Blood cancers + bleeding disorders Flashcards
Cancer and bleeding disorders
1
Q
What are the two categories of haematological stem cells?
A
Myeloid stem cell
Lymphoid stem cell
2
Q
What cells do myeloid stem cells differentiate into?
A
Erythrocytes
Megakaryocytes –> platelets
Myeloblasts -> granulocytes (eosinophil/basophil/neutrophil)
Monoblasts –> monocytes
3
Q
What cells do lymphoid stem cells differentiate into?
A
Lymphoblasts –> Lymphocytes + NK cells
4
Q
Define leukaemia
A
A group of blood cancers originating in the bone marrow and resulting in high numbers of abnormal blood cells (blasts)
Dysfunctional cells crowd out the bone marrow and prevent the formation of other important blood cells
5
Q
What are the complications of bone marrow failure?
A
Anaemia- fatigue, pallor, breathlessness
Neutropenia- recurrent infections
Thrombocytopenia- bleeding and easy bruising
6
Q
What is AML?
A
Rapid proliferation of myelobast cells
–> features of neutropenia, anaemia and thrombocytopenia
7
Q
What are the risk factors for AML?
A
Down’s
Irradiation
Anti-cancer drugs
Increasing incidence with age (average = 68yr)
8
Q
What are the symptoms of AML?
A
Features of bone marrow failure:
- fatigue
- pallor
- breathlessness
- recurrent infx
- bleeding
- bruising
Tissue infiltration:
- swollen gums
- mild splenomegaly
9
Q
What are the investigations for AML? What would you see?
A
Blood film/cytology: AUER RODS
Immunohistochemistry: myeloblast granules are positive for Sudan Black staining
10
Q
What is promyelocytic leukaemia?
A
A hyper aggressive subtype of AML
Due to genetic translocation t(15;17)
Associated with DIC
11
Q
What is ALL?
A
Uncontrolled proliferation of lymphoblasts- most commonly B CELLS
–> features of neutropenia, anaemia and thrombocytopenia
12
Q
What are the clinical features of ALL?
A
FEATURES OF BM FAILURE
- Pallor
- Bleeding
- Infections
TISSUE INFILTRATION
- Hepatosplenomegaly
- Lymphadenopathy
- Swollen testes
- Thymic mass (if T cell ALL)
- Tender bones
B SYMPTOMS- FLAWS
13
Q
What are the investigations for ALL?
A
Bloods: very raised WCC, low Hb, low Plt
Bone marrow biopsy: >20% lymphoblast
14
Q
What is CLL?
A
Progressive accumulation of functionally incompetent lymphocytes (unable to undergo apoptosis)
-> OCCASIONAL features of bone marrow failure, hypermetabolism
Caused by a failure of apoptosis
15
Q
What are the clinical features of CLL?
A
Asymptomatic in 50%
Occasional non-tender lymphadenopathy (small lymphocytic lymphoma).
Occasional bone marrow failure symptoms.
Usually diagnosed by routine blood test – lymphocytosis
SMUDGE CELLS
16
Q
What are the investigations leukaemia?
A
Bloods: FBC, LDH, Blood Smear
Bone Marrow Aspirate- DIAGNOSTIC
Immunophenotyping- involves looking at cell markers and antigens to identify cell lineage
CXR- look for mediastinal lymphadenopathy
17
Q
What is Evan’s syndrome?
A
When CLL is associated with autoimmune thrombocytopenia and anaemia
18
Q
What is Richter’s syndrome?
A
When CLL develops into an agressive NHL
19
Q
What is CML?
A
Hyperproliferation of granulocyte precursors in the BM but with a slower progression than AML
-> features of bone marrow failure, hypermetabolism and hyperviscosity
20
Q
Pathophysiology of CML
A
PHILADELPHIA CHROMOSOME (>80% cases)
t(9;22) forming BCR-ABL
Forms a continuously active TK receptor -> continuous cell proliferation
21
Q
What are the clinical features of CML?
