Common Causes of Anaemia and Thrombocytopenia

Question 1

What are examples of Macrocytic anaemia?

Answer 1

B12, Folate, metabolic (e.g. thyroid/liver disease)
Marrow damage (alcohol, drugs, marrow diseases)
Haemolysis (due to reticulocytosis)

Question 2

What are examples of normocytic anaemia?

Answer 2

Anaemia of chronic disease / inflammatory

Question 3

What are examples of microcytic anaemia?

Answer 3

Iron deficiency
Haemoglobin disorders
(sometimes chronic disease)

Question 4

What lab tests can be used to establish low iron?

Answer 4

FBC
Fettitin
% hypochromic cells

Question 5

What are the main causes of iron deficiency?

Answer 5

Blood loss from anywhere
Increased demand - pregnancy/growth
reduced intake- diet/malabsorption

Question 6

What are the main causes of iron deficiency in children?

Answer 6

diet
growth
malabsorption

Question 7

What are the main causes of iron deficiency in young women?

Answer 7

Menstrual loss/problems
Pregnancy
Diet

Question 8

What are the main causes of iron deficiency in older people?

Answer 8

Bleeding

GI problems e.g. ulcer, malignancy, diverticulitis

Question 9

What forms of iron treatment are available?

Answer 9

Oral iron - Often unreliable
IM iron - painful,out of date
IV iron - increasingly used

Question 10

What is megaloblastic anaemia caused by?

Answer 10

characteristic cell morphology caused by impaired DNA synthesis

Question 11

How do B12 + Folate cause anaemia?

Answer 11

DNA consists of purine/pyrimidine bases
folates are required for their synthesis
B12 is essential for cell folate generation
So low Folate or B12 starves DNA of bases

Question 12

What are food sources of B12?

Answer 12

animal sources

Question 13

Where is B12 absorbed in the body?

Answer 13

vitamin B12 binds to haptocorrin - produced by the salivary glands and the parietal cells in the stomach
in duodenum, pancreatic proteases degrades the haptocorrin and vitamin B12
Then binds to Intrinsic Factor produced by parietal cells
in the mucosal cells of the distal ileum the vitamin B12-Intrinsic Factor complex is recognised by special receptors
Vitamin B12 then enters the blood bound to transcobalamin = active B12

Question 14

Can B12 be stored and for how long?

Answer 14

Yes can store

sufficient for some years

Question 15

Who tends to suffer from B12 deficiency?

Answer 15

Nutritional - vegans
Gastric problems - Pernicious anaemia,
gastrectomy
Small bowel problems - Terminal ileal resection, Crohns, stagnant loops, jejunal diverticulosis, tropical sprue, Fish tapeworm

Question 16

What sources of food contain lots of folic acid?

Answer 16

Must be consumed!
green vegetable
beans
peas
nuts
liver

Question 17

Where is folic acid absorbed?

Answer 17

upper small bowel

Question 18

How long does the body store folic acid?

Answer 18

4 months

Question 19

What can cause folic acid deficiency?

Answer 19

Mainly dietary/malnutrition
Malabsorption/small bowel disease
Increased usage: pregnany, haemolysis, inflammatory disorders
Drugs/alcohol/ITU (intensive therapy unit)

Question 20

What clinical features are present in someone with B12/folate deficiency?

Answer 20

Megaloblastic anaemia
Can have pancytopenia if more severe - deficiency of red cells, white cells and platelets
Mild jaundice
Glossitis (inflammation of the tongue)/angular stomatitis (inflammation of corners of the mouth)
anorexia/weight loss
sterility - incapability to reproduction

Question 21

What are the lab features B12/folate deficiency?

Answer 21

Blood count and film, marrow sometimes
Bilirubin and Lactate Dehydrogenase 
B12 and folate levels
Antibodies
B12 absorption tests +/- IF
GI investigations e.g. crohns, blind loop

Question 22

What is pernicious anaemia?

Answer 22

Autoimmune disease
Antibodies to parietal cells/intrinsic factor
Atrophic gastritis with achlorhydria - absence of hydrochloric acid in the gastric secretions
Don’t form intrinsic factor
Incidence of stomach cancer

Question 23

What is subacute combined degeneration of the cord (SACDC)?

