Haematology And Oncology Flashcards
1
Q
Causes of anaemia in infancy
A
Physiologic anaemia of infancy Anaemia of prematurity Blood loss Haemolysis Twin-twin transfusion Haemolytic disease of the newborn Hereditary spherocytosis G6PD deficiency
2
Q
Physiologic anaemia of infancy
A
Normal dip in Hb at 6-9weeks
Due to high oxygen delivery, decreased production Hb
EPO production decreases in kidneys
Less bone marrow stimulation
3
Q
Why are premature neonates more likely to 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 EPO levels
Blood tests remove a significant portion of the circulating volume
4
Q
Causes of anaemia in older children
A
Iron deficiency anaemia, diet Blood loss: menstruation in older girls Sickle cell anaemia Thalassaemia Leukaemia Hereditary spherocytosis Hereditary elliptocytosis Sideroblastic anaemia
Helminth infection:
Roundworm, hookworm, whipworms
Albendazole or mebendazole
5
Q
Causes of microcytic anaemia
TAILS
A
Thalassaemia Anaemia of chronic disease Iron deficiency anaemia Lead poisoning Sideroblastic anaemia
6
Q
Causes of normocytic anaemia
3As
2Hs
A
Acute blood loss Anaemia of chronic disease Aplastic anaemia Haemolytic anaemia Hypothyroidism
7
Q
Causes of macrocytic anaemia
Megaloblastic
A
Megaloblastic anaemia: impaired DNA synthesis prevents cell from dividing normally
B12 deficiency
Folate deficency
8
Q
Normoblastic macrocytic anaemia
A
Alcohol Reticulocytosis (haemolytic anaemia or blood loss) Hypothyroidism Liver disease Azathioprine
9
Q
Symptoms of anaemia
A
Tiredness SoB Headaches Dizziness Palpitations Worsening of other conditions
10
Q
Symptoms specific to iron deficiency anaemia
A
Pica: cravings for dirt, ice
Hair loss: iron deficiency anaemia
11
Q
Genetic signs of anaemia
A
Pale skin
Conjunctival pallor
Tachycardia
Raised RR
12
Q
Signs of iron deficiency anaemia
A
Koilonychia
Angular cheilitis
Atrophic glossitis
Brittle hair and nails
13
Q
Sign of haemolytic anaemia
A
Jaundice
14
Q
Sign of thalassaemia anaemia
A
Bone deformities
15
Q
Complications of chemotherapy
A
Failure to treat leukaemia Stunted growth and development Immunodeficiency and infections Neurotoxicity Infertility Secondary malignancy Cardio toxicity
16
Q
Investigations for anaemia
A
FBC Blood film Reticulocyte count Ferritin B12 and folate Bilirubin: raised in haemolysis Direct Coombs test: positive in autoimmune haemolytic anaemia Haemoglobin electrophoresis: thalassaemia, sickle cell anaemia
17
Q
Iron deficiency anaemia causes
A
Dietary insufficiency
Loss of iron, heavy menstruation
Inadequate iron absorption, e.g. Crohn’s disease
PPI as iron needs acid in stomach to stay soluble 2+
Coeliac/ Crohn’s reduce absorption in duodenum and jejunum
18
Q
How to calculate transferrin saturation
A
Transferrin saturation = serum iron/ total iron binding capacity
Should be around 30%
Increased value of results with:
Iron supplements
Acute live damage
19
Q
Management of iron deficiency anaemia
A
Treat underlying cause
Dietician input
Ferrous sulphate or ferrous fumarate
SE: constipation and black stools
20
Q
Leukaemia
A
Cancer of stem cells in bone marrow
Unregulated production of certain types of blood cells
21
Q
Types of leukaemia
A
Acute lymphoblastic leukaemia: most common in children
Acute myeloid leukaemia
Chronic myeloid leukaemia: rare
22
Q
Epidemiology leukaemia
A
All peaks at 2-5 years
Males > females
23
Q
Pathophysiology leukaemia
A
Genetic mutations, infections
Disruption in regulation and proliferation of lymphoid precursor cells in bone marrow
Excessive production of immature blast cells
Drop in numbers of functional RBC, WBC, platelets
24
Q
Leukaemia risk factors
A
Radiation exposure Down’s syndrome Kleinfelters syndrome Noonan syndrome Fanconis anaemia
25
History of leukaemia
```
Anaemia: lethargy, pale
Thrombocytopenia: easy bruising, bleeding, petechiae
Leukopenia: unexplained fevers, infections
Bone pain: hyper plastic marrow
Weight loss
Malaise
CNS involvement: headaches, seizures
Night sweats
Abdominal pain
```
26
Leukaemia examination
Pale
Unexplained bruising, bleeding
Lymphadenopathy
Hepatosplenomegaly
27
DD bruising
```
Leukaemia
Immune thrombocytopenia
Trauma
Non-accidental injury
Ehler-Danlos
VitC deficiency
```
28
DD lymphadenopathy
```
Infective:
Infectious mononucleosis
HIV, seroconversion illness
Eczema with secondary infection
Rubella
Toxoplasmosis
CMV
TB
Roseola infantum
```
Neoplastic:
Leukaemia
Lymphoma
Others:
Autoimmune conditions: SLE, rheumatoid arthritis
Sarcoidosis
Drugs: phenytoin, allopurinol, isoniazid
Graft vs host disease
