HAEM; Lecture 11 and Tutorial 12, 13 - Abnormal White Cell count

Question 1

What is haemopoiesis?

Answer 1

Production of blood cells in Marrow

Question 2

What is normal haemopoiesis?

Answer 2

Polyclonal healthy/reactive -> normal/reactive marrow

Question 3

What is malignant haemopoiesis?

Answer 3

Abnormal/clonal -> leukaemia (lymphoid, myeloid), myelodysplasia, myeloproliferative

Question 4

How does normal haematopoiesis work?

Answer 4

Self-renewing cells (haemopoietic cells)

Question 5

How does a myeloblast differentiate into a neutrophil?

Answer 5

NB: In peripheral blood the precursors are not seen in normal conditions -> BUT in CML you will see all precursors in peripheral blood or in chemotherapy with GCSF; in septic blood you can also find some myeloid precursors

Question 6

What factors control differentiation and proliferation?

Answer 6

Cytokines -> Erythroid part = erythropoietin, lymphoid = IL2, myeloid = G-CSF and M-CSF

Question 7

What happens if DNA is damaged during differentiation and proliferation of white cells?

Answer 7

Cancer -> leukaemia, lymphoma, myeloma

Question 8

What are the different lymphoblasts in the bone marrow?

Answer 8

Myeloblasts, promyelocytes, myelocytes, metamyelocytes

Question 9

What are the immunocytes and phagocytes present in peripheral blood?

Answer 9

Immunocytes: T/B and NK cells. Phagocytes: Granulocytes - neutrophils, eosinophils, basophils; monocytes

Question 10

What are the different reasons why abnormal WBC occur?

Answer 10

Increased or decreased number of WBC -> either increase/decrease cell production, decreased/increase cell survival

Question 11

When do WBC pass from the bone marrow to the peripheral blood and how does that differ in Haemopoietic cancers?

Answer 11

Question 12

What are the 2 types of eosinophilia infections causing increased cell numbers?

Answer 12

Reactive and Primary (malignant)

Question 13

How does reactive eosinophilia affect haemopoiesis and what are the causes?

Answer 13

Keeps it normal, stimulating by inflammation, infection, increased cytokine production (distant tumour, haemopoietic or non haemopoietic)

Question 14

How does primary eosinophilia affect haemopoiesis and what are the causes?

Answer 14

Causes abnormal haemopoiesis (autonomous cell growth) -> cancers of haemopoietic cells, leukaemia (myeloid/lymphoid, chronic/acute), myeloproliferative disorders

Question 15

How does malignant haematopoiesis affect differentiation?

Answer 15

Haemopoietic stem cells have had DNA damage which means that when it differentiates can lead to an increased number of megakaryocytes, granulocytes and monocytes

Question 16

How do you investigate a raised WCC?

Answer 16

History and examination (if recent infection, enlarged spleen), Hb and platelet count, Automated differential (machine can’t recognise immature cells), examine blood film (most important to make a diagnosis), abnormality in white cells only or all 3 (red/platelets/white), 1 white cell type only or all (common in reactive conditions to see more than one), mature cells only or mature and immature?

Question 17

If mature white cells ONLY are elevated, what could the diagnosis be?

Answer 17

No underlying leukaemia as no immature cells

Question 18

If immature white cells ONLY are elevated, what could the diagnosis be?

Answer 18

Blasts +, low Hb, low platelets = acute leukaemia(?) (leukocytosis or pancytopoeina associated)

Question 19

If mature and immature white cells are elevated, what could the diagnosis be?

Answer 19

Neutrophils+ (not a good sign as = neoplastic process), myelocytes+, basophils, = Chronic myeloid leukaemia (?)

Question 20

What is a normal range of a FBC?

Answer 20

Question 21

What are the common causes of abnormal neutrophil counts?

Answer 21

If develops in: minutes = demargination (move from tissues into PB), hours = early release from BM, days = increased production (3* in infection)

Question 22

What are neutrophils?