Answer 23

Any cause of severe B12 deficiency - Anaemia not an absolute requirement
Demyelination of dorsal + lateral columns
Peripheral nerve damage

Question 24

How does subacute combined degeneration of the cord (SACDC) present?

Answer 24

Peripheral neuropathy/Paraesthesiae
Numbness and distal weakness
Unsteady walking
Dementia

Question 25

What is the treatment for B12 and folate deficiency?

Answer 25

Give both B12 + Folate until B12 deficiency excluded B12 x5 then 3 monthly for life Folic acid 5mg daily to build stores

Question 26

What are the causes of haemolysis (simply)?

Answer 26

Things wrong inside the red cell Things wrong with the red cell membrane Things wrong external to the red cell

Question 27

What are common causes of haemolysis inside the cell?

Answer 27

``` Haemoglobinopathy (Sickle cell) Enzyme defects (G6PD) ```

Question 28

What are common causes of haemolysis with the membrane?

Answer 28

Hereditary Spherocytosis/elliptocytosis (RBC the wrong shape)

Question 29

What are common causes of haemolysis outside the cell?

Answer 29

Antibodies (warm/cold) Drugs/toxins Heart valves Vascular/vasculitis/‘microangiopathy

Question 30

What tests show the presence of haemolysis?

Answer 30

Anaemic (can be compendated for) High MCV, macrocytic High Reticulocytes - an immature red blood cell without a nucleus having a granular appearance Blood film (fragments/spherocytes) Raised bilirubin, LDH (lactate dehydrogenase) Low haptoglobins - protein that binds to haemoglobin Urinary Haemosiderin - brown urine

Question 31

What is the treatment for autoimmune haemolytic anaemia?

Answer 31

steroids immunosuppression Transfusion can be tricky as hard to cross match

Question 32

Why is there reduced red cell production in anaemia of chronic disease?

Answer 32

Inflammatory cytokines control mechanism of absorption of iron - Hepcidine is the key regulator of iron absorption and release from macrophages Abnormal iron metabolism poor erythropoetin response blunted marrow response

Question 33

What are the features of anaemia of chronic disease?

Answer 33

``` No other causes of anaemia - diagnosis of exclusion A suitable medical history Usually mild anaemia, normal MCV Often raised inflammatory markers Normal/high ferritin + low serum iron Normal % Saturation transferrin ```

Question 34

What is the treatment for anaemia of chronic disease?

Answer 34

The cause if possible Erythropoetin Iron? IV? Transfusion?

Question 35

What is immune thrombocytopenic purpura (ITP)?

Answer 35

``` isolated low platelet count characteristic purpuric rash increased tendency to bleed immune disorder Occurs on its own or as part of: Other autoimmune diseases, Lymphomas, CLL, HIV Can be acute/chronic/relapsing ```

Question 36

What are the clinical features of immune thrombocytopenic purpura (ITP)?

Answer 36

``` Bruising characteristic purpuric rash increased tendency to bleed low platelet count No definitive test ```

Question 37

What is the treatment for immune thrombocytopenic purpura (ITP)?

Answer 37

``` Steroid - first line IV immunoglobulin Other immunosuppressives splenectomy Newer thrombo-mimetics: Eltrombopag, Romiplostin ```

Question 38

What is the outcome after treatment for immune thrombocytopenic purpura (ITP)?

Answer 38

Usually rapid responses Can relapse after therapy Rarely life-threatening commonly recurrent

Question 39

What is Thrombotic thrombocytopenia purpura (TTP)?

Answer 39

blood clots form in small blood vessels throughout the body Rare but urgent diagnosis Most are immune

Question 40

Apart from thrombosis forming, what other symptoms are present in thrombocytopenia?

Answer 40

Fever Neurological symptoms Haemolysis

Question 41

What urgent therapy is used in Thrombotic thrombocytopenia purpura (TTP)?

Answer 41

Plasma exchange with FFP/plasma Steroids Outcomes vary – can see relapses