PAEDS - ONCOLOGY / HAEMATOLOGY Flashcards
LEUKAEMIA
What is leukaemia?
A malignant proliferation of haemopoietic stem cells (immature blood cells)
LEUKAEMIA
Name 4 sub types of leukaemia
AML - Acute Myeloid Leukaemia
CML - Chronic Myeloid Leukaemia
ALL - Acute Lymphoblastic Leukaemia
CLL - Chronic Lymphoblastic Leukaemia
LEUKAEMIA
Give 3 environmental causes of leukaemia
Radiation exposure
Chemicals (benzene compounds)
Drugs
ALL
What is acute lymphoblastic leukaemia (ALL)?
- Affects precursors to B + T cells
- It leads to uncontrolled proliferation of immature blast cells affecting both the blood + bone marrow (lymphoid progenitor cells and lymphoblasts)
ALL
What is the epidemiology of ALL?
- 80% of leukaemias in children,
- peaks at 2–5y
- associated with ionising radiation
ALL
What are the risk factors for acute lymphoblastic leukaemia (ALL)?
- Trisomy 21,
- immunocompromised (HIV, immunosuppressants)
ALL
What are the broad categories of clinical presentation in ALL?
- General = anorexia, fever, weight loss, night sweats
- Bone marrow infiltration = pancytopenia
- Reticuloendothelial infiltration = hepatmospenolmegaly, lymphadenopathy
- Other organ infiltration (more common at relapse) = headache, testicular enlargement, bone pain
ALL
How does bone marrow infiltration present in ALL?
- Anaemia (pallor, lethargy),
- neutropenia (frequent or severe infections),
- thrombocytopenia (bruising, petechiae, epistaxis)
ALL
How does reticuloendothelial infiltration present in ALL?
- Hepatosplenomegaly,
- lymphadenopathy
ALL
How is organ infiltration presented in ALL?
- CNS = headaches, vomiting + nerve palsies,
- testicular enlargement,
- bone pain
ALL
What are the investigations for ALL?
- FBC + blood film = pancytopenia, WCC up or down, circulating blast cells
- Bone marrow aspiration to Dx - blast cells
- CXR + CT to identify mediastinal mass and abdominal lymphadenopathy
- LP to identify CNS involvement
ALL
What do blood and bone marrow tests show in ALL?
FBC and blood film = WCC usually high
Blast cells on film and in bone marrow
ALL
What are some good prognostic factors in ALL?
- Age 2-10
- Female
- WCC <20
- No CNS disease
- Caucasian
ALL
What are some complications of ALL?
- Psychological impact of childhood cancer
- Fertility = offer to freeze eggs or sperm before Tx
- CNS development, growth impact, delayed puberty, cardiac + renal toxicity
ALL
What is the supportive management for ALL?
- Correct abnormalities with blood/platelet transfusion
- Fluids for hydration
- Allopurinol to protect kidneys from tumour lysis syndrome
ALL
What is the management for ALL?
- Blood and platelet transfusion
- Chemotherapy
- Steroids
- Allopurinol to prevent tumour lysis syndrome
- Intrathecal drugs, e.g. methotrexate
- Acute control of infections with IV antibiotics
- Neutropenia makes this high risk
- Stem cell transplant
ALL
Explain the precise management in…
i) remission induction
ii) consolidation + CNS protection
iii) interim maintenance
iv) intensification
v) continuing maintenance
i) Combo chemo often IV vincristine + dexamethasone
ii) IT chemo (methotrexate)
iii) Mod intensity chemo, co-trimoxazole prophylaxis for PCP
iv) Intensive chemo to consolidate remission
v) 2y for girls, 3y for boys as higher recurrence
ALL
What is the management for relapse or high risk patients?
- Bone marrow transplantation
AML
What is acute myeloid leukaemia (AML)?
Neoplastic proliferation of blast cells (immature blood cells)
affects myeloid progenitor cells and myeloblasts
AML
What are the risk factors for AML?
Preceding haematological disorders
Prior chemotherapy
Exposure to ionising radiation
Down’s syndrome
AML
what are the clinical features of AML?
Anaemia -> breathlessness, fatigue, pallor
Infection
Hepatosplenomegaly
Peripheral lymphadenopathy
Gum hypertrophy
Bone marrow failure and bone pain
AML
Why are anaemia, infection and bleeding symptoms of leukaemia?
Because of bone marrow failure
AML
Why are hepatomegaly and splenomegaly symptoms of leukaemia?
Because of tissue infiltration
AML
What investigations do you do on someone who you suspect has AML?
FBC - anaemia, thrombocytopaenia, neutropoenia
Blood film - leukaemic blast cells
Bone marrow biopsy - Auer rods
Cytogenetic analysis and immuno-phenotyping
AML
What would you expect to see on an FBC and bone marrow biopsy in someone you suspect to have AML?
