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
State some signs of myeloma that can be seen on x-ray
- Lytic lesions
- Punched out lesions
- Pepper pot skull
Outline why hyperviscosity occurs in paraproteinaemias, how it might present, what investigations to do and how it is managed
Oncological emergency - caused by aggregation of paraproteins within the blood, leading to increased viscosity
Presentation:
- Abnormal bleeding e.g. epistaxis
- Visual changes e.g. double/blurred vision
- Headaches, dizziness, seizures and other neurological symptoms
- Heart failure
Investigations:
- Bloods (FBC, U&Es, coagulation)
- Serum viscosity
- Fundoscopy
Management:
- IV fluids
- Chemotherapy to treat underlying cause
- In serious cases, consider plasmaphresesis
Outline how spinal cord compression can occur in paraproteinaemias, how it might present, what investigations to do and how it is managed
Oncological emergency - increased activity of osteoclasts, causing osteolytic bone lesions which can cause vertebral fractures and spinal cord compression
Presentation:
- Back pain (most common and first)
- Focal neurological signs
- Signs of cauda equina syndrome
Investigations:
- Urgent MRI whole spine and pelvis
Management:
- Dexamethasone
- Radiotherapy
- Surgical decompression
+ bed rest and analgesia
Outline how renal failure can occur in paraproteinaemias, how it might present, what investigations to do and how it is managed
Paraproteins are nephrotoxic and cause damage to: glomeruli, proximal and distal tubules
Damage can be exacerbated by dehydration, nephrotoxic drugs or hypercalcaemia
Presentation:
- Oligouria
- Loss of weight
Investigations:
- Serum creatinine
- 24 hr urinary creatinine and protein
Management:
- IV fluids if dehydration
- Dexamethasone and Bortezomib combination
- Stop any nephrotoxic drugs
May need to consider dialysis
Primary amyloidosis - state the following:
- Pathophysiology
- Presentation
- Investigations
- Management
Pathophysiology:
- Disease where light chains of immunoglobulins misfold
- Misfolded proteins cause amyloid plaques, which can be deposited around the body (then broken down very slowly by the body
Presentation:
- Dementia
- Organomegaly (spleen or liver)
- Macroglossia
- CHF or cardiomegaly
- Nephrotic syndrome
- Weight loss (from malabsorption)
Investigations:
- Biopsy and congo red staining of affected organ e.g. skin
- Can do bone marrow biopsy
Management:
- Symptomatic relief if HF e.g. pacemaker
- Chemotherapy / targeted therapy (target plasma cells)
- Bone marrow stem cell transplant
State some risk factors for primary amyloidosis
- Multiple myeloma
- Lymphoma
- Older age
- Waldenstrom’s macroglobulinemia
Pancytopenia - state the following:
- Pathophysiology
- Presentation
- Investigations
- Management
Pathophysiology:
Not a diagnosis in itself
Combination of three cellular abnormalities:
1. Anaemia (low haemoglobin)
2. Leukopenia (low white cells)
3. Thrombocytopenia (low platelets)
Presentation (relating to low cell lines):
Anaemia - breathlessness, pallor, tachycardia, tachypnoea, palpitations etc.
