Anaemia - Presentation, Diagnosis and Treatment

Question 1

What factors may be considered when diagnosing anaemia?

Answer 1

• All biological measurements will have a range of normality
• Range will be age/gender related
• Expressed as reference range- often a “normal distribution”

Question 2

What Hb range is used to diagnose anaemia?

Answer 2

For Hb typically in adult male 135-175, female 120-155 g/ (previously g/dl)

Question 3

What are the symptoms of anaemia?

Answer 3

“Tired all the time”- need to unpack this
Symptoms relating to reduced O2 delivery
- short of breath
-muscle pain on exertion
-dizzy
-angina
Symptoms relating to the cause of the anaemia

Question 4

What are the clinical signs of anaemia?

Answer 4

• Palor in skin and conjunctiva
• Tachycardia
• Rapid breathing
• Peripheral oedema if severe anaemia
• Signs relating to cause of anaemia

Question 5

What are the symptoms of mild anaemia?

Answer 5

Mild anaemia likely to cause no symptoms unless extreme exertion

Question 6

What is the effect of anaemia on cardiac output?

Answer 6

Cardiac output increases- rate and stroke volume

• Changes in distribution of blood flow

Question 7

What factors are used to classify the type of anaemia?

Answer 7

• Under-production or increased loss of RBC
• Congenital or acquired
• Acute or chronic
• By mean cell volume (MCV) – microcytic/normocytic/macrocytic

Question 8

How do you calculate the classification of anaemia by mean cell volume?

Answer 8

Haematocrit (Hct) (%) X10
RBC count (number as 1012/l)
• MCH- mean cell Hb - Hb RBC
• MCHC- mean cell Hb concentration- Hb Hct
•RDW red cell distribution width is a measure of spread of RBC size eg retics/transfusion

Question 9

What is a mean cell volume of 60-80fl indicative of?

Answer 9

Microcytic anaemia- iron def, thalassaemia

Question 10

What does microcytic anaemia refer to?

Answer 10

Abnormally small erythrocyte, linked to certain types of anaemia

Question 11

What is a mean cell volume of 80-100fl indicative of?

Answer 11

Normocytic anaemia - blood loss, anaemia of chronic disease,

renal impairment

Question 12

What does normocytic anaemia refer to?

Answer 12

An anaemia caused by chronic disease, v prevalent in over 85 y/o

Question 13

What is a mean cell volume of 100 -120fl indicative of?

Answer 13

Macrocytic anaemia - megaloblastic anaemia- B12/folate deficiency, myelodysplasia

Question 14

What does macrocytic anaemia refer to?

Answer 14

Abnormally large erythrocytes linked to certain types of anaemia

Question 15

What is hypochromic anaemia?

Answer 15

Any type of anaemia where the erythrocyte is paler than normal, iron def, thalassaemia

Question 16

What is the most common cause of anaemia worldwide?

Answer 16

Iron deficiency anaemia

Question 17

What is the pathology of iron deficiency anaemia?

Answer 17

Typically reduction in MCV (microcytic) to 65-80, then in Hb, low ferritin, low transferrin saturation with iron. Rest of blood count normal- ?raised platelets if bleeding.

Question 18

What may cause iron deficiency anaemia?

Answer 18

-Poor intake of iron

• Blood loss- menstrual
• —GI tract ?haematemesis or melaena eg peptic ulcer/cancer/angiodysplasia/hookworm
• Malabsorption- coeliac disease
• Increased need eg growth spurt/pregnancy

Question 19

What are the clinical features of iron deficiency anaemia?

Answer 19

• Pale
• Tachycardia
• Koilonychia
• Hair loss
• Pica
• Glossitis/angular stomatitis
• Features relating to the cause eg wt loss/abdo pain/bowel change/heavy periods

Question 20

How should one investigate iron deficiency anaemia?

Answer 20

• Be guided by history- recent and past and clinical findings
• Confirm iron def by low ferritin and typical FBC •Screen for coeliac disease (IgA tissue transglutaminase or tGA)
• Upper and lower endoscopy for all except pre-menopausal women
• Consider other imaging/capsule endoscopy

Question 21

How should one orally treat iron deficiency anaemia?

Answer 21

• Oral- replacement with sufficient iron for long enough period eg ferrous sulfate 200mg 2 or 3 per day- 65mg elemental iron per dose
• Side effects- nausea/abdo pain/constipation- dose related- may improve if changed to ferrous gluconate or fumarate
• Typically patients need 3 months of iron AFTER correction of anaemia to build up iron stores
• Treat the underlying cause
• Rise in Hb generally 10g/l per week if not bleeding

Question 22

How should one treat iron deficiency anaemia parenterally?

Answer 22

• Intramuscular- not used now- painful, multiple doses, stains skin
• Intravenous-
Ferric carboxymaltose- ferinject- over 15-30mins. Often needs 2 doses Iron dextran- cosmofer- over 4-6 hours after a test dose.

All IV iron preparations can cause ‘flu like symptoms and a small risk of hypersensitivity reaction or anaphylaxis

Question 23

Describe B12 deficiency

Answer 23

Think KT
• Typically a macrocytic anaemia- MCV 100-120 and later a pancytopenia. Often bilirubin and LDH raised
• Can also cause peripheral neuropathy- demyelination and posterior column damage
• B12 result can be falsely low in pregnancy/oral contraceptive/on metformin
• Pernicious anaemia- gastric atrophy and auto antibodies to parietal cells and intrinsic factor preventing absorption
• Strict vegan or terminal ileal disease also possible

Question 24

What treatments are available for B12 deficiency?

