Oncology & Haematology Flashcards
(79 cards)
1
Q
Main site of haemopoiesis in fetus and postnatal?
A
Fetus - Liver
Postnatal - BM
2
Q
Hb and WBC, and platelet counts as neonate?
A
High Hb (14-21g/dL) - drops to 10 by 2m High WBC (10-20x10^9/L) Platelet similar to adult
3
Q
Hb in anaemia in
a) neonate
b) 1-12m
c) 1-12y
A
a) <14g/dL
b) <10g/dL
c) <11g/dL
4
Q
3 mechanisms anaemia may arise?
A
Reduced RBC production
Increased RBC destruction
Blood loss
5
Q
Causes of anaemia in children?
A
Reduced RBC production
- Red cell aplasia
- Ineffective erythropoiesis (Fe/folate/B12 deficiency)
Increased RBC destruction
- RBC membrane disorders (hereditary spherocytosis)
- RBC enzyme disorders
- Haemoglobinopathies (thalassaemias, sickle cell)
- Immune (haem disease of newborn)
Blood loss
- Fetomaternal bleeding
- Chronic GI blood loss (Meckel’s)
- Inherited bleeding disorders (vWillebrands)
6
Q
MCV in
a) iron deficiency anaemia?
b) folic acid deficiency?
A
a) low
b) high
7
Q
Causes of iron deficiency anaemia?
A
Inadequate intake
Malabsorption
Blood loss
8
Q
At what level of Hb does anaemia become symptomatic?
A
6-7g/dL
9
Q
Main causes of microcytic anaemia?
A
- Iron deficiency
- beta-thalassaemia trait
- alpha-thalassaemia trait
- Anaemia of chronic disease (e.g. renal failure)
10
Q
Management of iron deficiency anaemia?
A
- Dietary advice and supplementation with oral iron
- Iron supplementation until 3m after Hb normal
- Hb should rise 1g/dL per wk with good compliance
- If no response → look for malabsoprtion (eg Coeliac) or chronic blood loss (eg Meckel diverticulum)
- Blood transfusion should never be necessary for dietary iron deficiency (even if Hb =2)
11
Q
Lifespan of RBC?
A
120d
12
Q
Main causes of haemolysis in children?
A
- -> Intrinsic abnormalities of RBCs
1. RBC membrane disorders eg hereditary spherocytosis
2. RBC enzyme disorders eg G6PD deficiency
3. Haemoglobinopathies eg thalassaemia
13
Q
Clinical features of haemolysis?
A
Anaemia Hepatomegaly Splenomegaly Increased unconjugated bilirubin XS urinary urobilinogen
14
Q
Diagnosis of haemolysis on blood film?
A
- Raised reticulocyte count
- Abnormal appearance of RBCs
15
Q
Genetics of hereditary spherocytosis?
A
- Usually autosomal dominant
- No FH in 25% - new mutation
16
Q
Pathophysiology of hereditary spherocytosis?
A
- Mutations in genes for proteins of RBC membrane (mainly spectrin, ankyrin or band 3)
- → RBC loses part of membrane when passes through spleen
- This causes cells to become spheroidal
- → Destruction in microvasculature of spleen
17
Q
Clinical features of hereditary spherocytosis?
A
- Often suspected because FH
- Clinical manifestations highly variable - may be asymptomatic
- Jaundice – usually develops during childhood, may be intermittent; may cause severe haemolytic jaundice in 1st few days of life
- Anaemia –mild (Hb 9–11 g/dl), but Hb may fall during infections
- Mild/mod splenomegaly – depends on rate of haemolysis
- Aplastic crisis – uncommon, transient (2–4w), caused by parvovirus B19 infection
- Gallstones – due to increased bilirubin excretion
18
Q
How is hereditary spherocytosis diagnosed?
A
Blood film usually diagnostic
19
Q
Management of hereditary spherocytosis?
A
- Most have mild chronic haemolytic anaemia and only treatment required = oral folic acid (raised folic acid requirement secondary to increased RBC production)
- Splenectomy beneficial but only indicated for poor growth or troublesome sx of anaemia (e.g. severe tiredness, loss of vigour)
- Usually deferred until after 7y because of risks of post splenectomy sepsis
20
Q
Inheritance of G6PD deficiency?
A
X-linked
Usually affects males
21
Q
Clinical features of G6PD deficiency?
