Red Cells and Anaemia

Question 1

What are the substances needed to make a red blood cell?

Answer 1

Metals: Iron, copper, cobalt, manganese
Vitamins: B12, folic acid, thiamine, Vit.B6, C,E
Amino acids
Hormones: Erythropoietin, GM-CSF, androgens, thyroxine, SCF

Question 2

What is the cell called that is the precursor to a red blood cell?

Answer 2

Reticulocyte

Question 3

Why do men have a higher Hg than women?

Answer 3

They have more androgen which is one of the hormones that drives red cell production

Question 4

Where does RBC breakdown happen?

Answer 4

Occurs in the reticuloendothelial system

Macrophages in Spleen, liver, lymph nodes, lungs etc

Question 5

What happens to haem during breakdown?

Answer 5

Turned to unconjugated bilirubin

Question 6

What is hereditary spherocytosis?

Answer 6

Congenital autosomal recessive anaemia
Defects in the different structural proteins mean that the red cell is spherical in shape so they are removed faster by the extravascular reticuloendothelial system than they would be if biconcave

Question 7

What is the presentation of hereditary spherocytosis?

Answer 7

Breaking down faster so more bilirubin-jaundice
Enlarged spleen larger as have to work harder to remove haem
Higher levels of bilirubin can precipitate out into gallbladder and cause stones
Variable presentation, depending on which protein is affected
Anaemia symptoms

Question 8

What is the normal life span of an RBC?

Answer 8

120 days

Question 9

What is the management of hereditary spherocytosis?

Answer 9

Folic acid (increased requirements)
Transfusion
Splenectomy-If remove spleen then the red cells might last longer, destroyed less readily, last resort

Question 10

What are three other disorders of the red blood cell’s membrane?

Answer 10

Hereditary Elliptocytosis-form elliptocytes
Hereditary Pyropoikilocytosis-cells are different shapes and sizes
South East Asian Ovalocytosis-oval shaped cells and usually relatively benign

Question 11

What is G6PD deficiency?

Answer 11

Cells vulnerable to oxidative damage due to affecting of the enzyme Glucose 6 Phosphate Dehydrogenase
Confers protection against malaria so most common in malarial areas
X Linked so affects males and there are female carriers
Cells are blistered and broken on a blood smear and cells fragment in the circulation and die
Intravascular haemolysis- cells bursting in the circulation, free haemoglobin which makes the urine darker

Question 12

What can precipitate a G6PD deficiency presentation?

Answer 12

Drug, broad bean or infection precipitated jaundice and anaemia

Question 13

What is the Bohr effect?

Answer 13

Bohr effect means haemoglobin will give up oxygen when needed so in acidosis, hyperthermia and hypercapnia and the graph will shift to the right

Question 14

What are the three types of haemoglobin and what chains are they made up of?

Answer 14

Haemoglobin A- two alpha chains and two beta
Haemoglobin A2- two alpha chains and two delta
Foetal haemoglobin- two alpha chains and two gamma

Question 15

What is thalassaemia?

Answer 15

Reduced or absent globin chain production
Alpha plus and alpha zero thalassaemias
If both parents are alpha zero carriers then child can’t make any foetal Hg in utero so incompatible with life

Question 16

What is sickle cell disease?

Answer 16

Autosomal recessive condition
Mutations leading to structurally abnormal globin chain
Usually a point mutation in a beta gene
In low O2 tension get polymerisation of abnormal haemoglobin and crystallises so red cells sickle. So red cells are made normal but only when low O2 (which happens physiologically) does it sickle which is irreversible. Sickle Hg has lower O2 affinity so gives up O2 more easily but will get haemolysis as abnormal shape

Question 17

What are the possible complications of sickle cell disease?

Answer 17

Attributed to vasoocclusive tissue damage
Painful Vaso-occlusive crises
Bone pain
Chest Crisis
Stroke
Increased infection risk
Hyposplenism 
Chronic haemolytic anaemia
Gallstones
Aplastic crisis
Sequestration crises
Spleen
Liver
Dactylitis

Question 18

What is an aplastic crisis?

Answer 18

high red cell turnover, if virus attacks then red cells dip (only last a week) as switches off red cell production which causes severe anaemia, which can present as slap cheek in children
Aplastic anaemia (AA) is defined by pancytopenia with hypocellular marrow and no abnormal cells

Question 19

What is the management of sickle cell disease?

Answer 19

Acute Events
Hydration 
Oxygenation
Prompt treatment of infection
Analgesia
Opiates
NSAIDs
Life long prophylaxis
Vaccination
Penicillin (and malarial) prophylaxis	
Folic acid
Blood Transfusion
Hydroxycarbamide increases Haemoglobin F production which doesn’t sickle
Bone marrow transplantation
Gene therapy

Question 20

What is the presentation of beta thalassaemia major?

Answer 20

Severe anaemia
Present at 3-6 months of age
Expansion of ineffective bone marrow
Bony deformities
Splenomegaly
Growth retardation
“Hair on end” appearance on scans seen on skull due to bone marrow expansion

Question 21

What is the management of thalassaemia?

