Haematology Flashcards
1
Q
What is Essential Thrombocytopenia (ET)?
A
A chronic myeloproliferative disorder characterised by sustained dysregulation of megakaryocytic formation resulting in increased levels of circulating platelets.
Usually identified on routine blood test.
2
Q
What are the features of ET?
A
Asymptomatic
Erythromyalgia (burning sensation in peripheries)
Arterial/venous thrombosis
Headaches
Increased risk of miscarriage/MI/stroke
Dizziness/paraesthesia
Hepatomegaly
Haemorrhage
Lived reticularis
50-70yo
Female
Priapism
Syncope and seizures
3
Q
What are the laboratory features for ET?
A
FBC with differential (platelets >450x10^9)
Bone marrow biopsy (large megakaryocytes)
Peripheral smear
Genetic testing (JAK2 mutation)
CRP/ESR
Serum ferritin
LDH (normal)
Hb normal
4
Q
What are the risk factors for ET?
A
Genetic mutations
- JAK2 (most common, increased risk of thrombosis)
- CALR
- MPL
Normally they kidneys and liver makes thrombopoietin which acts on haematopoietic stem cells. This activates JAK2 which causes proliferation to megakaryocytes and therefore platelets.
When mutated this pathway is always on.
5
Q
What are the differentials for ET?
A
Infection
Tissue injury
Acute/chronic inflammation (IBD/RA)
Cancer
Haemorrhage
Other myeloproliferative condition
Iron deficiency
Redistribution of platelets (post-splenectomy/hyposplenism)
6
Q
What is the management for ET?
A
Low risk
- Modify comorbidities
- Aspirin (anti platelet to prevent clot development)
High risk
- Chemotherapy (hydroxycarbamine/interferon alpha)
- Plasmapheresis
- Give allopurinol after treatment due to increased cell turnover and high levels of uric acid
7
Q
What are the side effects of hydroxycarbamine?
A
Mouth & skin ulcers (give B12/folate)
Poor wound healing (switch to interferon if due operation)
8
Q
What is the MOA of aspirin?
A
Irreversibly inhibits cyclo-oxygenase (COX1 inhibitor) and blocks the production of thromboxane.
9
Q
What is the follow up for ET?
A
Asymptomatic: blood counts every 3 months
After chemo once stable: haemogram and platelets every 3-4 months
10
Q
What is the prognosis for ET?
A
Normal life expectancy
Development to AML and myelofibrosis is rare
11
Q
What are the complications of ET?
A
AML
Myelofibrosis
Arterial and venous thrombosis
Haemorrhage (acquired VWD)- seen in cases of really bad thrombocytosis
Spontaneous abortion/IUD/IUGR
12
Q
What is polycythaemia vera (PCV)?
A
Philadelphia chromosome negative myeloproliferative neoplasm. Clonal haematopoietic disorder characterised by erythrocytosis, and often thrombocytosis, leucocytosis and splenomegaly.
Increased risk of bleeding and thrombosis.
13
Q
What are the clinical features of PCV?
A
Aquatic pruritus (due to increased basophils/mast cells releasing histamine)
Plethoric complexion
Thromboembolism (DVT/Stroke/MI/Budd-Chiari Syndrome: liver veins blocked by clots)
Hyperviscosity symptoms (dizziness/headache/visual disturbances/myalgia/fatigue)
Splenomegaly (excess RBCs build up in spleen)
Burning peripheries
Gout/kidney stones (increased uric acid levels from increased cell turnover)
Bruising
Hyperhydrosis
14
Q
What are the investigations for PCV?
A
FBC with differential
- Hct >0.52 (males) >0.48 (females) (Haematocrit is the volume of blood of total blood volume made up of erythrocytes, normally 0.45)
- Raised Hb, raised WCC, raised platelets
Serum EPO
Serum ferritin
Renal and liver function
Genetic testing (JAK2 mutation)
(You get microcytic erythrocytes in PCV, however the Hb is not reduced)
15
Q
What are the differentials for PCV?