A
- Neonatal jaundice – onset in 1st 3d of life
- Acute haemolysis – precipitated by:
– Infection = most common precipitating factor
– Certain drugs (antimalarials, antibiotics, analgesias)
– Fava beans (broad beans)
– Naphthalene in mothballs - Haemolysis predominantly intravascular
- → Associated with fever, malaise and passage of dark urine - contains Hb as well as urobilinogen
- Hb level falls rapidly and may drop <5 g/dl over 24–48 h
22
Q
How is G6PD deficiency diagnosed?
A
- B/w episodes, almost all pts have completely normal blood picture and no jaundice or anaemia
- Diagnosis made by measuring G6PD activity in RBCs
- During haemolytic crisis, G6PD levels may be misleadingly elevated due to higher enzyme conc in reticulocytes → produced in increased numbers in response to destruction of RBCs
- Repeat assay required in steady state to confirm diagnosis
23
Q
Management of G6PD deficiency?
A
- Parents given advice about signs of acute haemolysis (jaundice, pallor and dark urine) and provided with a list of drugs, chemicals and food to avoid
- Transfusions rarely required, even for acute episodes
24
Q
What is
a) Sickle cell anaemia?
b) HbSC disease?
c) Sickle beta-thalassaemia?
d) Sickle cell trait?
A
a) Pts homozygous for HbS (virtually no HbA, small amount HbF) - most severe
b) HbS from 1 parent, HbC from other (no HbA)
c) HbS 1 parent, B-thalassaemia other –> no HbA - same picture as SC anaemia
d) HbS 1 parent, HbA other - carrier
25
What is sickle cell anaemia exacerbated by? (3)
- Low O2 tension
- Cold
- Dehydration
26
Manifestations of sickle cell anaemia? (6)
```
Anaemia
Infection - increased susceptibility
Painful crises - vaso-occlusive
Acute anaemia - haemolytic/aplastic/sequestration crisis
Priapism
Splenomegaly
```
27
Long-term problems of sickle cell anaemia?
- Short stature and delayed puberty
- Stroke and cognitive problems
- Adenotonsillar hypertrophy
- Cardiac enlargement – from chronic anaemia
- Heart failure – from uncorrected anaemia
- Renal dysfunction
- Pigmented gallstones
- Leg ulcers – uncommon in children
- Psychosocial problems – education and behavioural difficulties
28
Which infections are people with sickle cell more susceptible to?
Pneumococci
H Influenzae
--> Due to hyposplenism due to microinfarction in spleen
29
Prophylaxis in sickle cell anaemia?
- Full immunisation
- Daily oral penicillin
- OD folic acid
- Avoid cold, dehydration, XS exercise, stress, hypoxia
30
Management of acute crises in SC anaemia?
- Painful crises → oral/IV analgesia according to need (pos opiates) and good hydration
- Infection → abx
- O2 if sats reduced
- Exchange transfusion indicated for acute chest syndrome, stroke and priapism
31
Management of chronic problems in SC anaemia?
- If recurrent hosp admissions for vasoocclusive crises or acute chest syndrome may benefit from hydroxyurea
- → Drug increases HbF prodn and helps protect against further crises
- Requires monitoring for SEs, esp WBC suppression
- Most severely affected children (1–5%) who have a stroke or don’t respond to hydroxyurea may be offered BM transplant
- → Only cure but can only be safely done if child has HLAidentical sibling who can donate BM – cure rate 90% but 5% risk of fatal transplantrelated complications
32
2 types of beta-thalassamia?
Major
- No HbA due to 2 abnormal beta-globin genes
Intermedia
- Small amount HbA or large amount HbF produced
- Only 1 abnormal beta-globin gene
33
Clinical features of beta-thalassamia?
- Severe anaemia - transfusion dependent, from 3–6m of age and jaundice
- FTT/growth failure
- Pallor
- Jaundice
- Splenomegaly
- Hepatomegaly
- Bossing of skull
- Maxillary overgrowth
34
Management of beta-thalassamia?
- Lifelong monthly blood transfusions (fatal w/o)
- Aim for Hb >10g/dL
- Iron chelation from 2-3yo
- BM transplant if HLA identical sibling
35
Problems with repeated blood transfusion due to iron overload? (5)
- Cardiac failure
- Liver cirrhosis
- Diabetes
- Infertility
- Growth failure
36
Complications of long-term blood transfusion in children? (4)
- Iron overload
- Antibody formation (10%)
- Infection (<10%)
- Venous access (common)
37
3 types of alpha-thalassamia?