A
50% are asymptomatic
90% MASSIVE SPLENOMEGALY
GOUT
HYPERMETABOLIC SYMPTOMS:
- weight loss
- malaise
- sweating
BM FAILURE:
- pallor
- bleeding
- infections
HYPERVISCOCITY SYMPTOMS:
- thrombotic events
- headaches
- visual disturbance
22
Q
What are the investigations for CML?
A
Bloods: WCC ofter >100
Cytogenetics: look for t(9;22)
No XS blasts (<5%)
-can develop into accelerated phase (10-19% blasts)
-can develop into acute leukaemia phase (>20% blasts)
23
Q
What is Hodgkin’s lymphoma?
A
Malignant proliferation of lymphocytes which accumulate in the lymph nodes
24
Q
What is the epidemiology/RF for HL?
A
Bimodal age distribution – peaks between 20-30 and >50
50% associated with EBV
25
What are the clinical features of HL?
PAINLESS ENLARGING MASS
- often in neck (sometimes axilla/groin)
- painful after alcohol consumption
B SYMPTOMS: fever, night sweats, weight loss
Non-tender rubbery LYMPHADENOPATHY with splenomegaly +/- hepatomegaly
26
What are the investigations for HL?
Lymph node biopsy under microscopy- Reed-Sternberg cells
Histopathology- Owl's eyes
Ann Arbour staging
27
What is non-Hodgkin's lymphoma? State the cell types involved
Malignancy of lymphoid cells in lymph nodes without Reed-Sternberg cells
85% are B cells
15% are T/NK cells
28
NHL associations
```
EBV
HIV
SLE
Sjogren's
Increased incidence with age
```
29
What are the clinical features of NHL?
- Painless enlarging mass in neck, axilla or groin
- B symptoms (less common than HL)
- Organ involvement – skin rashes, headache, hepatosplenomegaly (more common than HL)
30
What are the investigations for NHL?
Lymph node biopsy- NO Reed-Sternberg cells
| - Ann Arbour staging
31
Name a subtype of NHL. What are its associations?
Burkitt's lymphoma- cancer of the B lymphocytes in the germinal centres of the lymphatic system
Strong association with EBV infection
32
What are the characteristics of Burkitt's lymphoma?
- African child- chronic malaria + HIV reduce resistance to EBV infection
- Rapidly enlarging lymph node in the jaw
- Under microscopy- starry sky appearance
33
What is multiple myeloma?
A haematological malignancy characterised by proliferation of plasma cells and the production of monoclonal antibodies (usually IgG or IgA)
34
What are the risk factors for MM?
```
Ionising radiation
HIV
Agricultural work, occupational chemical exposure (eg pesticides)
>70
Afro-Caribbean
```
35
What is MGUS?
Monoclonal gammopathy of undetermined significance
Pre-malignant condition with accumulation of some monoclonal plasma cells.
1% acquire additional mutations -> multiple myeloma.
Absent CRAB features.
36
What are the CRAB features of MM?
Calcium
- hypercalcaemia: stones bones moans groans
Renal impairment (20%)
- Ig deposits in the kidney
- worse prognosis
Anaemia
- due to marrow infiltration + crowding by plasma cells
- at risk of infections due to low levels of other Ig
Bone lesions
- increased osteoclast activity -> back/rib pain
37
What are the investigations for MM? What would you see?
Bloods
- Raised ESR, CRP, Urea, Cr, Ca. NORMAL ALP.
- Serum monoclonal protein: >30g/L
Blood Film
- Rouleaux Formation
Serum/Urine Electrophoresis
- Bence Jones Proteins
Bone Marrow Aspirate
- Raised Plasma Cells >10%
X-rays
- Assess osteolytic lesions.
38
What are myelodysplastic syndromes?
Group of syndromes where the immature blood cells do not mature normally.
Causes chronic pancytopaenia (anaemia, neutropenia, thrombocytopenia)
39
What are the clinical features of myelodysplastic syndromes?
Features of BM failure
| NO SPLENOMEGALY
40
What are the investigations for myelodysplastic syndromes? What would you see?
Incidental finding on FBC: low Hb, Plt, WCC
| BM biopsy: hypercellular due to ineffective erythropoiesis
41
What pathology can myelodysplastic syndromes develop into?