29
DD pallor
```
Pernicious anaemia
Axillary/ brachial embolus
Acute lymphoblastic leukaemia
Neonatal hypoglycaemia
Myeloma
Neuroblastoma
```
30
Acute lymphoblastic leukaemia investigations
```
FBC: pancytopenia
Blood film: blast cells
CXR to exclude mediastinal mass
Bone marrow aspirate/ trephine
Lumbar puncture
```
31
Risk scoring acute lymphoblastic leukaemia
Cytogenetic testing
Age: 1-10 at presentation have a good prognosis
WCC>50 poorer prognosis
Females > male prognosis
CNS involvement: blasts within CSF, poorer prognosis
Leukaemia characteristics
32
Diagnosis of leukaemia
Urgent FBC within 48 hours
33
Management of acute lymphoblastic leukaemia
| Immediate
Resuscitate and stabilise unwell child
If high WCC: hyperhydration to prevent hyper viscosity
If mediastinal mass: steroids to reduce airway compromises
Infection/ sepsis: broad spectrum antibodies
34
Definitive and long-term management of acute lymphoblastic leukaemia
UKALL 2011 protocol
IV chemotherapy, orally, intra-thecally (into CSF)
Supportive care with blood products (red cells, platelets)
Prophylactic anti-fungal therapy throughout treatment
No role for radiotherapy in management
Maintenance treatment is 2 years for girls and 3 years for boys
35
Prognosis and complications of acute lymphoblastic leukaemia
```
90% survival
Infertility
Avascular necrosis
Peripheral neuropathy
Anxiety
```
Regular follow-up and assessment for 5 years after completion of treatment
36
Acute myeloid leukaemia pathophysiology
Cancer of blood and bone marrow
Myeloid stem cell-> RBC, WCC, platelets
Self-renewal and developmental arrest of progenitor cells at a particular point in their differentiation
Creating immature cells (myeloblasts) that infiltrate bone marrow, RES
Less room in blood and bone marrow for health cells
Infection, anaemia or easy bleeding can occur
Leukaemia cells can spread to CNS, skin and gums. Occasionally leukaemia cells form a solid tumour called a chloroma or granulocytic sarcoma
37
FAB classification of AML
```
MO: AML with minimal evidence of myeloid differentiation
M1: AML without maturation
M2: AML with maturation
M3: acute promyelocytic leukaemia
M4: acute myelomonocytic leukaemia
M5: acute monocytic/ monoblastic leukaemia
M6: acute erythroleukaemia
M7: acute megakaryoblastic leukaemia
```
38
Risk factors for acute myeloid leukaemia
```
Down’s syndrome
Li-Fraumeni syndrome
Aplastic anaemia
Myelodysplasia
Affected sibling
```
39
Clinical features of acute myeloid leukaemia
Classification signs of anaemia, thrombocytopenia, hepatosplenomegaly, or lymphadenopathy
40
Bone marrow failure in AML
| Symptoms/ signs
Anaemia: pallor, lethargy, shortness of breath, dizziness, palpitations, reduced exercise tolerance
Neutropenia: fever, recurrent infections, unusual infections
Thrombocytopenia: brushing, petechia, epistaxis
41
Blast infiltration of other tissues in acute myeloid leukaemia
Symptoms/ signs
Bone marrow: limb pains
Reticuloendothelial: hepatosplenomegaly, lymphadenopathy, expiratory wheeze (secondary to a mediastinal mass due to lymphadenopathy or thymic infiltration/ expansion)
Testes: testicular enlargement
42
Systemic effects of cytokines released by leukaemic cells and of increased plasma viscosity (leucoastasis) due to extremely high WCC
Signs/symptoms
Acute myeloid leukaemia
Cytokine release: fever, malaise, fatigue, nausea
Leucostasis: headache, vomiting, cranial nerve palsies, seizures, stroke, shortness of breath, heart failure
43
DD of acute myeloid leukaemia
Acute lymphocytic leukaemia: pancytopenia
Iron deficiency anaemia: pallor, lethargy, SoB
Immune thrombocytopenic purpura
Immunodeficiency: recurrent infections
44
Acute myeloid leukaemia
| Laboratory tests
FBC: pancytopenia
| Blood film: blasts present, elevated overall WCC, atypical cells in blood film, presence of leukoerythroblastic features
45
Acute myeloid leukaemia
| Imaging or invasive tests
CXR: information on whether any of the lymph glands in chest are enlarged
Bone marrow aspirate and trephine- bone marrow examination allows definitive diagnosis of acute leukaemia
Lumbar puncture: checks for leukaemia cells in CSF, may require intra-thecal chemotherapy as part of their treatment
Biopsy: AML diagnosed by biopsy of a chloroma
46
Bone marrow examination in acute myeloid leukaemia
Aspirate: morphological, immunological, genetic information. Information used alongside clinical factors and initial response to chemotherapy
Light microscopy: allows classification as acute lymphoblastic leukaemia or acute myeloid leukaemia