FBC = anaemia and thrombocytopenia and neutropenia
BM biopsy = leukaemic blast cells (with Auer rods)
AML
Describe the treatment for AML
Blood and platelet transfusions
IV fluids
Allopurinol to prevent tumour lysis
Infection control with IV antibiotics
Chemotherapy
Steroids
Sibling matched allogenic bone marrow transplant
CML
What is chronic myeloid leukaemia (CML)?
Uncontrolled clonal proliferation of myeloid cells (basophils, eosinophils and neutrophils)
CML
What chromosome is present in >80% of people with CML?
Philadelphia chromosome
forms a fusion gene BCR/ABL on chromosome 22 – has tyrosine kinase activity – simulate cell division
CML
what are the clinical features of CML?
Insidious onset
Symptomatic anaemia
Abdominal pain - splenomegaly
Weight loss, tiredness, palor
Gout - due to purine breakdown
Bleeding - due to platelet dysfunction
CML
what are the investigations for CML?
FBC - anaemia, raised myeloid cells, high WCC (eosinophilia, basophilia, neutrophilia)
Increased B12
Blood film - left shirt, basophilia
Bone marrow biopsy - increased cellularity
Philadelphia chromosome seen in 80+% of cases t(9;2) - Stimulates cell division
CML
What is the treatment for CML?
Chemotherapy
Tyrosine kinase inhibitors, e.g. Imatinib - Given orally
Stem cell transplant
CML
Why does the Philadelphia chromosome cause CML?
FORMS fusion gene BCR/ABL on chromosome 22 –> tyrosine kinase activity –> stimulates cell division
CLL
What is Chronic lymphoblastic leukaemia (CLL)?
Proliferation of mature B lymphocytes leads to accumulation of mature B cells that have escaped apoptosis
Chronic malignant transformation of mature lymphoid cells
CLL
what are the investigations for CLL?
● Normal or low Hb
● Raised WCC with very high lymphocytes
● Blood film – smudge cells may be seen in vitro
CLL
What is the treatment for CLL?
Watch and wait
Chemotherapy
Monoclonal antibodies, e.g. rituximab
Targeted therapy, e.g. bruton kinase inhibitors (ibrutinib)
LYMPHOMA
What is lymphoma?
- Malignancies of lymphocytes which accumulate in lymph nodes, may also infiltrate organs + divided histologically
LYMPHOMA
What are the types?
- Hodgkin’s lymphoma (more common in adolescence)
- Non-Hodgkin’s (more common in childhood)
LYMPHOMA
What causes lymphadenopathy?
What might make you think of malignancy?
- Mostly self-limiting like viral URTI (cold, tonsillitis)
- Can be HIV, autoimmune or malignancies
- Enlarging node without infective cause, persistently enlarged, unusual site (supraclavicular), presence of B Sx or abnormal CXR
HODGKINS LYMPHOMA
What is the clinical presentation of Hodgkin’s lymphoma?
Fever and sweating
Enlarged rubbery non-tender nodes
Systemic ‘B’ symptoms, e.g. fever
Painful nodes on drinking alcohol
some patients (commonly young women) have disease localised to the mediastinum
HODGKINS LYMPHOMA
what is required for a diagnosis of hodgkin’s lymphoma?
Presence of Reed-Sternberg cells in lymph node biopsy
HODGKINS LYMPHOMA
What blood results may you see in someone with Hodgkin’s lymphoma?
- high ESR
- FBC = anaemia (normochromic normocytic)
- reed sternberg cells
- low Hb
- high serum lactase dehydrogenase
HODGKINS LYMPHOMA
How is Hodgkin’s lymphoma staged?
Using the Ann Arbor system
- I = confined to single LN region
- II = ≥2 nodal areas on same side of diaphragm
- III = nodal areas on both sides of diaphragm
- IV = spread beyond LNs e.g. liver
- Each staged subdivided to A if no systemic Sx or B if ‘B’ Sx
HODGKINS LYMPHOMA
What is the management of Hodgkin’s lymphoma?
- Combination chemo ± radiotherapy (overall 80% cured)
- ABVD
- Adriamycin
- Bleomycin
- Vinblastine
- Decarbazine
- autologous marrow transplant
NON-HODGKINS LYMPHOMA
What is non-Hodgkin’s lymphoma?
Any lymphoma not involving Reed-Sternberg cells
NON-HODGKINS LYMPHOMA
What are the 3 broad presentations of Non-Hodgkin’s lymphoma?
- T-cell malignancies
- B-cell malignancies
- Extra-nodal disease
NON-HODGKINS LYMPHOMA
How do T-cell malignancies present?
- May present as ALL or non-Hodgkin lymphoma both being characterised by a mediastinal mass with bone marrow infiltration
- Mediastinal mass may cause SVC obstruction
NON-HODGKINS LYMPHOMA
How do B-cell malignancies present?