Leukopenia - recurrent infections, ulcers, oral candidiasis
Thrombocytopenia - easy bruising, epistaxis, gum bleeding, petechiae/purpura
Investigations:
Bloods
- FBC and reticulocyte count (identify poor production or increased destruction)
- Vitamin B12 / folate
- LFTs and lactate dehydrogenase
- Peripheral blood smear (blasts, leukocytes or immature cells)
If abnormal cells on blood smear
- Bone marrow aspirate + biopsy
- If inconclusive, cytogenetic testing, flow cytometry of bone marrow / blood or molecular studies
- Check for infection e.g. HIV
- Serum calcium, PTH and TFTs
Management:
Based on underlying cause
Can do supportive measures e.g. blood transfusion / platelet transfusion
- Correct any nutritional deficiencies
- Treat any underlying infections e.g. HIV
- If malignancy / autoimmune, manage with chemotherapy / immunosuppression
Supportive measures if reversible underlying cause found
State some causes of pancytopenia
- Decreased production (central)
- Decreased production (bone)
- Increased destruction
Decreased production (central):
- Aplastic Anaemia
- Nutritional Deficiencies
- Infection/Sepsis
- Chemotherapy / radiotherapy
- Methotrexate
Decreased production (bone):
- Lymphoma
- Acute myeloid leukaemia
- Acute lymphoid leukaemia
- Multiple Myeloma
- Granulomatous disorders
- Metastatic tumours
Increased destruction:
- Autoimmune destruction
- Splenic sequestration
- Liver failures
- Drug-induced e.g. Rifampicin
State some causes of neutrophilia
- Bacterial infection
- Corticosteroid use
- Myeloproliferative disorders
- Physiological stress e.g. trauma
- Active inflammation
State some causes of neutropenia
- Sepsis
- Viral infection
- Drugs e.g. chemotherapy
- Bone marrow failure
- Hypersplenism
State some causes of lymphocytosis
- Acute viral infection (EBV / CMV especially)
- Chronic atypical infection (TB. toxoplasmosis)
- Lymphoproliferative disorders e.g. lymphoma, CLL
- Hyposplenism
- Physiological stress e.g. trauma
State some causes of eosinophilia
- Parasite infection
- Allergy e.g. to drug
- Inflammatory diseases
- Skin disorders e.g. eczema, psoriasis
State some causes of thrombocytopenia
Decreased production
- Bone marrow failure
- Myelosuppressive drugs
Increased destruction
- ITP
- Hypersplenism
- Consumption e.g. DIC
State some causes of thrombocytosis
Primary:
- Essential thrombocytosis
Secondary (precipitant):
- Bleeding
- Infection
- Iron deficiency
- Hyposplenism
- Trauma / surgery
State some cancer-specific risk factors for VTE events
Medication
- Chemotherapy
- Tamoxifen and other hormonal therapies
- Thalidomide and lenalidomide- used in multiple myeloma
Patient Factors:
- Immobility
- Requiring hospitalization
- Infection risk
- Likely having procedures such as PICC line insertion
Site:
- VTE is a common risk factor of solid organ cancers
- Multiple myeloma due to hyperviscosity and high burden of disease
- Metastasis
State some primary cancer sites that have higher incidence of VTEs
- Pancreatic
- Gastric
- Glioblastomas
. - Renal
- Ovarian
- Lung
- Oesophageal
Outline some symptoms of intra-abdominal clots
Severe abdominal pain
N&V
Diarrhoea
Bloating
+/- signs of peritonitis
Outline some symptoms of cerebral clots
(Stroke symptoms)
Headache
Visual disturbance
N&V
Neuromuscular issues
Speech difficult
Hearing loss
LOC
Outline the steps for suspected DVT
Calculate Wells score:
Wells > 2 = DVT likely -> ultrasound scan
Wells < 2 = DVT unlikely -> D-dimer test
If d-dimer negative -> consider low risk
If d-dimer positive -> ultrasound scan
Outline the steps for suspected PE
Calculate Wells score:
Wells > 4 = PE likely -> CTPA
Wells < 4 = PE unlikely -> D-dimer test
If d-dimer negative -> consider low risk
If d-dimer positive -> CTPA
Outline how VTEs are managed once identified on imaging
1st line: DOAC e.g. Edoxaban, Rivaroxaban, Apixaban
2nd line: LMWH
State which cancer patients receive VTE prophylaxis
- Myeloma patients receiving certain chemotherapy agents e.g. Thalidomide