Answer 21

Chronic transfusion support - 4-6 weekly
Normal growth and development
Iron overloading from transfusions needs to be managed with Iron chelation therapy
Bone marrow transplant is curative

Question 22

What defects in haem formation causes what kind of anaemias?

Answer 22

Defects in mitochondrial steps of haem synthesis result in sideroblastic anaemia
Defects in cytoplasmic steps result in porphyrias

Question 23

What are the reference ranges for haemoglobin in men and women?

Answer 23

Male 12-70 (140-180)
Male >70 (116-156)

Female 12-70 (120-160)
Female >70 (108-143)

Question 24

What are some underlying causes of anaemia?

Answer 24

Evidence of bleeding
Menorrhagia
Dyspepsia, PR bleeding				
Symptoms of malabsorption
Diarrhoea
Weight loss
Jaundice
Splenomegaly/Lymphadenopathy
Pregnancy
Coeliac disease
Diet deficiency

Question 25

What are MCV and MCH?

Answer 25

MCV = Mean cell volume  (cell size)
MCH = Mean cell haemoglobin (cell colour)

Question 26

What are the three morphological descriptions of anaemia?

Answer 26

Microcytic and hypochromic
Normocytic and normochromic
Macrocytic

Question 27

What can be the underlying cause of a microcytic and hypochromic anaemia and what should the investigations be?

Answer 27

Iron deficiency anaemia
Thalassaemia
Secondary anaemia
Sideroblastic anaemia
Do a serum ferritin and if low then could be iron deficiency anaemia and if normal then could be thalassaemia or secondary anaemia

Question 28

What can be the underlying cause of a normocytic and normochromic anaemia and what should the investigations be?

Answer 28

Haemolytic anaemia
Bone marrow tumour
A reticulocyte count indicates if the bone marrow is normal, if low then could be a bone marrow tumour or aplastic anaemia or a secondary anaemia, if high then could be a haemolysing anaemia or acute blood loss

Question 29

What can be the underlying cause of a macrocytic anaemia and what should the investigations be?

Answer 29

B12 or folate deficiency
Bone marrow tumour
Do a B12 and folate levels, if normal then do reticulocyte count to look at bone marrow

Question 30

What is secondary anaemia?

Answer 30

Iron levels are normal but being used inefficiently to make blood. Ferritin goes up with CRP if active inflammatory process, so can mask an anaemia.
“Anaemia of chronic disease”
70% normochromic normocytic
30% hypochromic microcytic
Defective iron utilisation
Increased hepcidin in inflammation
Ferritin often elevated
Identifiable underlying disease
Infection, inflammation, malignancy

Question 31

What are some intra and extravascular haemolytic anaemias?

Answer 31

Intravascular- Mechanical eg.artificial valve
Severe infection/DIC
PET/HUS/TTP
G6PD enzyme deficiency
Extravascular- Auto-immune haemolytic anaemia
Hereditary spherocytosis

Question 32

What test can be used to tell if an acquired haemolytic anaemia is immune (extravascular) or non immune (intravascular)?

Answer 32

Coomb’s test
Take patient’s blood in blood transfusion lab
In lab add anti-globulin antibody and cross links red cells, so they agglutinate in the tubes
Tells you that antibodies are on surface of the cell and there is an immune cause to the anaemia-immune mediated anaemia
If negative then not immune mediated

Question 33

What is the management for haemolytic anaemia?

Answer 33

Support marrow function 
Folic acid
Correct cause 
Immunosuppression if autoimmune
Steroids
Treat trigger eg.CLL, Lymphoma
Remove site of red cell destruction
Splenectomy
Treat sepsis, leaky prosthetic valve, malignancy etc. if intravascular
Consider transfusion

Question 34

What are megaloblastic anaemias?

Answer 34

Megaloblastic anaemia is B12 or folate deficiency

Question 35

What are some non-megaloblastic causes of macrocytic anaemia?

Answer 35

Myelodysplasia (bone marrow cancer)
Marrow infiltration
Drugs

Question 36

What are the causes of B12 deficiency anaemia?

Answer 36

If problem with stomach or terminal ileum or diet deficiency then can have low B12
Or get antibodies against intrinsic factor which affects binding-pernicious anaemia

Question 37

What are the causes of a folate deficiency anaemia?

Answer 37

Dietary
Increased requirements (haemolysis)
GI pathology (eg.coeliac disease)

Question 38

What is the management of megaloblastic anaemias?

Answer 38

Replace vitamin
B12 deficiency
B12 intramuscular injection
Loading dose then 3 monthly maintenance

Folate deficiency
Oral folate replacement
Ensure B12 normal if neuropathic symptoms, Check B12 before giving folate as can make neuropathy worse, so give both until get results

Question 39

What are some causes other than anaemia for a macrocytosis?

Answer 39

Alcohol
Drugs
-Methotrexate, Antiretrovirals, hydroxycarbamide
Disordered liver function
Hypothyroidism
Myelodysplasia