Haematology of Systemic Disease Flashcards

1
Q

A patient with lymphoma is referred by the GP with new onset jaundice, anaemia and raised LDH.

A

Lymphoma stage 4 with bone marrow +liver involved
Lymphoma with nodes compressing the bile duct plus anaemia of inflammation
Lymphoma with Acquired auto immune haemolytic anaemia

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2
Q

What can be the first presentation in cancer

A

Anaemia

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3
Q

What are the forms of anaemia associated with cancer

A

Iron deficiency
Anaemia of inflammation (chronic disease)
Leucoerythroblastic anaemia
Haemolytic anaemia

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4
Q

What cancers can cause secondary polycythaemia

A

Renal cell cancer

Liver cancer

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5
Q

What are the lab findings in iron deficiency anaemia

A

Reduced ferritin
Reduced transferrin saturation
Raised TIBC

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6
Q

Reduced ferritin
Reduced transferrin saturation
Raised TIBC

A

Iron deficiency anaemia

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7
Q

What is the major cause of iron deficiency anaemia until proven otherwise

A

Bleeding until proved otherwise

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8
Q

What cancers can cause occult blood loss

A

GI cancer: gastric, colonic/rectal

Urinary tract cancer: renal cell carcinoma (physicians tumour), bladder cancer

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9
Q

What may cause acquired haemolytic anaemia in cancer

A

Immune mediated

Non-immune mediated - fragmentation (micro-angiopathic haemolytic anaemia)

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10
Q

What is leucoerythroblastic anaemia

A

Red cell and white cell precursor anaemia

Variable degree of anaemia

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11
Q

What are the morphological features on blood film of leucoerythroblastic anaemia

A

Teardrop RBCs (and aniso and poikilocytosis)
Nucleated RBCs
Immature myeloid cells

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12
Q

What can cause a leucoerythroblastic film

A

Bone marrow infiltration

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13
Q

What are some causes of bone marrow infiltration (producing leucoerythroblastic film)

A

Cancer: haemopoietic (leukaemia, lymphoma, myeloma), non-haemopoietic (breast, bronchus, prostate)
Severe infection: MTB, severe fungal infection
Myelofibrosis: massive splenomegaly, dry tap on BM aspirate

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14
Q

What process underpins haemolytic anaemias

A

Shortened red cell survival

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15
Q

What are some key markers looked for to distinguish causes of haemolytic anaemias

A

Anaemia (may be compensated)
Reticulocytosis
Raised bilirubin (unconjugated)
Reduced haptoglobins

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16
Q

Subsets of haemolytic anaemia

A

Inherited: defects of the red cell
Acquired: defects of the environment in which the red cells find themselves

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17
Q

Components of a RBC

A

Membrane
Haemoglobin
Enzymes

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18
Q

Defects of RBC membrane leading to haemolytic anaemia

A

Spherocytosis

Ellipotcytosis

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19
Q

Defects of RBC haemoglobin leading to haemolytic anaemia

A

Structural - sickle cell disease

Quantitative - thalassaemias

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20
Q

Defects of RBC enzymes leading to haemolytic anaemia

A

G6PD

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21
Q

Types of acquired haemolytic anaemia

A

Immune

Non-immune

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22
Q

How do you distinguish an immune from a non-immune haemolytic anaemia

A

Direct antiglobulin test (Coombs test)

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23
Q

Spherocytes

DAT +ve

A

Auto-immune haemolytic anaemia

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24
Q

What are the associated systemic disorders with auto-immune haemolytic anaemias

A

Cancer of the immune system: lymphoma
Disease of the immune system: SLE
Infection (disturbing the immune system)

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25
Q

Causes on non-immune acquired haemolytic anaemias

A

Infection (malaria)

Micro-angiopathic haemolytic anaemia (MAHA)

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26
Q

What are the manifestations of MAHA

A

Red cell fragments
Low platelets
DIC/bleeding
Underlying adenocarcinoma

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27
Q

Micro-angiopathy in malignancy - e.g. adenocarcinomas with low grade DIC

A

Platelet consumption
Fibrin deposition and degradation
Red cell fragmentation (microangiopathy)
Bleeding

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28
Q

True polycythaemia

A

raised red cell mass

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29
Q

What can cause true polycythaemia

A

Cancer

30
Q

Types of true polycythaemia in cancer

A
Secondary (raised EPO) 
Polycythaemia vera (PV)
31
Q

Causes of secondary true polycythaemia

A

Inappropriate: hepatocellular cancer, bronchial cancer, renal cancer
Appropriate: high altitude, hypoxic lung disease, cyanotic heart disease

32
Q

Normal mature WBCs

A

Phagocytes: granulocytes - neutrophils, eosinophils, basophils; monocytes.

