Haem 6 - Abnormal white cell counts Flashcards
Explain how neutrophil differentiation and maturation occurs
Myeloblast –> promyelocyte –> myelocyte –> metamyelocyte –> band cells –> neutrophil
Myeloid precursors are not normally seen in peripheral blood
When is it not uncommon to see myeloid precursors?
In sepsis patients
How are cell numbers controlled in haematopoiesis
Cytokines influence differentiation and proliferation.
Erythroid - controlled by erythropoietin
Lymphoid - controlled by IL-2
Myeloid - controlled by G-CSF and M-CSF
What are the causes of abnormal WBC
Increased WBC:
- Increased cell production - Reactive (infection/inflammation), Malignant (leukaemia/myeloproliferative)
- Increased cell survival - failure of apoptosis
Decreased WBC:
1. Decreased cell production - impaired bone marrow function, B12/Folate deficiency, bone marrow failure (aplastic anaemia/post chemo/metastatic cancer/haematological cancer)
- Decreased cell survival - immune breakdown
What happens when there are haematopoietic cancers
Immature and mature cells are released into the circulation
Normally, should just be mature cells
What are the 2 causes of eosinophilia
- Reactive - normal haemopoiesis. Stimulated by inflammation, infection, increased cytokine production (as a result of a distant tumour, e.g.)
- Primary (malignant) - abnormal haemopoiesis (autonomous cell growth). Caused by cancers of haemopoietic cells, leukaemia (myeloid / lymphoid, both chronic and acute), myeloproliferative disorders
In chronic myeloid leukaemia, where does the mutation occur?
Mutation occurs at the GM-CFC phase - causes massive proliferation of myeloid cells beyond this point
How to investigate a raised WCC?
- History and examination
- Hb and platelet count
- Automated differential
- Examine blood film
- Are all 3 lineages (RBC, WBC, platelet) affected or just WBC?
- Is it only one type of WBC affected?
How to suspect leukaemia and acute leukaemia?
If immature cells in the blood film
If ONLY immature cells with low Hb and low platelets - acute leukaemia
Why might lymphocytes be elevated?
- Viral infections
- Chronic lymphocytic leukaemia
In leukaemia, neutrophils don’t have granules (whereas there are granular neutrophils In infection)
Describe neutrophils
- Present in bone marrow, blood and tissues
- Lifespan of 2-3 days in tissues
- 50% neutrophils - marginated - stuck onto wall of damaged vessel (hence not counted in RBC)
Give 3 instances when neutrophilia can develop
Minutes - demmargination
Hours - early release from bone marrow
Days - increased production
What are the causes of neutrophilia
- Infection
- Tissue inflammation
- Physical stress
- Adrenaline
- Corticosteroids
- Underlying neoplasia
- Malignant neutrophilia (myeloproliferative disorders, chronic myeloid leukaemia)
How can we deduce a viral infection
Low neutrophil count but other features of infection
What are some reactive causes of eosinophilia
- Parasitic infection
- Allergic disease (e.g. asthma, RA, polyarteritis, pulmonary eosinophilia)
- Neoplasms (e.g. Hodgkins, non-hodgkins lymphoma)
- Hypereosinophilic syndrome
Give a genetic cause of eosinophilia
Malignant Chronic Eosinophilic Leukaemia (PDGFR fusion gene)
- very rare
- can be detected by FISH (fluorescent)
Hodgkins disease can cause eosinophilia - how can you tell if someone has Hodgkins disease?
- Increased mediastinal mass on CXR
2. IL-5 secretion - stimulating reactive eosinophilia
When is monocytosis seen
Rare - seen in certain chronic infections and primary haematological disorders
e.g. TB, Brucella, typhoid
Viral - cmv, Varicella zoster
Sarcoidosis, chronic myelomonocytic leukaemia (MDS- myelodysplastic syndrome)
How can we distinguish lymphocytosis types
If mature cells - reactive to infection, primary disorder
If immature cells - primary disorder (leukaemia/lymphoma)
What is a typical blood film of Chronic lymphoid leukaemia
cells may look similar if autoimmune / inflammatory conditions
Mature lymphocytes - big nucleus with little cytoplasm
Oligo
Describe the appearance of immature lymphoblasts
Immature lymphoblasts = much larger than mature lymphoblasts. Can also see nucleolus in immature lymphoblasts.
Can be seen in acute lymphoblastic leukaemia
What is secondary (reactive) cause of lymphocytosis
Polyclonal response to infection, chronic inflammation or underlying malignancy
What is a primary cause of lymphocytosis
Monoclonal lymphoid proliferation - all cells will look the same - mutated cell expanding and making clones of itself
e.g. CLL
Name some causes of reactive lymphocytosis
- Infection (e.g. EBV, CMV, toxoplasma, etc)
- Autoimmune disorders
- Neoplasia
- Sarcoidosis
Describe mononucleosis syndrome
“Atypical lymphocyte” - reactive looking lymphocyte
Mononucleosis syndrome is typical of?
Glandular fever
If you see a high White cell count, and find reactive looking lymphocytes, you can be reassured that it is 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 - results in lifelong sub-clinical infection
- Glandular fever - more common in young people
Lymphocytosis in elderly is more likely to be caused by?
Chronic lymphocytic leukaemia - mature lymphocytes (and maybe smear cells).
When responding to infection, you get a polyclonal response. Lightchains in antibody can be which ?
Kappa or lambda
If polyclonal expansion in B cells, 50/50 split in kappa and lambda
But if monoclonal expansion - you get Light chain restriction - B cells produce only kappa or only lambda
So if MONOCLONAL - kappa/lambda restriction - NOT response to infection
Explain gene rearrangement in lymphocytosis
Immunoglobulin genes (Ig) and T cell receptors (TCR) genes undergo recombination in antigen stimulated B/T cells
In PRIMARY MONOCLONAL Proliferation - all daughter cells carry identical configuration of Immunoglobulin gene, or TCR gene - can be detected by southern blot analysis
2 likely causes of eosinophilia?
- Parasitic infection - schistosomiasis
- Underlying lymphoma (Hodgkins / NHL)
- Allergic autoimmune disorder
If kappa / lambda restriction, what should I do
To distinguish further - test light chain restriction or test for T cell receptor arrangement
If K/L restriction present, most likely to be chronic lymphocytic leukaemia
Blood film features of CML
- Myelocyte precursors (shouldn’t be present normally)
- No toxic granules present in neutrophils (would be present in infection)
- Basophil seen
- Expansion of myeloid cells
