Anaemia and haematinic deficiencies

Question 1

What is blood made up of?

Answer 1

plasma 55% (91% is water)
buffy coat (white cells and platelets + red blood cells - 45%

Question 2

What is anaemia?

Answer 2

lack of blood - reduction in Hb, red cell count or haematocrit

Question 3

What are the normal levels of haemoglobin?

Answer 3

males >130 g/L
females >120g/L 
pregnant woman >110 g/L 
children 6-59 months >110g/L 
children 5-11 years >115 g/L
children 12--14 years >120 g/L

Question 4

How many new red cells are made per day and what is their life span?

Answer 4

10 to the power of 12 new ones per day
life span: 120 days
form in the bone marrow from myeloid cells - differentiate from blasts which are regulated by erythropoietin
the nucleus of the cell is removed just before leaving the bone marrow

Question 5

What are the 3 main types of anaemia?

Answer 5

Microcytic (MCV <80fL)
Normocytic (MCV 80-90fL)
Macrocytic (MCV >95 fL)

The size of the red blood cells can help determine the cause

Question 6

What are the causes of microcytic anaemia?

Answer 6

Thalassaemia and thalassaemia trait (NOT sickle cell)
Iron deficiency (most common cause worldwide)
Anaemia of chronic disease
Sideroblastic anaemia (congenital or acquired)

Question 7

What are the causes of normocytic anaemia?

Answer 7

Anaemia of chronic disease
Acute blood loss
Mixed haematinic deficiencies
Bone marrow failure (not able to produce enough cells) - aplastic anaemia, drugs e.g chemo

Question 8

What are the causes of macrocytic anaemia?

Answer 8

Megaloblastic anaemia 
Myelodysplasia- ware and tare on the bone marrow 
Haemolytic anaemia
liver disease 
Alcohol 
Drugs - esp. antiepileptics, hydrocarbamide 
Hypothyroidism
Pregnancy 

It is typical with b12 and folate deficiencies

Question 9

What is MCV?

Answer 9

mean corpuscular volume = average volume of a red blood cell

Question 10

What are the main causes of acquired anaemia?

Answer 10

unable to make red cells
- deficiencies in b12, folate, iron
- bone marrow pathology - aplastic anaemia, myelodysplasia, myeloma
- displacement of bone marrow - leukaemia, myelofibrosis
- chronic disease- renal failure, chornic inflammatory conditions
destroying red blood cells
- haemolysis
- bleeding

Question 11

What are the main causes of congenital anaemia?

Answer 11

membrane defect

• hereditary spherocytosis
• hereditary epilptocytosis

haemoglobin defect

• sickle cell anaemia
• thalassemia

enzyme defect

• G6PD deficiency
• pyruvate kinase deficiency

Question 12

What happens during bleeding?

Answer 12

Rapid loss of whole blood= hypotensive - Hb conc remains the same
Then plasma vol expands to try and maintain BP = dilution of red cells so Hb falls but MCV remains the same (normocytic)

Chronically, iron stores deplete due to making new red cells but Hb and MCV remain relatively normal
However, once iron stores are depleted, you become iron deficient, microcytic hypochromic red cells being made

Question 13

What are haemotinics?

Answer 13

B12, folate, iron - needed to make healthy red blood cells

Question 14

What are the signs and symptoms of anaemia?

Answer 14

Signs: pica, koilonychia, pallor, tachycardia, flow murmur, hyperdynamic circulation

Symptoms: restless leg, breathlessness, palpitations, fatigue, tinnitus

Question 15

Why might someone that’s unwell have low serum iron levels?

Answer 15

iron is stored away to protect it from bacteria because bacteria feed off iron

Question 16

What are the causes of iron deficiency?

Answer 16

Most common cause of anaemia worlwide
In men and post menopausal women = GI malignancy until proven otherwise

1) poor intake - diet
2) poor absorption- coeliac disease, CD
3) Increased requirement - pregnancy
4) iron loss - bleeding
- GI: cancer, angiodysplasia, ulcers, gastritis, infection
- menorrhagia
- urinary

Question 17

How do you diagnose iron deficiency?

Answer 17

History and exam: diet, bleeding
FBC and film: microcytic hypochromic anaemia, target cells, pencil cells
Ferritin (measure of iron stores): low in iron deficiency, raised with inflammation
Iron studies: serum iron, transferrin saturation, total iron binding capacity

Question 18

What is maelena?

Answer 18

bleeding in stool

Question 19

What does it mean by functional iron deficiency?

Answer 19

Evolutional advantage to keeping iron out of the way of bacteria
Increased iron stores in infection/inflammation
Decreased absorption via hepcidin in enterocyte basolateral membrane
Not available for erythropoiesis

Question 20

How do you manage iron deficiency?

Answer 20

Find the underlying cause:
- gastroscopy and colonoscopy unless frail or menstruating women
-low threshold for investigating young people with fam history - 2x1st degree relatives or 1 if <40
- unless gastroscopy shows gastric malignancy or coeliac disease, must proceed to lower GI investigation
Treat deficiency

Question 21

What concentration of oral iron is given and what is unusual about this?

Answer 21

100-200mg elemental iron/day
- normally we absorb about 3mg of iron per day but in iron deficiency pts they can absorb about 10mg a day yet we give them way over that limit therefore it is not surprising they get side effects

Should take for 3 months post normal Hb to relpenish stores

Question 22

What are some ways to improve adherence and absorption of oral iron supplementation?

Answer 22

start at a low dose
take on an empty stomach
avoid tea because the tanins prevent its absorption t
take with orange juice

Question 23

What is an alternative to oral iron?

Answer 23

Intravenous iron- venofer, cosmofer, monofer, gerinject
- guaranteed delivery, faster increase in Hb, large dose delivered
Contraindicated in active bacterial infection but otherise very safe
Also more expensive

Question 24

How do we produce DNA?