Answer 24

• Hydroxocobalamin 1mg IM alternate days for 5 doses then 3 monthly if confirmed ongoing need eg pernicnious anaemia
• Cyanocobalamin available orally but not available on prescription

Question 25

Describe Folate deficiency

Answer 25

* Blood count and film appearance same as B12 def. * Limited stores of folate so deficiency can develop in weeks * Poor intake, increased use eg pregnancy/haemolysis, malabsorption, drugs eg anti-epileptics or trimethoprim * Replacement with oral folic acid 5mg per day * Pre-conception folic acid reduces neural tube defects. Likely plan to add folic acid to flour

Question 26

Describe anaemia due to blood loss

Answer 26

• Hb immediately after blood loss will be normal • Drop after fluid replacement • Each 500ml loss gives approx drop of Hb by 10-15 g/l • Retic response within hours/days • May need blood transfusion to replace loss eg trauma/GI bleed/around delivery

Question 27

Describe anaemia of chronic disease

Answer 27

* Typically a normocytic anaemia associated with chronic inflammatory disease * Plentiful iron stores but poor transfer to RBC due to hepcidin and cytokines * History of chronic disease, inflammatory markers increased eg CRP/ESR/plasma viscosity, exclusion of other causes * Will respond to treatment of underlying disease

Question 28

Describe anaemia of renal failure

Answer 28

* Drop in Hb once creatinine clearance drops below 20-30 ml/min chronically * Mainly due to lack of erythropoietin * Contribution from blood loss at dialysis, inflammatory disease * Responds well to erythropoietin eg weekly or alternate weeks s/c

Question 29

Describe effects and causes of haemolysis

Answer 29

• Increased RBC destruction, marrow can increase production 5 -10 fold • Can be acute or chronic, congenital or acquired • Issues to do with- RBC membrane - RBC enzymes -Globin chains in Hb

Question 30

What are the causes of haemolysis of the RBC membrane due to disease?

Answer 30

* Congenital spherocytosis- autosomal dominant defect in spectrin causing spherical cells – less able to deform so shortened survival * Auto-immune haemolysis- auto antibodies against RBC surface antigens- Fc portion recognised by macrophages in spleen. Treated with steroids/splenectomy/rituximab

Question 31

What are the mechanical and enzyme based causes of haemolysis of the RBC membrane?

Answer 31

Prosthetic heart valve- mechanical Disseminated intravascular coagulation (DIC)- eg in sepsis, prostate cancer causing RBC fragmentation by fibrin RBC enzyme def eg G6PD or pyruvate kinase can cause shortened RBC survival

Question 32

What is the cause of anaemia due to abnormal haemoglobin?

Answer 32

Haemoglobinopathy eg Sickle cell disease- single point mutation causing Hb polymerisation in hypoxic cells in homozygotes

Question 33

Describe anaemia due to abnormal haemoglobin

Answer 33

• Haemoglobinopathy eg Sickle cell disease- single point mutation causing Hb polymerisation in hypoxic cells in homozygotes • Shortened RBC survival, reduced production • Chronic anaemia and bone/liver/lung/brain “crisis” ie acute infarction • Treated by supportive care, hydroxycarbamide to increase HbF production, ??stem cell transplant

Question 34

Describe anaemia due to thlassaemia

Answer 34

* Inbalance of globin chain production * Beta thalassaemia- as Hb F (2 alpha, 2 gamma chains) declines after birth- progressive anaemia. Supportive care, transfusion, ?stem cell transplant * Progressive iron overload * Antenatal screen for Hb-opathy and thalassaemia

Question 35

What is the physiological cause and treatment of anaemia due to marrow infiltration?

Answer 35

• Myeloma- B cell malignancy of mature plasma cells- produce monoclonal immunoglobulin or light chains Presents as chance finding, anaemia, renal failure, hypercalcaemia, bone pain or fracture Treatment- supportive care, chemotherapy, radiotherapy

Question 36

How does one discover anaemia due to marrow infiltration?

Answer 36

Presents as chance finding, look in anaemia, renal failure, hypercalcaemia, bone pain or fracture

Question 37

Give a brief overview of anaemia due o marrow infiltration

Answer 37

* Haematological malignancy eg lymphoma, acute leukaemia * Diagnosed by sampling marrow- pelvis or sternum * Treated by chemotherapy/immunotherapy * Other “solid” tumours can spread to marrow eg prostate, breast, small cell lung

Question 38

What anaemias are caused by marrow failures?

Answer 38

* Myelodysplastic disorders- progressive decline in Hb, neutrophils, platelets, macrocytosis. Tendency to progress to acute leukaemia. Treated by supportive care, chemotherapy or stem cell transplant in some. * Aplastic anaemia- pancytopenia. Expected result post chemotherapy but can be drug induced eg NSAIDs, chloramphenicol or idiopathic. Treated by supportive care, anti- thymocyte globulin, stem cell transplant

Question 39

In summary, what be anaemia?

Answer 39

* Anaemia is a blood count finding with associated symptoms and signs * Multiple causes relating to underproduction or increased loss * Use other blood count indices to identify a likely cause * Treatment relates to cause and underlying disease