Paediatrics Haematology Flashcards
(125 cards)
1
Q
What is haemoglobin made from?
A
4 protein subunits
Fetal haemoglobin (HbF) = two alpha and two gamma
Adult haemoglobin (HbA) = two alpha and two beta
2
Q
Draw the oxygen dissociation curve for fetal and adult Hb?
A
3
Q
When does the production of HbF decrease?
A
From 32 to 36 weeks gestation (HbA is produced in greater quantities)
4
Q
What is the problem in sickle cell disease?
A
Genetic abnormality for the beta subunit responsible for causing the sickle shape of the RBCs (doesn’t happen in fetal haemoglobin)
5
Q
What is the treatment in sickle cell disease?
A
Hydroxycarbamide to increase production of fetal Hb
6
Q
What is anaemia?
A
Low level of Hb in the blood (not a disease - the result of one)
7
Q
What is haemoglobin?
A
Protein found in RBCs (iron is needed to make it)
8
Q
What are the causes of anaemia in infancy?
A
Physiologic anaemia of infancy
Anaemia of prematurity
Blood loss
Haemolysis
Twin-twin transfusion
9
Q
What are the causes of haemolysis in a neonate?
A
Haemolytic disease of the newborn
Hereditary spherocytosis
G6PD deficiency
10
Q
When does physiologic anaemia of infancy occur and why?
A
At six to nine weeks of age in healthy term babies - high oxygen delivery to tissues caused by high Hb levels at birth cause negative feedback - production of erythropoietin by the kidneys is suppressed and there is reduced production of Hb by the bone marrow
11
Q
Why do premature neonates become anaemic?
A
Less time in utero receiving iron from mother
RBC creation can’t keep up with rapid growth in first few weeks
Reduced erythropoietin levels
Blood tests remove a significant proportion of circulating volume
12
Q
How to test for haemolytic disease of the newborn?
A
direct Coombs test (DCT)
13
Q
What are the 2 main causes of anaemia in older children?
A
Iron deficiency anaemia secondary to dietary insufficiency
Blood loss from menstruation in older girls
14
Q
What are the rarer causes of anaemia in children?
A
Sickle cell anaemia
Thalassaemia
Leukaemia
Hereditary spherocytosis
Hereditary eliptocytosis
Sideroblastic anaemia
15
Q
What is a common cause of chronic anaemia and iron deficiency worldwide?
A
Helminth infection with roundworms, hookworms or whipworms
Can be very common in developing countries
16
Q
What is the treatment of helminth infection?
A
Albendazole
Mebendazole
17
Q
What are the causes of microcytic anaemia?
A
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
18
Q
What are the causes of normocytic anaemia?
A
A – Acute blood loss
A – Anaemia of Chronic Disease
A – Aplastic Anaemia
H – Haemolytic Anaemia
H – Hypothyroidism
19
Q
What are the two types of macrocytic anaemia?
A
Megaloblastic (result of impaired DNA synthesis preventing cell from dividing normally - vitamin deficiency)
Normoblastic
20
Q
What are the causes of megaloblastic anaemia?
A
B12 deficiency
Folate deficiency
21
Q
What is normoblastic macrocytic anaemia caused by?
A
Alcohol
Reticulocytosis (usually from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs e.g. azathioprine
22
Q
What are the symptoms of anaemia?
A
Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of other conditions
23
Q
What symptoms are specific to iron deficiency anaemia?
A
Pica - dietary cravings for abnormal things e.g. dirt
Hair loss - iron deficiency anaemia
24
Q
What are some generic signs of anaemia?
A
Pale skin
Conjunctival pallor
Tachycardia
Raised resp rate
25
What are the specific **signs of iron deficiency anaemia**?
**Koilonychia** (spoon shaped nails)
**Angular chelitis**
**Atrophic glossitis** (smooth tongue due to atrophy of papillae)
**Brittle hair** and **nails**
26
What sign is specific to **haemolytic anaemia**? and **Thalassaemia**?
**Haemolytic** = Jaundice
**Thalassaemia** = bone deformities
27
What are the **initial investigations for anaemia**?
**Full blood count** for haemoglobin and MCV
**Blood film**
**Reticulocyte count**
**Ferritin** (low iron deficiency)
**B12 and folate**
**Bilirubin** (raised in haemolysis)
**Direct Coombs test** (autoimmune haemolytic anaemia)
**Haemoglobin electrophoresis** (haemoglobinopathies)
28
What does a **high level** of reticulocytes indicate in anaemia?
