Haematology Flashcards
(137 cards)
1
Q
What cells are characteristic of Hodgkin’s lymphoma?
A
Reed-Sternburg Cells (multinucleate giant polymorphic cells)
2
Q
What 2 age groups are most likely to have Hodgkin’s lymphoma?
A
Teenager/Young adult
Elderly
3
Q
Main presentation of Hodgkin’s lymphoma?
A
Lymphadenopathy - enlarged, painless, non-tender, rubbery superficial lymph nodes Cervical > Axilla > Inguinal Cyclical fever Constitutional B cell symptoms Worsening symptoms after alcohol
4
Q
What staging system is used for Hodgkin’s lymphoma?
A
Ann Arbor staging system
5
Q
What is the treatment for Hodgkin’s lymphoma?
A
Combination chemotherapy (ABVD)
- Adriamycin (doxorubicin)
- Bleomycin
- Vinblastine
- Dacarbazine
6
Q
Why are lymphomas more likely to be B cell in origin rather than T cell?
A
Because B cells undergo class switching and somatic hypermutation in response to invading pathogen. These processes involve DNA replication and the more DNA replication there is, the more opportunity for mutations to occur. T cells do not undergo replication to the same extent.
7
Q
What cells make antibodies?
A
Plasma cells
8
Q
Risk factors for Hodgkin’s lymphoma?
A
Affected sibling EBV SLE? Immunosuppression eg post-transplantation, HIV Obesity
9
Q
Risk factors for Non-Hodgkins lymphoma?
A
Immunodeficiency eg drugs, HIV HTLV-1 H.pylori Toxins Congenital
10
Q
What haematological malignancy is associated with coeliac disease?
A
Small bowel T cell lymphoma
11
Q
Which age groups are more likely to have Non-Hodgkins lymphoma?
A
Incidence increases with age
12
Q
Extranodal presentations of Non-Hodgkin’s lymphoma?
A
Skin - T cell lymphoma
Oropharynx - Waldeyer’s ring lymphoma
Gut - Gastric MALT, Non-MALT gastric lymphomas and small bowel lymphomas
13
Q
Types of cytopenia?
A
Anaemia Thrombocytopenia Neutropenia Leukopenia Pancytopenia
14
Q
What is the treatment of Non-Hodgkin’s lymphoma?
A
Combination chemotherapy (R-CHOP) -Rituximab -Cyclophosphamide -Hydroxydaunomycin (doxorubicin) -Vincristine -Prednisolone Just CHOP for T cell lymphomas
15
Q
For how long does the patient need to be anticoagulated for DVT and PE?
A
DVT - 3 months
PE - 6 months
16
Q
What is the definition of multiple myeloma?
A
Clonal proliferation of plasma cells
17
Q
How is multiple myeloma diagnosed?
A
Serum electrophoresis
Bone marrow biopsy
18
Q
What are the symptoms of multiple myeloma?
A
C - Hypercalcaemia - stone, bones, groans, thrones, moans
R - Renal failure - N+V, weight loss, lethargy (Uraemia)
A - Anaemia (+thrombocytopaenia - causes viscous blood and soft tissue swelling)
B - Bone lesions - bone pain
I - Recurrent infections
19
Q
What are the symptoms of hypercalcaemia?
A
Stones - renal stones
Bones - Ostetitis fibrosa cystica, arthritis, osteoporosis
Groans - Constipation, indigestion, nausea and vomiting
Thrones - Constipation and polyuria
Psychiatric moans - Depression, lethargy, psychosis, fatigue, delirium
20
Q
What is seen on FBC in a patient with myeloma?
A
Normochromic, normocytic anaemia
21
Q
What are the 3 conditions on the myeloma spectrum?
A
MGUS - multiple gammaopathy of undetermined significance
Asymptomatic myeloma
Multiple myeloma
22
Q
What is the difference between MGUS and asymptomatic myeloma?
A
Plasma cells are <10% in MGUS and >10% in Asymtomatic myeloma
23
Q
What does the tallest peak seen on serum electrophoreses represent?
A
Albumin
24
Q
What genetic abnormality is commonly seen in CML patients?
A
Philadelphia chromosome - reciprocal translocation between chromosome 9 and 22. Results in BCR-ABL fusion gene, which activates tyrosine kinase.
25
What haematological malignancy is related to Philadelphia chromosome?
CML
26
Name 4 types of myeloproliferative disorders and the cells they derive from?
Polycythaemia - RBC
CML - WBC
Essential thrombocytopenia - platelets
Myelofibrosis - Fibroblasts
27
What are the symptoms of CML?