A
Relative
- dehydration
- alcohol excess
- diuretics
Primary
- PCV
Secondary
- Central hypoxia
- Renal hypoxia
- Hepatocellular carcinoma
- Renal cell carcinoma
- Uterine tumours
- Phaechromocytoma
- Wilm’s tumour
(Ectopic EPO)
16
Q
What are the risk factors for PCV?
A
JAK2 mutation
Age >40 (median age 60)
17
Q
How do you manage PCV?
A
Venesection (if >5x per year, other treatment is required)
Aspirin 75mg daily
Anticoagulation if thrombus already present (rivaroxaban)
Chemotherapy (interferon/hydroxycarbimide)
Antihistamine for pruritus (cetirizine: non-sedating, chlorphenamine: sedating)
18
Q
What are the complications of PCV?
A
AML
Myelofibrosis (spent phase)
Haemorrhage
Thrombosis
Treatment related leukaemia
Pruritus
19
Q
How do you follow up a patient with PCV?
A
Continuous blood monitoring
Chemo: every 1-2 weeks until stable, then every 3-6 months
Monitor complications
20
Q
What is the prognosis of PCV?
A
Normal life expectancy.
Risk of development to AML/myelofibrosis/severe thrombosis
Deaths are usually from cardiovascular complications.
21
Q
What is the spent phase of PCV?
A
Normally the kidneys produce EPO which bind to the JAK2 gene on haemaotpoeitic stem cells.
Mutation means that JAK2 is always activated. Cells divide in absence of EPO.
Mutated cels proliferate and become the predominant haematopoietic stem cells in marrow.
Eventually these cells die out and form scar tissue so marrow can no longer produce blood cells: anaemia, thrombocytopenia, leukopenia= MYELOFIBROSIS (requires blood transfusion)
22
Q
What is myelofibrosis?
A
Myeloproliferative disorder
Abnormal production of WBC, RBCs and platelets and associated marrow fibrosis with extramedullary haematopoiesis.
Hyperplasia of abnormal megakaryocytes. Release platelet derived fibroblast growth factor which stimulates fibroblasts (connective tissue cells)
23
Q
What are the risk factors for myelofibrosis?
A
Radiation exposure
Industrial solvent exposure
Age >65
24
Q
What are the classifications of myelofibrosis?
A
Primary
- Mutation in the JAKSTAT pathway
- Results in rapid cell division which fills up the bone marrow
- Mostly megakaryocytes
Secondary
- PCV
- ET
25
What are the diagnostic features of myelofibrosis?
Constitutional symptoms (low grade fever, night sweats, fatigue, cachexia, pruritus, weight loss)
Splenomegaly
Hepatomegaly
Signs of extramedullary haematopoiesis
Anaemia
Bone pain
26
What are the differentials for myelofibrosis?
PCV
ET
TB
Myelodysplastic syndrome
CML
Lymphoma
27
How do you investigate myelofibrosis?
FBC with differential (anaemia, high WCC early disease, late disease pancytopenia)
Peripheral blood smear (tear drop poikilocytes)
Bone marrow aspiration (dry tap)
Bone marrow biopsy (trephine)
High urate and LDH due to increased cell turnover
28
How do you treat myelofibrosis?
Ruxolitinib: inhibits JAKSTAT pathway (helps with constitutional symptoms and decreases spleen size) as it targets JAK1/3 pathways also so helps with B symptoms.
Anaemia: EPO
Pancytopenia: Blood transfusion
Haematopoietic stem cell transplant is a potential cure
29
What are the different types of myeloproliferative neoplasms?
ET
PCV
Myelofibrosis
CML
30
What are some neoplastic causes of lymphadenopathy?
Lymphoma
Leukaemia
31
What are some infective causes of lymphadenopathy?
EBV
HIV
TB
Eczema with secondary infection
Rubella
CMV
Toxoplasmosis
Roseola Infantum (HHV6)
32
What are some other causes of lymphadenopathy?