1/3 can develop into AML
42
What is haemophilia?
Bleeding disorder caused by the inherited deficiency of a clotting factor
Clotting factor disorder = problem with secondary haemostasis = DEEP bleeding presentation
43
What is the genetic pattern for haemophilias?
X-linked recessive inheritance, typically only affects boys
44
What is the factor deficiency for haemophilia A?
Factor VIII- this is more common than B
45
What is the factor deficiency for haemophilia B?
Factor IX
46
What are the risk factors for haemophilia?
FHx
| Ashkenazi Jews
47
How does haemophilia present?
Usually presents early in life or after surgery/trauma.
- Haemarthrosis = bleeding into joints – swollen and painful
- Haematoma = painful bleeding into muscles
- Excessive bruising and haematuria
- Signs of IDA
48
How is haemophilia diagnosed?
Prolonged APTT: factor 8 + 9 are in the intrinsic pathway
Factor assay to confirm diagnosis: which clotting factor is reduced -> distinguish between haemophilia A + B
49
What are the roles of VWF?
vWF mainly has a role in primary haemostasis :
- Platelet Adhesion: Forms bridge between damaged sub-endothelium and platelets, via GP1b receptor.
- Platelet Aggregation: Facilitates platelets binding to each other.
Also a bit in secondary:
- Factor 8 Stabilisation: Binds to Factor 8 and prevents its degradation.
50
What are the 3 types of VWD and what is their inheritance pattern?
Type 1: reduced levels of vWF (AD)
Type 2: defective vWF (AD)
Type 3: complete lack of vWF and highly reduced FVIII
(AR)
51
What is the presentation for vWD?
SUPERFICIAL BLEEDING
- Bruising, epistaxis, menorrhagia
- Prolonged gum bleeding after dental procedures
- Prolonged bleeding from minor wounds
Type 3 is more severe with reduced Factor 8 -> deep bleeding into joints and soft tissues
52
What are the investigations for vWD?
PROLONGED BLEEDING TIME: impaired primary haemostasis
PROLONGED APTT and NORMAL PT: factor 8 reduction
REDUCED vWF – except in Type 2
Normal platelets
53
Define DIC
Generalised activation of the clotting cascade 2/2 underlying pathology e.g. sepsis
54
What causes microangiopathic haemolytic anaemia?
Activation of fibrinolysis -->
| Fibrin strand deposition --> fragmentation of RBCs (like cheesewire)
55
What can trigger DIC?
Sepsis, trauma, obstetric complications, malignancy
56
What are the clinical features of DIC?
Signs of underlying aetiology eg. sepsis --> fever, shock
ACUTE DIC: petechiae, purpura, ecchymoses, epistaxis, mucosal bleeding, haemorrhage, respiratory distress
CHRONIC DIC: signs of venous/arterial thrombosis
57
What are the investigations for DIC? What would you see?
FBC- dec Plt, Hb
Clotting- dec fibrinogen, inc PT/APTT, inc fibrin degradation products
Peripheral blood film: schistocytes (MAHA)
58
A 5 year old boy of Indian ethnic origin presented with lymphadenopathy and a mediastinal mass on CXR.
WBC: 180 x 109/L
Hb: 93 g/L
Plts: 43 x 109/L
Blood film shows blast cells
What is the most likely cause of the mediastinal mass?
```
A. Thymoma
B. Acute myeloid leukaemia
C. Acute lymphoblastic leukaemia
D. Haemorrhage into the mediastinum
E. Pneumonia with leukaemoid reaction
```
C. Acute lymphoblastic leukaemia
The very high WCC in a child means a Dx of leukaemia is almost certain. The low Hb and plts count are the result of bone marrow infiltration. The mediastinal mass is the thymus, which is infiltrated by T lymphoblasts.
59
An 83 year old man with no abnormal physical findings is found to have a high white cell count and high lymphocyte count on a blood test.
A blood film is requested and it is found to have smear cells.
What is the most likely diagnosis?
