Abnormal white cell counts Flashcards
What is pancytopenia
All lineages reduced
What is the types of malignant haemopoeisis
Leukaemia (lymphoid, myeloid) = cancer of blood cells
Myelodysplasia = immature cells
Myeloproliferative = too many cells
Where are neutrophils found and how do they develop
Found in the peripheral blood
- myeloblast
- promyelocyte
- myelocyte
- metamyelocyte
- neutrophil (only one in the peripheral blood)
How are cell numbers controlled
Different cytokines will increase different cell numbers
Erythroid - Erythropoietin
Lymphoid - IL2
Myeloid - G-CSF, M-CSF
DNA dictates differentiation and proliferation of blood cells
DNA damage can lead to cancer ie leaukaemia, lymphoma (blood cancer of lymphocytes), myeloma (cancer of blood plasma cells)
Which cells are found in the peripheral blood
Immunocytes - T, B and NK cells
Phagocytes - granulocytes (neutrophils, eosinophils, basophils) and monocytes
Why may there be an increase WBC production
Reactive - infection or inflammation
Malignant - leukaemia or myeloproliferative
Why may there be a decrease in WBC production
Impaired bone marrow function - Aplastic anaemia - Post chemo - Metastatic cancer - Haematological cancer B12 or folate deficiency
Why may there be an increase in cell survival
Failure of apoptosis e.g. acquired cancer causing mutation in some lymphomas
Why may there be a decrease in cell survival
immune breakdown
What is normal reactive haemopoiesis (eosinophilia) stimulated by
Inflammation
Infection
Increased cytokine production (Distant tumour, Haemopoietic or non haemopoietic)
What is abnormal primary (malignant) haemopoiesis (eosinophilia) due to
Cancers of haemopoietic cells
Leukaemia (Myeloid or lymphoid, Chronic or acute)
Myeloproliferative disorders
What happens to white blood cells in malignant haematopoeisis (chronic myeloid leukaemia)
Increase in myeloid cells
GM-CFC
Granulocutes
Megakaryocytes
Monocytes
How should a raised white cell count be investigate
History and examination
Haemoglobin and platelet count
Automated differential
Examine blood film
Abnormality White cells only, or all 3 lineages (red cells/platelets/white cells) ?
White cells 1 cell type only, or all lineages? (e.g. neuts/eos/monocytes/lymphocytes)
Mature cells only or mature and immature cells?
What are the possibilities if only mature cells are present
All lineages or just one - reactive/infection
Only lymphocytes - reactive or cancel (chronic lymphocytic leukaemia)
What are the possibilities if both mature and immature cells are present
Could be chronic myeloid leukaemia (neutrophils + myelocytes + basophils)
What are the possibilities if only immature cells are present
Blasts + low Hb + low platelets = acute leukaemia
Describe neutrophil presence in the blood
Present in bone marrow, blood and tissues
Life span = 2-3 days in tissues
50% circulating are marginated (stuck to vessels wall)
Why may neutrophilia develop according to time span
minutes - demargination
hours - early release from BM
days - increased production (x3 in infection)
Describe neutrophils in the peripheral blood during infection
Neutrophils > 7.5 x 10^9/L
Toxic granulation
Vacuoles
Describe neutrophils in the peripheral blood during leukaemia
neutrophilia and precursor cells (myelocytes) seen
What are the causes of neutrophilia
Infection
Tissue inflammation (e.g.colitis, pancreatitis)
Physical stress, adrenaline, corticosteroids
underlying neoplasia
Malignant neutrophilia (myeloproliferative disorders CML)
Describe neutrophilia in infection
Localised and systemic infections
acute bacterial, fungal, certain viral infections
Some infections characteristically do not produce a neutrophilia e.g. brucella, typhoid, many viral infections.
What are the causes of reactive eosinophilia
Parasitic infestation
Allergic diseases (e.g. asthma, rheumatoid, polyarteritis,pulmonary eosinophilia)
Neoplasms (esp. Hodgkin’s, T-cell NHL)
Hypereosinophilic syndrome
What is a non-reactive cause of eosinophilia
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 (MDS)
What infections can be indicated by reactive elevated phagocyte counts for neutrophils, eosinophils, basophils and monocyte
Neutrophils - bacterial
Eosinophils - parasitic
Basophils - pox virus
Monocytes - chronic (TB, brucella)
What kind of inflammation can be indicated by reactive elevated phagocyte counts for neutrophils and eosinophils
N - Auto-immune tissue necrosis
E - Allergic (asthma, atopy, drug reaction)
What may indicate a neoplasia from a reactive elevated phagocyte count
N - all types
E - Hodgkins, NHL
What may cause lymphocytosis
Mature - reactive to infection or a primary disorder (e.g. CLL)
Immature - primary disorder (leukaemia/lymphoma), acute lymphoblastic leukaemia
What is the difference between primary and reactive lymphocytosis
Secondary (reactive) - polyclonal response to infection, chronic inflammation, or underlying malignancy
Primary - monoclonal lymphoid proliferation e.g. CLL
What may reactive lymphocytosis be due to
Smoking
Infection
- EBV, CMV, toxoplasma
- Infectious hepatitis, rubella, herpes infections
Autoimmune disorders
- neoplasia
- sarcoidosis
Describe atypical lymphocytes
Mononucleosis syndrome/glandular fever
Looks immature but is actually a reactive, infection induced lymphocytosis
Describe glandular fever
EBV infection of B-lymphocytes via CD21 receptor
Infected B-cell proliferates and expresses EBV associated antigens
Cytotoxic T-lymphocyte response
Acute infection resolved resulting in lifelong sub-clinical infection
Result = lymphocytosis with atypical lymphocytes
How can you differentiate between mature lymphocytes and elderly patients with lymphocytosis
reactive to underlying auto immune disorder or chronic lymphocytic leukaemia
Morphology
Immunophenotype
Gene re-arrangement
How can you evaluate lymphocytosis using light chain restriction
Check what light chains the lymphocytes
Kappa and lambda = polyclonal
Only kappa or only lambda = monoclonal (cancer)
How can you evaluate lymphocytosis using gene rearrangement
Immunoglobulin genes (Ig) and T cell receptor (TCR) genes undergo recombination in antigen stimulated B cells or T cells.
With primary monoclonal proliferation all daughter cells carry identical configuration of Ig, or TCR gene. This can be detected by Southern Blot analysis