Autoimmune disease (SLE/RA/sarcoidosis)
Graft vs Host disease
Phenytoin
Allopurinol
Isoniazid
33
How does blood enter the spleen and pass through it?
Enters via the splenic artery.
RBCs pass through the red pulp.
WBCs and plasma pass through the white pulp.
34
What are the functions of the spleen?
Blood pooling (source of blood in haemorrhage)
Sequestration and phagocytosis (removes defective/old RBCs)
Immunological (T & B cells)
Extramedullary haematopoiesis
35
What are some causes of hyposplenism?
Splenectomy (trauma/cancer)
GI conditions (UC/Crohn's/Coeliac)
Autoimmune conditions (SLE/RA/Hashimoto's)
Sickle cell disease (multiple infarcts and fibrosis)
36
What do you see on a blood film for a patient with hyposplenism?
Howell-Jolly Bodies
- include DNA remnants
37
What are some causes of massive splenomegaly?
Malaria
Schistiomiasis
CML
Myelofibrosis
Risk of rupture as the spleen is not protected by the rib cage.
38
What are some causes of moderate splenomegaly?
Liver cirrhosis with portal HTN
Glandular fever
Leukaemia
Lymphoma
Myeloproliferative disorders
39
What are some causes of mild splenomegaly?
Infective hepatitis
Endocarditis
Infiltrative disorders (sarcoidosis)
Autoimmune disease (SLE/ITP)
40
What do you need to ensure if a patient has had a splenectomy?
Prophylactic antibiotics to protect against encapsulated bacteria (H.Influenza/Strep.Pneumonia/Meningococcus)
Amoxicillin/clarithromycin
41
What are myelodysplastic syndromes?
A group of clonal stem cell disorders characterised by ineffective and dysplastic haematopoiesis resulting in 1 or more cytopenias and a varying predilection to develop AML.
Characterised by <20% blast cells.
42
What is the pathophysiology of myelodysplastic syndromes?
Damaged haemotpoietic stem cells divide and produce immature cells called blasts.
These cannot mature any further and remain as blasts.
These usually die in the marrow or soon after leaving.
Eventually these immature cells fill the bone marrow.
Primary= unknown
Secondary= chemo/radiotherapy
43
What are the risk factors for myelodysplatic syndromes?
Alkylating agents
Topoisomerase inhibitors
Tobacco
Benzene
Previous haematopoietic stem cell transplant
Ionising radiation
Age >70
Aplastic anaemia
Trisomy 21
44
What are the diagnostic features of myelodysplastic syndromes?
Old age
Asymptomatic
Pallor
Fatigue
Exercise intolerance
RBC reduction: anaemia
WBC reduction: bacterial and fungal infections
Platelet reduction: bruising
45
What are the differentials for myelodysplastic syndromes?
Aplastic anaemia
HIV infection
AML
B12 deficiency anaemia
Autoimmune conditions (ITP)
Myelofibrosis
Bone marrow toxicity
Heavy metal poisoning
46
What investigations would you do if you suspect myelodysplastic syndrome?
FBC with differential
Peripheral blood smear
Bone marrow biopsy and aspiration
Chromosomal analysis
47
How do you treat myelodysplastic syndrome?
Supportive
- Abx
- Blood transfusions (platelets/RBCs)
Low risk
- EPO
- Immunosuppressants
- If have 5q- mutation: lenalidomide
High risk
- Hypomethylating agents (azacitidine)
- Bone marrow transplant (only cure)
48
What are the complications of myelodysplastic syndromes?
AML (40-50%)
Infection
Haemorrhage
Iron overload due to repeat transfusions (treat with iron chelating drug: deferasirox)
49
What is Hodgkin Lymphoma?
Haematological malignancy of mature B cells characterised by the presence of Hodgkin & Reed Sternberg cells.
Uncommon.
Better prognosis.
Most commonly presents with painless cervical/supra-clavicular lymphadenopathy.
50
What are the risk factors for Hodgkin lymphoma?
