Haematology Flashcards
1
Q
80% of chidhood leukaemias are what type? what are 15% of the others?
A
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
2
Q
5 syndromes that have increased likelihood of developing leukaemia?Type of anaemia assocaited with AML?
A
Down's Syndrome (AML in early life, ALL later) Bloom Syndrome Fanconi Syndrome (AML) Noonans Syndrome Kostmanns Syndrome Diamond black fan anaemia
3
Q
What leukaemia do Down’s Syndrome individuals have increased chances of developing?
A
AML in early life (1/100)
ALL in later life
4
Q
Bloom syndrome risk of developing leukaemia?
A
1/8
5
Q
Noonan’s syndrome what is the leukaemia they are prone to developing? how is it treated?
A
Juvenille myelomonocytic leukaemia
Need bone marrow transplant without chemo beforehand
6
Q
Type of leukaemia has nearly a 100% concordance in twin children?
A
infant acute lymphoblastic leukaemia
7
Q
What is the Kinlen hypothesis of leukaemia development?
A
after intense population mixing there are higher rates of infection in the previously unexposed individuals
8
Q
What type of leukaemia can benzene cause?
A
Acute myeloid leukaemia
9
Q
If blast cells are found in the peripheral blood stream what is this known as? who is most effected?
A
Transient myeloproliferative disorder
Down’s syndrome
10
Q
How long does transient myeloproliferative disorder last for?
A
8-12 weeks
11
Q
What are you more likely to develop if you suffer transient myeloproliferative disorder?
A
Acute myeloid leukaemia
12
Q
Clinical presentation of leukaemia?
A
low Hb - pallor, tired low neutrophils - infections, sepsis low platelets - petechiae, bruising bone pain hepatosplenomegaly lymphadenopathy Leukaemic skin deposits
13
Q
What does a bone marrow aspirate differentiate between?
A
Myeloid leukaemias, T cell, B cell precursors (early pre b, pre-b, c(mu))
14
Q
3 trisomies that relate to development of leukaemia?
A
4,10,17
15
Q
which 3 gene mutations lead to leukaemia?
A
BCR-ABL
TEL-AML1
MLL
16
Q
What 4 fusion transcripts does PCR tell you regarding leukaemia diagnosis?
A
BCR-ABL (p190:p210)
MLL-AF4
E2A-PX1
TEL-AML1 t(12:21)
17
Q
Which type of mutation is Philadelphia positive ALL?
A
BCR - ABL (p190:p210)
18
Q
Why do you perform a lumbar puncture in leukaemia?
A
See if there has been any infiltration into the CNS with blast cells
19
Q
CSF count of white cell and blasts. what is classified as CNS 1, CNS 2 and CNS 3?
A
CNS 1 = less than 5 WBC, no blasts
CNS 2 = less than 5 WBC but blasts
CNS 3 = more than 5 WBC and blasts
20
Q
What prophylaxis is given to children to prevent leukaemia spreading to the CNS?
A
Methotrexate
21
Q
When is minimal residual disease checked for in children with leukaemia?
A
after 1 month of chemo, PCR
22
Q
What is the risk of relapse if you dont have minimal residual disease less than 1 in 1x10^4
A
30-40%
23
Q
5 drugs that can cause secondary AML
A
Cyclophosphamide Ifosfamide Melphanan Etoposide Myelodysplasia
24
Q
How does infant ALL present differently to older children?
A
High WCC
CNS involved
myeloid features
CD10 negative - pro-b phenotype
25
What 3 MLL gene arrangements are common in Infant ALL?
```
MLL T(4:11)
MLL T(11:19)
MLL T(9:11)
```
26
Define primary immune thrombocytopenia?
an isolated platelet count of less than 100 x10^9, normal WBC and RBC
27
What is primary immune thrombocytopenia sometimes called?
Idiopathic thrombocytopenic purpura
28
What is primary immune thrombocytopenia usually following in children?
infection, viral illness
29
Persistent vs chronic primary immune thrombocytopenia?
```
Persistent = 3 months - 1 year
Chronic = over a year
```
30
How long does primary immune thrombocytopenia usually persist for?