- Pancreatic cancer receiving chemotherapy (given LMWH)
- Other risk factors for VTE (ignoring the cancer)
State the difference between an autologous and allogenic stem cell transplant
Autologous stem cell transplant
- involves mobilising and collecting a patient’s stem cells, providing chemotherapy to deplete the bone marrow, and then retransfusing their stem cells
- less complex
- less potential side effects than an allogeneic stem cell transplant
Allogeneic stem cell transplant
- involves depleting a patient’s bone marrow using chemotherapy, and then transfusing another (matched) patient’s stem cells
- both replacing their haematopoietic cells with normal cells
- provides some degree of graft-vs-disease effect
Immune thrombocytopenia (ITP) - state the following:
- Pathophysiology
- Presentation
- Investigations
- Management
Pathophysiology:
- Autoimmune condition, caused by antibody production against platelets
- Leads to thrombocytopenia
- Generally a diagnosis of exclusion, once other causes are ruled out
Presentation:
- Bleeding e.g. epistaxis, gum bleeding, poor to slow bleeding
- Absence of concerning systemic features e.g. weight loss, fevers
- Absence of other concerning features e.g. lymphadenopathy, splenomegaly or hepatomegaly
Investigations - bloods:
- FBC
- Peripheral smear (no evidence of abnormal cells or myelodysplasia)
- HIV, hepatitis B and C
- H pylori test
- TFT
Management - depends on platelet count:
- Asymptomatic adults with platelets >30 + no additional risk factors = observation and monitoring
- If platelets < 30 = Corticosteroids +/- IV immunoglobulins (IVIG)
For the following blood film findings, briefly explain what they are and when they are seen
- Anisocytosis
- Reticulocytes
- Target cells
- Sideroblasts
- Schistocytes
- Spherocytes
Anisocytosis = variation in sizes of RBCs
- Myelodysplastic syndrome
- Some forms of anaemia
Reticulocytes = immature RBCs, appear larger than mature RBCs and RNA within them, shows bone marrow is very active
- Haemolytic conditions e.g. haemolytic anaemia
- Acute bleeding
Target cells = central pigmented area
- Iron deficiency anaemia (in small numbers)
- Haemaglobinaemias
- Post-splenectomy
Sideroblasts = immature RBCs with iron deposits, bone marrow unable to incorporate iron into Hb
- Myelodysplastic syndrome
- Alcoholism
Schistocytes = fragments of RBCs, indicates damage during transport
- Haemolytic anaemia
- Metallic heart valves
- DIC
- Haemolytic uraemic syndrome
- ITP / TTP
Spherocytes = spherical RBCs, without dip in middle
- Hereditary spherocytosis
- Haemolytic anaemia
For the following blood film findings, briefly explain what they are and when they are seen
- Heinz bodies
- Howell-Jolly bodies
Heinz bodies = blobs within RBCs caused by denatured globin
- G6PD deficiency
- alpha-thalassaemia
Howell-Jolly bodies = blobs of DNA material within RBCs, normally removed by spleen
- Post-splenectomy
- Hyposplenism
What is basophilic stippling and when is it seen?
Blue staining of ribosomes within the cytoplasm
Seen in:
- Thalassaemia
- Megaloblastic anaemia
- Sideoblastic anaemia
- Alcohol abuse
List causes of normocytic anaemia
AAA, HH
Acute blood loss
Anaemia of chronic disease
Aplastic anaemia
Haemolytic anaemias e.g. sickle cell, sideroblastic anaemia
Hypothyroidism
List causes of microcytic anaemia
TAILS
Thalassaemia
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning
Sideroblastic anaemia
List causes of macrocytic anaemia
FAT RBC
Foetus (pregnancy)
Alcohol
Thyroid (hypothyroidism)
Reticulocytes
B12 and folate deficiency
Cirrhosis / chronic liver disease
All normoblastic macrocytic anaemia, except B12 and folate deficiency = megaloblastic macrocytic anaemia (from impaired DNA synthesis)
List some clinical findings specific to iron-deficiency anaemia (vs other causes of anaemia)
- Hair loss / brittle hair
- Brittle nails
- Koilonychia
- Angular cheilitis
- Atrophic glossitis
+ pica