EBV
FHx
Young person from high socioeconomic background
HLA type
Jewish
Male
Bimodal distribution
51
What are the features of Hodgkin lymphoma?
Night sweats
Painless lymphadenopathy
Weight loss
Fever
Dyspnoea
Cough
Chest pain
Abdominal pain
Pruritus
Superior vena cava syndrome
Alcohol induced pain at sites
Tonsillar enlargement
Hepato/splenomegaly
52
What are the investigations for Hodgkin lymphoma?
FBC with differential (bone marrow involvement)
Peripheral blood smear
Excisional lymph node biopsy
CXR (mediastinal mass)
ESR (prognostic factor)
PET CT (Staging)
Metabolic panel (prior to starting treatment)
Immunohistochemistry (CD15+, CD30+)
53
How do you stage Hodgkin lymphoma?
Ann Arbor Staging
1- 1 lymph node region
2- 2 or more lymph node regions involved on one side of the diaphragm
3- Nodes involved both side of the diaphragm
4- Extra-nodal involvement
54
How do you treat Hodgkin lymphoma?
Watch & Wait
Chemo/radiotherapy
Stem cell transplant if bone marrow is involved
55
What are some differentials for Hodgkin Lymphoma?
Non-Hodgkin Lymphoma
Glandular fever
Reactive lymph nodes
Metastases (breast/H&N)
56
What are the complications following Hodgkin Lymphoma?
Chemo/radio related malignancies.
Chemo/radio related cardiac disease.
Radiotherapy induced thyroid disease.
Pulmonary toxicity.
Ovarian/testicular dysfunction.
57
How do you monitor someone who has had Hodgkin Lymphoma?
FBC with differential (bone marrow suppression after treatment)
TFTs annually
Breast screening 5-10 years after treatment (or at age 40)
58
What is Non-Hodgkin Lymphoma?
Heterogenous group of malignancies of the lymphoid system.
More common (6th most common in UK)
Absence of Reed-Sternberg cells.
Extra-nodal involvement is more common.
CD20+
59
What is the pathophysiology of Non-Hodgkin Lymphoma?
Genetic mutation in lymphocytes causing it to divide uncontrollably becoming neoplastic.
Usually in the lymphnodes but can be extra nodal.
Can spread via the blood to other areas:
- GI system: bowel obstruction
- Bone marrow: suppression
- Spine: cord compression
60
What are the risk factors for Non-Hodgkin Lymphoma?
EBV
Male
>50 yo
Breast implants
Organ transplants
HIV
RA/SLE
Sjogren's Syndrome
Coeliac
H Pylori
Pesticides
Kleinfelter syndrome
61
What are the features of Non-Hodgkin Lymphoma?
Night sweats
Weight loss
Painless lymphadenopathy
Unexplained fever
Fatigue/malaise
Abdo pain
SOB
Cough
GI obstruction
Spinal cord compression
Bone marrow suppression signs
Hepato/splenomegaly
Headache
Dizziness
Ataxia
Pallor
Jaundice
62
What investigations do you do for Non-Hodgkin Lymphoma?
FBC with differential
Lymphnode/skin/marrow biopsy
Peripheral blood smear
Raised LDH
LFTs (liver involvement)
PET CT (staging)
HIV testing
63
What is the treatment for Non-Hodgkin Lymphoma?
Watch and wait if asymptomatic and low grade
Chemo/radiotherapy
CD20+= rituximab (complement mediated lysis)
64
What are the complications of Non-Hodgkin Lymphoma?
Tumour Lysis Syndrome
Radiotherapy complications
Chemotherapy complications
Bone marrow transplant complications
65
What is the difference between lymphoma and leukaemia?
Leukaemia originates in the bone marrow.
Lymphoma originates in the lymphatic system.
66
What are the types of indolent Non-Hodgkin Lymphoma (B cell)?
