Haematology Flashcards
1
Q
Define Multiple Myeloma.
A
Malignant proliferation of plasma cells accumulating in the bone marrow.
2
Q
What is the result of Malignant Myeloma?
A
Overproduction of Ig or Ig fragments (paraprotein) causing:
- Dysfunction of many organs (esp. kidneys)
- Bone marrow failure
- Destructive bone disease
- Hypercalcaemia
3
Q
What is a major characteristic of Malignant Myeloma?
A
Excess secretion of a monoclonal antibody.
4
Q
What is a paraprotein?
A
Abnormal immunoglobulins produced by clonal plasma cells.
Can be intact immunoglobulins or parts of immunoglobulins (usually light chains).
5
Q
Describe the pathophysiology of Malignant Myeloma.
A
Development of a malignant clone of plasma cells → secretes excess amounts of monoclonal antibody.
This is due to cytogenetic abnormalities.
6
Q
What is the clinical presentation of Multiple Myeloma related to?
A
Infiltration of plasma cells and secretion of monoclonal antibodies.
7
Q
What are the signs and symptoms of Multiple Myeloma?
A
CRAB:
- hyperCalcaemia
- Renal impairment
- Anaemia
- Bone lesions (aka lytic lesions eg. osteoporosis)
8
Q
How does bone disease arise in multiple myeloma?
A
- Proliferation in bone marrow
- Lytic lesions
- Fractures
9
Q
How does impaired renal function arise in multiple myeloma?
A
Light chain nephropathy.
10
Q
How does anaemia arise in multiple myeloma?
A
- Bone marrow destruction by proliferation of malignant plasma cells
- Renal disease can contribute to EPO deficiency
11
Q
How does hypercalcaemia arise in multiple myeloma?
A
Multiple myeloma-induced bone demineralisation.
12
Q
How does recurrent/persistent- bacterial infection arise in multiple myeloma?
A
- Immune dysfunction and hypogammaglobulinemia
- Suppression of normal plasma cell function
13
Q
What investigations are ordered for someone with suspected multiple myeloma?
A
- Bloods
- Protein electrophoresis
- Urine protein electrophoresis
- Serum light free chains
- Bone marrow aspirate/biopsy
- Skeletal survery
- CT/MRI
- Beta-2 microglobulin
14
Q
What bloods results would be indicative of multiple myeloma?
A
- FBC - marrow failure
- ESR - raise
- Blood film - Rouleaux formation
- U&Es - raised urea and creatinine
- Hypercalcaemia
15
Q
What protein electrophoresis and immunofixation results are indicative of multiple myeloma?
A
- Increased number of antibodies
- Monoclonal protein band
16
Q
What urine protein electrophoresis results are indicative of multiple myeloma?
A
Bence Jones’ protein - monoclonal light chains
17
Q
What serum free light chains results are indicative of multiple myeloma?
A
Ratio of light chains kappa and lamda.
18
Q
What bone marrow aspirate/biopsy is indicative of multiple myeloma?
A
Increased plasma cell.
19
Q
What skeletal survey (X-ray) results are indicative of multiple myeloma?
A
Lytic lesions:
- Pepperpot skull
- Vertebral collapse
- Lytic punches out lesions
- Fracture risk
20
Q
What CT/MRI results are indicative of multiple myeloma?
A
Lesions (may be unidentified by X-ray)
21
Q
What is the relevance of β2 micro-globulin?
A
Prognostic indicator.
22
Q
What is the principle behind treatment of multiple myeloma?
A
It is incurable → treatment aims to increase periods of disease remission.
23
Q
What are the 4 key areas of management of multiple myeloma?
A
- Induction therapy
- Autologous stem cell transplantation
- Maintenance
- Relapse/refractory disease
24
Q
What is induction therapy in multiple myeloma?
A
- Initial treatment option
- Combination of 3 drugs
Choice is dependant on high-risk features, co-morbidities and plan for ASCT.
25
What is ASCT in multiple myeloma?
- Transplant is the best option for long periods of remission
- Stem cells are mobilised, harvested and stored
- High dose chemotherapy
- Stem cells re-infused
26
What is maintenance in multiple myeloma?
- Bortezomin/lenalidomide
- Maintain disease remission for as long as possible
27
What is the scoring system for multiple myeloma?
International Staging System (ISS) for myeloma, divides patients into three groups (I, II, III) based on serum beta-2 microglobulin and albumin levels.