List some initial investigations for a patient presenting with anaemia (low Hb), and extra tests to consider if the patient is > 40
- Hb check
- MCV (microcytic, normocytic or macrocytic)
- B12 and folate
- Ferritin
- Peripheral blood film
May consider further tests if > 40:
- OGD
- Colonoscopy
- Bone marrow biopsy if cause is unclear
List some questions to consider asking in a patient with suspected anaemia (low HB)
- Dietary history / vegetarian / vegan
- Sources of potential blood loss e.g. menorrhagia or malaena
- Any absorption issues e.g. gastrectomy, coeliac disease
- Any family history of haematological disorders
- Check for diagnosis of any chronic diseases e.g. cardiac, renal, hepatic
Outline common causes of iron-deficiency anaemia
- Chronic blood loss (menorrhagia, chronic bleeds e.g. malaena)
- Dietary deficiency
- Malabsorption
- Increased requirements during childhood or pregnancy
State the findings for iron-deficiency anaemia
MCV
Serum iron
Transferrin saturation
Ferritin
Total iron-binding capacity
Low MCV = <80
Serum iron = low
Transferrin saturation = low
Ferritin = low
Total iron-binding capacity = high (inverse relationship between ferritin and TIBC)
Explain what the following parameters indicate in terms of anaemia
- Serum iron
- Ferritin
- Total iron binding capacity
- Transferrin saturation
Serum iron = amount of iron in the blood during that time
- Varies throughout the day, not a good measure alone
Ferritin = form of iron when deposited in tissue and cells
- If low, highly suggestive of iron deficiency anaemia
Total iron binding capacity = indicates the amount of space available on the iron carrier protein, transferrin
- Actually increases in iron deficiency
Transferrin saturation = indication of total iron in the body
- Fasting sample is needed, as it will go up after eating
State some symptoms of B12 deficiency anaemia
Neurological symptoms:
- Paraesthesia
- Loss of vibration or proprioception
- Visual changes
- Mood or cognition changes
If a patient has folate deficiency and B12 deficiency, state which one you should correct first and why
Should correct B12 deficiency first
Treating folate deficiency when a patient still has B12 deficiency can cause subacute combined degeneration of the spinal cord
List some causes of haemolytic anaemia (inherited and acquired)
Inherited:
- Sickle cell
- Thalassaemia
- Hereditary spherocytosis
- Hereditary elliptocytosis
- G6PD deficiency
Acquired:
- Autoimmune haemolytic anaemia
- Alloimmune haemolytic anaemia (transfusion reaction, haemolytic disease newborn)
- Microangiopathic haemolytic anaemia / prosthetic valve
- Paroxysmal nocturnal haemoglobinuria
For the following tests, state what you would see with a patient with haemolytic anaemia
- FBC
- Blood film
- Direct coombs test
- Reticulocyte count
FBC = normocytic anaemia
Blood film = schistocytes
Direct coombs test = positive if autoimmune haemolytic anaemia
Reticulocyte count = raised (rapid turnover of cells)
Thalassaemia - state the following:
- Pathophysiology
- Presentation
- Investigations
- Management
Pathophysiology:
- Haemoglobinopathy where there is a defect in haemoglobin protein chains
- Autosomal recessive
- Mutation in either alpha or beta chains (2 of each in a normal hb molecule)
- These abnormal cells are more fragile and haemolyse more easily, leading to increased removal and sequestration by the spleen
Presentation
- Generic anaemia symptom e.g. pallor, fatigue
- Splenomegaly
- Jaundice
- Gallstones
- In children, failure to thrive, pronounced forehead and malar eminences
- Microcytic anaemia
Investigations:
- FBC (microcytic anaemia)
- Haemoglobin electrophoreses
- DNA testing
(screened for during pregnancy)
Management:
Alpha thalassaemia
- Monitoring for complications
- Blood transfusions
- May do splenectomy
- Bone marrow transplant can be curative
Beta thalassaemia
Minor = monitor
Intermedia = monitoring and occasional blood transfusions
Major = regular blood transfusions and splenectomy +/- bone marrow transfusion