Follicular
- Common
- Translocation 14 & 18
Marginal (MALT: Mucosa Associated Lymphoid Tissue)
- usually in the lining of the stomach
- associated with chronic inflammation of stomach (H. Pylori)
Lymphoplasmacytic
- Involves spleen, marrow and nodes
- Produces M proteins (IgM) which cause hyper viscosity= Waldenstroms Macroglobulinaemia
67
What are the types of aggressive Non-Hodgkin Lymphoma (B cell)?
Burkitt
- Highly aggressive
- In Africa: associated with EBV and involvement of the jaw
- Outside Africa: less associated with EBV, associated with involvement of the GI tract (ileocaecal junction)
- Chromosomal translocation 8 & 14
Mantle
- Chromosomal translocation 11 & 14
Diffuse large B cell
- Most common
68
What are the types of T cell Non-Hodgkin Lymphoma?
Adult T cell
- Caused by HTLV
- Can get leukocytes into the blood
- Also called Adult T cell leukaemia
Mycosis Fungiodes
- T cell lymphoma of the skin
- Can cause Sezary syndrome (erythroderma)
- CD4+
69
What is MGUS (Monoclonal Gammopathy of Undetermined Significance)?
Asymptomatic premalignant disorder associated with risk of developing Multiple Myeloma or related plasma cell proliferative malignancies.
Patients with higher levels of M protein (Non-IgG) are at increased risk of developing MM.
70
What is the criteria for diagnosis of MGUS?
M protein (IgM)
- <30g/L serum
- <500 mg/24hr urine
<10% plasma cells in bone marrow
(Only indicated to do it M protein >15g/L)
Absence of lytic bone lesions, renal insufficiency, amyloidosis, hypercalcaemia and anaemia
71
What are the diagnostic features of MGUS?
>50
Male
African
Asymptomatic
FHx
Peripheral neuropathy
Recent infections/immunocompromised
Pesticide/radiation exposure
72
What investigations do you for for MGUS?
Electrophoresis and immunofixation & serum immunoglobulins (repeated after 6 months, then annually)
FBC with differential (normal)
Serum Ca+
Serum creatinine
Whole body low dose CT
Urinalysis and 24 hours urine collection with electrophoresis and immunofixation
Serum free light chain assay (abnormal suggests risk factor for MM, normal is 0.26-1.65)
73
How do you treat MGUS?
Counselling
Routine blood tests annually (Hb, Ca, renal function)
Check levels of M protein.
Followed up annually to check for complications (renal failure/pathological fractures)
74
What is Benign Polyclonal Hypergammaglobulinaemia (BPH)?
Results from an infection/autoimmune condition/malignancy and causes an increase in immunoglobulins in your blood (usually IgG)
75
What is the pathophysiology of BPH?
Immune system dysfunction.
Overall the immune activity is reduced.
76
What are the symptoms of BPH?
Fatigue
Stiffness
Swollen lymph nodes
Inflammation
Increased gammaglobulins
Decreased levels of certain antibodies: increased levels of infections, anaemia and autoimmune conditions
77
How do you treat BPH?
Treat underlying cause.
Rarely you require immunoglobulin replacement therapy.
78
What is amyloidosis?
Deposits of amyloid protein in tissues or organs.
(Extracellular deposition of insoluble fibrillar proteins)
Any specimen that binds Congo red and demonstrates green birefringence when viewed under polarised light is amyloid protein.
79
What is the pathophysiology of amyloidosis?
Deposition causes tissue and organ damage.
Most common form: Immune light chain amyloidosis (clonal plasma cells produce abnormal immunological light chains, larger than normal so build up)
80
What are the risk factors for amyloidosis?
Chronic infections (DM, UTI, osteomyelitis)
MGUS
IBD
Arthritis
Ankylosing spondylitis
Castelman's Disease
Familial periodic fever syndrome
81
What are the features of amyloidosis?
