Haematology And Oncology Flashcards
If a child presents with abnormal bleeding/bruising, what broad aetiologies could be considered?
Coagulation factor deficiencies
Platelet deficiency/dysfunction
Microvascular abnormalities
Trauma (Accidental/Non Accidental)
How would a coagulation factor deficiency present?
Excess blood loss following surgery/dentistry
Recurrent bruises >1cm
Muscle haematomas
Joint haemarthroses
How could Platelet Deficiencies present?
Purpura
Petichiae
Mucosal Bleeding
How would microvascular abnormalities present?
Palpable purpura suggestive of vasculitis
What would make you think bruising/bleeding from trauma was NAI?
Immobile child
Disproportionate to injury sustained
Multiple sites/clusters
Shape of hand/ligatures
State four associated features in bruising/bleeding that could point to an underlying cause
Hepatosplenomegaly (Haemolysis)
Anaemia
Lower Limb bruising (HSP)
Arthritis (HSP)
In abnormal bleeding/bruising then a range of bloods would be done, including PT and APTT. If APTT was prolonged, what would be done next and why?
50:50 dilution with normal plasma
If the value fails to return to normal then its suggestive of an inhibitor (heparin, or antibodies)
If the value returns to normal then it suggests a deficiency
If the first line bloods for abnormal bleeding/bruising were normal, what further investigations could be done?
Platelet function assay
Von Willebrands Disease Screen
Autoantibody screen
Bone marrow aspirate
If abnormal bleeding/bruising, IM injections, ABG and NSAIDs should be avoided. When should you urgently assess for leukaemia?
Unexplained Petichiae
Hepatosplenomegaly
Suggestive FBC
If abnormal bleeding/bruising, IM injections, ABG and NSAIDs should be avoided. When should you urgently assess for Neuroblastoma?
Periorbital bleeding
Palpable abdominal mass
What would a normal PT/APTT in a bruising/bleeding child suggest?
Platelet abnormality
Vasculitis
What would an increased PT in a bruising/bleeding child suggest?
Deficiency of Factor VII or Vitamin K
Liver Disease
What would an increased APTT in a bruising/bleeding child suggest?
Deficiency of factors VIII, IX, XI or XII
AKA Haemophilia A/B, Von Willebrands Disease
What would an increased PT AND APTT in a bruising/bleeding child suggest?
Deficiency in in factors II/V/X/Fibrinogen
What would a decreased fibrinogen in a bruising/bleeding child suggest?
DIC
Define lymphadenopathy
Generalised lymphadenopathy is an enlargement of >2 non contiguous lymph node groups
NOTE: Most children have palpable lymph nodes, increasing in size until 8-12, then atrophy
Name four specific things you would want to ask about in a lymphadenopathy history
TB Contact
Recent travel
Contact with Pets/Livestock
Family history
Give 5 red flags for lymphadenopathy
Sever pallor Fever Unexplained bruising Unexplained bleeding Mediastinal Mass (eg audible on auscultation)
Name four infective causes of lymphadenopathy
Infectious Mononucleosis
TB
Toxoplasmosis
CMV
Give four non infective causes of lymphadenopathy
SLE
Lymphoma
Leukaemia
Neuroblastoma
How would you manage lymphadenopathy?
Simple reassurance
If still enlarging, review after 2-3 weeks
If red/tender then suggests Bacterial Lymphadenitis so give 10d Co-Amoxiclav and review
Children should be referred as an emergency if they are not responding to antibiotics in bacterial lymphadenitis. When should children be referred via 2 week wait?
Axillary/Epitrochlear/Supraclavicular >1cm
Inguinal >1.5cm
Cervical >2cm and increasing in size/persistent
Over 10 years with any lymph node >1cm for >2 weeks
What is physiological anaemia in infancy?
Normal dip at 6-9 weeks
High oxygen delivery due to high haemoglobin at birth causes negative feedback and suppresses EPO
Describe the pathophysiology of Anaemia of Prematurity
Less time in utero receiving iron from mother
Reduced EPO
Blood tests remove significant circulating volume
Other than physiological and prematurity, give three other causes of Anaemia in Infancy
Blood loss
Twin to twin transfusion
Haemolysis
Name the two common causes of Anaemia in Older Children
Dietary Insufficiency Blood loss (ie through menstruation)
Name the causes of Microcytic Anaemia (TAILS)
Thalassaemia Anaemia of Chronic Disease Iron Deficiency Lead Poisoning Sideroblastic
Name the causes of Normocytic Anaemia (3As and 2Hs)
Acute Blood Loss Anaemia of Chronic Disease Aplastic Anaemia Haemolytic Anaemia Hypothyroidism
Macrocytic Anaemia can be megaloblastic or normoblastic. Give examples of each.