6 months
31
What is the most common bleeding sites associated with primary immune thrombocytopenia?
GI, epitaxis
| Intracranial haemorrhage but rare
32
What does bone marrow film show in primary immune thrombocytopenia?
increased number of megakaryocytes
33
What is usual presentation of a child with primary immune thrombocytopenia?
Petechiae rash following by viral illness/URTI
History of bleeding - gums, epitaxis, bruising, blood in stools
Diarrhoea
34
When would a rash be more suspicious of meningitis than primary immune thrombocytopenia?
If there was a fever
35
What questions do you ask in the history of someone with suspected primary immune thrombocytopenia ?
```
Any vaccinations?
Any fevers?
is purpura non-blanching (will be)
any anaemia (shouldnt be)
Any lymphadenopathy or splenomegaly (shouldnt be)
```
36
Differential diagnosis for low platelet counts?
Meningitis - usually very unwell
viral - parvovirus B19, CMV, HIV
Leukaemia
Primary immune thrombocytopenia
37
Rare causes of thrombocytopenia?
aplastic anaemia - fanconi anaemia, radiation, virus, drugs
| Evans syndrome
38
What are the 3 features of Evans syndrome?
anaemia, thrombocytopenia and a positive Coombs
39
Presentation of thrombocytopenia what investigations are performed?
```
FBP
Reticulocyte count
Coagulation screen
Blood group with a group and hold
Peripheral blood film and bone aspirate if abnormalities are then seen
```
40
When is a bone marrow aspirate performed on children presenting with thrombocytopenia?
If abnormalities are seen on peripheral blood film
| If thrombocytopenia becomes chronic
41
If thrombocytopenia has not resolved in 6 months what investigations do you perform?
Direct antiglobulin test
Quantitive Ig level
Virology - CMV and parvovirus and HIV
42
What is the bleeding score?
a score to determine whether intervention is necessary with treatment
43
Description of grade 1 on the bleeding scale
grade 1 = petechiae not too many, bruises less than 5 and no mucosal bleeding
44
Description of grade 2 on the bleeding scale
Grade 2 = more than 100 petechiae, more than5 large bruises and no mucosal bleeding
45
Description of grade 3 on the bleeding scale
Grade 3 = moderate bleeding and mucosal bleeding
46
Description of grade 4 on the bleeding scale
Grade 4 = mucosal bleeding and suspected internal haemorrhage
47
How do you manage patients who are monitored on the bleeding scale but discahrged home
```
Appropriate information to parents, contact number in emergencies at all times and only when there is a lack of significant bleeding
Avoid contact activities
no diving in the swimming pool
helmet when cycling
attend school - monitored outside
no herbal remedies
Chicken pox contact - medical advice
```
48
If a child must be admitted for treatment of thrombocytopenia what 2 treatment options are there?
Prednisolone 2mg/kg for 7 days and then wean over 7 days
| Ig 1g/kg
49
What is the last resort treatment for thrombocytopenia?
Splenectomy
50
SE of short term steroids?
Mood, appetite, appearance
| Mask leukaemia
51
SE of long term steroids?
```
Osteoporosis
Hypertension
Growth disorders
diabetes
suppress stress response
suppress immune system
```
52
Why is suppressing the immune system a nasty side effect of steroids in children?
Chicken pox infection so much worse - need Varicella Ig
53
How many donors go into Igs?
10,000
54
What are the 2 treatment options for chronic ITP?
Rituximab and Eltrompopag
55
Short term SE of Rituximab?
Chills, fever, headache, tiredness, allergic reaction
56
Long term SE of Rituximab?
neutropenia, infection, haematological malignancy
57
What is classified as anaemic in children 3 months old through to puberty?
Below 110g/L
58
How can you tell whether the anaemia is normocytic/microcytic/macrocytic?
MCV
59
In iron deficiency anaemia what happens to MCV, MCH, MCHC?
all decrease
60
Iron deficiency anaemia vs chronic anaemia - what is the iron level and the iron binding capacity
In iron deficiency anaemia there is decreased iron but increase iron binding capacity whereas in chronic anaemia there is decreased iron and decreased iron binding capacity
61
Clinical features of anaemia in babies?
anaemic, glossitis, angular stomatitis, nail changes, irritable, cognitive changes, developmental delays
62
If a baby is presenting as anaemic, what do you need to rule out the cause being?
coeliac
63
What is the iron supplement dosage in an anaemic child?
