Haematology Flashcards
1
Q
Pathological increase of myeloid cells?
A
myeloproliferative neoplasms
leukaemia (acute and chronic)
2
Q
Physiological increase of myeloid cells?
A
neutrophilia
eosinophilia
monocytosis
3
Q
Examples of myeloproliferative neoplasms?
A
Polycythaemia Rubra Vera Essential thrombocytosis Chronic Myeloid Leukaemia Primary myelofibrosis Systemic mastocytosis
4
Q
Causes of neutropenia?
A
inadequate production (bone marrow infiltration, cytotoxic chemo) accelerated destruction (fever, autoimmune, drugs, splenic sequestration)
5
Q
Causes of lymphopenia?
A
Retrovirus (HIV) Drugs (steroids, chemo) Autoimmune Malnutrition Immunodeficiency Some acute viral infections (CMV, EBV)
6
Q
What is caused by the Epstein-Barr Virus?
A
Infectious mononucleosis
7
Q
What virus causes infectious mononucleosis?
A
Epstein-Barr Virus
8
Q
What is infectious mononucleosis and what symptoms does it cause?
A
benign, self-limiting lymphoproliferative disorder
fever, lymphadenopathy, splenomegaly, sore throat
symptoms last 4-6 weeks
(sometimes hepatitis, meningoencephalitis, pneumonitis)
9
Q
When do symptoms of infectious mononucleosis begin to appear?
A
When the host response is initiated- cellular immunity mediated by CD8 cytotoxic T cells and NK cells
10
Q
What is leukaemia?
A
neoplasms of white blood cells, which present with involvement of bone marrow, usually with large numbers of cells in peripheral blood
11
Q
What is lymphoma?
A
neoplasms of lymphocytes, which present as discrete tissue masses
start in LNs and sometimes spread to bone marrow
12
Q
Types of acute leukaemia?
A
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
13
Q
Types of chronic leukaemia?
A
Chronic myeloid leukaemia
Chronic lymphoid leukaemia
14
Q
What is the Philadelphia Chromosome and what does it occur in?
A
t (9,22) translocation
Chronic Myeloid Leukaemia
15
Q
Blast cells in blood film indicates?
A
AML or ALL
16
Q
What is myelodysplasia?
A
pre-leukemic condition that presents with infection of anaemia
17
Q
Who is early myelodysplasia common in?
A
The elderly
18
Q
What occurs in myelodysplasia?
A
Macrocytosis very likely
Mild neutropenia is common
Thrombocytopenia is less common
19
Q
3 types of anaemia?
A
Microcytic
Macrocytic
Normocytic
20
Q
What is the commonest cause of anaemia worldwide?
A
Iron deficiency anaemia
21
Q
Symptoms and signs of iron deficiency anaemia?
A
fatigue, shortness of breath Pica- coal, ice sore mouth nail changes- koilonychia pallor
22
Q
Causes of iron deficiency?
A
inadequate intake
failure of absorption (coeliac)
inc. blood loss (blood loss from bowel, menorrhagia)
inc. requirements (pregnancy)
23
Q
What type of anaemia is iron deficiency anaemia?
A
Microcytic
24
Q
Causes of microcytic anaemia?
A
TAILS Thalassemia Anaemia of chronic disease Iron deficiency Lead poisoning Sickle Cell/ Sideroblastic (also myelodysplasia)
25
Causes for raised ferritin levels?
```
acute inflammation
acute liver disease
lymphomas
solid tumours
haemochromatosis
```
26
Diagnosis of anaemia of chronic disease?
MCV normal or reduced slightly
MCH normal
ESR raised
CRP raised
27
Mechanisms behind anaemia of chronic disease?
shortened red cell survival
impaired marrow response to anaemia
impaired erythropoietin production
defective iron transport
28
Causes of macrocytic anaemia?
```
Megaloblastic anaemia
Vit B12 deficiency
Folate deficiency
Myelodysplasia
Liver disease
Alcohol
Hypothyroidism
Aplastic anaemia
Cytotoxic drugs
Smoking
```
29
What is Vitamin B12 important for?
pyrimidine synthesis in the production of DNA
30
What does Vitamin B12 attach to to facilitate its absorption?
