular cheilitis, glossitis, brittle nails, koilonychia (spoon-shaped nails).
  • Pica: appetite for non-food items such as clay or paper.
  • Restless legs syndrome.

  Investigations

  • ↓Ferritin, a marker of depleted iron stores and a defining feature of absolute iron deficiency.
  • ↓Iron, ↑TIBC, ↓TSAT (transferrin saturation = [Iron ÷ TIBC] x 100). These abnormalities in the presence of normal or elevated ferritin suggest functional iron deficiency i.e. impaired use of iron stores; this is usually due to inflammation (i.e. anaemia of chronic disease) or EPO-stimulating agents (ESA).
  • Blood film: poikilocytes (abnormally-shaped RBCs).
  • Investigate cause e.g. endoscopy.

  Management

  PO ferrous sulphate/fumarate:

  • Taken on an empty stomach.
  • Adding vitamin C may aid absorption, though evidence is weak.
  • 3-6 months treatment usually needed to normalize ferritin.
  • Side effects: nausea and vomiting, constipation, black poo (but not as foul-smelling as melena).

  IV iron:

  • Quicker and more reliable uptake.
  • Indications: failure of oral therapy, impaired GI absorption (e.g. IBD, gastrectomy), concomitant ESA use in CKD, alternative to RBC transfusion if rejected (e.g. for religious reasons).
  • New formulations (e.g. iron sucrose, ferric carboxymaltose) have much lower hypersensitivity risks than the older high-molecular-weight iron dextran.

• Vitamin B12 deficiency

  B12 physiology

  • Vitamin B12 (aka cobalamin), along with folate, plays a key role in DNA synthesis and hence in cells with rapid turnover e.g. haematopoietic cells. Also plays a role in myelin formation.
  • In the stomach, gastric acid aids the release of B12 from food. In the duodenum, B12 binds to intrinsic factor (IF), a protein produced by gastric parietal cells. The B12-IF complex is then absorbed in the terminal ileum.

  Causes

  Impaired gastric function:

  • Pernicious anaemia: autoimmune destruction of gastric parietal cells.
  • Gastrectomy
  • Zollinger-Ellison

  Impaired intestinal absorption:

  • Crohn's
  • Ileal resection.

  Decreased intake:

  • Vegan diet. B12 is found only in animal products: meat, dairy.
  • Malnutrition

  Drugs:

  • PPIs, H2-blockers.
  • Metformin
  • Alcohol

  Presentation

  Megaloblastic anaemia:

  • Fatigue
  • Glossitis: red-raw tongue.
  • Angular cheilitis.

  Neurological manifestations can be motor (upper or lower MN) or sensory:

  • Underlying pathology is subacute combined degeneration of the spinal cord, involving demyelination of the dorsal column (sensory) and the lateral corticospinal tract (motor), as well as peripheral neuropathy.
  • Leads to impaired proprioception and hence unsteadiness, spastic paraparesis (upper MN), dysaesthesia, extensor plantars (upper MN), but absent knee and ankle reflex (lower MN).
  • Can also cause impaired cognition and psychosis.

  Pancytopaenia:

  • Possible but very rare presentation.

  Investigations

  • FBC: ↓Hb, ↑MCV.
  • ↓Serum cobalamin.

  Management

  • Hydroxocobalamin IM 1st line. Continue life-long, 3-monthly, for chronic causes. Cyanocobalamin PO 2nd line if there is poor adherence.
  • Avoid blood transfusion in the acute stage due to heart failure risk.

• Folate deficiency

  Causes

  • Small bowel disease: IBD, coeliac.
  • ↑Needs: pregnancy.
  • Drugs: methotrexate, sulfasalazine, phenytoin, trimethoprim.
  • Dietary deficiency is almost never the cause, as folate is present in most food, especially green vegetables.

  Signs and symptoms

  • Clinically hard to distinguish from vitamin B12 deficiency, including glossitis.
  • Neurological symptoms are milder than B12 deficiency and generally limited to peripheral neuropathy.
  • In pregnant women, may lead to neural tube defects.

  Management

  Folate 5 mg PO OD for 3 months.