HAEM; Lecture 11 and Tutorial 12, 13 - Abnormal White Cell count Flashcards
What is haemopoiesis?
Production of blood cells in Marrow
What is normal haemopoiesis?
Polyclonal healthy/reactive -> normal/reactive marrow
What is malignant haemopoiesis?
Abnormal/clonal -> leukaemia (lymphoid, myeloid), myelodysplasia, myeloproliferative
How does normal haematopoiesis work?
Self-renewing cells (haemopoietic cells)
How does a myeloblast differentiate into a neutrophil?
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
What factors control differentiation and proliferation?
Cytokines -> Erythroid part = erythropoietin, lymphoid = IL2, myeloid = G-CSF and M-CSF
What happens if DNA is damaged during differentiation and proliferation of white cells?
Cancer -> leukaemia, lymphoma, myeloma
What are the different lymphoblasts in the bone marrow?
Myeloblasts, promyelocytes, myelocytes, metamyelocytes
What are the immunocytes and phagocytes present in peripheral blood?
Immunocytes: T/B and NK cells. Phagocytes: Granulocytes - neutrophils, eosinophils, basophils; monocytes
What are the different reasons why abnormal WBC occur?
Increased or decreased number of WBC -> either increase/decrease cell production, decreased/increase cell survival
When do WBC pass from the bone marrow to the peripheral blood and how does that differ in Haemopoietic cancers?
What are the 2 types of eosinophilia infections causing increased cell numbers?
Reactive and Primary (malignant)
How does reactive eosinophilia affect haemopoiesis and what are the causes?
Keeps it normal, stimulating by inflammation, infection, increased cytokine production (distant tumour, haemopoietic or non haemopoietic)
How does primary eosinophilia affect haemopoiesis and what are the causes?
Causes abnormal haemopoiesis (autonomous cell growth) -> cancers of haemopoietic cells, leukaemia (myeloid/lymphoid, chronic/acute), myeloproliferative disorders
How does malignant haematopoiesis affect differentiation?
Haemopoietic stem cells have had DNA damage which means that when it differentiates can lead to an increased number of megakaryocytes, granulocytes and monocytes
How do you investigate a raised WCC?
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?
If mature white cells ONLY are elevated, what could the diagnosis be?
No underlying leukaemia as no immature cells
If immature white cells ONLY are elevated, what could the diagnosis be?
Blasts +, low Hb, low platelets = acute leukaemia(?) (leukocytosis or pancytopoeina associated)
If mature and immature white cells are elevated, what could the diagnosis be?
Neutrophils+ (not a good sign as = neoplastic process), myelocytes+, basophils, = Chronic myeloid leukaemia (?)
What is a normal range of a FBC?
What are the common causes of abnormal neutrophil counts?
If develops in: minutes = demargination (move from tissues into PB), hours = early release from BM, days = increased production (3* in infection)
What are neutrophils?
Present in BM, blood and tissues; life span of 2-3d in tissues, 50% circulating neutrophils are marginated (not counted in FBC)
What occurs to peripheral blood in infection?
Neutrophilia and toxic granulation vacuoles in the neutrophils (abnormal distribution of vacuoles), cytoplasmic granulation
What occurs to peripheral blood in leukaemia?
Chronic (myeloid) leukaemia, neutrophilia and precursor cells (myelocytes)
What are the causes of neutrophilia?
Infection (most common), Tissue inflammation (colitis/pancreatitis), physical stress, adrenaline, corticosteroids, underlying neoplasia (could be a tumour/malignancy), malignant neutrophilia causes: myeloproliferative, disorders, CML
Which infections cause neutrophilia?
Localised and systemic infections - acute bacterial, fungal, certain viral infections
Which infections characteristically don’t produce neutrophilia?
Brucella, typhoid, many viral infections
What are the causes of eosinophilia?
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)
What is monocytosis?
Rare but seen in certain chronic infections and primary haematological disorders -> TB, brucella, typhoid, Viral, CMv, varicella zoster, sarcoidosis, chronic myelomonocytic leukaemia
What causes reactive elevated phagocyte count?
How do you differentiate between mature or immature lymphocytosis?
Mature if reactive to infection or primary disorder; immature if primary disorder (leukaemia/lymphoma)
What are the types of mature lymphocytosis?
CLL, autoimmune/inflammatory disease
What are the types of immature lymphocytosis?
Acute lymphoblastic leukaemia
How do you know if mature lymphocytosis is primary or reactive?
Secondary: polyclonal response to infection, chronic inflammation or underlying malignancy; Primary: monoclonal lymphoid proliferation
What causes reactive lymphocytosis?
Infection: EBV, CMV, Toxoplasma, infectious hepatitis, rubella, herpes infections; AI disorders, neoplasia, sarcoidosis
What is glandular fever?
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
How do you differentiate lymphocytosis?
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
How do you evaluate lymphocytosis?
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
What is eosinophilia?
Increase numbers of eosinophils
Parasitic infestation (schistosomiasis), underlying lymphoma (HL or T NHL), allergic AI disorder (asthma/urticaria)
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)
Acute leukaemia
Secondary to Chronic myeloid leukaemia