Intrinsic Factor (IF)
31
Causes of Vitamin B12 deficiency?
strict vegetarianism
| malabsorption (pernicious anaemia, gastrectomy, coeliac, disease involving terminal ileum)
32
What is pernicious anaemia?
autoimmune disorder that results in gastric atrophy
33
What antibodies are present in pernicious anaemia?
anti parietal antibodies (90%)
| anti intrinsic factor antibodies (70%)
34
Clinical features of B12 deficiency?
anaemia
peripheral neuropathy
loss of vibration and position sense
demyelination of spinal cord
35
Diagnosis of pernicious anaemia?
B12 levels
IF/Parietal cells antibodies
Bone marrow
36
Treatment of pernicious anaemia?
Lifelong B12 replacement
37
Causes of folate deficiency?
Diet (infancy and old age)
Malabsorption (coeliac)
Inc. utilisation (pregnancy, breastfeeding, haemolytic anaemia)
Antifolate drugs (methotrexate, anticonvulsants)
37
Causes of folate deficiency?
Diet (infancy and old age)
Malabsorption (coeliac)
Inc. utilisation (pregnancy, breastfeeding, haemolytic anaemia)
Antifolate drugs (methotrexate, anticonvulsants)
38
2 types of haemolytic anaemia?
Congenital
| Acquired
39
2 types of acquired haemolytic anaemia?
Immune-related
| Non-immune
40
3 types of immune-related haemolytic anaemia?
autoimmune
alloimmune
drug-induced
41
2 types of autoimmune haemolytic anaemia?
Warm antibody
| Cold antibody
42
Causes of warm antibody autoimmune haemolytic anaemia?
Idiopathic
| Secondary to CLL, CT disorders, lymphomas, drugs (methyldopa)
43
Causes of cold antibody autoimmune haemolytic anaemia?
Idiopathic
| Secondary to mycoplasma, mono, lymphoma, paroxysmal cold haemoglobinuria
44
Features of warm antibody autoimmune haemolytic anaemia?
usually IgG
max activity @ 37 degrees
any age, either sex
splenomegaly
45
Diagnosis of warm antibody autoimmune haemolytic anaemia?
micro-spherocytes and polychromasia on blood film
| Direct Coombes Test positive
46
Features of cold antibody autoimmune haemolytic anaemia?
usually IgM
| max activity @ 4 degrees
47
Diagnosis of cold antibody autoimmune haemolytic anaemia?
Cold agglutination on blood film
| Positive DCT
48
Causes of alloimmune haemolytic anaemia?
haemolytic transfusion reactions (ABO mismatch)
| Rhesus disease of the new-born
49
Non-immune causes of haemolytic anaemia?
Red cell fragmentation
Infections
Chemical/Physical
50
Clinical features of haemolytic anaemias?
```
anaemia symptoms
jaundice
pigmented gallstones
splenomegaly
leg ulcers (sickle cell, hereditary spherocytosis)
```
51
3 groups of congenital haemolytic anaemias?
Red cell membrane defects
Red cell metabolism disorders
Abnormal haemoglobins
52
What causes hereditary spherocytosis?
defect in a red cell membrane protein
| cells destroyed prematurely in the spleen (splenomegaly common)
53
Inheritance pattern of hereditary spherocytosis?
Autosomal Dominant
54
Abnormalities of Red Cell Metabolism include?
Glucose-6-phosphate dehydrogenase deficiency
| Pyruvate Kinase deficiency
55
2 types of abnormal haemoglobins causing haemolytic anaemia?
Disorders of globin chain synthesis (thalassemia)
| Structural defects of haemoglobin (sickle cell)
56
What causes sickle cell anaemia?
point mutation in the beta globin gene
| causes insolubility of Haemoglobin in the deoxygenated state
57
What occurs as a consequence of sickle cell anaemia?
Vascular occlusion
| Severely -> bone pain, stroke, visceral infarction, dactylitis (children), acute chest syndrome
58
Inheritance pattern of the Thalassemias?