- Major
- HbH disease
- Alpha-thalassaemia trait
38
What is alpha thalassaemia major?
- Most severe α-thalassaemia, (also known as Hb Barts hydrops fetalis)
- Deletion of all 4 αglobin genes → no HbA (α2β2)
- Occurs mainly in SE Asian origin
- Presents in midtrimester with fetal hydrops (oedema and ascites) from fetal anaemia
- → Always fatal in utero or within hours of delivery
- Only longterm survivors are those who have received monthly intrauterine transfusions until delivery followed by lifelong monthly transfusions after birth
- Diagnosis is made by Hb electrophoresis or Hb HPLC (highperformance liquid chromatography), which shows only Hb Barts
39
What is HbH disease?
- Only three αglobin genes deleted
- Affected children have mild–moderate anaemia
- Occasional pts are transfusion dependent
40
What is alpha-thalassaemia trait?
- Deletion of 1 or 2 αglobin genes
- Usually asymptomatic and anaemia mild or absent
- RBCs may be hypochromic and microcytic → may cause confusion with iron deficiency
41
5 main components of normal haemostasis?
1. Coagulation factors
2. Coagulation inhibitors
3. Fibrinolysis
4. Platelets
5. Blood vessels
42
What is mucous membrane and skin haemorrhage characteristic of?
Platelet disorder or von Willebrand disease
43
What is bleeding into joints/muscles characteristic of?
Haemophilia
44
What are haemophilia A and B?
```
A = coagulation factor VIII deficiency
B= coagulation factor IX deficiency
```
45
Clinical features of haemophilia?
- Most present end of 1st y of life
- 40% present as neonates --> ICH, bleeding post-circumcision or prolonged bleeding from venepuncture/heel-prick
- Bleeding episodes most frequent into joints/muscles
46
How is haemophilia severity classified?
Mild --> FVIII:C 5-40%, bleed after surgery
Mod --> FVIII:C 1-5%, bleed after minor trauma
Severe --> FVIII:C <1%, bleed spontaneously into joint/muscles
47
Management of haemophilia?
- Recombinant FVIII or IX
- Given IV whenever bleeding
- Raising level to 30%sufficient to treat minor bleeds
- 100% for surgery and maintained at 30-50% for 2w after
- Injections every 12h or by infusion
- Pts/children taught to administer at home
- Prophylactic FVIII given to all with severe disease to raise level >2% → better joint function in later life
- Desmopressin may allow for mild haemophilia A to be managed without blood products (stimulates FVIII + vWF release) – ineffective in type B
- Specialised physio
- IM injections, aspirin and NSAIDs avoided in all pts
48
What are the 2 roles of von willebrand factor?
1. Facilitates platelet adhesion to damaged endothelium
| 2. Acts as carrier protein for FVIII:C, protecting it from inactivation and clearance
49
Clinical features of von willebrand disease?
- Bruising
- XS, prolonged bleeding after surgery
- Mucosal bleeding such as epistaxis and menorrhagia
- In contrast to haemophilia, spontaneous soft tissue bleeding such as large haematomas and haemarthroses uncommon
50
Management of von willebrand disease?
DDAVP
More severe --> plasma-derived FVIII
IM injections, aspirin and NSAIDs avoided
51
Name 3 acquired bleeding disorders?
- Vit K deficiency (mainly neonates)
- Liver disease
- Thrombocytopenia (DIC, ITP etc)
52
Define thrombocytopenia
Platelet count <150 × 10^9/L
- Severe <20 (spontaneous)
- Mod 20-50 (mild trauma/ ops)
- Mild 50-150 (major op/severe trauma)
53
Commonest cause of thrombocytopenia in childhood?
ITP
| - Usually caused by destruction of circulating platelets by anti-platelet IgG autoantibodies
54
Clinical features of ITP?
| Prognosis?
- Most b/w 2 -10y
- Onset often 1–2w after viral infection
- In majority, short hx of days-wks
- → Petechiae, purpura +/or superficial bruising
- Epistaxis/other mucosal bleeding
- Profuse bleeding uncommon, despite platelet count often <10 × 10-9/L
- Intracranial bleeding = serious but rare complication (0.1–0.5%) → mainly if long period of severe thrombocytopenia
In 80% → disease is acute, benign and selflimiting, usually remitting spontaneously within 6–8w
55
If suspect ITP, what would lead to a BM examination? (5)
- Anaemia
- Neutropenia
- Hepatosplenomegaly
- Lymphadenopathy
- Treated with steroids (may mask ALL)
56
ITP management?