Immunophenotyping using flow cytometry, identifies patterns of cell surface antigens associated with particular subtypes of acute myeloid leukaemia
47
Management of acute myeloid leukaemia
| Initial management
Indication; induces remission
| Post-remission consolidation/ intensification; reduces risk of relapse
48
Management of acute myeloid leukaemia
| Induction
Two cycles of chemotherapy given four weeks apart
Examining bone marrow after each cycle will allow monitoring of response to induction
Aim of induction: no evidence of leukaemia in bone marrow after induction is completed (remission)
49
Definitive and long term management of acute myeloid leukaemia
Post-remission therapy
| Bone marrow transplant
50
Post-remission therapy AML
Further chemotherapy to destroy any remaining leukaemia cells and to prevent recurrence
Varying number of cycles of intensive chemotherapy and/or allogenic haematopoeitic stem cell transplantation
51
Bone marrow transplant AML
Reserved for children with an suboptimal response to standard chemotherapy Or if leukaemia relapses
20% of AML will require a transplant
52
Complications of treatment of acute leukaemia
```
Neutropenic sepsis: multi-organ failure
Bone marrow suppression (myelosuppression), pancytopenia
Nausea and vomiting
Mucositis
Hair loss
```
53
Specific side effects of chemotherapy agents
Doxorubicin- cardiotoxicity
Vincristine- peripheral neuropathy
Cyclophosphamide- reduced fertility
Cytarabine- hepatotoxicity
54
Lymphoma
Malignancy of the lymphatic system
| Divided into Hodkin’s lymphoma and non-Hodgkins lymphoma
55
Epidemiology of lymphoma
Accounts for 10% of childhood cancers
More common in boys than girls
More common in older children
More than half of lymphoma cases are non-Hodgkin lymphoma
56
Pathophysiology of lymphoma
Multifactorial development; infection, genetic factors, environmental exposures
Lifestyle factors in adults: obesity, smoking, alcohol intake
57
History of lymphoma
EPV implicated in development of lymphoma. Immunosuppressed patients and those who have been treated for other cancers in the past are also at increased risk of lymphoma
B symptoms: weight loss, night sweats, fevers
Lethargy and anorexia
Visible or palpable mass
58
Examination of lymphoma
Non-tender lymphadenopathy
Non visible/ palpable if mediastinal or intra-abdominal lymph nodes are involved
Mediastinal lymphadenopathy: cough, wheeze or other difficulty in breathing, SVC obstruction or airway compromise can occur
59
DD of lymphoma
Reactive lymphadenopathy, History of recent infection. If lymph nodes themselves have become infected (lymphadenitis) they are likely to be tender and potentially fluctuant if an abscess has formed
Leukaemia: lymphadenopathy with signs/symptoms of anaemia and/or thrombocytopenia
Lymphadenopathy: can also be a sign of metastatic malignancy from another site
60
Lymphoma laboratory tests
Blood tests: FBC
U&E for tumour lysis syndrome can occur before treatment begins in lymphomas with rapid cell turnover
LDH: levels are usually elevated
61
Lymphoma imaging
USS of the area can help identify other nodes, and assists with biopsy
CXR: required if there are symptoms of mediastinal node involvement
Full body CT to determine extent of disease
Biopsy: lymph node biopsy for definitive diagnosis
62
Risk scoring lymphoma
Stage 1: single group of lymph nodes or a single organ
Stage 2: disease is present in 2 or more groups of lymph nodes or organs on the same side of the diaphragm
Stage 3: disease is present in lymph nodes or organs on both sides of the diaphragm
Stage 4: diffuse involvement of lymph nodes and organs such as the liver and bones
63
Lymphoma B symptoms
| Associated with worse prognosis
Weight loss
Night sweats
Fevers
64
Immediate management of lymphoma
Presence of a mediastinal mass with potential airway compromise is an emergency
Treatment with high dose steroids and airway support if required
SVCO may require stenting of veins to keep them patent, usually resolve with treatment of the underlying malignancy
Suggestion of tumour lysis syndrome, then hyperhydration is important. Allopurinol or rasburicase are also used
65
Definitive and long-term management of lymphoma
Treatment is with chemotherapy ans possibly radiotherapy, depending on the stage of disease
66
Prognosis of lymphoma
Hodgkins > non-Hodgkins
| Majority will recover coompletley
67
Complications of lymphoma
Tumour lysis syndrome: rapid lysis of tumour cells cases release of large amounts of phosphorous, potassium and calcium