Distended JVP (restrictive cardiomyopathy)
Extremity oedema (hypoalbuminaemia due to nephrotic syndrome)
Fatigue
Weight loss >9kg
Dyspnoea on exertion (cardiomyopathy)
Claudication
Peripheral and central neuropathy
Shoulder pad sign
N&V
Abdominal pain
Muscle weakness (hypertrophy when infiltrated and atrophy when there is vascular occlusion)
Periorbital purpura/petechial eyelids
Macroglossia
Hepatomegaly
Orthostatic hypotension
Submandibular salivary gland enlargement
Carpal tunnel
82
How do you investigate for amyloidosis?
Serum immunofixation
Urine immunofixation
Immunological free serum light chain assay
Metabolic panel
83
What is the treatment for amyloidosis?
Manage complications
High dose autologous (patients' own stem cells) stem cell transplant
84
What are the signs of poor prognosis for Hodgkin's lymphoma?
B symptoms
Increasing age
Male sex
Stage 4 disease
Lymphocyte depleted subtype
85
How do you treat someone with tumour lysis syndrome?
IV allopurinol
or
IV rasburicase
Usually given prophylactically
86
How do you treat someone with tumour lysis syndrome?
IV allopurinol
or
IV rasburicase
Usually given prophylactically
87
What is the reversal agent for dabigatran?
IV Idarucizumab (reverses within minutes)
88
What do you expect to see on a FBC for someone who drinks excess alcohol?
Macrocytic anaemia
Thrombocytopenia
88
What do you expect to see on a FBC for someone who drinks excess alcohol?
Macrocytic anaemia
Thrombocytopenia
89
What type of anaemia does methotrexate cause?
Megaloblastic microcytic anaemia due to secondary folate deficiency
90
What type of anaemia does methotrexate cause?
Megaloblastic microcytic anaemia due to secondary folate deficiency
91
What is the most common organisms causing neutropenic sepsis?
Staphylococcus epidermis
(gram positive)
91
What is the most common organisms causing neutropenic sepsis?
Staphylococcus epidermis
(gram positive)
92
How long prior to an operation should the COCP be stopped?
4 weeks before surgery and advise on alternate contraception methods.
93
What is CLL?
Chronic Lymphocytic Leukaemia
Lymphoproliferative disorder where monoclonal B lymphocytes (>5x10^9) are predominantly found in peripheral blood.
94
What is the pathophysiology of CLL?
Cells mature partially (in acute leukaemia, the cells do not mature at all)
These cells do not die when they should, causing too many of these premature cells which fill up the marrow and spill out into blood.
Healthy cells get crowded out= cytopenias
These premature cells can move to the lymphnodes causing lymphadenopathy and can eventually cause lymphomas.
95
What can CLL lead to?
Mature CLL (Lymphocytic Lymphoma)
> Richter transformation: transform to high grade non-hodgkin lymphoma
Autoimmune haemolytic anaemia
Hypogammaglobulinaemia
96
What are the risk factors for CLL?
>60
Male
White ethnicity
FHx
97
What are the symptoms of CLL?
Fatigue (anaemia)
Bleeding (thrombocytopenia)
Infections (leukopenia)
Lymphadenopathy
SOB
98
What investigations would you do to investigate for CLL?
WBC with differential (Lymphocytosis >5x10^9), these are weak so cannot fight infection
Blood film (smudge cells- damage to lymphocytes during slide prep)
Hb (anaemia indicates poor prognosis)
Platelet count (thrombocytopenia indicates poor prognosis)
Flow cytometry (CD23+, CD19+, CD5+)
Genetic testing
99
How do you treat CLL?
Watch and wait
Chemotherapy
Stem cell transplant
Bone marrow transplant
Treatment needed when you have anaemia/thrombocytopenia/painful glands/fever/weight loss/WBCs multiplying rapidly
100
What are the complications of CLL?
2nd malignancies
Treatment induced CMV reactivation
Tumour lysis syndrome
ITP
Chemo induced neutropenic fever
101
What is CML?
Chronic Myeloid Leukaemia
Malignant disorder of the haemaotpoietic stem cell that results in marked myeloid hyperplasia of the bine marrow
102
What is the pathophysiology of CML?
