White Cell Disorders – Investigation of Neutropenia, Leukaemia and Leukemoid Reactions
LOBs:
• Discuss the approach to the investigation of leucocytosis
• Discuss the reactive changes that occur in blood in infection
• Define leukaemia, it’s different types, laboratory findings and clinical manifestations
• Define neutropenia and discuss it’s causes
• Define the management of a patient with neutropenia
Key Topics:
• Blood
• Neutropenia
• Leukaemia
• Neutrophilia
Blood
There are three key cell groups in blood:
• Erythrocytes
o These function to transport oxygen to tissue
• Platelets
o These function to form a haemostatic plug over the vascular endothelium
• White Blood Cells
o Monocytes/Macrophages
▪ These plays a role in chemotaxis, phagocytosis and killing of some microorganisms,
antigen presentation and the modulation of the inflammatory response.
o Eosinophils
▪ These are involved in the immune response to parasites and regulate
hypersensitivity reactions by inactivating the histamine and leukotrienes released by
basophils and mast cells.
o Lymphocytes
▪ B Cells
• These become activated into Plasma Cells to produce antibodies
▪ T Cells
• These are involved in cell mediate immunity against viruses, fungi and
mycobacteria.
• They also have a role in interacting with B-Cells to trigger their antibody
production.
• T Cells are also implicated in Delayed Hypersensitivity reactions.
o Basophils
▪ The mediate immediate type hypersensitivity and modulate inflammatory responses
by releasing heparin and proteases.
o Neutrophils
▪ These function to phagocytose and destroy bacteria.
Red Blood Cells have a lifespan of 120 days.
Neutrophils/Eosinophils have a half-life of ~7 Hours.
• This therefore means they’re a useful marker of acute inflammation/infection.
Platelets have a lifespan of 9-12 days.
Cells of the blood are produced in the bone marrow, in a process called haematopoiesis.
Neutropenia
Neutropenia is when there is an abnormally low concentration of Neutrophils. This can have many
potential causes:
• Infection
o Actiev Infection
o Post Infection
▪ HIV, EBV, VZV, Measles, Rubella, Mycobacteria
• Autoimmune – Autoantibodies at specific neutrophil antigens
o Primary Autoimmune
o Secondary Autoimmune
o Felty’s Syndrome
▪ This is a serious condition in RA in which a person has RA, Splenomegaly and
neutropenia.
• Dietary
o B12/Folate Deficiency
o Copper Deficiency
o Anorexia
• Medication
o Antibiotics
▪ Cephalosporins, Vancomycin, Macrolides, Dapsone
o Antifungals
o Antimalarials
o Anti-Inflammatories
▪ Sulphasalazine
o Antipsychotics
▪ Clozapine
o Cardiovascular Drugs
• Bone Marrow Infiltration
o This can occur in acute Leukaemia and results in pancytopenia’s.
There can also be congenital causes of Neutropenia:
• Fanconi Anaemia
o This can result in Bone Marrow Failure.
Investigations
Age
History
• Ask about infections, drug exposure, autoimmunity
• B Symptoms/Bleeding
Family History
Examination
• Syndromic Features
• Infection
• Skin changes/arthropathy
• Hepatosplenomegaly
• Lymphadenopathy
Investigations
• FBC
• Blood Film
• Haematinics
• Viral screen
• TFTs
• Autoimmune
Screen
Second Line
• CXR
• USS Abdomen
• Bone Marrow
Biopsy
Leukaemia
Investigations for
Leukaemia:
• FBC
• U&E’s
• LFTs
• CRP
• Coagulation
• Virology
• Blood Film
• Bone Marrow
o Morphology
o Immunophenotyping
o Cytogenetics
o Molecular Analysis
Leukaemia can be divided into Acute vs Chronic and Myeloid vs
Lymphoid Lineage.
• Acute Myeloid Leukaemia
o This is more common in children.
o There are multiple subtypes of this.
• Acute Lymphoid Leukaemia
• Chronic Myeloid Leukaemia
o This is a myeloproliferative disorder of which granulocytes are the major proliferative
component.
o This can arise from a chromosomal translocation between chromosomes 22 and 9, leading
to the formation of the Philadelphia Chromosome (BCR-ABL Protein). This can be treated
with Tyrosine Kinase Inhibitors.
o This presents with:
▪ Fatigue
▪ Splenomegaly
▪ B Symptoms
o This presents with a leucoerythroblastic film with a myeloid peak, due to immature white
blood cells.
o Anaemia is very common.
• Chronic Lymphoid Leukaemia
o This is characterised by excessive lymphoid cell proliferation and thus presents with
Lymphocytosis.
o This can present with lymphadenopathy and splenomegaly.
o If this progresses it can lead to bone marrow infiltration and pancytopenia’s.
o This can be staged according to the effects it has:
▪ Stage 0 – Lymphocytosis
▪ Stage I to II – Lymphadenopathy/Splenomegaly
▪ Stage III to IV – Anaemia/Thrombocytopenia
Neutrophilia
Leucocytosis is the increase in the total white cell count
• Neutrophil Leucocytosis is the absolute increase in the total number of neutrophils.
• Lymphocytosis is the absolute increase in the total number of Lymphocytes.
In inflammation there is usually neutrophilia accompanied with an increase in platelets.
A leukemoid reaction is when there is very high white blood cell counts that is not the result of leukaemia.
A leucoerythroblastic film where there is
the presence of myelocytes (immature
neutrophil precursor) and nucleated red
blood cells (immature RBC).
• This is suggestive of bone marrow
infiltration.
There are many potential causes of
Neutrophilia:
• Physiological
o Pregnancy
o Lactation
o Exercise
o Neonates
• Infection/Inflammation
o Acute Infections
o Burns
o Rheumatoid Arthritis
o Haemorrhage
• Metabolic
o Uraemia
o Diabetic Ketoacidosis
o Gout
• Malignancies
o Carcinoma
o Melanoma
o Myeloproliferative Disorders
o Lymphoma
• Drugs
o Steroids
o Cigarettes
o Adrenaline
o Lithium
