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YEAR 5: Haematology AS > Haem: Haematology of Systemic Disease (Laz) > Flashcards

Haem: Haematology of Systemic Disease (Laz) Flashcards

(53 cards)

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1
Q

What may protein C deficiency lead to?

A

thrombotic tendency

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2
Q

Primary vs secondary disorder of haematology?

A

primary: inherited/ acquired disease of blood i.e. polycythaemia or thalassaemia
secondary: normal haem system reacting to non-haem condition i.e. high altitude, AIHA

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3
Q

what is FIX padua?

A

inherited condition causing excess factor IX: it is being used in gene therapy

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4
Q

give 2 examples of germline mutations affecting erthrocytes

A

B globin gene mutation causes sickle cell HbS

high affinity Hb mutation causes polycythaemia

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5
Q

What acquired mutation causes polycythaemia vera

A

JAK2

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6
Q

What mutation causes paroxysmal nocturnal haemoglobinuria?

A

PIG A - deficiency of erythrocytes

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7
Q

Factor IX deficiency can cause…

A

haemophilia B

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8
Q

List some ways in which lymphoma can cause jaundice.

A
  • Direct liver involvement
  • Compression of the bile duct
  • Causing autoimmune haemolytic anaemia
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9
Q

Which types of anaemia can be cause by cancer?

A
  • Iron deficiency
  • Anaemia of chronic disease
  • Haemolytic anaemia
  • Leucoerythroblastic anaemia
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10
Q

Which types of cancer are associated with causing secondary polycythaemia?

A
  • Renal cell carcinoma
  • Liver cancer
  • Due to the production of EPO
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11
Q

What is the most common cause of iron deficiency anaemia?

A

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

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12
Q

What are the typical laboratory findings of iron deficiency anaemia?

A
  • Low ferritin
  • Low transferrin saturation
  • High TIBC
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13
Q

What is leucoerythroblastic anaemia?

A

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

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14
Q

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

A
  • Tear drop red blood cells (aniso- and poikilocytosis)
  • Nucleated RBCs
  • Immature myeloid cells
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15
Q

What does leucoerythroblastic anaemia tend to be caused by?

A
  • Bone marrow infiltration (leukaemia, lymphoma, myeloma, solid tumours, myelofibrosis, military TB, severe fungal infection)
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16
Q

Define haemolytic anaemia.

A

Anaemia caused by reduced red blood cell survival

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17
Q

List some key laboratory findings in haemolytic anaemia.

A
  • Anaemia
  • Raised reticulocytes
  • Raised unconjugated bilirubin
  • Raised LDH
  • Low haptoglobins

NOTE: LDH is an intracellular enzyme that is released when RBCs are destroyed

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18
Q

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

A

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
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19
Q

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

A

DAT or Coombs’ test

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

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20
Q

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

A

Spherocytes

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21
Q

List some systemic diseases that can cause autoimmune haemolytic anaemia.

A
  • Cancer involving the immune system (e.g. lymphoma)
  • Disease of the immune system (e.g. SLE)
  • Infections (mycoplasma)
  • idiopathic
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22
Q

List some causes of non-immune haemolytic anaemia.

Study These Flashcards
A
  • Infection (e.g. malaria)
  • Microangiopathic haemolytic anaemia (MAHA)
23
Q

List some key features of MAHA.

Study These Flashcards
A
  • Usually caused by underlying adenocarcinoma
  • Red cell fragments
  • Low platelets
  • DIC/bleeding
  • may be due to HUS
24
Q

Outline the mechanism of MAHA.

Study These Flashcards
A
  • 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

25
List some causes of secondary polycythaemia.
* Cancer (renal, hepatocellular, bronchial) * High altitude * Hypoxic lung disease * Congenital cyanotic heart disease
26
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
27
List some causes of neutrophilia.
* pyogenic infection * Corticosteroids (due to demargination) * Underlying neoplasia * Tissue inflammation (e.g. colitis, pancreatitis) * Myeloproliferative/leukaemia disorder
28
List some infections that characteristically do not cause neutrophilia.
* Brucella * Typhoid * Many viral diseases
29
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
30
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
31
what would you see on blood film of CML
neutrophils basophils myelocytes (in AML: myeloblasts)
32
What are some key blood film features suggestive of AML?
* Neutrophilia * Myeloblasts
33
List some causes of monocytosis.
* Bacteria: TB, Brucella, typhoid * Viral: CMV, VZV * Sarcoidosis * Chronic myelomonocytic leukaemia
34
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)
35
Which gene mutation causes chronic eosinophilic leukaemia?
FIP1L1-PDGFRa fusion gene
36
Which type of virus typically causes basophilia?
Pox viruses
37
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)
38
List some causes of reactive lymphocytosis.
* Infection (EBV, CMV, toxoplasmosis, rubella, HSV) * Autoimmune diseases (NOTE: these are more likely to cause lymphopaenia) * Sarcoidosis
39
Causes of lymphopaenia
infection: HIV autoimmune disorders inherited immune deficiency syndromes drugs: chemo
40
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
41
What does immature lymphoid cells in peripheral blood suggest?
acute lymphocytic leukaemia
42
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
43
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)
44
Why do we not see acquired mutations of soluble factors like VIII or IX
produced by liver cells or endothelial cells, which do not have high turnover rates like blood cells
45
Deficiency of factor VIII is caused by…
primary: haemophilia A secondary: anti-FVIII autoantibodies - acquired haemophilia A
46
Excess factor VIII antibodies are caused by…
inflammatory response or normal in pregnancy
47
Why is thrombosis risk increased in chronic inflammation?
raised factor VIII levels
48
Folate deficiency + Howell Jolly bodies = diagnosis?
coeliac disease
49
Give examples of sources of blood loss which may be responsible for iron deficiency anaemia
GI: PU or gastric cancer, IBD or colonic cancer Urinary tract: RCC, bladder cancer
50
Give examples of sources of blood loss which may be responsible for iron deficiency anaemia
GI: PU or gastric cancer, IBD or colonic cancer Urinary tract: RCC, bladder cancer
51
Why so many types of blood cancer?
multiple lineages multiple stages of differentiation
52
How can acquired somatic mutations causing leukaemia and lymphoma be classified?
type 1: cellular proliferation i.e. BCR-ABL= CML, JAK2 type 2: impair/ block cellular differentiation i.e. acute PML RARA or prolong cell survival/ anti-apoptotic i.e. BCL2 and follicular lymphoma
53
Haemato-oncology diagnosis
* morphology * immunophenotype with flow cytometry * cytogenetics with FISH * molecular genetics for mutation * use biopsy

YEAR 5: Haematology AS (20 decks)

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