Haematology Flashcards
State first line antibiotic in neutropenic sepsis
Tazocin
(Meropenem if penicillin allergic)
State some fungal biomarkers which can be used to monitor for fungal infections in haematological malingancy
Aspects of fungal wall
- Beta D-Glucan
- Galactomannan
- Aspergillus PCR
State 2 additional antibiotics to consider if Tazocin isn’t working in suspected neutropenic sepsis and why they are given
Vancomycin - to cover gram positive bacteria
Gentamicin - if suspect overwhelming gram negative bacteria from urine/gut
State some prophylactic medications to consider in patients with neutropenia
Aciclovir - prevent varicella and herpes
Posaconazole / other antifungals - prevent fungal infection
Co-trimoxazole - prevent PCP pneumonia
G-CSF - can reduce severity and duration of neutropenia
- Consider antibacterials but risk of resistance
State some side effects of G-CSF
- Bone pain
- Headache
- Fatigue
- Nausea
State some types of IV access
- Cannula
- Tunnelled central line
- PICC line (peripherally inserted central catheter)
- Portacath
State some complications of IV lines
- Infection!!
- Thrombosis (fairly common)
- Bleeding (especially if first put in)
- Failure (block if blood clots, if not been flushed properly)
Always take cultures from line if the patient is septic
State the threshold for platelets:
- Normally
- If patient is septic
- If patient requires surgery
Normally = 10
If septic = 20
If needing surgery = 50
Outline how fertility can be managed for patients starting chemotherapy
Discussions regarding fertility is important
Need to tell patients that they need to be on contraception
Males - sperm banking
Females - if urgent chemo not much can do (if delayed, oocyte presevation or ovarian tissue preservation)
State the main 5 haematological malignancies
- Leukaemia
- Lymphoma
- Myeloma
- Myelodysplastic syndromes
- Myeloproliferative neoplasms
State 3 findings of bone marrow failure on basic blood tests
- Anaemia
- Thrombocytopaenia
- Neutropaenia
= pancytopenia
State some constitutional symptoms of cancer
- Unintentional weight loss (quantify)
- Drenching night sweats
- Fevers
- Pruritis
State some symptoms of hypercalcaemia
- Fatigue
- Abdo pain
- N&V
- Constipation
- Confusion
- Headaches
- Polydipsia
- Polyuria
State some symptoms of hyperviscocity
- Headache
- Somnolence
- Visual disturbance
- Ischaemic events
State some routine bloods to investigate haematological malignancies
FBC
U&E
LFT
CRP
Ca2+
Blood film
Reticulocyte count (reflects bone marrow functioning)
Haematinics
Suggest some blood tests to do to determine potential causes of an anaemia
Repeat FBC
U&Es
LFTs
Thyroid function
Iron studies
B12 and folate
Blood film
Reticulocytes + reticulocyte haemoglobin
Haemoglobin electrophoresis
Serum electrophoresis and serum free light chains
State some ‘special’ bloods to investigate haematological malignancies
- LDH & urate (product of DNA when cells die - part of tumour lysis syndrome)
- Myeloma screen (immunoglobulins +/- serum free light chains)
- Beta 2 Microglobulin (B2M)
- Immunophenotyping (flow cytometry)
State some imaging and more invasive tests to investigate haematological malignancies
Imaging:
- CT scan
- PET scan (lymphoma / myeloma)
- MRI spine / pelvis (myeloma)
Invasive tests:
- Tissue biopsy (morphology, flow cytometry, immunohistochemistry, cytogenetics, mutationals)
- Bone marrow aspirate and trephine
State some complications of essential thrombocythemia
- Thrombosis (arterial/venous)
- Haemorrhage – more common if plt count >1500
- Splenomegaly
- Transformation to myelofibrosis
- Transformation to AML
Use cytoreduction in high risk patients (reduce platelet number)
State what cell line is affected in polycythaemia vera
Erythrocytes (RBCs)
State what cell line is affected in acute myeloid leukaemia
Myeloid stem cells
State what cell line is affected in acute lymphoid leukaemia
Lymphoid stem cells
State what cell line is affected in myeloma
Plasma cells (antibody-producing cells)
State what % of blast cells are required on a film to fulfil a diagnosis of ACUTE myeloid/lymphoid leukaemia, vs diagnosis of CHRONIC myeloid/lymphoid leukaemia