3-6mg/kg/day
64
what is an acceptable increase rate of iron in baby?
10g/L every month
65
Hereditory haemolytic anaemias can take what 2 forms?
Defect in red cell membranes
| Defect in red cell metabolism
66
What is an example of a defect in red cell membranes causing hereditory haemolytic anaemia?
Hereditory spherocytosis
67
What is hereditory spherocytosis and what symptoms does it present with? Treatment?
Spherical RBCs
Jaundice, splenomegaly, anaemia, increased reticulocyte
Treatment is qith splenectomy and iron supplements
68
What is an example of a defect in red cell metabolism that causes hereditory haemolytic anaemia? mode of inhertiance? How does it present?
G6PD deficiency
X-linked
presents with haemolysis after exposure to oxidising agents - antimalarials, antibiotics, mothballs, chinese remedies
69
Acquired haemolytic anaemia will be positive in what test?
Coombs
70
2 types of acquired haemolytic anaemias?
warm auto-immune haemolytic anaemias and cold auto-immune haemolytic anameias
71
Describe warm-autoimmune haemolytic anaemias? mediated by? associated to? presents as?
Ab present at 37 degrees
associated with other autoimmune like lupus
IgG mediated
Splenomegaly, haemolytic anaemia
72
What is the treatment for warm autoimmune haemolytic anaemia?
corticosteroids
IV Ig
potentially blood transfusions and folic acid supplements
73
what is the difference in mediating factors between warm and cold autoimmune haemolytic anaemia
```
Warm = IgG mediated
Cold = cd3 complement mediated
```
74
What 2 infections can lead to haemolytic anaemia?
EBV
| Mycoplasma
75
What is the name for the acute episode of haemolysis occuring after a cold episode?
Paroxysmal cod haemoglobinuria
76
How does ABO incompatability occur?
IgG transfer from mother to baby
77
What can rhesus disease cause in the newborn?
Hydrops Fetalis and IUD
78
What can hydrops fetalis result in for the baby if left untreated?
Kernicterus
79
What is the dominant haemoglobin after 3-6 months of age and what is the formula version?
HbA 2alpha 2 beta
80
What is the dominant haemoglobin in fetal life and what is the formula version?
HbF 2 alpha 2 gamma
81
What is the haemoglobin that develops in 1.5-3% of people past 3-6 months of life and what is the formula version?
HbA2 2 alpha 2 delta
82
What mutation leads to alpha thalassaemia syndrome?
Point or delete mutation
83
What happens if all 4 alpha genes are lost?
hydrops fetalis
| death in utero
84
What happens if 3 alpha genes are lost?
beta 4
HbH
microcytic, hypochromic, splenomegaly
85
What happens in alpha thalassaemia trait?
loss of 1 or 2 alphas
no anaemia
MCV and MCH both drop
86
How is alpha thalassaemia trait diagnosed differently to more severe alpha thalassaemia?
```
Trait = DNA analysis
Severe = electrophoresis
```
87
Inheritance pattern and mutation involved in beta thalassaemia?
Autosomal recessive
| point mutation
88
Beta 0 vs beta +?
```
B0 = no beta chains produced
B+ = small amount of beta chains are produced
```
89
Symptoms of beta thalassaemia?
Severe anaemia, hepatosplenomegaly, marrow hyperplasia - extramedullary haemopoiesis, fractures
90
What will the Hb be made up of primarily in beta thalassaemia?
HbF
91
What is the management of major beta thalassaemia?
```
Blood transfusions
folic acid
splenectomy if needed
Endocrine if there is end organ failure or puberty delay
Bone marrow transplant
```
92
Symptoms of beta thalassaemia minor?
often symptomless maybe minor aneamia
93
What is the mutation that occurs in sickle cell anaemia?