Leading to potential kidney damage
Neutropenia, alopecia, sub-fertility
Life-long follow up for complications
68
Nephroblastoma
Wilm’s tumour
Most common renal tumour affecting children
Usually unilateral but can be bilateral
69
Nephroblastoma epidemiology
Affects 80 children per year in UK
Generally presents in the pre-school age group
3.5years being median age at diagnosis
Slight female predominance
70
Pathophysiology of nephroblastoma
Tumours arise from nephrogenic rests;embryonal remnants seen in around 1% of infants at birth
71
Risk factors for nephroblastoma
Children with certain genetic and overgrowth syndromes
WAGR (Wilms tumour, aniridia, genitourinary malformations, retardation)
Denys-drash and beckwith-wiedemann
72
Nephroblastoma history
Abdominal mass found incidentally
Noted by parents during bathing or dressing in an otherwise well child
Abdominal swelling, abdominal pain, fever, or haematuria
73
nephroblastoma examination
Abdominal distension
Unilateral or bilateral palpable masses
Hypertension may be noted
Rarely, in cases of advanced disease, signs of compression of other intra-abdominal structures
74
DD of nephroblastoma
Polycystic kidney disease and hydronephrosis
Most common malignant DD in a pre-school child is a neuroblastoma: presents with HTN, abdominal pain or fever
Neuroblastoma: periorbital ecchymosis, abdominal mass which crosses midline, signs of bone marrow infiltration
75
Nephroblastoma laboratory tests
FBC
U&E
Urine dip for haematuria
Evaluate child’s general heath at presentation
76
Nephroblastoma imaging or invasive tests
Initial characterisation of a renal/ abdominal mass: USS, CT/MRI for staging
Biopsy
77
Risk scoring nephroblastoma
1: tumour is only confined to the kidney and can be completely removed with surgery
2: tumour has begun to spread beyond the kidney, but can still be completely removed with surgery
3: tumour cannot be completely surgically resected because it has spread to neighbouring lymph nodes or ruptured before/during surgery
4: distant metastases, most commonly to lungs
5: bilateral tumours
78
Initial management nephroblastoma
Supportive care
| Treat co-existing infection and ensure nutrition and hydration are optimised
79
Definitive and long-term management nephroblastoma
Stage 1 and 2 tumours may be treated solely with surgery
No additional benefit to giving chemotherapy which has additional risks later in life
Aim of surgery: preserve renal function while removing the malignant tissue
Chemotherapy: used to reduce the volume of malignant tissue before surgery, or to treat any areas of malignant disease not removed by surgery (nephrectomy)
Surgery consists of nephrectomy: in bilateral disease, attempt to preserve as much functioning renal tissue as possible
80
Complications and prognosis nephroblastoma
Steps must be taken to protect the remaining kidney
Maintain blood pressure
Avoidance of contact sports, which could lead to abdominal trauma
Monitor for cardiotoxicity and/or radiotherapy
81
Neuroblastoma
Paediatric cancer
Derived from neural crest cells, arising in adrenal glands or abdominal sympathetic chain
Most common cancer in children <1 year old, much less common in >5s
82
Epidemiology of neuroblastoma
Affects around 90 children per year in the UK
Most common solid tumour in children under one year of age
36% of neuroblastomas arise from the medulla of the adrenal glands, with another 18% arising from the sympathetic chain
10% are bilateral, 10% arise from an unknown source and are first diagnosed as secondary metastases
83
Pathophysiology of neuroblastoma
Neuroblastoma arises from poorly differentiating embryonic cells (blasts)
In this case from neural crest
Neural crest cells are derived from developing ectoderm, and normally migrate throughout the body to form SNS and adrenal medulla
When migration is stalled, neural crest cells have the potential to acquire mutations that eventually lead to neuroblastoma
Associated with genetic mutations, MYCN and ALK oncogenes, as well as loss-of-function of the tumour suppressor PHOX2B
84
Risk factors for neuroblastoma
No identified cause
Hirschsprung’s disease
Congenital central hypoventilation syndrome
85
History of neuroblastoma
Abdominal distension
Fatigue
Appetite loss
Weight loss
Increased catecholamine: sweating, agitation
Metastasis: bone pain that prevents sleep, recurrent infections
Compression of SNS can lead to urinary incontinence
Occasionally, neuroblastomas can arise from the thoracic portion of sympathetic chain, causes SOB and chest pain
86
