Haem: Haematology of Systemic Disease (Laz) Flashcards
List some ways in which lymphoma can cause jaundice.
- Direct liver involvement
- Compression of the bile duct
- Causing autoimmune haemolytic anaemia
Which types of anaemia can be cause by cancer?
- Iron deficiency
- Anaemia of chronic disease
- Haemolytic anaemia
- Leucoerythroblastic anaemia
Which types of cancer are associated with causing secondary polycythaemia?
- Renal cell carcinoma
- Liver cancer
- Due to the production of EPO
What is the most common cause of iron deficiency anaemia?
Occult blood loss (e.g. GI cancers, urinary tract cancers)
What are the typical laboratory findings of iron deficiency anaemia?
- Low ferritin
- Low transferrin saturation
- High TIBC
What is leucoerythroblastic anaemia?
Anaemia is characterised by the presence of red and white cell precursors
What are the morphological features of leucoerythroblastic anaemia seen on blood film?
- Tear drop red blood cells (aniso- and poikilocytosis)
- Nucleated RBCs
- Immature myeloid cells
What does leucoerythroblastic anaemia tend to be caused by?
- Bone marrow infiltration (leukaemia, lymphoma, myeloma, solid tumours, myelofibrosis, military TB, severe fungal infection)
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Define haemolytic anaemia.
Anaemia caused by reduced red blood cell survival
List some key laboratory findings in haemolytic anaemia.
- Anaemia
- Raised reticulocytes
- Raised unconjugated bilirubin
- Raised LDH
- Low haptoglobins
NOTE: LDH is an intracellular enzyme that is released when RBCs are destroyed
What are the two main groups of haemolytic anaemia? List some examples.
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
Which test distinguishes immune-mediated and non-immune mediated haemolytic anaemia?
DAT or Coombs’ test
DAT +ve means that the haemolytic anaemia is mediated through immune destruction of red cells
What morphological change is seen on the blood film of patients with autoimmune haemolytic anaemia?
Spherocytes
List some systemic diseases that can cause autoimmune haemolytic anaemia.
- Cancer involving the immune system (e.g. lymphoma)
- Disease of the immune system (e.g. SLE)
- Infections (disturbs the immune system)
List some causes of non-immune haemolytic anaemia.
- Infection (e.g. malaria)
- Microangiopathic haemolytic anaemia (MAHA)
List some key features of MAHA.
- Usually caused by underlying adenocarcinoma
- Red cell fragments
- Low platelets
- DIC/bleeding
Outline the mechanism of MAHA.
- 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
List some causes of secondary polycythaemia.
- Cancer (renal, hepatocellular, bronchial)
- High altitude
- Hypoxic lung disease
- Congenital cyanotic heart disease
What is the main difference seen in the blood film of patients with acute and chronic leukaemia?
- Chronic - mature white cells are raised
- Acute - immature blast cells are raised
List some causes of neutrophilia.
- Corticosteroids (due to demargination)
- Underlying neoplasia
- Tissue inflammation (e.g. colitis, pancreatitis)
- Myeloproliferative/leukaemia disorder
- Infection
List some infections that characteristically do not cause neutrophilia.
- Brucella
- Typhoid
- Many viral diseases
List some key features of a reactive neutrophilia on a blood film.
- 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
What are some key blood film and clinical features suggestive of a myeloproliferative disorder?
- Neutrophilia
- Basophilia
- Immature myelocytes
- Splenomegaly
NOTE: you may see raised Hb and raised platelets in CML if it affects those lineages
What are some key blood film features suggestive of AML?
- Neutrophilia
- Myeloblasts
List some causes of monocytosis.
- Bacteria: TB, Brucella, typhoid
- Viral: CMV, VZV
- Sarcoidosis
- Chronic myelomonocytic leukaemia
List some causes of reactive eosinophilia.
- 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)
Which gene mutation causes chronic eosinophilic leukaemia?
FIP1L1-PDGFRa fusion gene
Which type of virus typically causes basophilia?
Pox viruses
What investigations are typically used when investigating lymphocytosis?
- Clinical examination
- FBC
- Light microscopy
- Flow cytometry (identify lineage and stage of differentiation)
- Molecular genetics (TCR or Ig gene)
List some causes of reactive lymphocytosis.
- Infection (EBV, CMV, toxoplasmosis, rubella, HSV)
- Autoimmune diseases (NOTE: these are more likely to cause lymphopaenia)
- Sarcoidosis
How would the lymphocytes seen on a blood film due to a viral infection be different from leukaemia/lymphoma?
- Viral infection: reactive or atypical lymphocytes (EBV)
- CLL or NHL: small lymphocytes and smear cells
Outline how flow cytometry is used to identify cell types.
- 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
What is light chain restriction?
- 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)