- Present as non-Hodgkin lymphoma with localised lymph node disease, usually in head + neck or abdomen
NON-HODGKINS LYMPHOMA
How does extra-nodal disease present?
- Often GI > pain from obstruction, a palpable mass or even intussusception
NON-HODGKINS LYMPHOMA
What are the signs and symptoms of non-hodgkins lymphoma?
Fever and sweating
Enlarged rubbery non-tender nodes
Systemic ‘B’ symptoms, e.g. fever
GI and skin involvement
NON-HODGKINS LYMPHOMA
What is the management of Non-Hodgkin’s lymphoma?
Steroids
R-CHOP
- Monoclonal antibodies to CD20 -> Rituximab
- CHOP regimen:
- Cyclophosphamide
- Hydroxy-daunorubicin
- Vincristine
- Prednisolone
BRAIN TUMOURS
What is the site of brain tumours?
- Almost always primary (unlike adults)
- 60% are infratentorial
BRAIN TUMOURS
What are the different types of brain tumours?
- Astrocytoma (#1) varies from benign to glioblastoma multiforme
- Medulloblastoma arises in the midline of posterior fossa, may have spinal mets
- Ependymoma mostly in posterior fossa where it behaves as medulloblastoma
- Brainstem glioma
- Craniopharyngioma
BRAIN TUMOURS
What is a craniopharyngioma?
How does it present?
- Developmental tumour arising from squamous remnant of Rathke pouch
- Not truly malignant but locally invasive (bitemporal hemianopia often lower quadrant as superior chiasmal compression)
BRAIN TUMOURS
What is the clinical presentation of brain tumours?
- Evidence of raised ICP
- Focal neurology dependant on where the lesion is
BRAIN TUMOURS
What are some signs of raised ICP?
- Headache worse in morning
- Papilloedema
- Vomiting, esp. in the morning
- Behaviour or personality change
- Visual disturbance (squint secondary to 6th nerve palsy, nystagmus)
BRAIN TUMOURS
What are some focal neurological signs?
- Spinal tumours = back pain, peripheral weakness of arms/legs or bladder + bowel dysfunction depending on level of lesion
- Ataxia, seizures
BRAIN TUMOURS
What is the best investigation for brain tumours?
- MRI for visualisation
- Avoid LP if raised ICP
BRAIN TUMOURS
What are some complications of brain tumours?
- Outcome depends on location, how much is cleared + how much healthy brain tissue removed
- Survivors face neuro disability, growth + endocrine problems, neuropsychological issues
BRAIN TUMOURS
What is the management of brain tumours?
- 1st line = surgical resection + ventriculoperitoneal shunt to reduce risk of coning + treat hydrocephalus
- Chemo (fewer options as less drugs cross BBB) or radiotherapy
NEUROBLASTOMA
What is a neuroblastoma? Epidemiology?
- Arise from neural crest tissue in the adrenal medulla + sympathetic nervous system,
- most common <5y,
- NOT brain tumour
NEUROBLASTOMA
Where is it located?
Mass anywhere along sympathetic chain so could lead to spinal cord compression
NEUROBLASTOMA
Why are neuroblastomas biologically unusual?
What types of neuroblastomas are there?
- Spontaneous regression sometimes occur in v young infants
- Spectrum from benign (ganglioneuroma) to highly malignant neuroblastoma
NEUROBLASTOMA
What is the clinical presentation of neuroblastoma?
- Abdominal mass
- Sx of metastatic = weight loss, hepatomegaly, pallor, bone pain + limp
- Uncommon = paraplegia, cervical lymphadenopathy, proptosis, periorbital bruising, skin nodules
NEUROBLASTOMA
How does the abdominal mass present?
- Often crosses midline + envelopes major vessels + lymph nodes
- Can grow very large
- Classically abdo primary is of adrenal origin
NEUROBLASTOMA
What are the investigations for neuroblastoma?
- Raised urinary catecholamine levels
- CT/MRI + confirmatory biopsy
- Evidence of metastatic disease = bone marrow sampling, MIBG scan ±bone scan
NEUROBLASTOMA
What is the management of neuroblastoma?
- Localised primaries + no mets can often be cured with surgery
- Metastatic = chemo, autologous stem cell rescue, surgery + radio
- Immunotherapy may be used for long-term maintenance
WILM’S TUMOUR
What is a Wilm’s tumour?
Epidemiology?
Risk factor?
- Nephroblastoma that originates from embryonal renal tissue, cure rate 80%
- > 80% present before age 5, rare after 10y
- FHx = Wilm’s tumour susceptibility gene
WILM’S TUMOUR
What is the clinical presentation of a Wilm’s tumour?