Answer 24

Absorb dietary folate in the gut and combine with b12 to produce DNA

Question 25

What is folate?

Answer 25

it is pteroylglutamic acid = family of compounds - extra carbon groups reduced at different positions

Question 26

How is folate absorbed and lost?

Answer 26

Proton-coupled transporter in the duodenum Lost in urine, sweat and skin - excretion in bile It is tightly bound intracellularly until cell death Require 100mg/day and body stores 15025mg = 4 months store (not as good a store of folate as B12) Veg are rich in folate

Question 27

What are good sources of folate?

Answer 27

liver, spinach, yeast, greens, nuts, fortified foos )bread and cereal) - certain groups that commonly have low folate levels: alcoholics, elderly, poor, psychiatrically disturbed

Question 28

What are the causes of folate deficiency?

Answer 28

Low intake Impaired absorption- coeliac/crohn's, selective malabsorption, drugs (cholestyramine) increased requirement - haemolysis, pregnancy, prematurity,inflammation increased excretion/loss - dialysis, drugs (dihyrdofolate reductase inhibitors)

Question 29

How can you measure folate levels?

Answer 29

Good assays for blood Elisa technique Serum - not that great because all you are really analysing is how much folate they had that morning, it is cincreased in b12 deficiency red cell - low in b12 deficicnec, this is more fiddeley but provides better results

Question 30

What are the signs and symptoms of folate /b12deficiency?

Answer 30

Signs: jaundice, glossitis, angular cheilosis, skin hyperpigmentation, pallor, tachycardia, flow murmur, Symptoms: breathlessness, palpitations, fatigue, tinnitus Can cause infertility and neural tube defects, pancytopenia (deficiency of all 3 cellular blood parts)

Question 31

How do you treat folate deficiency?

Answer 31

Replacement - almost always oral 5mg/day 4 months depending on cause 400mcg given prophylactically in pregnancy, 5mg for previous NTD

Question 32

What is the role of B12 and how is it made? What are the requirements?

Answer 32

DNA synthesis and amking succinyl coA in krebs cycle Synthesised by micro-organisms Require 5-30mg per day in average diet - loss 1-2mg per day stores 2-3 mg per day (store for about 3-4 years)

Question 33

How is B12 absorbed?

Answer 33

passive - <1% absorbed in the duodenum and ileum Active- binds intrinsic factor produced by parietal cels and this protects it, also binds haptocorrins (saliva), cubulin receptor (ileum), transbalamin (circulation), enterohepatic circulation

Question 34

What are the neurological features of b12 deficiency?

Answer 34

``` Neurological symptoms: - parasthesiae - muscle weakness - difficulty walking - confusion, slowness signs: - peripheral neuropathy - long tract demyelination - dementia, psychosis ```

Question 35

What are the causes for b12 deficiency?

Answer 35

Poor intake - liver, kidney, shellfish, eggs, cheese and milk Malabsorption- gastric, ileal, drugs (metformin) Congenital Nitrous oxide Apparent deficiency in HRT/pregnancy Measure: B12 assay which is much better than hva to test bone marrow (can look low in women taking contraceptive pill), schilling test

Question 36

What is pernicious anaemia?

Answer 36

Associated with other autoimmune disorders Common in older women Destruction of intrinsic factor = impaired absorption Look for 2 different antibodies but intrinsic factor ab is the most important, the other one is parietal cell antibody

Question 37

What is the treatment for b12 defiency?

Answer 37

oral replacement if no evidence of PA/malabsorption - 1mg cyanocobalamin 1MG HYDROXYCOBALAMIN intamuscularly - 3/week x6 doses then every 3 months continue indefinitely unless clear reversal of cause Routine post gastrectomy or ileal resection

Question 38

What is assessed in a haemolysis screen?

Answer 38

FBC Blood film- LDH - measure of cell turnover Haptoglobin - measure of free haem Unconjugated bilirubin - breakdown product of Hb Direct antiglobulin test - only tells you if in the presence of haemolysis whether it is an immune cause

Question 39

What are the key features of autoimmune haemolytic anaemia (warm)?

Answer 39

IgG Associated with other autoimmune disease especially ITP May be precipitated by infection or cancer Treatment with steroids, splenectomy or rituximab

Question 40

What are the key features of autoimmune haemolytic anaemia (cold)?

Answer 40

``` IgM Associated with EBV, mycoplasma pneumonia, lymphoma Does not respond to steroids keep warm transfuse (through a blood warmer) treat underlying infection/lymphoma ```

Question 41

What is hereditary spherocytosis?

Answer 41

autosomal dominant membrane disorder many different proteins-usually spectrin deficiency different phenotypes but consistent in familiies symptoms exacerbated by intercurrent illness Treatment: folic acid, splenectomy, rarely transfusion

Question 42

What is an example of an enzymopathy and what are the features of it?

Answer 42

G6PD deficiency - ATP is required for membrane shape change, ion exchange, reduce methaemoglobin to deoxyghaemoglobin - mature red cells are unable to synthesis protein and have no mitochondria - ATP from anaerobic glycolysis X-linked - total deficinecy is incompatible with life Red cells unable to deal with oxidative stress (neonatal haemolytic anaemia, acute non-spherocytic haemolytic anaemia Treatment: avoidance of precipitating factors, folic acid, splenectomy

Question 43

What is acquired non-immune haemolytic anaemia?

Answer 43

mechanical intravascular destruction of red cells - microangiopathic haemolytic anaemia e.g. thrombotic thrombocytopenic purpura = shearing of red cells as they pass through fibrin strands - macrovascular e.g. valve haemolysis, march haemolysis