Chronic and insidious constitutional symtoms eg Weight loss, fever, sweats
+/- Gout
+/- Abdominal discomfort (splenomegaly)
+/- Bleeding/bruising (platelet dysfunction)
28
Treatments for CML
Imatinib - Specific BCR-ABL tyrosine kinase inhibitor
| Bone marrow transplant - only cure
29
Treatment for Essential Thrombocytosis
Low dose aspirin
| Hydroxycarbamide
30
Secondary causes of thrombocytosis
Iron deficiency
Infection/inflammation
Trauma
Bleeding
31
Difference between absolute and relative polycythaemia
Relative - normal RBC, low plasma volume eg due to dehydration
Absolute - Chronic due to hypertension, obesity, smoking, alcoholism
32
Secondary causes of polycythaemia
Hypoxia - high altitudes, congenital heart disease, chronic lung disease, heavy smoking
Increased erythropoietin secretion - renal or hepatocellular carcinoma
33
What is polycythaemia rubra vera?
Primary polycythaemia due to JAK2 mutation resulting in excess proliferation of RBCs, WBCs and platelets, leading to hyper viscosity and risk of thrombosis.
Independent of EPO
34
What is erythropoietin?
A glycoprotein cytokine produced by interstitial fibroblasts in the kidney in response to hypoxia to simulate the production of red blood cells
35
How can primary and secondary polycythaemia be determined?
Serum erythropoietin
Primary - Low
Secondary - High
36
How is polycythaemia rubra vera treated?
Venesection
Hydroxycarbamide
Low dose aspirin
37
Symptoms of hyper viscosity that may be seen in polycythaemia rubra vera?
```
Headaches
Dizziness
Tinnitus
Visual disturbance
Itch after hot bath
Erythromelalgia – burning sensation in fingers and toes
```
38
What does bone marrow biopsy show in polycythaemia rubra vera?
Hyper cellularity (more cells), erythroid hyperplasia (RBC precursors)
39
What is myelofibrosis?
Hyperplasia of megakaryocytes which produce platelet derived growth factor and results in bone marrow fibrosis and myeloid metaplasia.
40
What conditions can polycythaemia rubra vera progress to?
Myelofibrosis
| AML
41
What is seen on blood film for myelofibrosis
Teardrop RBCs
42
What are myelodysplastic syndromes?
A group of disorders characterised by bone marrow failure (pancytopenia), either primary or secondary (post chemo or radiotherapy) in cause. Can progress to AML.
43
What cells are characteristic of myelodysplastic syndrome?
Ring sideroblasts
44
Symptoms of AML
Bone marrow failure: bleeding (low platelets), bruising, infection (low WCC), anaemia (low Hb)
Infiltration: hepatosplenomegaly, gum hypertrophy, skin involvement
45
What cell type, seen on microscopy, is diagnostic of AML?
Auer rods
46
Which age group is most at risk of AML?
Incidence increased with age, most commonly affects people 50-60yrs
47
What is the treatment for AML?
Suuportive care
Chemotherapy (daunorubicin and cytarabine)
Bone marrow transplant
48
How is AML diagnosed?
Bone marrow biopsy
49
Which pathway of the coagulation cascade results in prolonged APTT?
Intrinsic
50
Which pathway of the coagulation cascade results in prolonged PT?
Extrinsic
51
Which factor deficiency causes a prolonged APTT but has no associated bleeding risk?
Factor 12
52
How does factor 13 deficiency first present?
Continuous oozing of umbilical cord
53
Which clotting factors are vitamin k dependant?
2,7,9,10
54
What condition is also known as Christmas disease?
Haemophilia B
55
Which factors are deficient in Haemophilia A and B?
A - Factor 8
| B - Factor 9
56
What type of inheritance pattern does Haemophilia have?
X-linked recessive
57
Which clotting test will be abnormal in haemophilia A?
APTT - increased because factor 8 is part of the intrinsic pathway
58
How can you tell if anaemia is due to bone marrow failure or not?
Low reticulocytes = bone marrow failure
| High reticulocytes = other cause
59
Treatments for Haemophilia A other than recombinant factor 8?
Analgesia
Antifibrinolytics eg tranexamic acid
Desmopressin
60
How does desmopressin work in haemophilia?
Promote the release of von Willebrand factor with subsequent increase in factor VIII survival secondary to vWF complexing
61
Characteristic appearance of skull xray in myeloma?
Pepperpot skull
62
What is the management of vitamin B12 deficiency?
If neurological involvement - Hydroxocobalamin 1mg IM on alternate days indefinitely, switch to 3 monthly when no more improvement in neurological symptoms
If no neurological involvement - Hydroxocobalamin 1mg IM 3 times a week for 2 weeks, then 3 monthly
63
What pathogens can precipitate an aplastic crisis in sickle-cell anaemia?