- Large abdominal mass found incidentally in an otherwise well child
- May have flank pain, anorexia, anaemia, painless haematuria + HTN
WILM’S TUMOUR
What are the investigations for Wilm’s tumour?
- USS ± CT/MRI showing intrinsic renal mass distorting the normal structure
- Mass with characteristic mixed tissue densities (cystic + solid)
- Staging for distant mets (often lung), biopsy for histology Dx
WILM’S TUMOUR
What is the management of a Wilm’s tumour?
- Initial chemo followed by delayed nephrectomy (full if 1 kidney, partial if bilateral but RARE)
- Radiotherapy for more advanced disease
BONE TUMOURS
What are bone tumours?
When do they occur?
- Osteogenic sarcoma more common than Ewing sarcoma but Ewing seen more in younger children
- Both have male predominance
- Uncommon before puberty
BONE TUMOURS
What is the clinical presentation of bone tumours?
- Limbs most common site (particularly femur, tibia + humerus)
- Persistent localised bone pain often precedes mass, otherwise well
- May be worse at night + cause disrupted sleep
BONE TUMOURS
What are some investigations for bone tumours?
- Raised ALP on bloods
- Plain XR followed by MRI + bone scan, ?PET scan + bone biopsy
- CT chest for lung mets + bone marrow sampling to exclude involvement
BONE TUMOURS
How might bone tumours present on radiographs?
- XR = destruction + variable periosteal new bone formation
- Periosteal reaction leads to classic “sunburst” appearance
- Ewing sarcoma often shows substantial soft tissue mass
BONE TUMOURS
What is the management for bone tumours?
- Combo chemo before surgery (amputation avoided if possible)
- Radio used in Ewing sarcoma for local disease, esp. if surgical resection is impossible or incomplete (e.g. pelvis or axial skeleton)
RETINOBLASTOMA
What is a retinoblastoma?
- Malignant tumour of retinal cells which can lead to severe visual impairment
RETINOBLASTOMA
What is a genetic cause of retinoblastoma?
How might it present?
- Retinoblastoma susceptibility gene on chromosome 13 = AD but incomplete penetrance > offer genetic screening
- All bilateral tumours are hereditary, 20% of unilateral are
RETINOBLASTOMA
What is the clinical presentation of retinoblastoma?
- White pupillary reflex noted to replace the normal red reflex or a squint
- May have decreased visual acuity + nystagmus
- Most present within 3y
RETINOBLASTOMA
What are the investigations for retinoblastoma?
- Screened for in NIPE
- MRI + Examination under anaesthetic
- Biopsy is avoided + treatment based on ophthalmological findings
RETINOBLASTOMA
What are some complications of retinoblastoma?
- Significant risk of second malignancy (especially sarcoma) amongst survivors of hereditary retinoblastoma
RETINOBLASTOMA
What is the management aims for retinoblastoma?
What is the management?
- Cure cancer + preserve vision
- Chemo, particularly if bilateral to shrink tumours > local laser treatment to retina
- Radiotherapy or enucleation of eye (removal) if advanced
- Most cured but many visually impaired
LIVER TUMOURS
What are liver tumours?
In neonates?
- Mostly hepatoblastoma or hepatocellular carcinoma
- Primary liver tumours in neonates = haemangioma
LIVER TUMOURS
What is the clinical presentation of liver tumours?
- Abdominal distension or mass are common
- Pain + jaundice rare
LIVER TUMOURS
What are the investigations for liver tumours?
- Elevated serum alpha fetoprotein in nearly all cases
- USS/CT/MRI to visualise the tumour + extent of disease
LIVER TUMOURS
What is the management of liver tumours?
- Chemo, surgery or liver transplant if inoperable
- Majority of hepatoblastoma can be cured but prognosis worse for hepatocellular
FANCONI SYNDROME
What is fanconi syndrome?
- Generalised reabsorptive disorder of renal tubular transport in the PCT resulting in…
– Type 2 (proximal) renal tubular acidosis
– Polydipsia, polyuria, aminoaciduria + glycosuria
– Osteomalacia/rickets
FANCONI SYNDROME
What are some causes of fanconi syndrome?
- Usually secondary to inborn errors of metabolism
– Cystinosis (AR > intracellular accumulation of cysteine, most common)
– Wilson’s disease, galactosaemia, glycogen storage disorders
FOETAL HAEMOGLOBIN
What is haemoglobin?
What is the structural difference between foetal and adult haemoglobin?
- Responsible for transporting oxygen around the body in RBCs
- HbF = 2 alpha + 2 gamma subunits
- HbA = 2 alpha + 2 beta subunits
FOETAL HAEMOGLOBIN
What is the main difference between HbF + HbA?
- HbF has greater affinity to oxygen than adult so oxygen binds more easily + is more reluctant to let go = crucial for oxygen to transport from maternal to foetal Hb
FOETAL HAEMOGLOBIN
When does HbF production reduce?