Immunocytes: T cells, B cells, natural killer cells

33
Q

Where are immature WBCs normally found

A

In the bone marrow

34
Q

What needs to be considered when looking at a high WBC count

A

Consider the FBC print out
Review the blood film

How high is the total WBC
Which lineage is elevated
Are the cells normal or abnormal in appearance
Are the cells mature or immature

35
Q

Causes of neutrophilia

A
Corticosteroids 
Underlying neoplasia 
Tissue inflammation (e.g. colitis, pancretitis) 
Myeloproliferative/leukaemic disorders 
Infection
36
Q

What infections do not produce neutrophilia

A

Brucella
Typhoid
Many viral infections

37
Q

What type of infections produce neutrophilia

A

Both localised and systemic infections

Acute bacterial, fungal, certain viral infections

38
Q

Reactive neutrophilia features

A

Presence of bands
Toxic granulation
Signs of infection/inflammation

39
Q

Malignant neutrophilia features

A

Neutrophilia, basophilia plus immature cells myelocytes, and splenomegaly (CML)
Neutropenia plus myeloblasts (AML)

40
Q

Causes of reactive eosinophilia

A

Parasitic infestation
Allergic diseases e.g. asthma, rheumatoid, polyarteritis, pulmonary eosinophilia
Underlying neoplasma, especially Hodgkin’s, T cell NHL (reactive eosinophilia)
Drugs (reactive erythema multiforme)

41
Q

Chronic eosinophilic leukaemia features

A

Eosinophils part of the ‘clone’

FIP1L1-PDGFRa fusion gene

42
Q

Causes of moncytosis

A

Rare, but seen in certain chronic infections and primary haematological disorders

TB, brucella, typhoid
Viral: CMV, varicella zoster
Sarcoidosis
Chronic myelomonocytic leukaemia (MDS)

43
Q

Infective causes of neutrophilia

A

Bacterial

44
Q

Infective causes of eosinophilia

A

Parasites

45
Q

Infective causes of basophilia

A

Pox virus

46
Q

Infective causes of monocytosis

A

Chronic (TB, brucella)

47
Q

Inflammatory causes of neutrophilia

A

Auto-immune

Tissue necrosis

48
Q

Inflammatory causes of eosinophilia

A

Allergic (asthma, atopy, drug reactions)

49
Q

Neoplastic causes of neutrophilia

A

All types

50
Q

Neoplastic causes of eosinophilia

A

Hodgkin’s

Non-Hodgkin’s

51
Q

Myeloproliferative causes of neutrophilia

A

CML

52
Q

Myeloproliferative causes of basophilia

A

CML

53
Q

Myeloproliferative causes of monocytosis

A

CML

54
Q

Types of lymphocytosis

A

Primary

Secondary

55
Q

Causes of primary lymphocytosis

A

Monoclonal lymphoid proliferation (e.g. CLL, NHL)

56
Q

Causes of secondary lymphocytosis

A

Polyclonal response to infection

Chronic inflammation

57
Q

How to interpret a lymphocytosis

A

Clinical: symptoms suggestive of infection or lymphoma
FBC: degree of lymphocytosis
Light microscopy/morphology: mature cells or primitive lymphoblasts
Flow cytometry: lineage: B or T cells, stage of differentation
Molecular genetics: rearranged: T cell receptor or immunoglobulin gene

58
Q

Causes of reactive lymphocytosis (secondary)

A

Infection: EBV, CMV, toxoplasma, infectious hepatitis, rubella, herpes, infections
Autoimmune disorders
Sarcoidosis

59
Q

How do you evaluate a patient with lymphocytosis

A

History
Clinical examination
Imaging

60
Q

Mature lymphocytes in peripheral blood

A

Reactive/atypical lymphocytes (IM)

Small lymphocytes and smear cells (CLL/NHL)

61
Q

Immature lymphoid cells in peripheral blood

A

Lymphoblasts (acute lymphoblastic leukaemia)

62
Q

What does immunopheotyping do

A

Looks at the antigens expressed on the cells

63
Q

Antigen on lymphoid stem cell

A

TdT

HLA-DR

64
Q

Antigens on pro B cells

A
HLA-DR
CD19
CD10
CD79
cyCD22
65
Q

Antigens on pre B cell

A
HLA-DR
cyIg
CD19
CD79
CD22
66
Q

Antigens on intermediate B cell

A
HLA-DR
CD19
CD5
CD79
CD22
67
Q

Antigens on mature B cell

A
HLA-DR
sIg
CD19
FMC7
CD79
CD22
68
Q

Antigens on plasma cell

A

cyIg
CD138
CD38

69
Q

Polyclonal antibodies

A

Kappa and lambda

70
Q

Monoclonal antibodies

A

Kappa only or lambda only