Megaloblastic - Vit B12 and Folate
Normoblastic - Alcohol, Hypothyroidism, Liver Disease
Describe some classical features of Iron Deficiency Anaemia
Glossitis Angular Cheilitis Koilonychia Pica Hair loss
Name five investigations for Anaemia
FBC and Haematinics Blood film Bilirubin Direct Coombs Haemoglobin Electrophoresis
Other than dietary insufficiency and blood loss, what are other causes for Iron Deficiency Anaemia?
Inadequate absorption (eg Crohns)
Reduced Stomach Acid (eg from PPIs) (required to keep iron in soluble form)
There are many specific tests for Iron Deficiency. What is TIBC?
Total space available on transferrin to bind
There are many specific tests for Iron Deficiency. What is Ferritin?
Form iron takes when it is stored/deposited
Increase seen in infection/malignancy
There are many specific tests for Iron Deficiency. What is Transferrin Saturation?
Serum Iron/TIBC
There are many specific tests for Iron Deficiency. What would you expect in Iron Deficiency?
Increased TIBC
Define DIC
Coagulation pathway activation leading to diffuse fibrin deposition in micro vasculature and consumption of coagulation factors and platelets
Leads to abnormal bleeding, end organ damage, and haemolytic anaemia
What are the causes of DIC in Neonates?
Severe Asphyxia
Sepsis
RDS
NEC
What are the causes of DIC in older children?
Sepsis
Severe Trauma
Burns
How does DIC present?
Bleeding from mucosal surfaces, tracts, wounds
Microthrombi leading to renal impairment, cerebral dysfunction
ARDS
Haemolytic Anaemia
What is the classical blood pattern for DIC?
Low platelets
Low fibrinogen
Increased PT/APTT/TT
How should DIC be managed?
A to E
IV and Blood transfusions
Only transfuse platelets if uncontrolled bleeding
If fibrinogen <500 then give FFP and Cryoprecipitate
What is the difference between Asplenia and Hyposplenia?
Asplenia is the absence of the spleen due to either a congenital anomaly or surgical procedure
Hyposplenia is reduced or absent function of the spleen
Why is the spleen particularly important in under 4s?
Clears encapsulated bacteria and at this age, few other alternative routes exist
There are many causes of hyposplenism. Give two vascular and two haematological.
Haematological - Sequestration Crises, Sickle Cell
Vascular - Splenic Artery Occlusion, Splenic Vein Thrombosis
Name four things you would see on a blood film of Asplenism/Hyposplenism
Howell Jolly Bodies (Nuclear Remnants)
Heinz Bodies (Denatured Haemoglobin)
Pappenheimer Bodies (Iron Deposits)
Target Cells
How can a Doppler be used to investigate Hyposplenism/Asplenism?
Assesses spleen size
Assesses direction of flow in splenic vein and portal vessels
How is Hyposplenism managed?
Immunised with pneumococcal, meningococcal and haemophilus vaccines
Antimicrobial prophylaxis
Medic Alert Bracelet
Define Sickle Cell
Autosomal recessive genetic mutation on chromosome 11, leading to sickle erythrocytes and subsequent haemolytic anaemia
Can be sickle trait with just one HbS (reduces severity of Malaria)
How is Sickle Cell screened?
Pregnant women who are at risk are screened in pregnancy
Newborn screening heel prick at 5 days
Give 5 complications of Sickle Cell
Anaemia Crises Priapism Avascular Necrosis of Hip etc Pulmonary Hypertension
What can you give Sickle Cell patients to prevent complications?
Up to date vaccinations
Antibiotic prophylaxis with Pen V
Avoid dehydration and other crises triggers
State three treatments of Sickle Cell
Hydroxycarbamide (stimulates production of foetal haemaglobin)
Bone Marrow Transplant
Blood Transfusion
State the four different types of Sickle Cell Crises
Vaso-Occlusive
Sequestration
Aplastic
Acute Chest
What is a Vaso-Occlusive crisis?
Sickle cells clog capillaries, causing distal ischaemia
Associated with dehydration and raises haematocrit
What is a Sequestration Crisis?
Red blood cells flow back into the spleen, causing an enlarged painful spleen, severe anaemia and circulatory collapse
If recurrent, will require a splenectomy
What is an Aplastic Crisis?