Acute leukaemia: >20% of blood film are blast cells
Chronic leukaemia: <20% of blood film are blast cells
State some presenting signs/symptoms of leukaemia
Bone marrow failure:
- Pale, tired (anaemia)
- Frequent bleeding / bruising (thrombocytopenia)
- Recurrent / severe infections (neutropenia)
Disease involvement:
- Lymphadenopathy
- Organomegaly
Constitutional symptoms:
- Night sweats
- Weight loss
- Fever / pruritis
Hpercalcaemia:
- Renal stones
- Bone pain
- Abdominal pain / constipation
- N&V
- Fatigue / depression
Outline some differences on a blood film between acute vs chronic leukaemia
Acute leukaemia:
- Many blast cells (>20%)
- Mostly 1 cell lineage
Chronic leukaemia:
- Few blast cells (<20%)
- Variety of cell lineages
State the general age ranges for developing acute myeloid leukaeamia
Occurs later in life
Mostly after age of 60
State the general age ranges for developing acute lymphoblastic leukaeamia
Commonly occurs early in life
Mostly under age of 4 (but slight peak after 80 years)
State how acute myeloid leukaeamia is generally treated
Multi-drug chemotherapy
State how acute lymphoblastic leukaeamia is generally treated
Intensive vs non-intensive management
Intensive: Undergo traditional chemotherapy, with an aim for remission
Non-intensive low-intensity therapy can be used if not suitable for above
Trial
Allogenic stem cell transplant (only helps if already in remission)
State what Auer rods are and in which disease they are found
Cells with abnormal granule development, leading to formation of rods within the cytoplasm
Commonly found in AML (acute myeloid leukaemia)
State the genetic translocation see in chronic myeloid leukaemia and how CML is managed, as well as general prognosis
AML caused by cytogenic translocation of 9:22 (Philadelphia) chromosome
Now considered potentially curable
- Use tyrosine kinase inhibitors e.g Imatinib
Prognosis:
- Long remission periods
- 95% go into cure/remission
- Normal life expectancy
State how chronic lymphocytic leukaemia is managed
- Chemotherapy
- Targeted immune therapy e.g. Ibrutinib
State 4 main myeloproliferative disorders
- Primary myelofibrosis
- Essential thrombocythemia
- Polycythaemia vera
- Chronic myeloid leukaemia (CML)
State 3 haematological changes in a myeloproliferative neoplasm
- Polycythaemia (increased RBC)
- Leukaemia (increased WCC)
- Thrombocythaemia (increased platelets)
Essential thrombocythemia - state the following:
- Pathophysiology
- Most common age
- Presentation
- Investigations
- Management
Pathophysiology:
- Essential thrombocythaemia refers to a high platelet count that is not caused by another health condition
- Myeloproliferative neoplasm, resulting from uncontrolled proliferation of megakaryocytes
- Causes excessive platelet production
- Mutation due to presence of the JAK2 V617F mutation (up to 50%)
Most common age:
- 50-70 years old (affects women more)
Presentation:
Many patients are asymptomatic (up to 50%)
- Headache
- Thrombosis
- Bleeding (paradoxical)
- Dizziness / syncope / headache
- Erythromelalgia (red/blue discolouration of the extremities, often accompanied by a burning pain)
- Livedo reticularis (net like purple rash)
- Splenomegaly
Investigations:
- FBC (significantly high platelet count) & WCC may be raised
- Blood smear
- If no clear precipitant JAK2 mutation testing
- Trephine biopsy (hypercellular marrow and pathological megakaryocytic clumping)
Management:
Based on risk stratification
Low risk = Aspirin alone
Medium risk = Aspirin and Hydroxycarbamide (or aspirin alone)
High risk = Aspirin and Hydroxycarbamide
State the risk stratification categories for essential thrombocythemia and how it changes management
Management based on risk stratification
Low risk
Age <40 years AND:
Fairly low Platelet count <1500 × 109/l
No history of thrombosis or haemorrhage
No CVS risk factors (diabetes, hypertension, obesity and smoking)
= Aspirin alone
Medium risk
Has any of the above
= Hydroxycarbamide and Aspirin (or aspirin alone)
High risk
Age >60 years OR
Significantly high platelet count >1500 × 109/l
