Haematology of systemic disease

Question 1

1. List some ways in which lymphoma can cause jaundice.

Answer 1

Direct liver involvement
Compression of the bile duct
Causing autoimmune haemolytic anaemia

Question 2

2. Which types of anaemia can be caused by cancer?

Answer 2

Iron deficiency
Anaemia of chronic disease
Haemolytic anaemia
Leucoerythroblastic anaemia

Question 3

3. Which types of cancer are associated with causing secondary polycythaemia?

Answer 3

Renal cell carcinoma
Liver cancer
Due to the production of EPO

Question 4

4. What is the most common cause of iron deficiency anaemia?

Answer 4

Occult blood loss (e.g. GI cancers, urinary tract cancers)

Question 5

5. What are the typical laboratory findings of iron deficiency anaemia?

Answer 5

Low ferritin
Low transferrin saturation
High TIBC

Question 6

6. What is leucoerythroblastic anaemia?

Answer 6

Anaemia characterised by the presence of red and white cell precursors

Question 7

7. What are the morphological features of leucoerythroblastic anaemia seen on blood film?

Answer 7

Tear drop red blood cells (aniso- and poikilocytosis)
Nucleated RBCs
Immature myeloid cells

Question 8

8. What does leucoerythroblastic anaemia tend to be caused by?

Answer 8

Bone marrow infiltration (leukaemia, lymphoma, myeloma, solid tumours, myelofibrosis, military TB, severe fungal infection)

Question 9

9. Define haemolytic anaemia.

Answer 9

Anaemia caused by reduced red blood cell survival

Question 10

10. List some key laboratory findings in haemolytic anaemia.

Answer 10

Anaemia
Raised reticulocytes 
Raised unconjugated bilirubin
Raised LDH 
Low haptoglobins
NOTE: LDH is an intracellular enzyme that is released when RBCs are destroyed

Question 11

11. What are the two main groups of haemolytic anaemia? List some examples.

Answer 11

Inherited (defects with the cell)
• Hereditary spherocytosis (membrane problem)
• G6PD deficiency (enzyme problem)
• Sickle cell disease, thalassemia (haemoglobin problem)
Acquired (defects with the environment)
• Immune-mediated
• Non-immune mediated

Question 12

12. Which test distinguishes immune-mediated and non-immune mediated haemolytic anaemia?

Answer 12

DAT or Coombs’ test

DAT +ve means that the haemolytic anaemia is mediated through immune destruction of red cells

Question 13

13. What morphological change is seen on the blood film of patients with autoimmune haemolytic anaemia?

Answer 13

Spherocytes

Question 14

14. List some systemic diseases that can cause autoimmune haemolytic anaemia.

Answer 14

Cancer involving the immune system (e.g. lymphoma)
Disease of the immune system (e.g. SLE)
Infections (disturbs the immune system)

Question 15

15. List some causes of non-immune haemolytic anaemia.

Answer 15

Infection (e.g. malaria)

Microangiopathic haemolytic anaemia (MAHA)

Question 16

16. List some key features of MAHA.

Answer 16

Usually caused by underlying adenocarcinoma
Red cell fragments
Low platelets
DIC/bleeding

Question 17

17. Outline the mechanism of MAHA.

Answer 17

An underlying adenocarcinoma produces procoagulant cytokines that activate the coagulation cascade
This leads to DIC and the formation of fibrin strands in various parts of the microvasculature
Red cells will be pushed through these fibrin strands and fragment
NOTE: always consider underlying adenocarcinoma in any patient presenting with MAHA

Question 18

18. List some causes of secondary polycythaemia.

Answer 18

Cancer (renal, hepatocellular, bronchial)
High altitude
Hypoxic lung disease
Congenital cyanotic heart disease

Question 19

19. What is the main difference seen in the blood film of patients with acute and chronic leukaemia?

Answer 19

Chronic – mature white cells are raised

Acute – immature blast cells are raised

Question 20

20. List some causes of neutrophilia.

Answer 20

Corticosteroids (due to demargination)
Underlying neoplasia
Tissue inflammation (e.g. colitis, pancreatitis)
Myeloproliferative/leukaemia disorder 
Infection

Question 21

21. List some infections that characteristically do not cause neutrophilia.

Answer 21

Brucella
Typhoid
Many viral diseases

Question 22

22. List some key features of a reactive neutrophilia on a blood film.

Answer 22

Band cells (presence of immature neutrophils (band cells) show that the bone marrow has been signalled to release more WBCs)
Toxic granulation
Clinical signs of infection/inflammation

Question 23

23. What are some key blood film and clinical features suggestive of a myeloproliferative disorder?

Answer 23

Neutrophilia
Basophilia 
Immature myelocytes
Splenomegaly
NOTE: you may see raised Hb and raised platelets in CML if it affects those lineages

Question 24

24. What are some key blood film features suggestive of AML?

Answer 24

Neutrophilia

Myeloblasts

Question 25

25. List some causes of monocytosis.

Answer 25

Bacteria: TB, Brucella, typhoid Viral: CMV, VZV Sarcoidosis Chronic myelomonocytic leukaemia

Question 26

26. List some causes of reactive eosinophilia.

Answer 26

Parasitic infection Allergy (e.g. asthma, rheumatoid arthritis) Underlying neoplasms (e.g. Hodgkin’s lymphoma, T cell lymphoma, NHL) Drug reaction (e.g. erythema multiforme) DRESS

Question 27

FIP1L1-PDGFRa fusion gene

Answer 27

27. Which gene mutation causes chronic eosinophilic leukaemia?

Question 28

28. Which type of virus typically causes basophilia?

Answer 28

Pox viruses

Question 29

29. What investigations are typically used when investigating lymphocytosis?

Answer 29

``` Clinical examination FBC Light microscopy Flow cytometry (identify lineage and stage of differentiation) Molecular genetics (TCR or Ig gene) ```

Question 30

30. List some causes of reactive lymphocytosis.

Answer 30

``` Infection (EBV, CMV, toxoplasmosis, rubella, HSV) Autoimmune diseases (NOTE: these are more likely to cause lymphopaenia) Sarcoidosis ```

Question 31

31. How would the lymphocytes seen on a blood film due to a viral infection be different from leukaemia/lymphoma?

Answer 31

Viral infection: reactive or atypical lymphocytes (EBV) | CLL or NHL: small lymphocytes and smear cells

Question 32

32. Outline how flow cytometry is used to identify cell types.

Answer 32

Fluorescently labelled monoclonal antibodies targeted at different antigens are washed over the cells Cells are passed through the flow cytometer and the fluorescence is recorded Dependent on the antigens present on the cells, you can identify the stage of maturation

Question 33

33. What is light chain restriction?

Answer 33

An individual B cell will either express kappa or lambda light chains (not both) In response to an infection, you will get a polyclonal B cell response so there will be a roughly even mixture of kappa and lambda light chains In lymphoproliferative disorders, monoclonal proliferation of a B cell expressing only one type of light chain (e.g. kappa) will mean that the proportion of kappa relative to lambda will increase (e.g. showing an overwhelming majority of kappa)