Haematology In Systemic Disease

Question 1

What are examples of changes to the blood in systemic disease ?

Answer 1

1) an increased expression in IL-6 or other cytokines.
2) complications of the disease which may causes bleeding
3) treatment may have adverse effects - methotrexate which is an immunosuppressant

Question 2

Why might anaemia may develop - in terms of reduced or dysfunctional erythopoiesis?

Answer 2

1) Anaemia can result from the lack of response in haemostasis loop eg chronic kidney disease where the kidney stops making EPO.
2) Anaemia can result from bone marrow being unable to recons to EPO.
3) Anaemia in chronic disease eg in rheumatoid arthritis where iron is not made available to marrow for RBC production

Question 3

Why. Is anaemiaof chronic disease a ‘ functional’iron deficiency?

Answer 3

Because there is suffieicient iron inn the body but not available to the developing erythroid cells.

Question 4

What is the role of hepcidin?

Answer 4

• inhibits ferroportin which is the main exporter of iron out of the macrophage and out of the gut cell. So you need ferroportin to recycle the iron.
• this prevents iron absorption from the gut. And prevents iron release from macrophages.

Question 5

How do inflammatory conditions regulate hepcidin production?

Answer 5

1) inflammatory condition which causes a release of cytokines for example IL6 from immune cells.
2. This increases production of hepcidin by the liver.
3. This results in inhibition of ferroportin.
4. This results in decreased iron release from RES. And decreased iron absorption in the gut. This leads to plasma iron reduced. Which leads to inhibition of erythropoiesis in bone marrow which leads to ANAEMIA.

Question 6

Would you prescribe iron supplements to someone with anaemia of chronic disease ?

Answer 6

No , because their issue is it that they don’t have enough iron. Their issue is that their iron is not released from cells. So giving iron would not help.

Question 7

How does chronic kidney disease lead to anaemia ? 5 causes

Answer 7

1. Increased hepcidin due to inflammatory cytokines. And reduced clearance of hepcidin. So hepcidin concentration in blood is very high.
2. Patients undergoing dialysis can damage red blood cells.
3. Reduced EPO production due to damaged kidney cells.
4. Reduced life span of RBC as a direct effect of uraemia, ( uraemia also inhibits megakaryocytes leading to low platelet count )
5. Underlying cause of chronic kidney disease is associated with cytokines
   .

Question 8

How do you treat anemia of chronic disease ?

Answer 8

MAIN - treat the underlying condition

2. If associated renal failure - recombinant human EPO. If you give this , you need to ensure there are all the correct building blocks eg ensure vit B12 , folate and iron stores are adequate.
3. Transfuse cells only if all else fails

Question 9

What are symptoms of Rheumatoid Arthritis

Answer 9

• swan neck deformity of fingers

2. Boutonnière deformity of thumb

Question 10

How is RA treated ?

Answer 10

1. Pain is treated using pain reliefs. For example NSAIDS. ( which are non-steroidal anti inflammatory drugs eg Iburprofen).
2. Disease modifying agents are often : DMARDS. For example corticosteroids , chemotherapy eg methotrexate , monoclonal antibodies against the cytokines.

Question 11

Why does anaemia develop from RA ? 3 causes

Answer 11

1. Could be due to anaemia of chronic disease ( increase in cytokines , increased production of hepcidin etc )
2. GI blood loss due to NSAIDS and steroids
3. risk of autoimmune haemolytic anaemia

Question 12

Platelet count and neutrophils in RA ?

Answer 12

High platelets and neutrophils when disease is active

And high CRP

However low platelets and neutrophils may occurs due to treatment , autoimmune reactions or hypersplenism ( splenomegaly can also occur )

Question 13

What is felty’s syndrome

Answer 13

Rare , potentially serious disorder that is defined by the presence of three conditions. RA , splenomegaly , neutropenia. Which causes repeated infections.

Question 14

Why neutropenia occur in feltys syndrome ?