**Active production of RBCs** to replace lost cells - anaemia is due to **haemolysis** or **blood loss**
29
What is the **management** of anaemia?
**Establish underlying cause** and direct treatment accordingly
If severe **then may need blood transfusions**
30
What are the **causes of iron deficiency**?
**Dietary insufficiency** - most common
**Loss of iron** e.g. in heavy menstruation
**Inadequate absorption** e.g. in Crohn's
31
Where is **iron mainly absorbed**?
**Duodenum** and **jejunum**
32
In what form is iron mainly absorbed? What can interfere with this?
In the soluble **ferrous** (Fe2+) form - when **less acid in stomach** it changes to the **insoluble ferric** (Fe3+ form)
PPIs can interfere and **coeliacs** / **Crohn's disease**
33
How does **iron travel around the blood**?
As **ferric ions** bound to **carrier proteins** called **transferrin**
34
What is the **total iron binding capacity** (TIBC)?
Total **space** on the **transferrin** molecule for the **iron to bind**
35
What is the **transferrin saturation**?
**Serum iron** / **TIBC**
36
What is **ferritin**?
Form that **iron takes** when it is stored in cells (extra is released when there is **inflammation** e.g. with infection or cancer)
37
What can cause low / high ferritin?
**Low = iron deficiency** (could still be normal especially if infection)
High = difficult to interpret and means **inflammation** usually
38
Is **serum iron** a useful measure?
No - significantly varies throughout the day - higher levels in the **morning** and **after eatin iron containing meals**
On its own its **not a useful measure**
39
What can increase the levels of serum ferritin, serum iron and TIBC?
**Supplementation with iron**
**Acute liver damage** (lots of iron is stored in the liver
40
What is the **management** of anaemia?
**Treat underlying cause**
Iron supplemented with **ferrous sulphate** or **ferrous fumarate** - slowly corrects the iron deficiency (causes constipation and black coloured stools - unsuitable for malabsorption)
**Blood transfusions are very rarely necessary**
41
What is **leukaemia**?
Cancer of a **particular line of the stem cells** in the **bone marrow** - causing unregulated production of certain types of blood types (**chronic** is slow and **acute** is fast) cell line **myeloid** or **lymphoid**
42
Draw out cell lineage?
43
What are the **types of leukaemia**?
**Acute lymphoblastic leukaemia** (ALL)
**Acute myeloid leukaemia** (AML)
**Chronic myeloid leukaemia** (CML) is rare
44
What age does ALL and AML peak?
**ALL** peaks aged 2-3 years
**AML** peaks aged under 2 years
45
What is the **result** of the excessive production of a single type of cell?
**Pancytopaenia**:
Low RBCs (anaemia)
Low WBCs (leukopenia)
Platelets (thrombocytopaenia)
46
What is the main **environmental risk factor** for leukaemia?
Radiation exposure
47
Which **conditions** are **predisposing** to leukaemia?
**Down's** syndrome
**Kleinfelter** syndrome
**Noonan** syndrome
**Faconi's** anaemia
48
Which **conditions** are **predisposing** to leukaemia?
**Down's** syndrome
**Kleinfelter** syndrome
**Noonan** syndrome
**Faconi's** anaemia
49
How does **leukaemia** present in children?
Persistent fatigue
Unexplained **fever**
**Failure to thrive**
**Weight loss**
**Night sweats**
Pallor (anaemia)
**Petechiae** and abnormal bruising (thrombocytopania)
**Abdo pain**
Generalised **lymphadenopathy**
Unexplained or **persistent bone or joint pain**
**Hepatosplenomegaly**
50
What is the first step if **leukaemia is suspected**?
FBC within 48 hours
51
What investigations to establish the diagnosis of leukaemia?
FBC for **anaemia, leukopenia,** **thrombocytopenia** and high numbers of WBCs
Blood film for **blast cells**
Bone marrow **biopsy**
Lymph node **biopsy**
52
What **testing** can be done to **stage leukaemia**?
Chest X-Ray
CT scan
Lumbar puncture
**Genetic analysis** and **immunophenotyping** of abnormal cells
53
What is the **treatment of leukaemia**?
**Chemotherapy**
Radiotherapy
Bone marrow transplant
Surgery
54
What are the **complications** of **chemotherapy**?
