Causes and treatment of anaemia

Question 1

What are the treatments for anaemia (5)

Answer 1

1. Iron supplementation is the mainstay of treatment, particularly in iron deficiency anaemia.
2. Injectable iron available for cases where speed of response important, or absorption of oral iron salts impaired.
3. Vitamin supplementation for replacement in specific deficiencies.
4. Erythropoiesis stimulating agents (ESAs) of particular use for stimulating erythropoiesis in patients with severe Chronic Kidney Dysfunction (CKD)
5. Blood transfusions for severe anaemia, or patients with active bleeding.

Question 2

What does anaemia treatment depend on

Answer 2

the cause and severity of the anaemia.

Question 3

What could be the source if iron deficiency anaemia (4)

Answer 3

1. Chronic Bleeding?
2. Medication?
3. Increased iron use? Pregnancy
4. Absorption issues?

Question 4

What is iron deficiency anaemia treated with (3)

Answer 4

1. Generally treated with oral iron supplements
2. Iron salts - mild to moderate
3. Intravenous iron and blood transfusions available for patients with severe iron deficiencies which require rapid correction.

Question 5

What is the appearance of cells in iron deficiency anaemia (3)

Answer 5

1. Pale - Hypochromic (lacks red Hb pigment)
2. Microcytic – small red cells
3. low Hb – due to iron deficiency

Question 6

What are the lab blood results for iron deficiency anaemia (4)

Answer 6

1. Reduced Hb
2. MCV (mean corpuscular volume)
3. Ferritin
4. Serum iron

Question 7

What are the symptoms of iron deficiency anaemia (6)

Answer 7

1. Pale
2. tired
3. Shortness of breath
4. dysphagia (swallowing problems)
5. pica
6. angular stomatitis

Question 8

How do oral iron preparations work (6)

Answer 8

1. Replace iron stores – haemoglobin, myoglobin & other heme enzymes and reticulocytes.
2. Onset of haematological action 3-10 days
3. Peak of reticulocytosis 5-10 days
4. Effect on haemoglobin levels evident after 2-4 weeks
5. Excreted through urine, sweat, sloughing of intestinal mucosa and menses (women only)
6. Ferrous Sulfate most commonly prescribed oral salt

Question 9

What are the oral iron salt preparations (6)

Answer 9

1. Many different oral ferrous salts are available, with only marginal differences in the efficiency of absorption of iron.
2. Choice of preparation is usually decided by patient factors, tolerability and cost.
3. 200mg OD (or even alternate days) is recommended.
4. Considerations of formulation (liquid, tablet, capsules) may be important for patient compliance and side effect profile.
5. Reductions to alternate daily dosing if not tolerate
6. Preparations often listed as “salt” content – need to consider ferrous iron

Question 10

How does intravenous iron work (4)

Answer 10

1. Intravenous Iron is available but reserved for patients unresponsive to oral iron or with the need for rapid iron replacement.
2. Intestinal absorption of iron is significantly impaired in renal dysfunction and inflammatory bowel conditions– oral iron is incapable of replenishing supplies.
3. The intravenous route is often preferred – can be administered intramuscularly (into the buttock) but is often very painful at the injection site.
4. Also potentially useful in patients with severe GI toxicity from oral formulations.

Question 11

What are the risks with injectable iron (5)

Answer 11

1. Potential for hypersensitivity reactions, including anaphylaxis.
2. Hypotension
3. Flu-like symptoms
4. Arthralgia/Myalgia (particularly of the chest)
5. Some clinical guidelines recommend pre-treatment with intravenous antihistamine, however, evidence suggests that there may be a greater incidence of adverse effects falsely attributed to iron with this approach.