Autosomal recessive
59
Laboratory findings in the Thalassemias?
variable anaemia
hypochromic microcytic cells
BM erythroid hyperplasia
DNA analysis
60
What is monoclonal gammopathy of undetermined significance?
presence of a monoclonal protein in the serum or urine without evidence of myeloma or other plasma cell disorders
61
What percentage of the population have monoclonal gammopathy of undetermined significance?
1%
| increases with age (14%>90yrs)
62
What is multiple myeloma?
abnormal plasma cells that build up in the bone marrow and form tumours in multiple bones of the body
63
Median age at diagnosis of multiple myeloma?
70 years
64
Clinical presentation of multiple myeloma?
```
bone pain
pathological fracture
recurrent infections
renal impairment
anaemia
hypercalcemia
hyperviscosity
```
65
Prognosis for multiple myeloma?
Can treat but can not cure
66
Main functions of platelets?
form a mechanical plug during the normal haemostatic response to vascular injury
67
What is the major regulator of platelet production and where is it produced?
Thrombopoietin
| liver and kidneys
68
Normal lifespan of platelets?
7-10 days
69
What is the normal amount of platelets in the spleen?
1/3
| if more- splenomegaly
70
What is von Willebrand factor involved in?
platelet adhesion and aggregation
| acts as a carrier protein for Factor VIII
71
Primary vs secondary haemostasis?
Primary haemostasis involves platelet adhesion and aggregation
Secondary haemostasis involves activation of the coagulation cascade
72
Stages of coagulation cascade?
Initiation- endothelial cells activated -> express tissue factor (TF) -> forms TF-FVIIa complex
Amplification- generates small amounts of thrombin
Propagation- positive feedback results in much larger amounts of thrombin
Thrombin results in fibrinogen being converted to fibrin
73
Inhibitors of coagulation?
Antithrombin
Protein C
Protein S
74
Which types of bleeding suggest primary vs secondary haemostasis defects?
Primary- mucosal superficial bleeding
| Secondary- deep tissue bleeding
75
What is the purpose of 50/50 mixing studies when investigating PT/APTT?
factor deficiencies- normal
| inhibitors- won't be normal
76
What is von Willebrand disease?
bleeding disorder due to defects involved with platelets
| chromosome 12
77
Types of von Willebrand disease?
Qualitative (type 1, 3) (Type 3 = near absence)
| Quantitative (type 2)
78
What type of bleeding predominates in von Willebrand disease?
Mucosal bleeding
79
Which type of von Willebrand disease is most common?
Type 1 (60-80%)
80
What population is Factor XI deficiency common in?
Ashkenazi Jews
| consanguinity
81
What factor is deficient in Haemophilia A?
Factor VIII
| X-linked
82
What factor is deficient in Haemophilia B?
Factor IX
| X-linked
83
Causes of quantitative platelet disorders?
```
consumptive
premature destruction
decreased production
drug reaction
congenital
```
84
Causes of qualitative platelet disorders?
drugs, uraemia, inherited
85
Risk factors for VTE?
```
major surgery
active cancer
neurological disease with leg paralysis
hospitalisation for acute illness
nursing home confinement
trauma/fracture
pregnancy/postpartum
oral contraception
```
86
When should combined oral contraception be avoided?
In patients who have a first degree relative with a history of thrombosis
87
What increases the risk of thrombus posed by the combined OCP?
smoking and obesity
| super additive is hereditary thrombophilia
88
What is the leading cause of death in pregnancy in UK and Ireland?
Thrombosis
89
Factors that further increase risk of thrombosis in pregnancy?
```
maternal age > 35
high BMI
immobility
operative delivery
thrombophilia
```
90
What is the second most common cause of death in cancer patients (after cancer itself)?
Thrombosis
91
What is Hospital Acquired Thrombosis (HAT)?
development of a thrombosis within 90 days of hospital admission
leading cause of preventable hospital morbidity
92
What does Lupus Anticoagulant in APS prolong and increase risk of?
Lupus Anticoagulant prolongs Activated Partial Thromboplastin Time
But increases risk of thrombosis, not bleeding
93
When can a Lupus Anticoagulant test give a false positive?