Sickle cell anaemia - state the following:
- Pathophysiology
- Presentation
- Investigations
- General management
Pathophysiology:
- Haemoglobinopathy where there is a defect in Haemoglobin S
- Autosomal recessive (if carrier, sickle cell trait)
- Repeated polymerisation under low O2 conditions causes sickling of RBCs, making them more fragile
Presentation:
- Generic anaemia symptom e.g. pallor, fatigue
- Splenomegaly
- Jaundice
- Gallstones
- In children, failure to thrive, pronounced forehead and malar eminences
- Microcytic anaemia
Investigations:
- Tested for on newborn heel prick test
General management:
- Avoid triggers e.g. cold, dehydration
- Up to date vaccinations
- Penicillin V (antibiotic prophylaxis)
- Folic acid
- Hydroxycarbamide (encourage HbF production)
- Blood transfusion if severe anaemia
- Bone marrow transplant can be curative
- Pain relief if needed
Outline how to manage a sickle cell crisis
No specific treatment - supportive care
- Analgesia (check for pain care plan)
- Treat / remove underlying triggers e.g. infection and keep warm
- Ensure hydrated (consider) IV fluids
= low threshold for admission to hospital
List some complications of sickle cell disease
- Sickle cell crises
- Anaemia
- Stroke
- Priapism
- Acute chest syndrome
- Chronic kidney disease
- Increased risk of infection
- Avascular necrosis
- Pulmonary hypertension
Outline acute chest syndrome in sickle cell disease, symptoms, how it is diagnosed and how it is managed
Severe lung-related complication of sickle cell disease
Potential causes:
- Infection
- Infarction (due to fat emboli from bone infarcts)
Can be a combination of both
Symptoms:
- Chest or back pain
- SOB
- Wheezing
- Tachypnea
- Cough, which may contain blood
- Fever
- Vaso-occlusive pain
Diagnosis:
- Fever or respiratory symptoms with new infiltrates on chest x-ray
Management:
- Analgesia
- Consider IV fluids if dehydrated
- Antibiotics / antivirals for infection
- Blood transfusion
- Incentive spirometry
- May require artificial ventilation
Leukaemia - state the following:
- 4 main types of leukaemia
- Pathophysiology
- Presentation
- Diagnosis
- Management
4 main types:
- Acute lymphoblastic leukaemia (ALL)
- Acute myeloid leukaemia (AML)
- Chronic lymphoblastic leukaemia (CLL)
- Chronic myeloid leukaemia (CML)
Pathophysiology:
- Cancer of the stem progenitor cells within the bone marrow
- Genetic mutation in either lymphoid or myeloid progenitor cells
- Leading to unregulated production of single type of white blood cell, which then suppresses other types (pancytopenia)
- Either acute or chronic (lymphoid or myeloid)
Presentation:
- Unexplained fever
- Night sweats
- Weight loss
- Persistent fatigue
- Petechiae / unexplained bruising e.g. frequent nose bleeds
- Bone or joint pain
- Hepatosplenomegaly
- Lymphadenopathy
- Pallor
- Pancytopenia (anaemia / thrombocytopenia / leukopenia)
Diagnosis:
- Very urgent FBC
- Peripheral blood smear
- Bone marrow biopsy (aspiration and trephine)
- Lymph node biopsy
- Further staging scans e.g. chest x-ray, CT scan, lumbar puncture, genetic analysis immunophenotyping of abnormal cells
Management:
- Chemotherapy predominantly
- Radiotherapy / bone marrow transplant / surgery
State the blood findings for acute lymphoblastic leukaemia (ALL):
- FBC (haemoglobin, WCC, platelets and reticulocytes)
- Peripheral blood smear
- Bone marrow aspiration
FBC:
- Normochromic normocytic anaemia
- High WCC (in 50%)
- Thrombocytopenia
- Low reticulocyte count
Peripheral blood smear:
- Leukaemic lymphoblasts
Bone marrow aspiration:
>20% of blood film are lymphoblast cells
State the blood findings for acute myeloid leukaemia (AML):
- FBC (haemoglobin, WCC, platelets and reticulocytes)
- Peripheral blood smear
- Bone marrow aspiration
FBC:
- Anaemia
- High WCC but neutropenia
- Thrombocytopenia
- Low reticulocyte count
Peripheral blood smear:
- Auer rods
- Myeloid blast cells
Bone marrow aspiration:
>20% of blood film are myeloid blast cells