Answer 22

Present in BM, blood and tissues; life span of 2-3d in tissues, 50% circulating neutrophils are marginated (not counted in FBC)

Question 23

What occurs to peripheral blood in infection?

Answer 23

Neutrophilia and toxic granulation vacuoles in the neutrophils (abnormal distribution of vacuoles), cytoplasmic granulation

Question 24

What occurs to peripheral blood in leukaemia?

Answer 24

Chronic (myeloid) leukaemia, neutrophilia and precursor cells (myelocytes)

Question 25

What are the causes of neutrophilia?

Answer 25

Infection (most common), Tissue inflammation (colitis/pancreatitis), physical stress, adrenaline, corticosteroids, underlying neoplasia (could be a tumour/malignancy), malignant neutrophilia causes: myeloproliferative, disorders, CML

Question 26

Which infections cause neutrophilia?

Answer 26

Localised and systemic infections - acute bacterial, fungal, certain viral infections

Question 27

Which infections characteristically don't produce neutrophilia?

Answer 27

Brucella, typhoid, many viral infections

Question 28

What are the causes of eosinophilia?

Answer 28

Reactive: Parasitic infection, allergic diseases (asthma, rheumatoid, polyarteritis, pulmonary eosinophilia), neoplasms (Hodgkin's or T-cell NHL), hypereosinophilic syndrome. Malignant Chronic Eosinophilic Leukaemia (PDGFR fusion gene)

Question 29

What is monocytosis?

Answer 29

Rare but seen in certain chronic infections and primary haematological disorders -\> TB, brucella, typhoid, Viral, CMv, varicella zoster, sarcoidosis, chronic myelomonocytic leukaemia

Question 30

What causes reactive elevated phagocyte count?

Answer 30

Question 31

How do you differentiate between mature or immature lymphocytosis?

Answer 31

Mature if reactive to infection or primary disorder; immature if primary disorder (leukaemia/lymphoma)

Question 32

What are the types of mature lymphocytosis?

Answer 32

CLL, autoimmune/inflammatory disease

Question 33

What are the types of immature lymphocytosis?

Answer 33

Acute lymphoblastic leukaemia

Question 34

How do you know if mature lymphocytosis is primary or reactive?

Answer 34

Secondary: polyclonal response to infection, chronic inflammation or underlying malignancy; Primary: monoclonal lymphoid proliferation

Question 35

What causes reactive lymphocytosis?

Answer 35

Infection: EBV, CMV, Toxoplasma, infectious hepatitis, rubella, herpes infections; AI disorders, neoplasia, sarcoidosis

Question 36

What is glandular fever?

Answer 36

EBV infection of B-cells via CD21 receptor; infected B-cell proliferates and expresses EBV associated antigens, cytotoxic T-cell response, acute infection resolved resulting in lifelong sub-clinical infection

Question 37

How do you differentiate lymphocytosis?

Answer 37

Mature lyphocytes (with smear cells), reactive to underlying AI disorder or chronic lymphocytic leukaemia -\> morphology (blood film = if pliomorphic lymphocytes is reactive, if all the same then malignant), immunophenotype, gene re-arrangement

Question 38

How do you evaluate lymphocytosis?

Answer 38

Light chain restriction -\> polyclonal (kappa and lambda); monoclonal (kappa only or lambda only); Ig genes and TCR genes undergo recombination in antigen stimulated B/T cells -\> primary monoclonal proliferation = all daughter cells carry identical config of Ig/TCR gene which is detected with Southern Blot

Question 39

What is eosinophilia?

Answer 39

Increase numbers of eosinophils

Question 40

Answer 40

Parasitic infestation (schistosomiasis), underlying lymphoma (HL or T NHL), allergic AI disorder (asthma/urticaria)

Question 41

Answer 41

Mature lymphocytes -\> yes it could be leukaemia (CLL); next investigation - immunophenotype test which indicates all cells are monoclonal and all antigens are B-cell markers with one T cell marker. Reactive (viral infection, TB), primary monoclonal (CLL)

Question 42

Answer 42

Acute leukaemia

Question 43

Answer 43

Secondary to Chronic myeloid leukaemia