Neuroblastoma examination
Dense abdominal swelling, across midline
Hypertensive and tachycardia due to excess catecholamine synthesis
Symptoms of metastasis: periorbital bruising for children with metastases to skull base
Neuroblastoma cells can metastasise to dermis: scattered purpura across skin to give blueberry muffin rash (non-specific)
Bone metastases: bone marrow infiltration, evidence of recurrent infections and thrombocytopenic purpura
87
Neuroblastoma differentials
Abdominal mass:
Cysts: hepatic, polycystic kidney disease
Hyperplasia: pyloric stenosis, hepatomegaly, splenomegaly
Neoplasia: Wilm’s tumour, lymphoma, rhabdomyosarcoma, hepatoblastoma
Blueberry muffin rash: TORCH infections or acute myeloid leukaemia
88
Lab tests neuroblastoma
Look for products of catecholamine breakdown: homovanilic acid, vanillylmandelic acid in urine
90% of patients will have raised HMA and VMA
Additionally: bone marrow and skin biopsies, evidence of metastasis to these sites
89
Neuroblastoma imaging
USS: paediatric abdominal lumps
MRI second line
For thoracic neuroblastomas: CXR
Definitive test for neuroblastoma: MIBG scan
Radioisotope of iodine is injected, and two scans are taken 24 hours apart
Iodine stays in tumour, becoming an intensely dark region on the scan
90-95% of children with neuroblastoma will have positive features on the MIBG-scan
90
Staging for neuroblastoma
| Imaging
Neuroblastoma risk group
1: fully resectable at surgery
2A: tumour is unilateral but not fully resectable, no spread to local lymph nodes
2B: tumour is unilateral but is not resectable, with spread to ipsilateral lymph nodes
3: tumour has crossed midline, or spread to Contralateral lymph nodes
4: distant metastasis outside of local lymph nodes
4S: metastases confined to liver, skin or bone marrow in <18monyjhs
91
Staging for neuroblastoma
| Surgical observations
L1: localised tumour that doesnt involve vital structures (surgically resectable)
L2: localised tumour that does involve vital structures (non-resectable)
M: distant metastases (excludes local lymph node metastases)
MS: metastases confined to liver, skin or bone marrow in patients <18months old
92
Management of neuroblastoma
<18months:
Will regress to a benign ganglioma
Monitoring
Older children, aggressive disease:
Surgery
L1- curative
L2;- need adjuvant chemotherapy or radiotherapy
93
Factors giving improved neuroblastoma prognosis
Younger age at diagnosis
Assigned female at birth
Lesser tumour stage at diagnosis
MYCN mutation absent
94
Complications of neuroblastoma
Relapse
Opsoclonus myoclonus ataxic syndrome: autoimmune disorder arising from antibody self-reactivity to proteins from dying neuroblast cells, which then lead to an immune reaction to CNS (cerebellum)
Opsoclonus: uncontrolled, irregular eye movements
Myoclonus: muscle spasm
Ataxia: lack of voluntary movement control
Confusion
Irritability
95
Astrocytoma
Low and high grade gliomas that develop from glial cells
96
Medulloblastoma
Usually develop in posterior fossa/ cerebellum
97
Ependymoma
Formed from CSF producing ependymal cells
98
Craniopharyngioma
Found at base of brain close to pituitary gland
99
Germ cell tumours
Arise from germ cells
| Found close to pituitary gland and pineal gland
100
Choroid plexus tumours
Develop from network of ependymal cells
101
Risk factors primary brain tumours
```
Personal/family history of brain tumour, leukaemia, sarcoma and early onset breast cancer
Prior therapeutic CNS irradiation
Neurofibromatosis 1 and 2
Tuberous sclerosis 1 and 2
Von Hippel-Lindau
```
102
History of brain tumour
```
Headache: mass effect or hydrocephalus
N/V
Behavioural change: due to tumours found in frontal lobe
Polyuria/poldipsia: diabetes insipidus
Seizures
Altered GCS
```
103
Primary brain tumour examination
General: behaviour, conscious level, alertness
Visual: diplopia, reduced visual acuity/fields, eye movement, fundoscopy
Motor signs: abnormal gait or coordination, swallowing difficulties, weakness
Delayed growth
Delayed, arrest or precocious puberty
Increased head circumference if under 2 years old (growth chart)
104
DD primary brain tumour
```
Migraine or tension headaches
Meningitis/ encephalitis
Intracranial haemorrhage/ stroke
Otitis media: unsteady gait
Neurofibromatosis
```
105
Brain tumour investigations
MRI
| 2nd: contrast enhanced CT
106
Management CNS malignancy
```
Analgesia, antiemetic, anticonvulsants, fluid/dietary support, treatment to lower ICP (steroids)
Surgical resection
CSF shunts for hydrocephalus
Radiotherapy
Chemotherapy: BBB?