Question 12

What are the products of injectable iron available (6)

Answer 12

1. available, but not interchangeable
2. Iron dextran (Cosmofer)
3. Iron sucrose (Venofer)
4. Ferric carboxymaltose (Ferinject)
5. Ferric derisomaltose (Diafer)
6. Specific doses, loading doses, infusion rates, etc, vary

Question 13

What is the appearance of cells in megaloblastic anaemia (2)

Answer 13

1. Macrocytic– large red cells in reduced numbers
2. Normochromic

Question 14

What are the lab results for megaloblastic anaemia (4)

Answer 14

1. Low Hb/RBCs
2. high MCV (mean corpuscular volume)
3. normal MCHC (Mean cell haemoglobin concentration)
4. low B12 +/- low folate

Question 15

What are the causes of megaloblastic anaemia (2)

Answer 15

1. Low Folate - Diet low in folate (also excess alcohol), Increased demand of folate in pregnancy, malabsorption (see below), medication?
2. Low B12 - Pernicious anaemia, malabsorption due to gastrectomy, coeliac disease, Crohn’s. Sometimes dietary

Question 16

What are the symptoms of megaloblastic anaemia (6)

Answer 16

1. Glossitis (sore, pale smooth tongue)
2. anorexia
3. tired
4. pale
5. Also specific to B12 deficiency - mild jaundice (increased breakdown of Hb)
6. neuropathy

Question 17

What is cobalamin (Vitamin B12) (6)

Answer 17

1. Used in treatment of pernicious anaemia where absorption of dietary Cobalamin cannot take place due to absence or malfunction of gastric intrinsic factor.
2. IF is produced by gastric parietal cells. It protects B12 from being broken-down, hence essential to absorption
3. Injectable Hydroxocobalamin generally considered the drug of choice.
4. Injectable Cyanocobalamin is also available but requires more frequent maintenance dosing
5. Oral Cyanocobalamin available for B12 deficiency of dietary origin.
6. A high dose (Orobalamin) (1-2mg daily) Cyanocobalamin preparation is low licensed for pernicious anaemia.

Question 18

What is Hydroxocobalamin (8)

Answer 18

1. Vitamer of Vitamin B12
2. Administered as an intramuscular injection
3. Intense red colour due to central cobalt ion.
4. Preferable for pernicious anaemia over Cyanocobalamin due to longer retention time in body
5. Requires less frequent administration as a result
6. Usually administered three times weekly over first two weeks to replenish Cobalamin stores, then reduced to three monthly maintenance.
7. Higher doses given to patients with neurological involvement (seizures etc)
8. Also used to treat Cyanide poisoning.

Question 19

What is folate (Vitamin B9) (7)

Answer 19

1. Used in the treatment of Folate deficiency anaemia and as supplementation in pregnant women.
2. Requires biotransformation by dihydrofolate reductase to active form.
3. Essential for production of healthy red blood calls, synthesis and methylation of DNA.
4. Deficiency can cause diarrhea, macrocytic anaemia, shortness of breath, peripheral neuropathy.
5. In pregnancy, deficiency can cause developmental disorders called Neural Tube Defects (i.e. Spina bifida, anencephaly)
6. Prescribable as Folic Acid.
7. Some compound preparations with iron (i.e. Ferrograd Folate), but less suitable for prescribing.

Question 20

What are Erythropoiesis Stimulating Agents (ESAs) (11)

Answer 20

1. Agents designed to stimulate erythropoiesis (red blood cell production)
2. Structurally and biologically similar to endogenous cytokine erythropoietin
3. Epoetin alfa – Human, recombinant
4. Epoetin beta – Synthetic, recombinant
5. Epoetin zeta – Human, recombinant
6. Darbepoetin alfa – Synthetic, recombinant
7. Particularly useful in the treatment of anaemia secondary to renal dysfunction and secondary to cancer chemotherapy
8. Only administered by injection (intravenous or subcutaneous)
9. Generally well tolerated – hypertension, headache, migraine reported.
10. More concerning is potential for thrombotic events (heart attacks, strokes, PE etc) – particularly if used to increase Hb levels over 13.0g/dl.
11. Darbepoetin produced in Chinese hamster ovary cells. Differs by containing two extra N-linked oligosaccharide chains. Claimed to be more potent and longer half-life although claims not entirely proven.