HbF production decreases from 32w with HbA + HbA2 production increasing
FOETAL HAEMOGLOBIN
When is Hb concentration highest?
When does the shift from HbF to HbA occur?
- At birth to compensate for low oxygen concentration in the foetus
- By 6m of age very little HbF produced so HbA predominates
ANAEMIA OVERVIEW
What is anaemia?
How is it defined in paeds?
- Hb level below the normal range
- Neonate = <14g/dL
- 1–12m = <10g/dL
- 1–12y = <11g/dL
ANAEMIA OVERVIEW
What are the 3 main mechanisms of anaemia?
- Increased red cell production
- Increased red cell destruction (haemolysis)
- Blood loss (uncommon in paeds like Meckel’s, vWD, foetomaternal bleeding)
ANAEMIA OVERVIEW
What are some causes of decreased red cell production?
What are some clues?
- Ineffective erythropoiesis (Fe, folate deficiency, CKD)
- Red cell aplasia
- Normal reticulocytes, abnormal MCV in nutrient deficiencies
ANAEMIA OVERVIEW
What are some causes of haemolysis?
What are some clues?
- G6PD deficiency, haemoglobinopathies, hereditary spherocytosis
- Raised reticulocytes, abnormal appearance on blood films, +ve direct antiglobulin test if immune cause
ANAEMIA OVERVIEW
What is haemolytic anaemia?
What is the normal lifespan of RBC?
- Characterised by reduced red cell lifespan due to increased red cell destruction in the circulation (intravascular haemolysis) or liver/spleen (extravascular)
- 120d
ANAEMIA OVERVIEW
How does haemolysis cause anaemia?
What is the difference in haemolytic anaemias in neonates + children?
- Red cell survival reduced significantly but bone marrow production increases too, anaemia = bone marrow cannot compensate
- Neonates = immune haemolytic anaemias, children = instrinsic abnormalities (G6PD)
ANAEMIA OVERVIEW
List 4 features of haemolytic anaemias
- Anaemia
- Hepatosplenomegaly
- Unconjugated bilirubinaemia
- Excess urinary urobilinogen
ANAEMIA OVERVIEW
What are some causes of anaemia in the neonate?
- Reduced RBC production = congenital red cell aplasia + congenital parvovirus infection > red cell aplasia
- Haemolytic anaemia = immune (haemolytic disease of newborn) or hereditary (G6PD etc)
ANAEMIA OVERVIEW
What are the main causes of anaemia of prematurity?
- Inadequate erythropoietin production
- Reduced red cell lifespan
- Frequent blood sampling whilst in hospital
- Iron + folic acid deficiency after 2-3m.
IRON DEF ANAEMIA
What is iron deficiency anaemia?
Why does it cause anaemia?
Iron physiology?
- # 1 cause of childhood anaemia
- Bone marrow requires iron to produce Hb
- Iron mainly absorbed in the duodenum + jejunum + requires acid from the stomach to keep iron in soluble ferrous (Fe2+) form, if acid drops it changes to insoluble ferric (Fe3+) form
IRON DEF ANAEMIA
What are some causes of iron deficiency anaemia?
- Inadequate intake = common as infants require additional iron for increasing blood volume
- Malabsorption = Crohn’s + coeliac
- Blood loss = common in menstruating females
IRON DEF ANAEMIA
What are some sources of iron?
What can affect iron absorption?
- Breast milk, formula, cow’s milk or weaning (cereals)
- Markedly increased when eaten with food rich in vitamin C + inhibited by tannin in tea
IRON DEF ANAEMIA
What are the symptoms of iron deficiency anaemia?
- Generic = fatigue, SOB, headaches, dizziness, palpitations
- Young infants feed more slowly + children tire easily
IRON DEF ANAEMIA
What are some signs of iron deficiency anaemia?
- Generic = pallor (inc. conjunctival), tachycardia, tachypnoea
- Pica = consumption of non-food materials
- Koilonychia, angular cheilitis, brittle hair + nails
IRON DEF ANAEMIA
What are some investigations for iron deficiency anaemia and what would you see?
- FBC = low Hb, microcytic (low MCV + MCH), normal reticulocytes
- Blood film = hypochromic microcytic red cells
- Iron studies:
– Low = serum ferritin, iron + transferrin saturation
– High = total iron binding capacity
IRON DEF ANAEMIA
What is…
i) transferrin saturation?
ii) total iron binding capacity?
i) Proportion of transferrin bound to iron
ii) Total space on transferrin for Fe to bind
IRON DEF ANAEMIA
What is the management of iron deficiency anaemia?
- Diet = eat red meat (beef, lamb), oily fish, green veg (broccoli, spinach), dried fruit (raisins)
- Children may be given polysaccharide iron complex (Niferex)
- Ferrous sulfate or fumarate often used
IRON DEF ANAEMIA
What are some side effects of treatment with oral iron supplementation?