Proton therapy
Stem cell transplantation
```
107
Complications of CNS malignancy
```
Epilepsy and seizures
Sleep disturbance
Effects on puberty/ fertility
Hearing loss
Impaired growth
Cognitive impairment
Secondary malignancy
```
108
Idiopathic thrombocytopenic purpura
```
Low platelet count
Causing a purpuric rash
TY2 hypersensitivity reaction
Antibodies target platelets
Non-blanching rash
```
109
Presentation of ITP
```
<10 years old
Recent viral illness
Symptoms onset 24-48hours
Bleeding: gums, epistaxis, menorrhagia
Bruising
Petechiae or purpuric rash, caused by bleeding under the skin
```
110
ITP management
Urgent FBC for platelets
Exclude heparin induced thrombocytopenia and leukaemia
Resolve <3 months
Active bleeding or severe thrombocytopenia:
Prednisolone
IV immunoglobulins
Blood transfusions
Platelet transfusions: temporarily work until antibodies destroy them too
111
Advice for patients with thrombocytopenia
```
Avoid contact sports
Avoid IM injections and lumbar puncture
Avoid NSAIDS, aspirin, blood thinners
Advice on managing nosebleeds
Seek help after any injury that may cause internal bleeding
```
112
ITP complications
Chronic ITP
Anaemia
Intracranial and subarachnoid haemorrhage
GI bleeding
113
Sickle cell anaemia
Genetic condition that causes sickle shaped RBC
| Makes them fragile and more easily destroyed, leading to haemolytic anaemia
114
Sickle cell anaemia pathophysiology
Haemoglobin is the protein in RBC that transports oxygen
HbF—>HbA at 6 weeks of age
HbS
Autosomal recessive
Abnormal gene for beta-haemoglobin on chromosome 11
115
Sickle cell and malaria
Sickle cell trait reduces risk of malaria
| Selective advantage
116
Sickle cell diagnosis
Newborn screening heel prick test at 5 days of age
117
Sickle cell complications
```
Anaemia
Increased risk of infection
Stroke
Avascular necrosis in large joints
Pulmonary hypertension
Painful and persistent penile erections
Chronic kidney disease
Sickle cell crises
Acute chest styndrome
```
118
Sickle cell disease management
Avoid dehydration and triggers
Ensure vaccines are up to date
Antibiotic prophylaxis: Penicillin V (phenoxymethylpenicillin)
Hydroxycarbamide: stimulates production of HbF
Blood transfusion for severe anaemia
Bone marrow transplant can be curative
119
Sickle cell crisis
```
Low threshold for hospital admission
Analgesia
Rehydrate
Oxygen
Treat infection
Keep warm
Penile aspiration to treat priapism
Blood transfusion
```
120
Vaso-occlusive crisis
| Sickle cell disease
Sickle shaped blood cells clogging capillaries and causing distal ischaemia
Associated with dehydration and raised haematocrit
Symptoms: pain, fever, symptoms of triggering infection
Priapism in men: trapping blood in penis, urological emergency and treated with aspiration of blood from the penis
121
Splenic sequestration crisis
RBC blocking blood flow within spleen
Causes acutely enlarged and painful spleen
Pooling of blood in spleen: severe anaemia, circulatory collapse (hypovolaemic shock)
Emergency
Management is supportive, with blood transfusions and fluid resuscitation to treat anaemia and shock
Recurrent crisis: splenectomy is management, as recurrent crises can lead to splenic infarction and susceptibility to infections
122
Aplastic crisis
Temporary loss of creation of new blood cells
Most commonly triggered by infection with parvovirus B19
Leads to anaemia
Management is supportive: blood transfusions, usually resolves spontaneously within a week
123
Acute chest syndrome
Diagnosis:
Fever or respiratory symptoms
New infiltrates seen on a CXR
Acute chest syndrome can be due to infection (pneumonia or bronchiolitis) or non-infective causes (pulmonary vaso-occlusion or fat emboli)
124
Acute chest syndrome management
Antibiotics or antivirals for infections
Blood transfusions for anaemia
Incentive spirometry using a machine that encourages effective and deep breathing
Artificial ventilation with NIV or intubation may be required
125
Thalassaemia
Genetic defect in the protein chains that make up haemoglobin
Normal Hb: 2 alpha and 2 beta