Question 21

Why are ESAs misused by cyclists (6)

Answer 21

1. ESAs designed to increase red blood cell levels.
2. More red blood cells allow more oxygen to be carried.
3. More oxygen allows for vigorous exercise to be continued at a greater intensity over a greater period of time.
4. No effective test for EPO until 2000.
5. Testing relied on Haematocrit testing (%volume of RBC)
6. Can be increased slightly by training at altitude (low oxygen levels)

Question 22

What is the problem with ESAs (2)

Answer 22

1. At high haematocrits, viscosity (thickness) of blood increases.
2. Increases pressure on left ventricle potentially causing left ventricular failure

Question 23

What are haemolytic anaemias (4)

Answer 23

1. When the rate of destruction exceeds the rate of production (i.e. reduced lifespan of RBC)
2. Sickle cell anaemia
3. Thalassaemia
4. Glucose-6-phosphate dehydrogenase deficiency

Question 24

What are the symptoms of haemolytic anaemias (8)

Answer 24

1. Malaise
2. fever
3. abdominal pain
4. dark urine
5. jaundice
6. enlarged spleen
7. muscle pain
8. raised bilirubin levels

Question 25

What is sickle cell anaemia (5)

Answer 25

1. Reduced oxygen capacity, sickle cell shape = less flexible, flow poorly tissue hypoxia and damage – particularly the spleen. 2. Reduced RBC life span (10-20 days) – cells are destroyed because of their shape 3. High reticulocyte count, low or high abnormal Hb (detected using electrophoresis, but not on standard FBC), high bilirubin 4. Patients experience sickle cell crisis / vaso-occlusive crisis – obstruction of circulation that can affect vital organs, severe pain - requires hospitalisation 5. Only 50% of patients live into their 50s

Question 26

What is used in sickle cell anaemia management (6)

Answer 26

1. Folic acid (increased folate demand, due to overactive bone marrow for chronic haemolysis) 2. Prophylactic penicillin (due to damaged spleen increased risk of bacterial infections – pneumococcal) 3. Vaccinations 4. Hydroxycarbamide (cytotoxic) thought to correct abnormal haemoglobin 5. Blood transfusion (introducing normal RBC) 6. If a vaso-occlusive crisis give strong opiates ? IV, fluids, IV antibiotics if infection, oxygen, RBC transfusion

Question 27

What is Glucose-6-phosphate dehydrogenase deficiency (5)

Answer 27

1. G6PD - enzyme needed to keep Hb in a reduced form, which protects it from oxidative damage 2. If deficient in G6PD Hb will oxidize – cell membrane damage haemolyse (reduced life span) 3. Trigger factors = fava beans, illness, certain drugs 4. Acute situation is self limiting – new young cells = higher levels of G6PD than old ones 5. No specific treatment - Identify and treat/ stop causative factor. Ensure hydration, avoid precipitating factors. Blood transfusion? Folic acid?

Question 28

What is thalassaemia (6)

Answer 28

1. Absence, or reduced levels of one of the globulin chains that form standard Hb 2. Reduced RBC lifespan 3. α or β thalassaemias of varying severity 4. Signs and symptoms vary massively from asymptomatic to severe haemolytic microcytic anaemia (low Hb/ MCV) & splenomegaly & organ damage 5. Treated by regular blood transfusions plus medication to chelate additional iron 6. Current / future role for stem cell transplants

Question 29

What is iron chelation therapy (6)

Answer 29

1. People who have regular blood transfusions for e.g. thalassaemia must also have treatment to remove excess iron from their body 2. Excess iron damages organs (liver, heart) – it is removed with chelation therapy (life long) 3. There are three chelating agents currently available, individually determined for the patient. 4. desferrioxamine (DFO) SC infusion – over 8-12 hours, potentially 5-6 times a week 5. deferiprone (DFP) - oral 6. deferasirox (DFX) - oral

Question 30

What is the main risk of using erythropoiesis-stimulating agents (ESAs) in anaemia treatment?

Answer 30

Increased risk of thrombotic events

Question 31

Why do patients with chronic haemolysis require folic acid supplementation?

Answer 31

To support rapid red blood cell turnover