When the patient is on anticoagulants
94
What is Thrombotic Thrombocytopenic Purpura (TTP)?
unexplained thrombocytopenia and non-immune haemolysis
thrombocytopenic but pro-thrombotic
medical emergency- 90% fatality if untreated
95
What causes Thrombotic Thrombocytopenic Purpura (TTP)?
Deficiency of ADAMST13 (regulator of von Willebrand factor)
96
What percentage of patients acquire Heparin Induced Thrombocytopenia?
3% in Unfractionated Heparin
| <1% in LMWH (tinzaparin, enoxaparin, dalteparin)
97
Consequences of VTE?
post-thrombotic syndrome
| Chronic Thromboembolic Pulmonary hypertension
98
Investigations of thrombophilia?
Antithrombin
Protein C
Protein S
99
When may Protein C and Protein S be spuriously low?
if the patient is on warfarin (as they are Vitamin K dependent factors)
100
When will antithrombin, Protein C and Protein S all be spuriously low?
At the time of clot diagnosis
| Used in the acute phase
101
Which anti-phospholipid syndromes can be tested for when the patient is on anticoagulants?
Anticardiolipin and anti-B2GPl antibodies
| NOT Lupus Anticoagulant
102
How long is documentation regarding blood transfusions kept in the EU?
30 years
103
2 major categories of Lymphoma?
Hodgkin Lymphoma
| Non-Hodgkin Lymphoma
104
Clinical presentation of Hodgkin Lymphoma?
painless lymphadenopathy (v small percent of patients experience pain after consuming alcohol)
itchy skin
+ systemic symptoms
105
Clinical presentation of Non-Hodgkin Lymphoma?
painless lymphadenopathy (low grade)
rapidly enlarging mass (high grade)
if extra nodal- symptoms relate to site
106
Characteristic features of Hodgkin lymphoma?
arises in a single node or chain of nodes and spreads anatomically
107
Most common site for Hodgkin lymphoma to arise?
cervical nodes
108
What distinctive cells are found in Hodgkin lymphoma?
Reed Sternberg Cells (giant cells)
109
Average age at diagnosis for Hodgkin Lymphoma?
32 years
110
Average age at diagnosis for Hodgkin Lymphoma?
32 years
111
2 major types of Hodgkin Lymphoma?
Nodular lymphocyte predominant Hodgkin Lymphoma
| Classical Hodgkin Lymphoma
112
What differentiates between NLPHL and CHL?
immunophenotype
| Reed-Sternberg cells express the protein CD30 in CHL but not in NLPHL
113
What percentage of Hodgkin Lymphomas are NLPHL?
5%
114
Cellular Features of Nodular Lymphocyte Predominant Hodgkin Lymphoma?
Popcorn cells/ L + H cells
| background of small B lymphocytes
115
Clinical features of Nodular Lymphocyte Predominant Hodgkin Lymphoma?
no bimodal age pattern
tend to be restricted to cervical nodes
v good prognosis
116
4 types of Classical Hodgkin Lymphoma?
```
Lymphocyte Rich (5%)
Nodular Sclerosis (66%)
Mixed Cellularity (25%)
Lymphocyte Depleted (>5%)
```
117
Who gets each of the 4 types of Classical Hodgkin Lymphoma?
Lymphocyte rich- M>F, older patients
Nodular sclerosis- M=F, young adults
Mixed Cellularity- M>F, true bimodal pattern
Lymphocyte depleted- M>F, older patients, HIV
118
Prognosis of Hodgkin Lymphoma?
generally better than NHL
depends more on stage than histological subtype
Stage I and II- 90-100% curable
Stage IV- 5yr survival 60-70%
119
Clinical divisions of Non-Hodgkin Lymphomas?
```
Low grade (slow-growing but resistant to therapy and rarely curable, painless generalised lymphadenopathy)
High grade (rapid-growing but sensitive to therapy and potentially curable, rapidly enlarging mass)
```
120
3 types of Non-Hodgkin Lymphoma?
Mature B Cell
Mature T/NK Cell
Precursor B and T Cell
121
4 types of mature B cell neoplasms?