Substitute occuring on the beta chain substituting a valine for glutamic acid at position 6
94
Why do red cells sickle?
when there is low oxygen tension causes them to crytallise
95
What occurs due to sickle HbSS?
severe anaemia, splenomegaly, gallstones
Venocclusive - infarction, infection, dehydration
Visceral crisis - chest, liver, spleen, acute abdomen
Aplastic crisis - parvovirus, folate deficiency
96
How do you manage a sickle cell crisis?
warm, rehydrate, treat cause, analgesia, blood plasma exchange to remove sickle, hydroxyurea to increase HbF
97
What is a curative treatment for HbSS?
stem cell transplant
98
3 times you need to be careful about sickle cell trait?
Pregnancy, anaesthetic, high altitudes
99
Fanconi anaemia inheritance pattern, type of anaemia, pathogenesis? risk of what else? treatment?
```
Autosomal recessive
Aplastic anaemia
Abnormal growth of skeleton
Defective DNA repair
AML
Need bone marrow transplant
```
100
In aplastic anaemia, what will be seen on blood film and bone marrow aspirate?
Blood film - pancytopenia
| Bone marrow aspirate - hypoplastic marrow with fat cells instead of haemopoietic tissue
101
3 forms of supportive care given in aplastic anaemia?
blood transfusions
platelet transfusions
treat infection
102
What treatment can be given for aplastic anaemia?
ALG - anti T cell Ig
ciclosporin or steroids
stem cell transplant
103
How is anaemia caused in diamond blackfan anaemia?
Red cell aplasia
104
Causes of transient anaemia in children?
Parvovirus B19
Transient myeloproliferative disorder
Congenital dyserythropoietic anaemia
105
Syndrome that can produce low neutrophil counts?
Kostmanns Syndrome
106
What is langerhans cell histiocytosis? LCH
| Treatment?
clonal expansion of langerhan cell precursor
dendritic cell family usually destroying invading organisms
Chemotherapy
107
Haemophagocytic lymphohistiocytosis? HLH
Presentation?
Findings on examination?
Proliferation of macrophages, nucleating red cells, platelets
Very unwell, temperatures
Hepatosplenomegaly, deranged LFTs, coag and reduced fibrinogen, increased ferritin and triglycerides
Sees haemophagocytosis in bone marrow
108
Treatment of haemophagocytic lymphohistiocytosis?
Immunosuppression
Chemo
SCT
109
Haemophillia A is inherited how? deficiency in what? presents as? complications lead to?
APTT/prothrombin?
```
X linked recessive
factor 8 deficiency
haemoathrosis and bruising, muscle haematomas
joint deformities
long APTT
normal prothrombin
```
110
Severe Haemophillia A diagnosed with levels below what IU/mL?
0.01 (1%)
111
Moderate Haemophillia A diagnosed with levels below what IU/mL?
0.01-0.05 (5%)
112
Mild Haemophilia A diagnosed with levels below what IU/mL?
over 0.05 (5-20%)
113
How do you manage someone with Haemophillia A?
Recombinant factor VIII in bleeding episode or 3 times a week prophylactically in severe cases
114
Haemophillia B refers to deficiency in what? inheritance pattern? management?
Factor IX deficiency
X linked recessive
Recombinant factor IX
115
What is the purpose of Von Willebrand factor?
Cause adhesion of platelets to damaged endothelium
| Carries factor 8
116
Inheritance pattern of VW disease?
autosomal dominant
117
Difference between Type 1, 2 and 3 VWD?
type 1 = lacking VW factor
Type 2 - defective vw factor
Type 3 = no VW factor
118
Clinical features of VWD?
```
bleeding mucous membranes
haemorrhage following surgery
menorrhagia
Increased bleeding time
Factor 8 deficiency
low VWF
```
119
How do you treat VWD related bleeding episode?
pressure on the wound
antifibrinolytic like tranexamic acid
desmopressin (DDAVP)
factor 8 concentrate (human derived factor 8 and VWF)
120
Vitamin K deficiency effects which coagulation factors?
2, 7, 9 , 10
121
Haemorrhagic disease of the newborn occurs how long after delivery and caused by what? treatment?
2-4 days
Vitamin K deficiency
Treat with vit K
122
Haemorrhagic disease of the new born presents how?