State the blood findings for chronic lymphocytic leukaemia (CLL):
- FBC (WCC, haemaglobin)
- Peripheral blood smear
- Bone marrow aspiration
FBC:
- High WCC persisting for > 3 months
May show anaemia
Peripheral blood smear:
- Smudge cells (cytoskeletal defects in lymphocytes)
Bone marrow aspiration:
< 20% of blood film are lymphoblast cells
State the blood findings for chronic myeloid leukaemia (CML):
- FBC (haemoglobin, WCC, platelets and reticulocytes)
- Bone marrow aspiration
FBC:
- High WCC persisting for > 3 months
May show anaemia or thrombocytopenia
Bone marrow aspiration:
< 20% of blood film are myeloid blast cells
Chronic lymphocytic leukaemia - state the following:
- Pathophysiology
- Presentation
- Investigations
- Management
Pathophysiology:
- Indolent haematological cancer, with profileration of B lymphocytes
- Occurs with increasing age
Presentation:
Usually incidental finding on FBC = lymphocytosis or as symptomatic lymphadenopathy
- Splenomegaly
- Lymphadenopathy
- Fatigue
- SOB
- May have B symptoms
Investigations:
- FBC
- Flow cytometry
- Bone marrow aspiration and biopsy showing smudge cells
Management:
If low-medium risk = active surveillance every 3 months (FBC, flow cytometry, physical examination)
If symptomatic or advanced-stage CLL = chemoimmunotherapy / targeted therapies
(Stem cell transplant for relapsed disease)
Chronic myeloid leukaemia - state the following:
- Pathophysiology
- Presentation
- Investigations
- Management
Pathophysiology:
- Malignant clonal disorder of haematopoietic stem cells
- Presence of Philadelphia chromosome
- ‘Chronic’ phase of the disease may transform to an ‘accelerated’ disease in 5-10% of patients (despite treatment with a tyrosine kinase inhibitor)
- Risk of transformation into ALL or AML
Presentation:
Up to 50% of patients asymptomatic
- Splenomegaly (50% patients) / LUQ pain
- B symptoms (fever, weight loss, night sweats)
- Malaise
Investigations:
- FBC
- Complete metabolic profile
- Peripheral blood smear
- Bone marrow biopsy
Management:
- Tyrosine kinase inhibitor e.g. Imatinib = well tolerated
Overall survival rates with 8-year follow-up are about 85-90%
Outline the difference between Hodgkin and non-Hodgkin lymphoma
Hodgkin lymphoma:
- Specific type of lymphoma
- Affects younger patients (30s + 70s)
- Local contagious spread from one lymph node to another
- Has Reed Sternberg cells (B cell)
- Systemic symptoms are more common / more likely to affect mediastinum
- Alcohol-induced lymph node pain
- Linked to EBV
- Generally better response to treatment
Non-Hodgkin lymphoma:
- All other types of lymphoma (that aren’t Hodgkin)
- Affects older patients (70s)
- B cell (70%) or T cell (30%) lymphoma
- NO Reed Steinberg cells
- Associated with some other conditions e.g. HIV, chronic H pylori infection
- Systemic symptoms are less common
- Generally less responsive to treatment
State some risk factors for Hodgkin’s lymphoma
- Family history / previous history
- EBV
- HIV
- Autoimmune conditions e.g. rheumatoid arthritis
State some risk factors for non-Hodgkin’s lymphoma
- Family history / previous history
- EBV
- HIV
- Hepatitis B / C infection
- Exposure to pesticides (Trichloroethylene)
- H. pylori (MALT lymphoma)
Non-Hodgkin lymphoma - state the following:
- Pathophysiology
- Presentation
- Diagnosis
- Management
More common 80% cases
Pathophysiology:
- GROUP of lymphomas (all lymphomas that aren’t Hodgkins)
- Genetic mutation in lymphocyte
- Tends to collect in the lymph nodes
- Most cases occur in people over the age of 50
Presentation:
KEY = non-tender lymphadenopathy
- Unexplained fever
- Night sweats
- Weight loss
- Failure to thrive
- Body itching
Diagnosis:
- Lymph node biopsy (excision)
- Further staging scans e.g. CT scan, MRI
- Bone marrow biopsy
- Ann Arbour used for staging
Management:
Depends on type
- Chemotherapy (high-grade aggressive)
- Monoclonal antibodies e.g. Rituximab
- Radiotherapy
- Bone marrow transplant
Ensure vaccinations are up to date!