Parvovirus B19
Streptococcus
Epstein Barr Virus
64
What does the triad of reticulocytopaenia, symptomatic anaemia and parvovirus IgM antibodies represent?
Aplastic crisis in sickle cell precipitated by Parvovirus B19
65
Macrocytic anaemia + neurological symptoms = ?
B12 deficiency
66
What investigation would you do for B12 deficiency?
Anti-intrinsic factor antibodies
67
What cells produce intrinsic factor?
Parietal cells of the stomach
68
Which cause of thrombpcytopaenia is associated with anti-platelet antibodies?
Idiopathic thrombocytopaenia purpura
69
What is characterised by the triad of thrombocytopenia, prolonged PT, APTT and low fibrinogen levels?
Disseminated Intravascular Coagulation
70
What are the haematological emergencies?
Sickle cell crisis
71
Investigations in Hodgkin's lymphoma?
Lymph node CORE NEEDLE biopsy
Imaging (CT)
Raised ESR, low Hb = worse prognosis
72
What is seen on histology for Burkitt's lymphoma?
Starry sky appearance
73
What is seen on blood film ALL?
Blast cells
| >20% = Acute haematological malignancy
74
What investigations are done for ALL?
FBC (bone marrow suppression)
Clotting
Bone marrow aspiration and biopsy
LP - might be CNS involvement
75
What cancer are people with Down's syndrome at increased risk of?
ALL
76
What are the poor prognostic factors for ALL?
Adult
Male
Philadelphia chromosome
CNS signs
77
What cell type is affected in AML?
Myeloblasts
78
What haematological malignancy present with swollen bleeding gums?
AML
79
Which cells are affected in CML?
Granulocytes eg eosinophils, basophils, neutrophils
80
What can CML progress to?
AML
81
What is the commonest leukaemia?
CLL
82
What cells are found on blood film for CLL?
Smudge cells (ruptured B cells)
83
What haematological malignancy can present with recurrent shingles?
CLL
84
What is the pathology if CLL?
Chromosomal abnormalities interfere with B-cell receptors so there is a build up of B lymphocytes and the avoid immunosurveillance and apoptosis
85
What is seen on urine electrophoresis for myeloma
Bence Jones proteins (free immunoglobulin light chains)
86
Diagnostic criteria for myeloma?
Monoclonal protein bands on serum electrophoresis
Increased plasma cells on bone marrow biopsy
Evidence of end organ damage
87
What drug is used for the induction of treatment for multiple myeloma? What is a SE of it?
What other management options are there?
Bortezomib - peripheral neuropathy
(+dexamethasone)
High-dose therapy chemotherapy and stem cell transplant
88
What adjuvant therapies are required in the management of myeloma?
```
Flu vaccine
Acyclovir
Bisphosphonates
LMWH (for thrombosis)
Ig replacement
```
89
What are the features of bone marrow failure?
Anaemia
Bleeding
Infection
90
Why is detecting infection in AML difficult?
Because AML itself can present with fever, common organisms present differently and few antibodies are made so cant be detected.
91
What is the hallmark of CLL?
Accumulation of B cells that have evaded apoptosis and undergone cell cycle arrest in G0/G1 stage
92
What are 3 complications of CLL?
Bone marrow failure
Infection due to hypogammaglobulinemia
Autoimmune haemolysis
93
What staging system is used in CLL?
Rai Staging
94
Why does ALL management involve intrathecal drugs?
Meningeal leukaemia prophylaxis
95
What blood results indicate worse prognosis in Hodgkin's lymphoma?
Increased ESR
| Low Hb
96
Causes of microcytic anaemia
Iron deficiency
Thalassaemia
Sideroblastic anaemia
97
Causes of normocytic anaemia
```
Haemolytic
- Sickle cell disease
- Autoimmune haemolytic anaemia
- Hereditary spherocytosis
- G6PD deficiency
Pyruvate kinase deficiency
Non-haemolytic
- Aplastic anaemia
- Chronic Kidney disease
- Chronic inflammatory disease
- Acute blood loss
- Pregnancy
```
98
Causes of macrocytic anaemia
```
Megaloblastic
- Pernicious anaemia
- B12 deficiency
- Folate deficiency
- Fanconi anaemia
Non-megaloblastic
- Hypothyroidism
```
99
What symptoms are specific to iron deficiency anaemia?
Slow eating
| Pica
100
Investigations in iron deficiency anaemia
FBC: Low Hb, Low ferritin, Increased TIBC
| Increased ZPP
101
What is the inheritance pattern of thalassaemia?