- Stage I: median survival 62 months
- Stage II: median survival 44 months
- Stage III: median survival of 29 months
28
Define Lymphoma.
Disorders caused by malignant proliferation of lymphocytes.
Accumulate in lymph nodes causing lymphadenopathy (enlarged lymph nodes)
29
What are the sub-types of lymphoma?
Histologically divided into:
- Hodgkins lymphoma
- Non-Hodgkins lymphoma
30
Describe the aetiology of Lymphoma.
- Primary immunodeficiency (eg. Wiscott-Aldrich syndrome)
- Secondary immunodeficiency (eg. HIV, transplant)
- Infection (eg. EBV, helicobacter pylori)
- Autoimmune disorders
31
Describe the pathophysiology of Lymphoma.
Not well understood, development is thought to be multi-factorial, with infection, genetic factors, and environmental exposures all potentially involved.
32
What symptoms are associated with Lymphoma?
- Non-tender lymphadenopathy
- Mediastinal lymphadenopathy (with breathing difficulties)
- Symptoms of compression syndromes
- General systemic 'B' symptoms
- Liver and spleen enlargement
33
What is the triad of B symptoms?
- Weight loss
- Night sweats
- Malaise
34
What are the Ann Arbor Classificaction for the diagnosis of Lymphoma?
- Stage I → single lymph node region
- Stage II → two or more nodal areas on same side of diaphragm
- Stage III → nodes on both sides of diaphragm
- Stage IV → spread beyond lymph nodes, e.g. liver or bone marrow
35
What other organs might lymphoma affect?
- Blood
- Liver
- Spleen
- Bone marrow
36
What are the two types of Hodgkin's Lymphoma?
- Classical Hodgkin's Lymphoma
- Nodular lymphocyte predominates Hodgkin's Lymphoma (NLPHL)
37
Histologically - what is needed for a specific diagnosis of Hodgkin's Lymphoma (vs. Non-Hodgkin's Lymphoma)?
Presence of Reed-Sternberg cells or NLPHL variant.
38
What are the risk factors associated with Hodgkin's lymphoma?
- Affected sibling
- EBV
- SLE
- Obesity
- Post-transplantation
39
What are the common clinical presentations of Hodgkin's lymphoma?
- Painless cervical lymphadenopathy and B symptoms (weight loss, fever, night sweats)
- Disease localised to mediastinum often presents with cough due to mediastinal lymphadenopathy
- Hepatosplenomegaly
40
What are the emergency clinical presentations of Hodgkin's Lymphoma?
- Infection
- SVC obstruction
- Increased JVP
- Dyspnoea
- Blackouts
- Facial oedema
41
How is Hodgkin's Lymphoma diagnosed?
- Lymph node excision or bone marrow biopsy
- Bloods
- CT/MRI of chest, abdomen and pelvis for staging
42
What is the treatment for Hodgkin's Lymphoma?
1. Stage I-A to II-A (less than 3 areas)
- Short course of ABVD followed by radiotherapy
2. Stage II-A to IV-B
- Longer courses of ABVD
ABVD = combination chemotherapy (Adriamycin, Bleomycin, Vinblastine, Dacarbazine)
43
What complications are associated with the treatment of Lymphoma?
1. Chemotherapy
- Myelosuppression
- Nausea
- Alopecia
- Infection
- Infertility
2. Radiotherapy
- Increased risk of secondary malignancies
- Increased risk of IHD
Hypothyroidism
- Lung fibrosis
44
What is Non-Hodgkin's Lymphoma?
All lymphomas without Reed-Sternberg cells; 80% B cell origin and 20% T cell origin.
45
How is Non-Hodgkin's graded in terms of severity?
- Low grade (eg. Follicular Lymphoma)
- High grade (eg. Diffuse Large B Cell Lymphoma)
- Very High Grade (eg. Burkitt's Lymphoma)
46
Describe the clinical presentation of Non-Hodgkin's Lymphoma.
- Nodal disease
- Extranodal disease
- Systemic B symptoms
- Pancytopenia
47
What is the prognosis of low-grade Non-Hodgkins Lymphoma?
- Slow growing
- Advanced at presentation
- Incurable
- Median survival: 10 years
48
Describe the prognosis of high-grade Non-Hodgkins Lymphoma?
- Nodal presentation
- Presents earlier than low grade
- Often curable
- Aggressive (can make patient very unwell)
49
What is involved in the diagnosis of Non-Hodgkin's Lymphoma?