Both conditions are autosomal recessive
Varying degrees of anaemia
RBC more fragile and break down more easily
Spleen removes dead RBC, splenomegaly
Bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia
Susceptibility to fractures and prominent features, such as a pronounced forehead and malar eminences (cheek bones)
126
Thalassaemia potential signs and symptoms
```
Microcytic anaemia (low mean corpuscular volume)
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences
```
127
Diagnosis of thalassaemia
FBC: microcytic anaemia
Haemoglobin and electrophoresis: used to diagnose globin abnormalities
DNA testing: genetic abnormality
Pregnant women offered a screening test for thalassaemia at booking
128
Thalassaemia iron overload
Iron overload due to faulty creation of RBC, recurrent transfusions and increased absorption of iron in the gut in response to anaemia
Monitor serum ferritin levels in thalassaemia
Management of iron overload: limiting transfusions and performing iron chelation
129
Iron overload in thalassaemia
| Effects
```
Fatigue
Liver cirrhosis
Infertility
Impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
```
130
Management of alpha thalassaemia
```
Monitoring the FBC
Monitoring for complications
Blood transfusions
Splenectomy may be performed
Bone marrow transplant can be curative
```
Caused by defects in the alpha globin chains
131
Beta thalassaemia management
Caused by defects in beta globin chains
Gene defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in beta globin protein at all
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
132
Thalassaemia minor
Carries of abnormally functioning beta globin gene
One normal and one abnormal gene
Mild microcytic anaemia, usually patients only require monitoring and no active treatment
133
Thalassaemia intermediate
Two abnormal copies of the beta globin gene
Can either be two defective genes or one defective and one deletion gene
Causes a more significant microcytic anaemia
Patients require monitoring and occasional blood transfusions
Iron chelation to prevent iron overload, when they require more transfusions
134
Thalassaemia major
Homozygous for deletion genes
No functioning beta globin genes at all
Presents with severe anaemia and failure to thrive in eagerly childhood
135
Causes of thalassaemia major
Severe microcytic anaemia
Splenomegaly
Bone deformities
136
Management of thalassaemia major
Regular transfusions
Iron chelation and splenectomy
Bone marrow transplant can potentially be curative
137
Hereditary spherocytosis
Condition where RBC are sphere shaped, making them fragile and easily destroyed when passing through spleen
Most common haemolytic anaemia in Northern European
Autosomal dominant
138
Presentation of hereditary spherocytosis
Jaundice
Anaemia
Gallstones
Splenomegaly
Haemolytic crisis
Aplastic anaemia
139
Haemolytic crisis in hereditary spherocytosis
triggered by infections, where haemolysis, anaemia and jaundice is more significant
140
Hereditary spherocytosis aplastic crises
Increased anaemia, haemolysis, jaundice
Without normal response from bone marrow of creating new RBCs
No reticulocyte response
Often triggered by infection with parvovirus
141
Diagnosis of hereditary spherocytosis
FH, clinical features
Along with spherocytosis on blood film
Mean corpuscular Haemoglobin concentration is raised on FBC
Reticulocytes raised due to rapid turnover of RBCs
142
Management of hereditary spherocytosis
Treat with folate Supplementation
Splenectomy
Cholecystectomy if gallstones are the problem
Transfusions may be required during acute crises
143
Hereditary elliptocytosis
| In hereditary spherocytosis
RBC ellipse shaped
Autosomal dominant
Presentation and management are very similar
144
G6PD deficiency
X-linked recessive, usually affects males
More common in Mediterranean, Middle Eastern, African patients
Crises that are triggered by infections, medications or fava beans (broad beans)
145
Pathophysiology of G6PD deficiency
Enzyme is responsible for helping protect cell from damage by reactive oxygen species