- Failure to treat leukaemia
- **Stunted growth and development**
- Immunodeficiency and infections
- Neurotoxicity
- Infertility
- Secondary malignancy
- Cardiotoxicity
55
What is the **prognosis** for leukaemia?
Overall cure rate for ALL is 80% but **prognosis depends on individual factors**
Outcomes **less positive** for AML
56
What is **idiopathic thrombocytopenic purpura**?
**Idiopathic** (spontaneous) **thrombocytopenia** (low platelet count) causing a **purpuric rash** (non-blanching rash)
57
What is ITP caused by?
**Type II hypersensitivity reaction** - antibodies which target and destroy platelets - can be **spontaneous** or **triggered by something** e.g. viral infection
58
How does ITP present?
Children under 10
Recent **viral illness**
Onset **over 24-48 hours**
**Bleeding** e.g. gums, epistaxis, menorrhagia
**Bruising**
**Petechial** or **purpuric rash** caused by **bleeding under skin**
59
What are **petechiae,** **purpura** and **ecchymoses**?
**NON BLANCHING REGIONS**
**Petechiae** = pin-prick spots (**around 1mm**) of bleeding under skin
**Purpura** = larger (**3-10mm**) spots of bleeding
**Ecchymoses** = large area of blood (**more than 10mm**)
60
How is **ITP diagnosed**?
Urgent **FBC** for the **platelet count** (other values in FBC should be normal)
**Other causes excluded** e.g. **heparin induced thrombocytopenia** and **leukaemia**
61
What is the treatment of ITP?
Only if **patient is actively bleeding** or **severe thrombocytopenia** (platelets below 10)
**Prednisolone**
**IV immunoglobulins**
**Blood transfusions** if required
**Platelet transfusions** only work temporarily
62
Why do **platelet transfusions only work temporarily**?
**Antibodies** against platelets will begin destroying the transfused platelets as soon as infused
63
What **advice** for patients with ITP?
**Avoid contact sports**
Avoid **IM injections**
Avoid **NSAIDs, aspirin and blood thinners**
Advice on **managing nosebleeds**
**Seek help after any injury** which may cause internal bleeding e.g. **car accidents or head injuries**
64
What are some **complications** of ITP?
Chronic **ITP**
**Anaemia**
Intracranial and **subarachnoid haemorrhage**
**Gastrointestinal** bleeding
65
What is **sickle cell anaemia**?
**Genetic condition** causing **sickle** (crescent) shaped **RBCs** - making them **fragile** and **more easily destroyed** leading to haemolytic anaemia
66
What is the **pathophysiology** of sickle cell anaemia?
Patients with **sickle cell disease** have an **abnormal variant** called **haemoglobin S** (HbS) - causing the RBCs to be "sickle" shaped
67
What is the **inheritance** for sickle cell anaemia? What does it affect?
**Autosomal recessive condition** where there is an abnormal gene for **beta-globin** on **chromosome 11** (one copy results in sickle-cell trait - usually asymptomatic)
68
What is the **relation of sickle cell disease** to **malaria**?
**Sickle cell disease** is more common in patients from areas affected by **malaria** e.g. africa, india, middle east, carribean. Having **one copy of gene** reduces the severity of malaria - more likely to **survive and pass on their genes** - there is **selective advantage** to having the gene
69
How is sickle cell disease diagnosed?
**Pregnant women** at risk of being carrier as offered **testing during pregnancy**
Also tested for on **newborn screening heel prick test** at 5 days of age
70
What are the **complications of sickle cell disease**?
Anaemia
Increased risk of infection
Stroke
**Avascular necrosis** in large joints e.g. hips
**Pulmonary hypertension**
Painful and persistent penile erection (**priapism**)
**Chronic kidney disease**
**Sickle cell crises**
**Acute chest syndrome**
71
What is the **general management of sickle cell disease**?
Avoid **dehydration** and **other triggers of crises**
Ensure **vaccines are up to date**
**Abx prophylaxis** to **protect against infection** usually with **pen V** (phenoxymethypenicillin)
**Hydroxycarbamide** used to **stimulate production of HbF** (protective against sickle cell crises and acute chest syndrome)
**Bone transfusion** for severe anaemia
**Bone marrow transplant** can be curative
72
What is a **sickle cell crisis**?