Cells mature only partially.
These premature cells do not die and build up in the bone marrow until they spill out into the blood.
Healthy cells get crowded out resulting in cytopenias.
Philadelphia chromosome (translocation between chromosome 9 & 22)
Now on chromosome 22 there is a BCR-ABL gene: this activates tyrosine kinases which switch on cell division.
Premature cells move to liver and spleen causing swelling.
As myeloid cells divide quicker than normal there is an increased risk of mutation (blast phase)
103
What are the different phases of CML?
Chronic
- stable, developing slowly, no symptoms
- bone marrow tests show mature functioning cells with some blast cells
Accelerated
- more symptoms, high number of blast cells
Blast
- transforms into acute leukaemia
104
What are the risk factors for CML?
65-74 yo
Ionising radiation
Male
105
What are the symptoms of CML?
Fatigue
Bleeding
Infection
Hepatosplenomegaly (feeling of fullness)
SOB
Epistaxis
Arthralgia
WL
Sternal tenderness
Sweating excessively
Fever
Pallor
Bruising
Retinal haemorrhage
106
What investigations would you do for CML?
FBC with differential (high WBC, anaemia, thrombocytopenia)
Blood film (increased granulocytes and monocytes)
Bone marrow biopsy
Cytogenetic studies
FISH
Genetic testing (Philadelphia chromosome)
107
How do you treat CML?
Tyrosine kinase inhibitor (imatinib)
Disease progression usually happens within 2-3 years after therapy
Chemotherapy
Stem cell transplant
Bone marrow transplant
108
What is AML?
Acute Myeloid Leukaemia.
Life threatening haematological malignancy caused by clinical expansion of myeloid blasts in the bone marrow, blood or peripheral blood.
Presence of >/=20% of blast cells (blast cells are large with little cytoplasm) in marrow/blood.
109
What is the pathophysiology of AML?
Primary disease or secondary transformation from a myeloproliferative disorder.
Down's syndrome is associated with AML/CML
110
What are the risk factors for AML?
>65yo
Previous chemo
Previous haematological disorders
Inherited genetic conditions
Males
Karyotype abnormalities
Radiation exposure
Benzene exposure
111
What are the diagnostic features of AML?
Pallor
Weakness
Ecchymoses/petechiae
Fatigue
Dizziness
Palpitations
Dyspnoea
Bone pain
Infections/fever
Lymphadenopathy
Hepatosplenomegaly
Swelling of gums
112
What are the poor prognostic factors for AML?
>60
>20% blasts after first course of chemo
Deletions of chromosome 5/7
113
What investigations would you do for AML?
FBC with differential (anaemia/neutropenia/thrombocytopenia)
Peripheral blood smear (>/=20% blast cells & AUER RODS)
Bone marrow biopsy
Coagulation panel (DIC)
Serum electrolytes and uric acid (tumour lysis)
Renal function & LFTs (baseline)
LDH
Genetic studies
114
How do you treat AML?
Dose intense chemotherapy
Targeted therapy (biological)
Stem cell/bone marrow transplant
Achieve remission (<5% blasts, neutrophil and platelet normal, no auer rods)
High incidence of relapse
115
What is ALL?
Acute Lymphocytic Leukaemia
Malignant clonal disease that develops when a lymphoid progenitor cell becomes genetically altered and undergoes uncontrolled proliferation
116
What are the poor prognostic factors for AML?
Age <2 or >10
WBC >20x10 at diagnosis
T/B cell markers
Non-caucasian
Male
117
What is the pathophysiology of ALL?
Chromosomal translocation (12/21 or 9/22- philadelphia)
or
Abnormal chromosome number
118
Is lymphadenopathy and hepatosplenomegaly more common in ALL or AML?
ALL
119
What are the risk factors for ALL?
Children <5
Mid-late 30's
Mid 80's
Genetics
FHx
Viruses
Smoking
Radiation exposure
Treatment with chemo
Male
White
Poor maternal diet
120
How do you investigate for ALL?