- Most at home with no treatment (even platelet<10)
- Treatment if major bleeding (e.g. intracranial or GI)
- Treatment if affecting daily life (epistaxis/menorrhagia)
* Oral prednisolone
* IV antiD
* IV immunoglobulin
* → All have significant SEs
* Platelet transfusions for lifethreatening haemorrhage as they raise platelet count only for few hrs
57
How many have chronic ITP and what is the management?
- 20% persists beyond 6m
- In most just supportive treatment
- Drug if chronic persistent bleeding affecting daily life
- Eg rituximab
- Splenectomy if drugs fail
58
What is DIC?
Disorder characterised by coagulation pathway activation → diffuse fibrin deposition in microvasculature and consumption of coagulation factors and platelets
59
Commonest causes of activation of coagulation in DIC? (4)
- Sepsis
- Meningococcal septicaemia
- Shock due to circulatory collapse
- Extensive tissue damage from tissue damage/burns
60
Clinical features of DIC? (3)
- Bruising
- Purpura
- Haemorrhage
- -> Whilst critically ill
61
What blood test abnormalities are there in DIC?
* Thrombocytopenia
* Prolonged PT
* Prolonged APTT
* Low fibrinogen
* Raised fibrinogen degradation products & D-dimers
* Microangiopathic haemolytic anaemia
62
Causes of purpura?
Non-thrombocytopaenic
- HSP
- Sepsis
- Trauma
Thrombocytopaenic
- ITP
- Leukaemia
- DIC
63
Illnesses that may indicate splenectomy? (4)
- Hereditary spherocytosis
- Lymphoma
- Chronic ITP
- Trauma to spleen with uncontrolled bleeding
64
Vaccinations needed to be given prior to splenectomy? (4)
- Pneumococcus
- Hib
- Meningococcus
- Influenza
65
Which leukaemia most common in children?
ALL (80%)
66
Clinical presentation of ALL?
- Peaks at 2-5y
- Mostly insidious presentation (several wks)
Gen --> malaise anorexia
BM infiltration
- anaemia (pallor, lethargy)
- neutropenia (infection)
- thrombocytopenia (bruising, petechiae, epistaxis)
- bone pain
Reticulo-endothelial infiltration
- hepatosplenomegaly
- lymphadenopathy
Other organ infiltration
- CNS--> headaches, vomiting, nerve palsies
- Testes --> testicular enlargement
67
Ix for ALL?
- FBC
- BM examination
- CXR (look for mediastinal mass characteristic of T cell disease)
68
2 types of ALL?
```
Common subtype (75%)
T-cell subtype (15%)
```
69
5 stages of treatment regimes for ALL?
```
Induction of remission
Consolidation and CNS protection
Interim maintenance
Delayed intensification
Continuing maintenance
```
70
Short term SEs of chemotherapy?
- Hair loss
- Anaemia
- Infection
- Bruising
- Sore mouth
- N+V
- Mood changes
- Wt gain
71
Long term SEs of chemo?
- Delayed puberty
- Reduced fertility
- Reduced growth
- Neurotoxicity, hepatotoxicity, renal toxicity, cardiotoxicity, pulmonary toxicity
- Secondary cancer
- Psychological effects
72
Which lymphoma more common?
Non-Hodgkin lymphoma (80%)
| Yet Hodgkin more common in adolescence
73
Common clinical features of neuroblastoma?
Mostly <5yo
- Pallor
- Wt loss
- Abdo mass (most have at presentation)
- Hepatomegaly
- Bone pain
- Limp
74
What is neuroblastoma?
Tumour of neural crest tissue in adrenal medulla and sympathetic NS
75
Ix for neuroblastoma?
- Urinary catecholamines
- MRI
- Confirmatory biopsy
- BM sample/ bone scan for metastatic disease
76
What is Wilm's tumour?
Nephroblastoma
- Commonest renal tumour of childhood
- Mostly <5yo
- V rare >10yo
77
Clinical features of Wim's tumour?
Common
- Abdo mass
Uncommon
- Abdo pain
- Anorexia
- Anaemia (haemorrhage into mass)
- Haematuria
- HTN
78
Associations with Wilm's tumour?
Overgrowth syndromes
| Trisomy 18
79
Most common presenting feature of retinoblastoma? (2)
White pupillary reflex replaces normal red one
| Squint