Give 3 examples of non-Hodgkin lymphomas
Diffuse large B cell lymphoma
Burkitt’s lymphoma
MALT lymphoma
Hodgkin lymphoma - state the following:
- Pathophysiology
- Presentation
- Diagnosis
- Management
Pathophysiology:
- Specific type of lymphoma (around 20% of lymphomas)
- Genetic mutation in lymphocyte
- Tends to collect in the lymph nodes
- Most cases occur in people between ages of 20-40 (young adults)
Presentation:
KEY = non-tender lymphadenopathy (generally cervical or supraclavicular)
- “B” symptoms (unexplained fever, night sweats, weight loss)
- Body itching
Alcohol-induced painful lymphadenopathy is a suggestive symptom
Diagnosis:
- Lymph node biopsy (excision) = Reed Sternberg cells
(LDH is often raised, but non-specific)
- Further staging scans e.g. CT scan, MRI
- Bone marrow biopsy
- Ann Arbour used for staging
Management:
- Chemotherapy (mainstay)
- Radiotherapy
- Bone marrow transplant
Describe some features of Reed Sternberg cells
Owl face with large eyes :)
- Abnormally large
- Multiple nuclei, with nucleoli within them
Describe the Ann Arbour staging system
System used for staging lymphomas (both Hodgkin and non-Hodgkin lymphomas)
Stage 1: one lymph node affected
Stage 2: more than one region affected, but on same side of diaphragm
Stage 3: lymph nodes affects above and below the diaphragm
Stage 4: widespread involvement of non-lymphatic tissue e.g. liver, lungs
A type = asymptomatic (no B symptoms)
B type = sympatomatic with constitutional symptoms e.g. night sweats, fever
State some differentials for petechiae
Leukaemia
Meningococcal sepsis
Henoch-Schonlein purpura (HSP)
Immune thrombocytopenia (ITP)
Vasculitis
Non-accidental injury in children and vulnerable adults
State the common ages to develop the following leukaemias
- Acute lymphoblastic leukaemia
- Chronic lymphocytic leukaemia
- Chronic myeloid leukaemia
- Acute myeloid leukaemia
Acute lymphoblastic leukaemia = under 5 & over 45
Chronic lymphocytic leukaemia = over 55
Chronic myeloid leukaemia = over 65
Acute myeloid leukaemia = over 75
Which other cancer is chronic lymphoid leukaemia at risk of transforming into
High-grade lymphoma (Richter’s transformation)
Outline the 3 main stages of chronic myeloid leukaemia
- Chronic phase
- Lasts around 5 years
- Often asymptomatic - Accelerated phase
- Abnormal blast cells take up a large proportion of the bone marrow and blood (10-20%), leading to symptoms of pancytopenia - Blast phase
- Even more abnormal blast cells take up an even larger proportion of the bone marrow and blood (>30%)
- Severe symptoms and pancytopenia
- Often fatal :(
State the initial steps to take for a patient with significant blood loss
- ABCDE approach
- Immediate senior involvement
- Attempt to control bleeding e.g. direct pressure
- Warmed IV fluids
- Request / transfuse RBCs
- Reverse any anticoagulation
- Consider tranexamic acid
State how to request major haemorrhage protocol and what details to provide
Nominate a blood bank coordinator!