Follicular lymphoma
Diffuse large B Cell lymphoma
MALT lymphoma
Burkitt lymphoma
122
How does follicular lymphoma present?
painless, generalised lymphadenopathy
usually in middle age
low grade
123
Prognosis of follicular lymphoma?
incurable but low grade and slow growing (median survival 7-9 years)
can transform to a high grade (usually DLBCL)
124
Cause of follicular lymphoma?
t(14;18)(q32;q21) translocation most frequent
| leads to excess bcl2 (anti-apoptosis -> slow collection of neoplastic cells)
125
Diffuse Large B Cell Lymphomas defining factors?
Large Cell size
Diffuse growth pattern
Express B-cell markers (CD20, CD79a)
126
2 groups of DLBCLs?
Germinal centre type (CD10)
| Activated B cell type (MUM1)
127
Presentation and Prognosis of Diffuse Large B Cell Lymphoma?
rapidly enlarging mass at a single nodal or extra nodal site
if untreated- rapidly fatal
if treated- 60-80% achieve remission, 50% cure
128
Causes of MALT lymphoma?
Gastric- H pylori
Salivary- Sjogren's Syndrome
Cutaneous- Borrelia Burgdorferi (Lyme)
Conjunctival- Chlamydia
129
What is Burkitt Lymphoma usually?
an extranodal lymphoma
130
Features of endemic Burkitt Lymphoma?
sub-Saharan Africa
M:F 2:1
age 4-7
tumours of jaw and facial bones
131
Features of sporadic Burkitt Lymphoma?
worldwide in children and young adults
| ileocecal, breasts, kidneys, ovaries
132
3 types of Burkitt Lymphoma?
Endemic
Sporadic
HIV- related
133
What is present in 100% of Endemic Burkitt Lymphoma and 20% of others?
latent EBV infection
134
Genetic factor of Burkitt Lymphoma?
translocations of c-MYC gene on chromosome 8
| t(8;14)
135
Prognosis of Burkitt Lymphoma?
```
v aggressive but usually responds well to high-dose, short-course chemotherapy
frequently curable (especially in children)
```
136
What percentage of Non Hodgkin Lymphomas are mature T/NK cell lymphomas?
15%
137
4 types of mature T/NK cell lymphomas?
mycosis fungoides/ Sezary syndrome
anaplastic large cell lymphoma
extra nodal NK/T cell lymphoma
peripheral T cell lymphoma
138
What cells are involved in mycosis fungoides/sezary syndrome?
CD4+ helper T cells
139
What is Sezary syndrome associated with?
a leukaemia of 'Sezary' cells in the blood
140
Prognosis of mycosis fungoides/Sezary syndrome?
low grade, median survival 8-9yrs
| may transform to high grade T cell lymphoma as terminal event
141
Types of cells involved in anaplastic large cell lymphoma?
'Hallmark cells' with horse-shaped nuclei
142
What gene is associated with anaplastic large cell lymphoma?
ALK gene
143
Prognosis of anaplastic large cell lymphoma?
Cases with ALK rearrangement- usually in children, v good prognosis
Cases without ALK rearrangement- usually in older adult, bad prognosis
144
Prognosis of extra-nodal NK/T cell lymphoma?
bad- aggressive and respond poorly to therapy
145
What are peripheral T cell lymphomas, NOS?
T cell lymphomas which can not be fitted into any of the other diagnostic categories
25%
v bad prognosis, rarely curable
146
Precursor B and T cell neoplasm?
Acute lymphoblastic lymphoma/leukaemia
147
What percentage of ALL are B cell and T cell?
85% B cell- childhood acute leukaemias
| 15% T cell- adolescent male lymphomas
148
Clinical features of ALL?
more common in males
abrupt stormy onset
depression of normal bone marrow (anaemia, infections)
bone pain and tenderness
lymphadenopathy, splenomegaly, hepatomegaly
CNS manifestations (tumour cells can cross the BBB)
149
Prognosis of ALL?
generally good with treatment
| 90% children achieve remission, 70% cure
150
Poor prognostic factors for ALL?
age < 2
adulthood
certain genetic abnormalities
151
What are Auer rods a typical finding in?
Acute myeloid leukaemia