- Constipation
- Black coloured stools
- Nausea
SICKLE CELL DISEASE
What is the pathophysiology of sickle cell disease?
How does it arise?
- Abnormal variant (haemoglobin S) which polymerises to be an abnormal sickle (crescent) shape + so more fragile + easily destroyed > haemolytic anaemia
- Amino acid substitution (glutamine > valine)
SICKLE CELL DISEASE
What issues can sickled red cells cause?
What can exacerbate this?
- Reduced lifespan so can get trapped in small vessels leading to vaso-occlusion > ischaemia
- Can be exacerbated by dehydration, cold, stress, infections + hypoxia, associated with raised haematocrit
SICKLE CELL DISEASE
What is the genetics behind sickle cell disease?
- Autosomal recessive
- Abnormal gene for beta-globin on C11
- Heterozygous = sickle-cell trait
- Homozygous = sickle cell disease (HbSS)
SICKLE CELL DISEASE
What is the epidemiology of sickle cell disease?
How could this be advantageous?
- More common in Africa, India + the Middle East (areas traditionally affected by malaria)
- Sickle-cell trait reduces the severity of malaria making them more likely to survive + pass the genes on
SICKLE CELL DISEASE
When does sickle cell disease present?
What do all sickle cell disease patients have?
- 6m as HbF unaffected so manifests as HbF reduces
- All have moderate anaemia with detectable jaundice from chronic haemolysis
- All have marked increase in infection susceptibility, esp. pneumococci + H. influenzae due to hyposplenism secondary to chronic sickling + microinfarction of the spleen
SICKLE CELL DISEASE
What is a severe, classic feature of sickle cell disease?
Common location?
Presentation?
Most severe?
- Vaso-occlusive (painful) crises
- Bones of limbs + spine common (may lead to avascular necrosis e.g. femoral heads)
- Pain, fever + often those of triggering infection
- Acute chest syndrome
SICKLE CELL DISEASE
What is acute chest syndrome?
What can cause it?
Management?
- Fever or resp Sx (CP, tachypnoea) with new infiltrates on CXR
- Can be due to infection (pneumonia, bronchiolitis) or non-infective (pulmonary vaso-occlusion or fat emboli)
- Emergency > Abx or antivirals, blood transfusions for anaemia, may need NIV or intubation
SICKLE CELL DISEASE
Name 2 other vaso-occlusive crises
- ‘Hand-foot syndrome’ common leading to dactylitis
- Priapism in men > urological emergency, aspiration
SICKLE CELL DISEASE
Sickle cell disease may present with acute anaemia (sudden drop in Hb).
What can cause this?
- Haemolytic crises (sometimes with associated infection)
- Aplastic crises (parvovirus causes cessation of RBC production)
- Sequestration crises
SICKLE CELL DISEASE
What is a sequestration crisis?
What is the management?
- Sudden hepatic or splenic enlargement, abdo pain + circulatory collapse from accumulation of sickled cells blocking blood flow
- Supportive = blood transfusions, fluid resus, splenectomy can prevent this + used in recurrent crises as can lead to splenic infarction > increased infection susceptibility
SICKLE CELL DISEASE
What are some investigations for sickle cell disease?
- Prenatal Dx via CVS
- Detection via Guthrie test
- FBC = low Hb, high reticulocytes
- Blood film = sickled RBCs
- Dx with Hb electrophoresis showing high amounts of HbSS + absent HbA
SICKLE CELL DISEASE
What are some complications of sickle cell disease?
- Short stature + delayed puberty
- Stroke + cognitive issues
- Pulmonary HTN
- Chronic renal failure
- Psychosocial issues
SICKLE CELL DISEASE
What is the general management for sickle cell disease?
- Fully immunised (PCV, HiB, meningococcus)
- Avoid vaso-occlusive crisis triggers
- PO phenoxymethylpenicillin prophylaxis
- PO folic acid as increased demands due to haemolysis
- Hydroxycarbamide + hydroxyurea can stimulate HbF production to prevent painful crises
- Bone marrow transplant curative + offered if failed response
SICKLE CELL DISEASE
What are some potential triggers of vaso-occlusive crises?
How might these be prevented?
- Cold, dehydration, excessive exercise, stress + hypoxia
- Dress warmly, plenty of drinks
SICKLE CELL DISEASE
What is the management of an acute crisis?
- PO or IV analgesia according to need (?opiates)
- IV fluids, oxygen
- Infection treated with Abx, blood transfusion for severe anaemia
- Exchange transfusion if severe (e.g. neuro complications)
THALASSAEMIA
What is thalassaemia?
Consequence?
What are the 2 types?