22 22 = state ‘Massive haemorrhage’ in exact location
Details:
- Coordinator’s name
- Name of senior clinician
- Incident location
- Extension number
- TYPE of haemorrhage e.g. obstetric, trauma
- Patient’s details
List some conditions for which you might instigate the major haemorrhage protocol
- Clinically obvious severe traumatic bleeding or collapse
- Major blood loss (>50% volume in < 3 hrs)
- Haemorrhagic shock e.g. SBP <70 or <90 after fluid bolus
- Bleeding rate of >150mL/min
Myelodysplastic syndrome - state the following:
- Pathophysiology
- Most common age
- Presentation
- Investigations
- Management
Pathophysiology:
- Blood cancer caused by dysfunctional myeloid bone marrow
- Specific subtypes of myelodysplastic syndromes
- Leads to pancytopenia (anaemia, thrombocytopenia and leukopenia)
Most common age:
- More common > 60
- More common in patients previously had chemotherapy / radiotherapy
Presentation:
May be asymptomatic
- Symptoms of pancytopenia e.g. tiredness, breathlessness, bleeding, recurrent infections
Investigations:
- FBC (abnormal)
- Blood film (blasts)
- Bone marrow aspirate and biopsy
Management:
Depends on levels and symptoms
- Watchful waiting if low risk
- Supportive treatment e.g. blood transfusion
- Chemotherapy
- Bone marrow transplant
List some differential diagnoses for lymphadenopathy (aka. causes)
- Malignancy
- Infective
- Rheumatological
Malignancy:
- Lymphoma (Hodgkin’s and non Hodgkin’s)
- Acute lymphocytic leukaemia
- Head and neck cancers, thyroid cancer
Infective:
- EBV (infectious mononucleosis)
- TB
- Hep C, CMV, HIV, syphilis
- Bacterial pharyngitis, ear infections, dental abscess
Rheumatological:
- SLE
- Rheumatoid arthritis
- Sjogren’s disease
+ post viral vaccines
List some examples of the following types of non-Hodgkin lymphomas:
1. B cell lymphoma
2. T cell / natural killer T cell lymphoma
- B cell lymphoma
- Diffuse large B-cell (most common)
- Follicular (2nd most common)
- Mantle cell
- Small lymphocytic - T cell / natural killer T cell lymphoma
- Anaplastic large cell (primary cutaneous type)
- Anaplastic large cell (systemic type)
- Peripheral T-cell, not otherwise specified (NOS)
- Angioimmunoblastic T-cell
List some examples of high grade / aggressive B cell lymphomas
- Diffuse large B- cell lymphoma (DLBCL)
- Mantle cell
- Burkitts
List some examples of low grade / indolent B cell lymphomas
- Follicular lymphoma
- MALT
List some examples of high grade / aggressive T cell lymphomas
- Systemic anaplastic
- Peripheral T-cell lymphoma
List some examples of low grade / indolent T cell lymphomas
- Mycosis fungoides
- Primary cutaneous anaplastic large cell lymphoma
List 3 markers that haemolysis of RBCs might be occuring
- Raised LDH
- Raised bilirubin
- Decreased haptoglobin
State what test you can do to determine an immune vs non-immune cause of haemolysis
Direct Coombs (antiglobulin) test
If there is a folate and B12 deficiency, which one should be corrected first and why?
B12 should be corrected first
Correcting folate before correcting B12 could cause subacute degeneration of the spinal cord
(remember B comes before F in the alphabet)
State what disease smudge cells are pathognomonic for
CLL (chronic lymphocytic anaemia)
State some reasons for anaemia in patients with cancer
- Infiltration of bone marrow
- Chemotherapy (suppress bone marrow)
- Anaemia of chronic disease
- Warm haemolytic anaemia (complication of CLL)
List some causes of splenomegaly (split into mild / moderate and massive)
Mild:
- Removal of defective RBCs e.g. haemolytic anaemias, sickle cell, thalassaemias
- Infiltrative conditions e.g. sarcoidosis
- Autoimmune conditions e.g. RA
- Hepatitis (infectious)
- Endocarditis
Moderate:
- Hematologic malignancies e.g. lymphomas, leukemias, myeloproliferative disorders
- Infections e.g. Glandular fever
- Portal hypertension e.g. liver cirrhosis
Massive:
- Malaria
- Schistosomiasis
- Myelofibrosis (bone marrow failure)
- CML
List some causes of hyposplenism
- Splenectomy
- Sickle cell disease
- GI disease e.g. IBD, coeliac disease
- Autoimmune conditions e.g. SLE, RA, Hashimotos
State how patients with hyposplenism are managed
Vaccination against:
- Strep pneumoniae
- Neisseria meningitidis
- Haemophilous influenzae type B
Lifelong prophylaxis:
- Penicillin V or Amoxicillin
List some causes of hypersplenism
Massive:
- CML
- Myelofibrosis
- Malaria / schistosomiasis
Moderate:
- Lymphoma / leukaemia
- Myeloproliferative disorders
- Liver cirrhosis
- Infections e.g. EBV
Outline some functions of the spleen
- Filter blood
- Hematopoiesis (RBCs +WCC)
- Immunological function
RBCs:
- Red blood cell and platelet storage
- Recycle iron
WCC:
- Produce antibodies