ROS are reactive molecules that contain oxygen, producing during normal cell metabolism and in higher quantities during stress on the cell
G6PD enzyme deficiency makes cells more vulnerable to ROS
Leading to haemolysis in RBC
Periods of increased stress, with higher production of ROS can lead to acute haemolytic anaemia
146
G6PD deficiency presentation
```
Neonatal jaundice
Anaemia
Intermittent jaundice
Gallstones
Splenomegaly
```
Heinz bodies may be seen on a blood film
Heinz bodies are blobs of denatured haemoglobin (inclusions) seen within RBCs
Diagnosis can be made by going a G6PD deficiency
147
Management of G6PD deficiency
Patients should avoid triggers of acute haemolysis where possible
Includes avoiding fava beans and certain medications
148
G6PD deficiency
| Medications that trigger haemolysis and should be avoided
```
Primaquine
Ciprofloxacin
Nitrofurantoin
Trimethoprim
Sulphonylureas
Sulfasalazine and other sulphonamide drugs
```
149
Henoch-schonlein purpura
IgA vasculitis
Presents with a purpuric rash affecting lower limbs and buttocks in children
IgA deposits in blood vessels
Inflammation occurs in the affected organs
Affects skin, kidneys, GI tract
Condition triggered by an upper airway infection or gastroenteritis
Most common <10 years
150
Four classic features of HSP
Purpura- lumps under skin containing blood
Joint pain
Abdominal pain
Renal involvement
151
HSP purpura
```
Purpura:
Palpable under skin
Start on legs and spread to buttocks
Also affect trunks and arms
Skin ulceration and necrosis can develop
Red-purple in colour
```
152
Arthralgia or arthritis HSP
Arthralgia or arthritis:
Mostly affecting knees and ankles
Joints can becomes swollen and painful
Reduced range of movement
153
HSP abdominal pain
```
Abdominal pain:
No GI involvement
GI haemorrhage
Intussusception
Bowel infarction
```
154
HSP kidneys
Kidneys:
IgA nephritis
HSP nephritis
Microscopic or macroscopic haematuria and proteinuria
>2+ protein on urine dipstick, child has developed nephrotic syndrome and will have a degree of oedema
155
Diagnosis of HSP
Exclude meningococcal septicaemia, leukaemia, ITP, HUS
```
FBC and blood film: thrombocytopenia, sepsis, leukaemia
Renal profile for kidney involvement
Serum albumin: nephrotic syndrome
CRP for sepsis
Blood cultures
Urine dipstick for proteinuria
Urine protein: creatinine ratio
Blood pressure for HTN
```
156
EULAR/PRINTO/PRES criteria for diagnosing HSP
Palpable purpura
+ one of
Diffuse abdominal pain
Arthritis or arthralgia
IgA deposits on histology (biopsy)
Proteinuria or haematuria
157
Management of HSP
Supportive, simple analgesia, rest, hydration
Urine dipstick for renal involvement
Blood pressure for HTN
Abdominal pain settles in a few days
Patients without kidney involvement recover in 4-6weeks
A third have a recurrence of disease within 6 months
ESRD in a small proportion
158
DIC
```
Tissue factor (transmembrane glycoprotein)
Exposed to circulation after vascular damage: present on surface of endothelial cells, macrophages, and monocytes
TF is released in response to exposure to cytokines (IL-1), TNF, and endo toxin
Abundant in lungs, brain and placenta
TF triggers extrinsic and intrinsic pathway
```
159
Causes of DIC
Sepsis
Trauma
Obstetric complications, e.g. amniotic fluid embolism or haemolysis, elevated LFT, low platelets (HELLP syndrome)
Malignancy
160
Diagnosis of DIC
```
Decreased platelets
Decreased fibrinogen
Increased PT & APTT
Increased FDP
Schiscocytes due to microangiopathic haemolytic anaemia
```
161
Diagnosis of hyposplenism
Radionucleotide labelled red cell scan
162
Causes of hyposplenism
Splenic artery embolizartion
| Splenectomy for trauma
163
Management of hyposplenism
Pneumococcal, Haemophilus TYB, meningococcal TYC vaccines. 2 weeks prior to splenectomy or two weeks following splenectomy
Annual influenza vaccine
Post-splenectomy crisis, penicillin or macrolides prophylaxis for high risk individuals
Risk of malaria
164
Hyposplenism blood film
```
Target cells
Howell-Jolly bodies
Pappenheimer bodies
Siderotic granules
Acanthocytes
```