```
A. Acute lymphoblastic leukaemia
B. Chronic lymphocytic leukaemia
C. HIV infection
D. Infectious mononucleosis
E. Whooping cough
```
B. Chronic lymphocytic leukaemia
60
A 28 year old male presents with a lump in his neck that has been getting bigger over the past month. He decided to come to A&E because last night he went out drinking with his friends and it became very painful. On questioning, he also reveals that he’s lost 4kg in the last few months unintentionally.
What is the most likely diagnosis?
```
A. Acute lymphoblastic leukaemia
B. Hodgkin’s lymphoma
C. Non-Hodgkin’s lymphoma
D. Grave’s disease
E. Burkitt’s lymphoma
```
B. Hodgkin’s lymphoma
61
Which one of the following about myelodysplastic syndromes is true?
A. Myelodysplasia has a bi-modal age distribution
B. There is no good correlation between the severity of the cytopenias and the overall life expectancy
C. White cell function is frequently preserved in MDS
D. One third of MDS patients can be expected to die from leukaemic transformation
E. Bone marrow biopsy will usually reveal a hypocellular BM
D. One third of MDS patients can be expected to die from leukaemic transformation
62
A 1 year old boy presented to A&E department with a swollen right elbow following minor trauma. On examination and radiology there was no evidence of bony injury. He was sent home.
3 days later he was brought back with increased pain and swelling. Joint aspiration yielded haemorrhagic fluid.
A coagulation screen was performed which showed a normal PT and a prolonged APTT of 96 seconds (NR 24-35s). The prolonged APTT was corrected by mixing the infant’s plasma with normal plasma.
What is the most likely diagnosis?
```
A. Disseminated intravascular coagulation
B. Von Willebrand’s disease
C. Haemophilia
D. Autoimmune thrombocytopenia
E. Fracture of the elbow
```
C. Haemophilia
63
A 16 year old boy presents to his GP complaining of nosebleeds and bleeding after brushing his teeth. He is unsure of how long it has been going on for but decided to seek advice after having to continually excuse himself from lessons. On examination you notice he has some skin bruises. A blood test shows a prolonged bleeding time and APTT. Platelet count and PT are normal.
What is the most likely diagnosis?
```
A. Von Willebrand disease
B. Liver disease
C. Disseminated intravascular coagulation
D. Congenital afribrinogenaemia
E. Haemophilia
```
A. Von Willebrand disease
64
A 72 year old man presents with a history of recurrent back pain. The doctor performs several investigations to see whether the underlying problem could be multiple myeloma.
Which of the following is NOT a feature of multiple myeloma?
```
A. Raised creatinine
B. >10% plasma cells in bone marrow aspirate
C. Hypercalcaemia
D. Serum monoclonal protein >30g/L
E. Raised ALP
```
E. Raised ALP
65
```
A 52-year-old male presented with a history of tiredness and frequent infections. On examination, a large spleen was palpable.
The patient was started on chemotherapy, but he is now suffering with gout.
What is the most likely diagnosis?
A. Hodgkin’s Lymphoma
B. Chronic Myeloid Leukaemia
C. Acute Lymphoblastic Leukaemia
D. Non-Hodgkin’s Lymphoma
E. Chronic Lymphocytic Leukaemia
```
A. Hodgkin’s Lymphoma
Reed-Sternberg cells (bi-nucleate lymphocytes) were not present
B. Chronic Myeloid Leukaemia
Large splenomegaly, male, symptoms of anaemia and neutropenia
C. Acute Lymphoblastic Leukaemia
Not an acute picture, older patient
D. Non-Hodgkin’s Lymphoma
No mention of any neck/axilla/groin lumps
E. Chronic Lymphocytic Leukaemia
No mention of smudge cells, large splenomegaly less likely in CLL
66
Chronic vs acute leukaemia
ACUTE
- Rapid increase in immature blood cells which crowd out the bone marrow.
- Abnormal differentiation + excessive proliferation.
- quickly symptomatic
CHRONIC
- Excessive build-up of abnormal but relatively mature white blood cells.
- Normal(ish) differentiation + excessive proliferation.
- may be asymptomatic at first
67
What would you see on cytology of acute promyelocytic leukaemia?