- AR disorder arising from ≥1 gene defects, resulting in a reduced rate of production of ≥1 globin chains
- RBCs more fragile + breakdown easily
- Alpha = defect in alpha globin chains
- Beta = defect in beta globin chains
THALASSAEMIA
What happens if there is deletion of 1 or 2 alpha globin chains?
- Alpha thalassaemia trait
- Often asymptomatic with mild or absent anaemia
- Red cells hypochromic + microcytic
THALASSAEMIA
What happens if there is deletion of 3 alpha globin chains?
- Mild-moderate hypochromic microcytic anaemia + splenomegaly
- Few patients are transfusion dependent
THALASSAEMIA
What happens if there is deletion of all 4 alpha globin chains?
- Alpha thalassaemia major
- Death in utero with foetal hydrops from foetal anaemia
- Occurs in families of South-East Asian origin, homozygotes
THALASSAEMIA
What is the epidemiology of beta thalassaemia?
What are the three types?
- Indian subcontinent, Mediterranean + Middle East
- Beta thalassaemia minor (1 abnormal + 1 normal gene)
- Beta thalassaemia intermedia (2 defective or 1 defective + 1 deletion genes)
- Beta thalassaemia major (homozygous for deletion genes)
THALASSAEMIA
What is beta thalassaemia minor?
How does it present?
Differentiate?
- Carriers of abnormally functioning beta-globin gene
- Mild microcytic + hypochromic anaemia (monitor)
- Differentiate from Fe deficiency by measuring serum ferritin (normal)
THALASSAEMIA
What is beta thalassaemia intermedia?
Management?
- More severe microcytic anaemia, beta-globin mutation allow a small amount of HbA and/or a large amount of HbF to be produced
- Monitor + occasional blood transfusion
THALASSAEMIA
What is beta thalassaemia major?
How does it present?
- Most severe form with no HbA as abnormal beta globin gene
- Severe transfusion-dependent anaemia from 3-6m, jaundice, failure to thrive
THALASSAEMIA
What is a complication of beta-thalassaemia major which isn’t common in developed countries?
- Extramedullary haematopoiesis can occur if no regular blood transfusions
- Leads to hepatosplenomegaly + bone marrow expansion leading to maxillary overgrowth + skull bossing
THALASSAEMIA
What are some investigations for beta thalassaemia?
- FBC + blood film = hypochromic microcytic anaemia
- HbA2 raised in beta-thalassaemia trait, HbA2 + HbF raised in major
- Serum ferritin to differ between Fe anaemia + check iron overload
- Hb electrophoresis for Dx
- DNA testing via CVS before birth
THALASSAEMIA
What is the main complication of thalassaemia?
How might this present?
- Repeated + Regular blood transfusions can cause chronic iron overload
- Heart (cardiomyopathy, heart failure)
- Liver (cirrhosis)
- Pancreas (diabetes)
- Pituitary (delayed growth + sexual maturation)
- Skin (hyperpigmentation)
- Arthritis + joint pain
THALASSAEMIA
What is the management of thalassaemia?
- Lifelong monthly blood transfusions for the most severe cases
- Desferrioxamine for iron chelation to prevent overload
- Bone marrow transplant can be curative, reserved for beta thalassaemia major
HAEMOPHILIA
What are the 2 types of haemophilia?
What causes it?
- Haemophilia A = factor VIII deficiency
- Haemophilia B = factor IX deficiency
- X-linked recessive (M>F), A>B, girls with Turner’s increased risk as 1 X
HAEMOPHILIA
How might haemophilia present?
- Neonates = intracranial haemorrhage, haematomas + cord bleeding
- Recurrent spontaneous bleeds, often large, into joints (haemoarthrosis) + muscles (cause arthropathy if not prevented)
- Easy bruising, haematomas, mouth/gum bleeding, haematuria
HAEMOPHILIA
When does haemophilia typically present?
Important differential?
- Around 1y as children become more mobile
- NAI
HAEMOPHILIA
What are some investigations for haemophilia?
- FBC + blood film
- Prothrombin time (factors 2, 5, 7, 10, extrinsic) normal
- Activated partial thromboplastin time (intrinsic) = greatly increased
- Severity dependent on amount of FVIII:C or FIX:C levels
- Prenatal Dx with CVS
HAEMOPHILIA
What is the management of haemophilia?
- IV infusion of recombinant FVIII or FIX concentrate if active bleeding (or prophylactic to reduce arthropathy risk)
- Desmopressin stimulates vWF release for bleeding/prevention, TXA
- AVOID aspirin, NSAIDs + IM injections (can worsen bleeding)
HAEMOPHILIA
What is a complication of the treatment for haemophilia?
- Formation of antibodies against the clotting factor can render it ineffective
VON WILLEBRAND DISEASE
What is the physiological role of von Willebrand factor?