Answer 14

Thought to be due to splenomegaly which contributes to destruction of neutrophils and failure of bone marrow to produce neutrophils. And there is insensitivity to GCSF.

Question 15

How does chronic liver disease lead to splenomegaly?

Answer 15

Chronic liver disease causes portal hypertension which causes splenomegaly which leads to splenic sequenstration of cells and overactive removal of cells.

LOW BLOOD COUTN

Question 16

How does chronic liver disease lead to blood loss ?

Answer 16

1. Chronic liver disease leads to portal hypertension which also leads to oesophageal and gastric varieties ( dilated veins more prone to bleeding).
2. Blood loss contributed by deficiency’s of coagulation factors , endothelial destruction , thrombocytopenia , defective platelet function. Clotting factors are usually produced by the liver.

Question 17

What sort of cells would you find on a blood film in chronic liver disease ?

Answer 17

Target cells due to increased cholesterol : phospholipid ratio

Question 18

Why do you often see thrombocytopenia in 75% patients with liver disease ?

Answer 18

1. Impaired production of thrombocytes due to thrombopoietin usually being produced in liver.
2. Splenic pooling ( excessive amounts of blood being trapped in spleen)
3. Increased destruction

Question 19

Post operative reactive changes in RBC

Answer 19

1) Blood loss which can cause anaemia

2) temporary relative polycythaemia which is due to dehydration

Question 20

Post operative reactive changes in neutrophils

Answer 20

1) neutropenia which arises from sepsis

2) neutrophilia which arises from post op infection and severe bleeding

Question 21

Post operative reactive changes in thrombocytes

Answer 21

1) drugs , sepsis m DIC could cause thrombocytopenia

2) post op infection , bleeding could result in thrombocytosis

Question 22

Infection with malaria can cause which type of anaemia ?

Answer 22

Haemolytic

Question 23

Bacterial infection is often associated with neutrophilia/neutropenia ?

Answer 23

Neutrophillia

Question 24

Severe bacterial infections such as sepsis can cause neutrophilia / neutropenia

Answer 24

Neutropenia

Question 25

Parasitic infections are associated with eosinophilia/eosinpenia

Answer 25

Eosinphillia

Question 26

Viral infections can cause lymphocytosis/ lymphopenia

Answer 26

Lymphocytosis

Question 27

Infection can cause thrombocytosis / thrombocytopenia

Answer 27

Thrombocytosis

Question 28

Severe infection can cause thrombocytopenia / thrombocytosis

Answer 28

Thrombocytopenia

Question 29

What is DIC ?

Answer 29

Disseminated intramuscular coagulation.

This is pathological activation of coagulation where numerous microthrombi are formed in circulation. This leads to consumption of clotting factors , platelets and as a result when blood cells try to travel through vessels they get damaged through the clot . This leads to microangiopathic haemolytic anaemia.

THIS TENDS TO ARISE FROM SEPSIS.

• clotting tests are affected - usually long clotting times , low fibrinogen and raised D dimers.

Risk of bleeding and thrombosis

Question 30

Haematological changes in cancer with regards to RBC , neutrophils , thrombocytes

Answer 30

1) RBC = bleeding due to cancers could cause fewer RBC. this leads to. Iron deficiency. Treatments such as chemotherapy can cause anaemia in cancer. Polycythaemia can also occur because of EPO producing tumours.
2) neutropenia can occur because of chemotherapy.
3) neutrophilia can occur due to inflammatiom and infection
4) thrombocytopenia can occur due to sepsis, DIC , chemotherapy
5) thrombocytosis can occur due to inflammation , bleeding , infection

Question 31

What is leucoerythroblastic film

Answer 31

Immature red and white cells are found on a film ( granulocytes precursors and uncleared RGC seen )

• this often occurs in sepsis
• severe megablastic anaemia
• primary myelofibrosis
• leukaemia
• storage disorders