Autosomal recessive
102
How can you differentiate between alpha and beta thalassaemia?
Hb electrophoresis
103
What chains make up normal adult and metal haemoglobin?
Adult: 2 x alpha and 2 x beta
Fetal: 2 x alpha and 2 x gamma
104
On what chromosome is the beta haemoglobin gene?
Chromosome 11
105
Symptoms of beta thalassaemia major
```
Failure to thrive
Vomiting
Irritability
Jaundice
Bossing of skull
Maxillary overgrowth
```
106
Management of beta thalassaemia major
```
Lifelong RBC transfusions
Iron chelation (sub cut desoferrioxarmine)
Stem cell transplant
```
107
What is beta thalassaemia?
Genetic mutation in beta haemoglobin chain so unable to produce normal adult haemoglobin.
108
Complications of beta thalassaemia major?
```
Hepatosplenomegaly
Cirrhosis
Infertility
Hyperpigmentation
Heart failure
```
109
What is alpha thalassaemia?
Adults have 4 copies of alpha haemoglobin chain gene (2 x HbA1 and 2 x HbA2, one from each parent).
Abnormal alpha haemoglobin chains.
Manifestation depends on the number of the alpha haemoglobin genes affected.
110
How does alpha thalassaemia major present?
Hydrops fetalis in 3rd trimester of pregnancy
111
How is alpha thalassaemia major treated?
Intrauterine transfusions followed by lifelong monthly transfusions.
112
What is the pathology of sickle cell disease?
Abnormal beta haemoglobin chains due to glutamine to valine amino acid substitution.
113
What is the inheritance pattern of sickle cell disease?
Autosomal recessive
114
4 subtypes of sickle cell disease?
HbSS - 2 copies of sickle haemoglobin chain mutation
HbSC - 1 copy of sickle haemoglobin chain mutation and 1 haemoglobin C gene mutation
Sickle beta thalassaemia - 1 copy of sickle haemoglobin mutation and 1 copy of beta thalassaemia gene
HbSA - 1 copy of sickle haemoglobin gene and 1 normal copy. Asymptomatic carrier with some protection against falciparum malaria
115
Presentation of sickle cell disease
```
Jaundice
Susceptibility to infection
Splenomegaly
Dactylitis
Priapism
Vaso-occlusive crises
```
116
What is a vaso-occlusive crisis?
Acute bone pain from microvascular occlusion due to sickled RBC.
117
What is the management of sickle cell disease?
```
Prophylaxis - Daily oral penicillin and folic acid
Analgesia and fluids for acute crisis
Hydroxycarbamide
Transfusions
Iron chelation therapy
Stem cell transplant
```
118
What is a contraindication of hydroxycarbamide?
Pregnancy
119
What patients are most commonly affected by sickle cell disease?
Afrocaribbeans
120
What patients are most commonly affected by thalassaemia?
People from India, middle east and mediterranean countries.
121
In what part of the GI tract is iron principally absorbed?
Duodenum
122
What conditions are treated with venesection?
Polycythaemia rubra vera
| Haemochromatosis
123
What is the inheritance of sideroblastic anaemia?
X-linked recessive
124
What is the most common inheritance of hereditary spherocytosis?
Autosomal dominant
125
What is the inheritance of autoimmune haemolytic anaemia?
Autosomal recessive
126
What are the acquired causes of autoimmune haemolytic anaemia?
```
CLL
Non-Hodgkin's lymphoma
EBV
CMV
Hepatitis
HIV
```
127
What is the most common gene mutation in heredity spherocytosis?
ANK1
128
How do you tell between B12 and folate deficiency?
B12 has autoantibodies (if due to pernicious anaemia), neurological sequelae
129
Vitamin K affects which coagulation factors?
II, VII, IX, X
130
Deficiency in which factors cause prolonged aPTT?
Those involved in the intrinsic pathway.
| XII, XI, IX, VIII
131
Prolonged PT means there is a deficiency in which possible factors?
Extrinsic pathway VII, V
132
Causes of schistocytes on blood film
DIC
TTP
HUS
133
What is Felty's syndrome?
Triad:
RA
Splenomegaly
Neutropaenia
134
Which causes schistocytes?
TTP
HUS
DIC
Mechanical valve
135
What does desmopressin do?
Stimulates release of vWF
136
Which cancers cause raised erythropoietin?
Renal carcinoma
| Hepatocellular carcinoma
137
What conditions are treated with IV Ig?
```
Kawasaki's disease
Multiple Myeloma
Guillain Barre Syndrome
Lambert Eaton Syndrome
Immune Thrombocytopaenic Purpura
```