**Umbrella term** for a **spectrum of acute crises** related to the condition - range from mild to **life threatening**
**Spontaneous** or **triggered by stresses** e.g. **infection**, **dehydration**, cold or significant life events
73
How are **sickle cell crises managed**?
Low threshold for **admission to hospital**
**Treat** any **infection**
Keep warm
Keep **well hydrated** with IV fluids
Simple analgesia e.g. paracetamol and ibuprofen (NSAIDs avoided in renal impairment)
Penile aspiration for **priapism**
74
What is a **vaso-occlusive crises**?
Sickle **shaped blood cells** clog capillaries causing **distal ischaemia**
Associated with **dehydration and raised haematocrit**
75
What are the **symptoms of a vaso occlusive crisis**?
**Pain**, **fever** and **symptoms of infection** (if present)
76
How is **priapism** caused by vaso-occlusive crisis **treated**?
**Aspiration of blood** from the penis
77
What is a **splenic sequestration crisis**?
**RBCs block blood** flow within the **spleen** - causing it to be **acutely enlarged and painful**
78
What can **pooling of blood** in spleen cause?
**Severe anaemia**
**Circulatory collapse** (hypovolaemic shock)
79
What is the **management of splenic sequestration crisis**?
Emergency treatment
Management is **supportive**
**Blood transfusions**
**Fluid resus**for anaemia and shock
80
What is the management of **recurrent splenic sequestration**?
**Splenectomy**
(recurrence can cause splenic infarction = susceptibility to infections)
81
What is **aplastic crisis**?
Temporary **loss of the creation of new blood cells** commonly caused by infection with **parvovirus B19**
Leads to **significant anaemia** - management is **supportive** with **blood transfusions** if necessary
Usually resolves spontaneously **within a week**
82
How is **acute chest syndrome** diagnosed?
**Fever** or **respiratory symptoms** with **new infiltrates** seen on **CXR**
83
What can **cause acute chest syndrome**?
**Infection** e.g. pneumonia or bronchiolitis
**Non-infective causes** (e.g. pulmonary vaso-occlusion or fat emboli)
84
What is the **management of acute chest syndrome**?
**Abx** or antivirals for infections
**Blood transfusions for anaemia**
**Incentive spirometry** using a machine which encourages effective and deep breathing
**Artifical ventilation** with NIV or intubation
85
What is **thalassaemia**?
**Genetic defect** in the **protein chain** that **makes up haemoglobin**
Defect in **alpha globin chain** = alpha thalassaemia
Defect in **beta globin chain** = beta thalassaemia
Both conditions are **autosomal recessive** = varying degrees of anaemia
86
Why does **thalassaemia lead to splenomegaly**?
RBCs are **more fragile** and **break down more easily** - spleen collects all destroyed RBCs
87
Why are patients with **thalassaemia** prone to **fractures** and prominent features e.g. **pronounced forehead** and **malar eminences** (cheek bones)?
**Bone marrow expands** to produce extra **RBCs**
88
What are the **signs and symptoms** of thalassaemia?
Microcytic anaemia (low **mean corpuscular volume**)
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences
89
How is **thalassaemia** diagnosed?
**FBC** for microcytic anaemia
**Haemoglobn electrophoresis** to diagnose **globin abnormalities**
**DNA testing** to look for genetic abnormality
Pregnant women are offered screening test for thalassaemia **at booking**
90
Why does **iron overload** occur in **thalassaemia**?
**Faulty creation of RBCs**
**Recurrent tranfusions**
Increased iron absorption in gut in response to anaemia
91
How are patients with thalassaemia **monitored for iron overload**?
**Serum ferritin** monitored
92
How is **iron overload managed**?
Limiting transfusions
Performing **iron chelation**
93
How does **iron overload** present?
**Fatigue**
Liver **cirrhosis**
**Infertility**
Impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
94
Where is the **genetic defect** for **alpha-thalassaamia**?
Protein on **chromosome 16**
95
What is the **management of alpha-thalassaemia**?
Monitoring FBC
Monitoring for complications
**Blood transfusions**
**Splenectomy** performed
**Bone marrow transplant** can be curative
96
Where is the defect for **beta-thalassaemi****a**?
**Chromosome 11** (can be **abnormal copy** or **deletion genes** where there is **no function in beta globin protein**)
97
What are the three types of **thalassaemia**?
Thalassaemia **minor** / **intermedia** / **major**
98
What are the **features of thalassaemia minor**?