- Raised lactose dehydrogenase (worse prognosis)
- Lymph node excision or bone marrow biopsy
- CT/MRI of chest, abdomen, and pelvis for staging
- Immunophenotyping and cytogenetics
50
What is the treatment for Non-Hodgkins Lymphoma?
- Radiotherapy
- Combined chemotherapy (R-CHOP)
- Monoclonal antibodies
R-CHOP = Rituximab, Cyclophosphamide, Hydroxy-Daunorubicin, Vincristine, Prednisolone
51
What are Myelodysplastic Syndromes?
Myelo = marrow
Dysplastic = abnormal
Bone marrow cells fail to make adequate numbers of healthy blood cells (both quantity and quality of cells).
52
What is Acute Myeloid Leukaemia?
The neoplastic proliferation of myeloid progenitor cells.
Characterised by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production.
53
What are the histological characteristics of AML?
Blast cells with Auer rods - red staining, needle-like bodies seen in the cytoplasm of myeloblasts.
54
What risk factors are associated with AML?
- Exposure to ionising radiation
- Preceding haematological disorders
- Prior chemotherapy
55
What is the median age for AML?
85-89 years.
56
What are the clinical presentations of Acute Leukaemia?
- Anaemia
- Infection
- Thrombocytopenia
- Bone marrow infiltration
- Symptomatically high WCC
- Disseminated Intravascular Coagulation
57
What is involved in the diagnosis of Acute Leukaemia?
- Rapid change in RBC
- Blood film
- Bone marrow biopsy
58
What is the treatment for Acute Leukaemia?
- Combined IV chemotherapy
- Haematopoietic stem cell transplantation
- Blood and platelet transfusions
- Prophylactic antivirals, antibacterials and antifungals
59
Define Acute Lymphoblastic Leukaemia.
Neoplastic proliferation of immature lymphoid cells lines (gives rise to T cells and B cells)
60
Define Chronic Myeloid Leukaemia.
Chronic, neoplastic proliferation of basophils, eosinophils and neutrophils.
61
What is the clinical presentation associated with CML?
- Symptomatic anaemia
- Dyspnoea
- Abdominal discomfort
- Weight loss
- Tiredness
- Pallor
- Fever and sweats
62
How is CML diagnosed?
- High WCC
- Low Hb
- Bone marrow aspirate
63
What is the treatment for CML?
- Oral Imatinib (specific BCR/ABL tyrosine kinase inhibitor) - Stem cell transplant
64
Define Chronic Lymphoblastic Leukaemia.
Proliferation of B lymphocytes leads to the accumulation of mature B cells that have escaped apoptosis.
Most common leukaemia.
65
What are the clinical presentations associated with CLL?
- Generally asymptomatic (often discovered via FBC)
- Anaemia
- Weight loss
- Sweats
- Anorexia
- Hepatosplenomegaly with enlarged, non-tender nodes
66
How is CLL diagnosed?
FBC:
- Normal or low Hb
- Raised WCC
- High lymphocytes
Blood film:
- Smudge cells in vitro
67
How is CLL treated?
The only curable treatment is a bone marrow transplant or allogeneic stem cell transplant.
Chemotherapy - tyrosine kinase inhibitors, MAbs, etc
68
What is normal haematocrit?
45%
69
What is haematopoiesis and where does it occur?
Synthesis of blood cells, occurs in the bone marrow.
70
Where does haematopoiesis occur?
Through the action of cytokines.
71
Define myeloproliferative neoplasms.
Haematological malignancies.
72
How do myeloproliferative neoplasms manifest?
Accumulation of mature blood cells in circulation.
73
Where do myeloproliferative neoplasms arise from and what causes them?
Genetic mutations in haematopoietic stem cells.
Cells inappropriately and permanently switched on by signalling cytokines that control haematopoiesis.
74
What is Polycythaemia Vera? (inc. epidemiology and prognosis)
A blood neoplasm resulting in the creation of too many RBCs.
Rare - 2/100,000 per year
13 years
75
What are the symptoms of Polycythaemia Vera?
Itch and fatigue.
76
What are the differential diagnoses for polycthaemia vera?
- Lung disease
- Alcohol
- Apparent erythrocytosis
- EPO secreting tumours
These potential causes must be eliminated.
77
How is polycythaemia managed?
- Venesection
- Aspirin 75mg daily
- Hydroxycarbamide 500mg daily
- Management of other CV risk factors (ie. blood pressure)
78
What complications are associated with polycythemia vera?