Temporary loss of blood cell creation
Often triggered by Parvo 19
How would an Acute Chest present in Sickle Cell? How is it managed?
Fever/Respiratory symptoms with new infiltrates on CXR
Antibiotics, Blood Transfusions, Ventilation
Thalassaemia is an autosomal recessive disease of protein chains making up Haemaglobin. Describe the pathophysiology.
Red blood cells are fragile and break more easily, causing splenomegaly
Bone marrow expands to compensate for chronic anaemia, causing pronounced forehead and malar eminences
Give five ways that Thalassaemias can present
Fatigue Pallor Jaundice Gallstones Splenomegaly
Name three investigations for Thalassaemia
FBC (Microcytic Anaemia)
Haemaglobin Electrophoresis
DNA Testing
Alpha Thalassaemia is a defect in alpha globin chains on chromosome 16. How is it managed?
Monitor FBC and complications
Blood transfusions
Beta Thalassaemia occurs due to a mutation on chromosome II. What are the three types?
Thalassaemia Minor (one abnormal and one normal gene) Thalassaemia Intermedia (two defective genes or one defective and one deleted) Thalassaemia Major (both genes deleted, severe anaemia and failure to thrive)
Reliance on transfusions increases with more defect
Hereditary Spherocytosis is an autosomal dominant cause of haemolytic anaemia. How can it present?
Jaundice/Anaemia/Gallstones
Aplastic Crises (often triggered by Parvo 19)
Haemolytic Crises (often triggered by infection)
What would the bloods of Hereditary Spherocytosis show?
Raised reticulocyte and raised MCHC
How would Hereditary Spherocytosis be managed?
Folate supplements
Splenectomy
Cholecystectomy
In acute onset - transfusions
What is G6PD Deficiency?
X Linked abnormality common in Mediterranean/Middle Eastern/African populations
Can have crises triggered by infections/medications/broad beans
How does G6PD Deficiency present?
Neonatal Jaundice
Anaemia/Intermittent Jaundice/Gall Stones
Give 5 medications that trigger G6PD
Primaquine Ciprofloxacin Nitrofurantoin Trimethoprim Sulphonylurea
How can you diagnose G6PD?
Blood Films - Heinz Bodies
G6PD Enzyme Assay
Define Leukaemia
Cancer of a particular line of stem cells in bone marrow (can be myeloid or lymphoid, acute or chronic)
ALL peaks between 2 and 3, ALL peaks at 2
Describe the pathophysiology of Leukaemia
Excess production of a single type of white cell, leading to suppression of other cell lines (resulting in Pancytopenia)
Risk Factors - Radiation exposure, Downs, Klinefelters, Noonans
How does Leukaemia present?
Persistent fatigue Unexplained fever Failure to thrive Night sweats Bruising and Bleeding Bone/Joint Pain(Hyperplastic Marrow) Persistent Lymphadenopathy
If Leukaemia is suspected, a full blood count should be done within 48 hours. What would it show?
Anaemia
Leukopenia
Thrombocytopenia
Increased Abnormal White Cells
Other than FBC, what investigations are required in Leukaemia?
Blood Films (Blast Cells)
Bone Marrow/Lymph Node Biopsy
CT Staging
Acute Lymphoblastic Leukaemia is the most common paediatric cancer. What other differentials could you consider?
Immunodeficiency
NAI
Reactive Lymphadenopthy
What factors indicate a better prognosis in ALL?
Aged between 1-10
WCC<50 at diagnosis
Females
No CNS involvement
How is ALL managed?
High WCC requires hydration to prevent hyperviscocity
Treat coinciding infections
Steroids if mediastinal mass
Chemo (2y if Girl, 3y if Boy)
90% survival
What is Lymphoma?
Malignancy of lymphatic system, commonly divided into Hodgekins and Non Hodgekins
More common in older children
Lymphoma aetiology is multifactorial, who is most at risk?
EBV
Immunosupressed (eg if solid organ transplant, or if treated for other infections in the past)
How would Lymphoma present?
B Symptoms (weight loss, night sweats, fever)
Lethargy
Anorexia
Non Tender Lymphadenopathy
How does Lymphoma present differently to Leukaemia?
Leukaemia may have signs of anaemia or thrombocytopenia
How is Lymphoma staged?
Ann Arbor for Hodgekins or St Judes for Non Hodgekins
1) Single group of lymph nodes/single organ
2) Disease in two or more lymph nodes/organs on same side of diaphragm
3) Disease in two or more lymph nodes/organs on both sides of diaphragm
4) Diffuse involvement
‘+B if any B symptoms’
Lymphoma is definitively managed with Chemotherapy and Radiotherapy. How would you treat Tumour Lysis Syndrome?