Previous history of thrombosis or haemorrhage
Diabetes or hypertension
= Hydroxycarbamide and Aspirin
State some potential complications of essential thrombocythemia (myeloproliferative disorder)
- Thrombosis (clotting)
- Paradoxical haemorrhage (esp. if platelet count >1500)
- Splenomegaly
- Can progress to myelofibrosis or AML
State the main differential to consider for essential thrombocythemia and some underlying causes for the differential
Secondary (reactive) thrombocytosis
- Infection
- Bleeding
- Chronic hypoxia
- Iron deficiency
- Splenectomy (loss of storage function)
- Thrombosis
- Trauma
- Recovery phase after bone marrow suppression e.g. after chemotherapy
Polycythaemia vera - state the following:
- Pathophysiology
- Blood results seen
- Presentation
- Investigations
- Management
Pathophysiology:
- Myeloproliferative neoplasm which causes excessive RBC / erythrocyte production
- An absolute increase in red cell blood volume
- JAK2 mutation found in 95% of patients
Blood results seen:
- Raised RBC level (but also raised platelets and WCC usually)
- Low EPO
Presentation:
Can be asymptomatic
- Hyperviscosity symptoms e.g. headache / visual disturbance
- Hypertension
- Splenomegaly
- Fatigue
- Tinnitus
- Itching / paraesthesia
- Thrombotic symptoms e.g. neurological deficits, DVT
Investigations:
- FBC (raised haemoglobin +/- raised haematocrit)
- Check EPO levels (reduced in polycythemia vera)
- LFTs (should be normal - to rule out other causes)
- JAK2 genetic testing (negative result doesn’t rule out)
- Bone marrow biopsy (helps distinguish primary from secondary)
- Imaging e.g. USS (identify splenomegaly)
Management:
- Aspirin (reduce risk thrombotic events)
- Venesection (maintain Hb in normal range)
- Chemotherapy e.g. Hydroxycarbamide
Outline some tests to distinguish primary polycythemia (polycythemia vera) from secondary polycythemia
EPO levels:
Low = primary
High = secondary
JAK2 genetic testing:
Mutation = primary more likely
No mutation = secondary more likely
Bone marrow biopsy:
Changes (hypercellular marrow) = primary more likely
No changes = secondary more likely
Outline some tests to distinguish essential thrombocythemia from differential causes
JAK2 genetic testing:
Mutation = essential thrombocytopenia more likely
No mutation = other diagnoses more likely
Bone marrow biopsy:
Changes (hypercellular marrow and pathological megakaryocytic clumping) = essential thrombocytopenia more likely
No changes = other diagnoses more likely
List some potential complications of polycythaemia vera
- Thrombosis (clotting)
- Risk of progression to myelofibrosis or leukaemia (5-15% progress)
- 20 year life expectancy after diagnosis
State some secondary causes of raised platelets (other than essential thrombocythemia)
- Infection / inflammation
- Post-surgery
- Bleeding
- Iron deficiency
- Splenectomy
State some secondary causes of raised RBCs (other than polycythemia vera)
Chronic hypoxia:
- Smoking
- Obstructive sleep apnoea
- Congenital heart disease
Endocrine disorders:
- EPO secreting tumours e.g. renal / hepatic
- Cushing’s syndrome
- Adrenal tumours
Use of EPO stimulating agents e.g. athletes
Myelofibrosis - state the following:
- Pathophysiology
- Most common age
- Presentation
- Investigations
- Management
Pathophysiology:
- Haematological malignancy that causes fibrosis of bone marrow and causes abnormal cell production
- Produce cytokines, leading to bone marrow fibrosis
- Can be primary, or occur secondary to polycythemia vera or essential thrombocythemia
- Often presents as pancytopenia, but can produce high numbers in some cell lines
- Results in bone marrow scarring, peripheral blood abnormalities, and enlarged spleen
- Associated with JAK2 mutation
Most common age:
- Typically affects older adults (>65 years)
Presentation:
- Bone pain
- Signs of bone marrow failure (anaemia, recurrent infection, and abnormal bleeding/bruising)
- Splenomegaly / hepatomegaly
- Constitutional symptoms – weight loss, fever, night sweats
Investigations:
- Bloods: urate and LDH (high)
- Blood film (tear drop-shaped RBCs) and a immature RBCs and WCCs