- Arterial thrombosis - MI/stroke
- Venous thrombosis - DVT, portal vein thrombosis
79
What is the possible progression of polycythaemia vera?
Transform to acute leukaemia and myelofibrosis.
80
What is essential thrombocytosis? (inc. epidemiology and prognosis)
An elevated platelet count.
Rare - 2/100,000 per year
Normal life expectancy
81
What causes essential thrombocytosis?
Mostly JAK mutation - thrombopoietin (TPO) always switched on
82
What are the differential diagnoses of essential thrombocytosis?
- Infection
- Inflammation (inc. post-surgical)
- Solid tumours
Secondary causes must be eliminated.
83
How is essential thrombocytosis managed?
- Assess and manage CV risk
- Aspirin 75mg daily
- Hydroxycarbamide 500mg daily
84
What complications are associated with essential thrombocytosis?
- Arterial thrombosis
- Venous thrombosis
- Bleeding
85
What is the possible progression of essential thrombocytosis?
Acute leukaemia and myelofibrosis.
86
What is myelofibrosis? (inc. epidemiology and prognosis)
Bone marrow cancer.
Very rare - 1/100,000 per year
5 years
87
What causes myelofibrosis?
Predominantly JAK2 mutation.
88
What are the symptoms of myelofibrosis?
- Weight loss
- Fatigue
- Features of cytopaenias
89
How is myelofibrosis managed?
- Blood transfusion if needed
- Erythropoietin injections
- Allogeneic stem cell transplant
- Ruxolitinib (JAK1/2 inhibitor)
90
What are the complications of myelofibrosis?
- Bone marrow failure
- Cytopaenias
- Bone marrow filled with reticulin fibrosis
- Elevated WCC
- Splenomegaly
91
What is the possible progression of myelofibrosis?
Transform to acute leukaemia.
92
What is chronic myeloid leukaemia and how common is it?
Elevated WCC, elevated platelets, and splenomegaly.
7 cases per year in the UK.
93
What causes chronic myeloid leukaemia?
Mostly a translocation between chromosome 9 and chromosome 22 that creates a 'fusion gene' from BCR and ABL kinase.
94
How is chronic myeloid leukaemia managed?
- Inhibitors of ABL kinase (eg. Imatinib 400mg daily)
- Monitor FBC
- Reassess spleen size at 3 months
95
What can chronic myeloid leukaemia progress to?
'Blast phase' acute leukaemia
96
What is anaemia?
- Low level of haemaglobin in the blood
- It is the result of an underlying disease, not a disease itself
97
What levels are considered anaemic in men and women?
At sea level:
- <135g/L for men (131-166g/L)
- <115g/L for women (110-147g/L)
98
What are the 3 categories of anaemia?
- Microcytic anaemia (low MCV)
- Normocytic anaemia (normal MCV)
- Macrocytic anaemia (high MCV)
99
What are the main causes of microcytic anaemia?
1. TAILS:
- Thalassaemia
- Anaemia of chronic disease
- Iron deficiency anaemia
- Lead poisoning
- Sideroblastic anaemia
100
What are the main causes of normocytic anaemia?
1. AHAHA
- Acute blood loss
- Anaemia of chronic disease
- Aplastic anaemia
- Haemolytic anaemia
- Hypothyroidism
101
What are the main causes of macrocytic anaemia?
- B12 deficiency
- Folate deficiency
- Alcohol
- Reticulocytosis
- Bone marrow disorders
102
What are the general symptoms of anaemia?
- Tiredness
- Dyspnoea
- Headaches
- Dizziness
- Palpitations
- Tachycardia
- Pale skin
103
What is iron-deficiency anaemia?
- Iron is required for formation of haemoglobin
- Microcytic anaemia
- MCV will be reduced
104
Where is iron absorbed and how is it transported?
Absorbed in the duodenum and jejunum.
Transported as transferrin, stored as ferritin and haemosiderin.
105
What causes iron-deficiency anaemia?
- Blood loss (most common cause esp in menstruating women)
- Dietary insufficiency is the most common cause in growing children
- Poor iron absorption
- Increased requirement during pregnancy
106
What is the presentation of iron-deficiency anaemia?
- Fatigue
- Pallor
- Nail changes
- Mouth changes (angular stomatitis/cheilitis)
- Faintness
- Dyspnoea
107
What are the principle investigations for iron deficiency anaemia?