Patients are **carriers** of an **abnormally functioning** beta globin gene (**one abnormal** and **one normal** gene)
99
What is the **management of thalassaemia minor**?
**Mild microcytic anaemia** usually patients require only monitoring
100
What are the **features of thalassaemia intermedia**?
Two abnormal copies of beta globin gene (**two defective** or **one defective** and **one deletion** gene)
Causes **more significant microcytic anaemia**
101
What is the treatment of thalassaemia intermedia?
Require **monitoring** and occasional **blood transfusions** (maybe also **iron chelation** to prevent iron overload)
102
What is the **genetic defect** in thalassaemia major?
**Homozygous** for the **deletion gene** - no functioning betal globin genes at all - most severe = **severe anaemia** and **failure to thrive in early childhood**
103
What are the **features** of **thalassaemia** **major**?
Severe **microcytic anaemia**
**Splenomegaly**
**Bone deformities**
104
What is the **management** of thalassaemia major?
**Regular transfusions**
**Iron chelation**
**Splenectomy**
**Bone marrow transplant** can potentially be curative
105
What is **hereditary spherocytosis**?
Condition where **RBCs** are **sphere shaped** making them **fragile** and **easily destroyed**
106
What is the **most common inherited haemolytic anaemia in northern europe**?
Hereditary spherocytosis
107
What is the **inheritance** of hereditary spherocytosis?
**Autosomal dominant**
108
How does **hereditary spherocytosis** present?
**Jaundice**
**Anaemia**
**Gallstones**
**Splenomegaly**
109
What is a **haemolytic crisis** in hereditary spherocytosis?
Haemolysis, anaemia and jaundice is more significant (often triggered by **infections**)
110
What is an **aplastic crisis**?
Increased **anaemia, haemolysis** and **jaundice** without normal response from **bone marrow** of creating new **red blood cells** (no **reticulocyte response** often triggered by infection with **parvovirus**)
111
How is **hereditary spherocytosis** diagnosed?
**Family history** and **clinical features** along with **spherocytes** on the **blood film**
112
What is the abnormality on **FBC** for hereditary spherocytosis?
Increased **mean corpuscular haemoglobin concentration** (MCHC)
Increased **reticulocytes**
113
What is the **management** of **hereditary spherocytosis**?
**Folate supplementation** and **splenectomy**
**Cholecystectomy** (removal of gallbladder) if gallstones a problems
**Transfusions** during acute crises
114
What are the **features** of hereditary **elliptocytosis**?
Similar to **hereditary spherocytosis** except RBC are ellipse shaped
**Autosomal dominant**
Presentation and management is similar to hereditary spherocytosis
115
What is **G6PD deficiency**?
Condition where there is a defect in the **G6PD enzyme** found in all cells in the body
116
Who is G6PD deficiency most common in?
Mediterranean
Middle eastern
African patients
117
What is the pattern of inheritance for G6PD deficiency?
**Inherited** in an **X linked recessive** pattern - usually only affects males as they have a single copy of the gene
118
What does G6PD deficiency cause?
Crises that are **triggered by infections**, **medications** or **fava beans** (broad beans)
119
What is the **function** of the **G6PD enzyme**?
Protects cells from damage by **reactive oxygen species** - molecule which **contain oxygen** produced during normal **cell metabolism** and during stress - v important in RBCs - a deficiency makes cells more vulnerable to ROS leading to **haemolysis** in RBCs - causing **acute haemolytic anaemia**
120
How does G6PD present?
Neonatal **jaundice**
121
What are the other **features of G6PD**?
**Anaemia**
**Intermittent jaundice** (particularly in response to triggers)
**Gallstones**
**Splenomegaly**
122
What may be seen on **blood film** for G6PD deficiency?
**Heinz bodies** - blobs of **denatured haemoglobin** ("inclusions") seen within the **RBCs**
123
How can **G6PD deficiency** be diagnosed?
G6PD enzyme assay
124
What is the **management** of G6PD deficiency?
**Avoid triggers** (including fava beans and certain medications)
125
Which medications **trigger haemolysis** and should be avoided?
**Primaquine** (an antimalarial)
**Ciprofloxacin**
**Nitrofurantoin**
**Trimethoprim**
**Sulfonylureas** (e.g gliclazide)
**Sulfasalazine** and other sulphonamide drugs