- Facilitates platelet adhesion to damaged endothelium
- Acts as carrier protein for FVIII:C, protecting it from inactivation + clearance
VON WILLEBRAND DISEASE
What is von Willebrand disease (vWD)?
What causes it?
Types?
- Deficiency of vWF leading to defective platelet plug formation + deficient FVIII:C > most common inherited bleeding disorder
- AD, type 1 most common + mildest
- Severity increases with type 2, type 3 has very low or no vWF (AR)
VON WILLEBRAND DISEASE
What is the clinical presentation of vWD?
- Bruising, excessive + prolonged bleeding after surgery, mucosal bleeding (epistaxis, menorrhagia, bleeding gums)
- In contrast to haemophilia = spontaneous soft tissue bleeding like large haematomas uncommon
VON WILLEBRAND DISEASE
What are some investigations for vWD?
- FBC (normal platelets) + blood film, biochemical screen including renal + liver function
- Prolonged bleeding time
- Prothrombin time normal
- APTT = elevated or normal
- vWF antigen decreased, vWF multimers variable
VON WILLEBRAND DISEASE
What is the management of vWD?
- Pressure applied if active bleeding
- Minimise bleeding with desmopressin or TXA
- Severe = plasma derived FVIII concentrate or vWF infusion
- AVOID aspirin, NSAIDs + IM injections as can worsen bleeding
VON WILLEBRAND DISEASE
How is desmopressin given?
What does it do?
- Nasal or s/c
- Release of vWF + FVIII concentrate
COAGULATION DISORDERS
What are acquired disorders of coagulation?
Secondary to
- Haemorrhagic disease of the newborn due to vitamin K deficiency
- Liver disease as location of clotting factor production
- ITP + DIC
COAGULATION DISORDERS
What is vitamin K essential for?
What does deficiency result in?
How can this be prevented?
- Essential for factors 2, 7, 9 + 10 (1972) production + naturally occurring anticoagulants like protein C + S
- Prolonged prothrombin time so increased bleeding
- All neonates get vitamin K IM to facilitate coagulation
COAGULATION DISORDERS
What can cause vitamin K deficiency?
- Inadequate intake = neonates, long-term chronic illness
- Malabsorption = coeliac, cystic fibrosis
- Vitamin K antagonists = warfarin
ITP
What is immune thrombocytopenic purpura (ITP)?
- Commonest cause of thrombocytopenia in childhood
- T2 hypersensitivity reaction with destruction of circulating platelets by anti-platelet IgGs
ITP
What is the clinical presentation of ITP?
- 1-2w post viral
- Petechiae or purpuric rash (petechiae are pin-prick, purpura are larger)
- Can cause epistaxis, other mucosal bleeding + bruising
ITP
What are the investigations for ITP?
- FBC shows marked thrombocytopenia
- May have compensatory megakaryocyte increase in bone marrow
ITP
What is the management of ITP?
- Often acute + self-limiting
- Severe bleeding may need prednisolone, IVIg, blood/platelet transfusions
HAEMOLYTIC DISEASE OF THE NEWBORN
what is the pathophysiology?
- rhesus positive father and negative mother have a rhesus positive baby
- mother + baby have incompatible antigens which induces primary immune response
- problems tend to occur in subsequent pregnancies + results in destruction of foetal haemoglobin
HAEMOLYTIC DISEASE OF THE NEWBORN
what is the clinical presentation?
- anti-D antibodies in mother detected by Coombe’s test that all women have at 1st antenatal appointment
- routine USS may detect hydrops fetalis or polyhydramnios
- mild cases = jaundice, pallor + hepatosplenomegaly, hypoglycaemia
- severe cases = oedema, petechiae + ascites
HAEMOLYTIC DISEASE OF THE NEWBORN
what are the investigations?
- indirect coombe’s test show antibodies
- antenatal USS shows hydrops fetalis
- fetal blood sample
HAEMOLYTIC DISEASE OF THE NEWBORN
what is the management in utero?
- transfusion of O negative packed cells cross-matched with maternal blood at 16-18 weeks
HAEMOLYTIC DISEASE OF THE NEWBORN
what is the management after delivery?
50% = normal haemoglobin + bilirubin but should be monitored for anaemia for 6-8 weeks
25% = require transfusion + may require phototherapy to avoid kernicterus
25% = stillborn or have hydrops fetalis
HAEMOLYTIC DISEASE OF THE NEWBORN
what are the complications?
- kernicterus which can cause extrapyramidal, auditory and visual abnormalities and cognitive deficit
- late-onset anaemia
- graft-versus-host disease
- portal vein thrombosis + portal hypertension
HAEMOLYTIC DISEASE OF THE NEWBORN
how can it be prevented?
identify all women who have been sensitised by coombe’s testing at first antenatal visit
anti-D immunoglobulin should be given to all rhesus negative women at 28 + 34 weeks