- Platelet count & WCC high initially, pancytopenia occurs later
- Bone marrow aspirate and trephine biopsy = ‘dry tap’ bone marrow aspiration
- JAK-2 genetic testing
Management:
Generally incurable :(
- Stem cell transplant (if good candidate < 70)
- Chemotherapy (can help control but not curative)
- JAK2 inhibitors e.g. Ruxolitinib
- Supportive care e.g. blood transfusion for anaemia, splenectomy
State what would be seen on the following investigations for myelofibrosis
- Bloods
- Blood film
- Bone marrow aspirate and trephine biopsy
- JAK-2 genetic testing
Bloods:
- Urate and LDH high
- Platelet count & WCC high initially, pancytopenia occurs later
Blood film:
- Tear drop-shaped RBCs
- Immature RBCs and WCCs
Bone marrow aspirate and trephine biopsy:
- ‘Dry tap’ bone marrow aspiration
JAK-2 genetic testing:
- Mutation may be present
What is a paraproteinaemia
A group of disorders characterised by overproduction of monoclonal antibodies by plasma cells
- Monoclonal immunoglobulins are produced by a colonial population of mostly plasma cells
- Pre-malignant and malignant types
Explain the different range of paraproteinaemias (outline spectrum)
Range of pre-malignant and malignant paraproteinaemic conditions
All conditions associated with a rise in paraproteins
- MGUS (monoclonal gammopathy of unknown significance)
- ASYMPTOMATIC + raised paraproteins (no CRAB features - often found incidentally)
- Non-cancerous
- Fairly normal in the population, found in 3% of over 50’s
- Only 1% will progress into cancer each year (higher risk of lymphoma and myeloma) - Smouldering myeloma
(asymptomatic but half way between MGUS and multiple myeloma) - Multiple myeloma
- Symptomatic (CRAB features)
- Malignant condition - Plasma cell myeloma
(more aggressive type of multiple myeloma)
List some non-modifiable risk factors for developing myeloma
- Family history
- Older age
- Male
- Obesity
- Black
Myeloma - state the following:
- Pathophysiology
- Most common age (and ethnicity)
- Presentation
- Investigations
- Management
Pathophysiology:
- Myeloma is cancer of plasma cells where a mutation in plasma cells leads to large quantities of monoclonal immunoglobulin (antibody) production = monoclonal paraprotein
- In 50% cases, IgG is overproduced
- Multiple myeloma is where the myeloma affects multiple areas of the body
Most common age:
- Over 60 (most cases over 70)
- Twice as common in black populations
Presentation:
CRAB
- Calcium elevation (hypercalcaemia symptoms)
- Renal dysfunction
- Anaemia (pallor, fatigue etc.)
- Bone marrow infiltration / osteolytic lesions (bone pain)
Investigations:
- FBC (anaemia)
- U&Es (renal impairment / hypercalcaemia)
- Blood film
- Myeloma screen
1. Serum protein electrophoresis
2. Serum free light chain assay
- Bone marrow aspiration and trephine biopsy
- Whole body MRI (or CT or skeletal survey)
Management:
MDT approach
- Chemotherapy e.g. Cyclophosphamide, Doxirubicin
- Corticosteroids e.g. Dexamethasone
- Immunomodulatory drugs e.g. Thalidomide
- Bisphosphonates / radiotherapy (bone disease)
- Erythropoietin analogues (anaemia)
- VTE prophylaxis
- High dose drug therapy / stem-cell transplant
Outline the difference between benign polyclonal hypergammaglobulinemia, MGUS and multiple myeloma
Benign polyclonal hypergammaglobulinemia
- Non-malignant condition of plasma cells with no malignant potential
- Polyclonal
- Asymptomatic
- Usually reactive to primary condition
MGUS
- Non-malignant condition of plasma cells with some malignant potential
- Monoclonal
- Asymptomatic
Multiple myeloma
- MALIGNANT condition of plasma cells
- Monoclonal
- Symptomatic = CRAB symptoms
State some clinical situations associated with benign polyclonal hypergammaglobulinemia
Autoimmune diseases
Liver disease
Acute / chronic inflammation
Infections
State some common places for myeloma bone disease to occur (destruction of bone secondary to cytokines released by cancerous plasma cells)
Osteolytic lesions:
- Spine
- Skull
- Ribs
- Long bones
List some complications of myeloma
Renal failure
Anaemia
Pain
Infection
Hyperviscosity
Peripheral neuropathy
Hypercalcaemia
Spinal cord compression