FBC with differential
Peripheral blood smear (>20% lymphoblasts)
Serum electrolytes
Serum uric acid
Renal/liver function
LDH
Coagulation profile
Bone marrow aspiration and trephine biopsy
Baseline virology
Cytogenetics (CD 10+)
Immunophenotyping
121
What are the diagnostic factors of ALL?
Lymphadenopathy
Hepatosplenomegaly
Pallor, ecchymoses, petechiae
Fever
Fatigue, dizziness, palpitations, dyspnoea
Bruising, epistaxis, menorrhagia
Papilloedema, nuchal rigidity, meningismus
Mediastinal mass
Pleural effusion
Skin infiltrations
Abdominal/bone pain
Renal/testicular enlargement
Neurological signs
122
What is the treatment for ALL?
Chemotherapy (does not cross BBB/blood testicular barrier so need prophylactic injections into scrotum and CSF)
Biological therapy
Stem cell transplant
Bone marrow transplant
123
What is the difference in presentation between T-ALL and B-ALL?
T-ALL: mediastinal mass (thymus)
- stridor
- wheeze
- pericardial effusion
- superior vena cava syndrome
B-ALL: abdominal masses
124
What is multiple myeloma?
Clonal proliferation of plasma cells in the bone marrow associated with monoclonal Ab (M protein/paraprotein) component in the serum/urine.
Chronic relapsing remitting malignancy which is incurable.
125
What are the risk factors for MM?
MGUS
70 yo
Black
FHx
Radiation/petroleum exposure
Abnormal free light chain ratio (amyloidosis)
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What are the diagnostic factors of MM?
Anaemia
Bone pain (lytic lesions)
MGUS
Infections (decreased production of normal immunoglobulins)
Fatigue
Renal impairment (immunoglobulins)
Constipation/confused (hypercalcaemia)
Renal failure
Anaemia
Back pain
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What is the diagnostic criteria for MM?
1 major & 1 minor
OR
3 minor
Major:
- plasmacytoma
- 30% plasma cells in marrow
- elevated M protein in blood/urine
Minor:
- 10-30% plasma cells in marrow
- minor elevation of M protein
- osteolytic lesions
- low levels of Abs in blood
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What investigations would you do for MM?
Peripheral blood film (ROULEAUX FORMATION)
Serum/urine protein electrophoresis (Bence- Jones protein): serum >/= 30g/L, urine >/= 500mg/day
Serum/urine immunofixation
Whole body low dose CT (osteolytic lesions/fractures)
Bone marrow biopsy and aspirate
Serum Ca+
FBC (normocytic anaemia)
Creatinine/urea
Serum albumin and beta-2-microglobulin (prognostic)
Plasma viscosity
ESR
Serum free light chain assay
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What is the management of MM?
Manage and control symptoms
Reduce complications
Autologous stem cell transplant after high dose chemotherapy
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What is Beta-thalassaemia major?
Absence of beta globulin chains (chromosome 11)
131
What are the features of Beta-thalassaemia major/
Presents in 1st year of life with failure to thrive & hepatosplenomegaly
Frontal bossing
Maxillary overgrowth
Microcytic anaemia
HbA2 & HbF raised
HbA absent
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How do you manage Beta-thalassaemia major?
Repeated transfusion
(can lead to iron overload and organ failure so iron chelation therapy is important)
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What is the inheritance pattern of Beta thalassaemia?
Autosomal recessive
134
What is beta thalassaemia trait?
Autosomal recessive condition characterised by mild hypo chromic, microcytic anaemia.
One functioning copy and one dysfunctional copy of the beta globin gene
Usually asymptomatic
135
What are the features of beta thalassaemia trait?
HbA2 raised
Mild hypochromic, microcytic anaemia (microcytosis is disproportionate to anaemia)
136
What are the features of beta thalassaemia trait?
HbA2 raised
Mild hypochromic, microcytic anaemia (microcytosis is disproportionate to anaemia)