- Hb and haematocrit
- MCV
- Mean corpuscular haemoglobin concentration
- Peripheral blood smear
- Iron studies
108
What is the treatment for Iron-deficiency anaemia?
- Oral iron (Ferrous sulphate 200mg 3 times daily)
- Blood transfusion
109
What is sickle cell anaemia?
- Haemoglobinopathy characterised by the inheritance of sickle haemoglobin
- Caused by inheritance of abnormal beta-globin gene
- Production of rigid, sickle-shaped RBCs
- Leads to chronic vaso-occlusion
110
What are the types of sickle cell disease?
- Sickle cell anaemia (HbSS)
- Sickle cell disease (HbSC)
- Sickle cell trait (HbS) - sickle carrier
- Sickle-thalassaemia (HbSb0)
111
What is the main cause of sickle cell anaemia?
Autosomal recessive single gene defect in the beta chain of Hb resulting in sickle cell haemoglobin (HbS).
112
What are the acute signs and symptoms of sickle cell disease?
1. Vaso-occlusive painful crises
2. Splenic sequestration crises
3. Acute chest syndrome
4. Sickle cell crisis
5. Infection
6. Stroke
113
What are the chronic signs and symptoms of sickle cell disease?
- Long-term organ damage
- Eyes and brain have progressive changes
- Long-term erectile dysfunction
114
What are the invetigations for sickle cell anaemia?
1. Hb (low)
2. Reticulocytes (high)
3. Bilirubin (high)
4. Peripheral blood smear
5. Sickle solubility test
6. Hb electrophoresis
115
What is the management of sickle cell anaemia?
1. Supportive care (pain management)
2. Blood transfusion
3. Hydroxycarbamide
4. Allogeneic bone marrow transplant
5. Gene therapy
116
What is vitamin B12 deficiency?
Macrocytic anaemia with peripheral neuropathy and neuropsych complaints.
Megaloblastic anaemia, as well as folate deficiency anaemia.
117
What are the causes of B12 deficiency?
- Poor diet (vegan, old age)
- Decreased gastric breakdown
- Malabsorption
- Drugs (metformin, PPI, H2 antagonists)
118
What are the signs and symptoms of B12 deficiency?
1. Anaemia (pallor, fatigue, dyspnoea etc)
2. Neurological symptoms
3. GI symptoms (eg. chronic GI illness)
4. Mouth signs (eg. glossitis)
119
What is the management for Vitamin B12 deficiency?
- Malabsorption = Hydroxocobalamin
- Dietary = Oral Hydroxocobalamin
120
What is folate deficiency anaemia?
- A type of macrocytic anaemia with absence of neurological signs
- Folate is required for cell division and DNA synthesis
- Megaloblastic anaemia
121
What are the causes of folate deficiency anaemia?
- Poor diet
- Increased demand
- Malabsorption
- Drugs, alcohol and methotrexate
122
What are the signs and symptoms of folate deficiency anaemia?
- Anaemia symptoms
- Headache
- GI symptoms (loss of appetite)
- Skin and mouth signs (eg. exfoliative dermatitis)
123
What is the hallmark of megaloblastic anaemia?
Headache, loss of appetite and weight loss.
124
How is folate deficiency anaemia treated?
- Macrocytosis without anaemia = oral folic acid
- Macrocytosis and pancytopenia = oral folic acid and packed RBC transfusion
125
What is haemolytic anaemia?
- Haemolysis is the premature breakdown of RBCs, prior to 120 day lifespan
- Bone marrow production of RBCs is not sufficient to replenish supply = anaemi
126
What are the causes of haemolytic anaemia?
1. Hereditary causes:
- Enzyme defects
- Membrane defects
- Abnormal Hb production
2. Acquired causes:
- Autoimmune haemolytic anaemia
- Non-immune mediated (eg. paroxysmal nocturnal haemoglobinuria)
127
What are the signs and symptoms of haemolytic anaemia?
- Anaemia symptoms
- Jaundice
- Splenomegaly
- Dark urine
128
What is the Coombs test?
Aka antiglobulin test.
Tests for autoimmune haemolytic anaemia.
129
What is the treatment for Coombs +ve anaemia?
- Treat underlying condition
- RBC transfusion
- Folic acid
130
What is the treatment for Coombs -ve anaemia?
- Valve (cardiology evaluation)
- Plasma exchange
- Corticosteroids and anticoagulation
