Haem: Haematology of Systemic Disease (Laz)

Question 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

Which types of anaemia can be cause by cancer?

Answer 2

• Iron deficiency
• Anaemia of chronic disease
• Haemolytic anaemia
• Leucoerythroblastic anaemia

Question 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

What is the most common cause of iron deficiency anaemia?

Answer 4

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

Question 5

What are the typical laboratory findings of iron deficiency anaemia?

Answer 5

• Low ferritin
• Low transferrin saturation
• High TIBC

Question 6

What is leucoerythroblastic anaemia?

Answer 6

Anaemia is characterised by the presence of red and white cell precursors

Question 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

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

Define haemolytic anaemia.

Answer 9

Anaemia caused by reduced red blood cell survival

Question 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

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

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

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

Answer 13

Spherocytes

Question 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

List some causes of non-immune haemolytic anaemia.

Answer 15

• Infection (e.g. malaria)
• Microangiopathic haemolytic anaemia (MAHA)

Question 16

List some key features of MAHA.

Answer 16

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

Question 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

List some causes of secondary polycythaemia.

Answer 18

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

Question 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

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

List some infections that characteristically do not cause neutrophilia.

Answer 21

• Brucella
• Typhoid
• Many viral diseases

Question 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

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

What are some key blood film features suggestive of AML?

Answer 24

• Neutrophilia
• Myeloblasts

Question 25

List some causes of monocytosis.

Answer 25

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

Question 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)

Question 27

Which gene mutation causes chronic eosinophilic leukaemia?

Answer 27

FIP1L1-PDGFRa fusion gene

Question 28

Which type of virus typically causes basophilia?

Answer 28

Pox viruses

Question 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

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

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

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

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 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)