Faggot Cells
| lots of Auer Rods
68
Epidemiology of ALL
Commonest cancer of childhood (75% are under 6)
| - Rest are elderly- most deaths are in elderly
69
RF for ALL
Genetics- inc. Down’s syndrome, neurofibromatosis
Radiation
Influenza
70
How does ALL differ from AML?
ALL = LYMPHADENOPATHY
| AML doesn't usually present with lymph node swelling
71
3 stages of CML?
Chronic phase
Accelerated phase
Blast crisis (basically acute leukaemia)
72
What are the features of CML?
- Hyperviscocity- due to accumulation of RBCs
- BM failure- granulocyte accumulation
- Hypermetabolism- increased myeloblast production
73
complication of CLL
Even though CLL seems like the mildest leukaemia, can transform into the aggressive:
RICHTER'S SYNDROME
74
What would you see on blood film of CLL?
SMEAR/SMUDGE CELLS
- remnants of lymphocytes (no cytoplasm etc.)
- they form because of cancer cells lacking a cytoskeletal protein called vimentin
75
Define lymphoma
A group of blood cancers which develop from lymphocytes and the tumours are mainly found in the lymph nodes
Patients often present with a lump and systemic/B symptoms – fever, weight loss, night sweats
76
What cells are diagnostic of HL?
REED-STERNBERG CELLS
| on lymph node biopsy = bi-nucleate lymphocytes
77
Compare NHL and HL
HL
- Reed-Sternberg Cells
- Skin excoriations
- NeutroPHILIA
NHL
- NO Reed-Sternberg Cells
- Skin rashes e.g. mycosis fungoides
- NeutroPENIA
78
what staging system is used for lymphoma?
Ann Arbor staging system
79
What is tumour lysis syndrome?
Metabolic abnormalities that arise as result of cancer treatment – especially leukaemia and lymphoma
80
Pathophysiology of tumour lysis syndrome- state cause of symptoms
The release of the contents of these cells causes a constellation of symptoms:
- Released phosphate forms calcium phosphate crystals.
- -> KIDNEY FAILURE and hypocalcaemia
- Released potassium causes hyperkalaemia -> ARRYTHMIA
- Released uric acid forms urate crystals -> GOUT
81
How can myelodysplastic syndromes by classified?
```
Primary = intrinsic bone marrow problem
Secondary = previous chemotherapy/radiotherapy
```
82
What are the 5 types of myelodysplasia?
Refractory anaemia
Refractory anaemia with ringed sideroblasts
Refractory anaemia with excess blasts
Refractory anaemia with excess blasts in transformation
Chronic myelomonocytic leukaemia
BLASTS = risk of developing into AML
83
Is myelodysplasia a blood cancer?
Myelodysplasia used to be considered a pre-malignant disease
Nowadays it’s classed as a cancer – it can sometimes develop into AML
84
A 70-year-old male attends a routine GP appointment and mentions that he has been experiencing some back pain. After a series of investigations, a diagnosis of multiple myeloma is made.
Which finding is consistent with his diagnosis?
```
A. Polyclonal Ig light chain in urine
B. Low Hb
C. Tetany
D. High ALP
E. Ringed sideroblasts
```
A. Polyclonal Ig light chain in urine
Bence Jones proteins in the urine are monoclonal Ig light chain
B. Low Hb
Anaemia is the A in CRAB
C. Tetany
Myeloma causes HYPERcalcaemia - tetany indicates hypocalcaemia
D. High ALP
ALP is normal in myeloma
E. Ringed sideroblasts
Not a feature of myeloma – may be present in myelodysplasia
85
State the key outcomes of primary and secondary haemostasis, factors involved and outcome of any disorders
PRIMARY HAEMOSTASIS
- Platelet aggregation and plug formation
- Depends on: platelets and VWF
- Disorders = superficial bleeding
SECONDARY HAEMOSTASIS
- Fibrin formation to stabilise platelet plug
- Depends on: clotting factors (cascade)
- Disorders = deep bleeding and bruising
86
state the 2 main clotting time blood tests and what they tell you about the clotting pathway
APTT = intrinsic pathway (8 + IXa --> activates X)
PT = extrinsic pathway (5a --> activates X)
(think you need an appointment to get in)