Hyper hydration
Allopurinol
What are the three different subtypes of Non Hodgekins Lymphoma?
Lymphoblastic
Mature B Cell
Large Cell
What is characteristic of Hodgekins Lymphoma on blood film?
Reed Sternberg Cells
Blood results are not used to diagnose Lymphoma. What is used?
Lymph Node Biopsy
What is Idiopathic Thrombocytopenic Purpura?
Spontaneous Thrombocytopenia causing purpuric rash (key differential for non blanching) due to type II hypersensitivity reaction against platelets
Can be spontaneous or triggered by infection
How does ITP normally present?
Children <10y with history of viral illness (typically)
Symptoms onset over 24-48h hours
Bleeding/Bruising/Petichial (<1mm)or Purpuric (3-10mm) Rash
What main differential needs to be excluded in ITP?
Leukaemia
ITP is normally self limiting and patients should avoid things which could cause them to bleed. How would active bleeding be managed?
Prednisolone
IVIG
Blood Transfusion if required
Note: Platelet infusion would just be destroyed
Give four causes of Pancytopenia
Acute Leukaemias
Bone Marrow Failure Syndromes
Infections
Megaloblastic Anaemias
Give four causes of Vitamin B12 deficiency
Vegan Diet
Lack of IF
Lack of Transcobalamin
Malabsorption
Give five causes of folate deficiency
Malnutrition
Malabsorption
Increased requirements (eg chronic Haemolysis)
Drugs (valproate, trimethoprim, phenytoin)
Metabolic Disorders (Lesch Nyhan Syndrome)
How does severe B12/Folate deficiency present?
Subacute degeneration of Cord
Ataxia
Paraesthesia of Hands and Feet
Why is red cell folate more reliable than serum folate?
Serum folate reflects recent intake
How should B12 deficiency be treated?
IM Hydroxycobalamin three times weekly until Hb normalises
How is Folate Deficiency managed?
Daily PO folic acid
Note:don’t treat with folate alone unless B12 is normal as it can precipitate subacute degeneration of the spinal cord
What is a Nephroblastoma/Wilms Tumour?
Most common childhood tumour of the kidney
Tumour suppressor genes are strongly implicated
Median age of diagnosis is 3.5y
How does a Nephroblastoma present?
Abdominal Mass
Pain
Fever
Haematuria
One of the main differentials for a Nephroblastoma is a Neuroblastoma. How does this present differently?
Abdominal mass (crossing midline)
Hypertension
Bone marrow infiltration
Periorbital Ecchymosis
Wilms Tumour requires a biopsy for definitive diagnosis and US and CT for staging. Describe the risk scoring.
1 - Only confined to kidney
2 - Begins to spread from kidney but can be completely removed with it
3 - Can’t be surgically respected due to LN spread
4 - Distant Metastases
5 - Bilateral tumours (can each have different stages)
How is Wilms Tumour managed?
Stage 1 and 2 with surgery (Nephrectomy)
Further stages will require chemotherapy
85% cure
What is Haemophila A?
X Linked Recessive deficiency in factor VIII
MILD - only requires desmopressin if surgery
MOD - bleeding is rare and normally involves soft tissue
SEV - Spontaneous Haemarthroses/most require FVIII prophylaxis
Haemophilia A commonly presents as child starts to mobilise (small lumpy pea sized bruises). What blood result is characteristic?
Increased APTT
What is Haemophilia B?
X linked deficiency in factor IX
Indistinguishable clinically from Haemophilia A
How does Desmopressin work in Haemophilia A?
Stimulates release of VWF
What is Von Willebrands Factor?
Carrier protein for factor VIII
Protects it from degradation and facilitates platelet adhesion
What are the three subtypes of Von Willebrands Disease?
70% Autosomal Dominant
25% Dominant or Recessive
5% Recessive (near absence of VWF)
What bloods are characteristic of VWD?
Increased APTT
Increased PFA
Decreased factor VIII
How is VWD managed?
Avoid NSAIDs and IM injection
Minor bleeding - pressure/Tranexamic acid
Significant - Desmopressin
Severe - FVIII concentrate, VWF
When would you treat ITP?
Generally if platelet counts <20
Would you still consider ITP if the child had splenomegaly?
No
What is the new developing treatment for ITP?
TPO agonists
Increasing production of platelets to compensate