GI bleeding, bleeding from cord, cephalohaematoma
123
Which babies usually experience haemorrhagic disease of the newborn?
Breast fed babies
124
In more severe cases of haemorrhagic disease of the newborn what can be given on top of Vit K?
FFP/prothrombin
125
Name 4 hereditary disorders of thrombosis?
Factor V Leiden
Protein S deficiency
Protein C deficiency
Antithrombin deficiency
126
Tests would you do on a child presenting with lymphadenopathy?
```
FBP
CRP ESR
LFT
LDH
Monospot
PCRs - EBV, CMV, HIV, Toxoplasmosis, Bartonella
CXR
USS
Biopsy
```
127
Tests for a child with splenomegaly?
```
Leukaemia
Thalassaemia
Sickle cell
haemolytic anaemia - G6PD, spherocytosis, warm/cold autoimmune
EBV infection
Portal vein hypertension
Systemic disease or storage disease
```
128
6 non haemolytic causes of anaemia?
B12, folate or iron deficiency
Malabsorption
bone marrow failure
blood loss
129
Haemolytic causes of anaemia?
```
Spherocytosis
G6PD deficiency
Alpha thalassaemia
Beta thalassaemia
Sickle cell disease
Leukaemia
```
130
History questions to ask about in a child with anaemia?
```
Lethargy
Poor feeding
Breathlessness
Pallor
Growth
Any bleeding or bruising
Infections
PICA
How long has the problem been there?
FH - ethnic minorities, sickle cell, thalassaemia
DH - NSAIDs?
Any blood loss
Birth history, antenatal
Dietary history - age of weaning
```
131
What is the nail condition that can result due to iron deficiency anaemia?
Koilonychia
132
Risk factors for iron deficiency anaemia?
```
Preterm
Low birth weight
multiple births
exclusive breast fed for over 6 months
cows milk excess
```
133
3 tests to confirm iron deficiency anaemia in child and what is usual reference ranges?
FBC, blood film, iron studies
| 110-130g/dL
134
Alternative to iron deficiency anaemia when presented with decreased Hb, MCV and MCHC?
Thalassaemia trait
Lead poisoning
Chronic disease
135
Dietary advice for iron deficiency anaemia?
Iron rich diet and avoids cows milk consumption
136
What is dose of iron supplement?
3-6mg/kg/day (max 200mg) in 2-3 divided doses
137
After 1 week of iron supplements whats should be checked in a child?
FBC and reticulocyte count
138
Normal age of presentation in sickle cell disease?
3 months - 6 years
139
Causes of a petechiae rash?
```
ITP
Leukaemia
Meningococcal disease
Coughing, crying
Trauma
Viral and bacterial infections
```
140
What additional blood tests could you perform once ITP is diagnosed with low platelets?
Blood film
Reticulocyte count
Coagulation screen
Blood group
141
What is ITP? how long does it usually last?
Immune mediated thrombocytopenia usually following infection
| Chronic after 12 months and need bone marrow aspirate
142
In the case of active bleeding in ITP what 2 things are given initially?
Prednisolone (2mg/kg/day for 7 days then wean over 14) and Ig (1g/kg IV
143
How often is platelet count taken in follow up after treatment for ITP?
Weekly for 1 month, monthly up to 6 months and then every 3 months
144
If thrombocytopenia persists for 6 months after treatment then what tests need to be performed?
DIrect antiglobulin test
Virology - CMV, Parvovirus, HIV
Check VZV immunity
145
Advice to parents about their child who has ITP?
```
Avoid contact sports
Avoid ibuprofen
Contact number for emergencies
Warning signs to look out for
Helmet when cycling
Written information from ITP association website
Inform doc if in contact with chicken pox and VZ Ig neg and on steroids
Supervision in playground
Emergency card
```
146
If someone with ITP bangs their head what questions do you want to ask them?
```
What happened
Witnesses
LOC? how did you feel before and after?
Vomiting
Cry immediately
Dizzy, personality changes, sight, hearing, headache, loss of appetite, fit or collapse, seizure, clear fluid from nose or ears?
```
