Haematology

Question 1

The most common cancers in children are?

Answer 1

1. Leukaemias
2. Brain and other CNS tumours
3. Lymphomas

(in order from most common)

Question 2

Explain what lymphoma is and the 2 groups?

Answer 2

• Malignant tumours derived from lymphoid cells which usually accumulate in the lymph nodes but they can also be extranodal and can also spill over into the blood
• (so basically lymphomas are more lump cancers whereas leukaemias are like circulating cancers but there’s some overlap)

Classically they are divided into 2 groups: Hodgkin Lymphoma and Non-Hodgkins lymphoma and in children it is about a 50/50 split

Question 3

Who gets lymphoma/ risk factors?

Answer 3

ends to be more adolescents/ teens than children
* EBV is implicated in the development of lymphoma
* Immunosuppressed patients e.g. those who have had a solid organ transplant or have been treated for other cancers in the past are also at increased risk of lymphoma

Question 4

Staging for lymphoma?

Answer 4

Ann Arbor staging is used for Hodgkins and NHL

Part of the staging involves using A for absence or B for presence of specific systemic symptoms:

A= a lump/ the lymphadenopathy
B symptoms= fever or night sweats or weight loss (10% over a 6 month period) (B symptoms are more common in Hodgkins lymphoma)

Question 5

Clinical features of lymphoma?

Answer 5

A= a lump/ the lymphadenopathy
B symptoms= fever or night sweats or weight loss (10% over a 6 month period) (B symptoms are more common in Hodgkins lymphoma)
Other potential symptoms of lymphoma not listed as B symptoms include:
- Itch without rash
- Alcohol induced pain of the lymph nodes
- Symptoms relevant to compression e.g. renal failure, SVC obstruction, effusions, marrow failure
- Haematological features: anaemia, thrombocytopenia, neutropenia, leucoerythoblastic features, inflammatory features e.g. raised ESR and CRP, LDH may also be raised

May get general symptoms depending on where the lymphoma is e.g. abdo pain if in the abdomen

Question 6

Investigations for lymphoma?

Answer 6

• Blood counts and blood films (looking for haematological features listed above)
• In most FNA and core biopsy of the lymph nodes will be insufficient and excision biopsy is the best
• May do imaging and CT to check the extent of spread
• There are specific genes that can be tested for in some lymphomas and immunophenotyping can be done
• With the biopsy pathology tend to do lots of immune/ genetic tests to categorise the lymphoma and the immunophenotyping can be done on the biopsy or using flow cytometry

Question 7

Pathological features of hodgkins?

Answer 7

• Almost always lymph node origin
• Characterised by the presence of Reed-Sternberg cells (large lymphocytes with more than 1 nucleus)
• Owl eye appearance of cells
• Spread to lymph node groups is orderly
• Generally ,has better prognosis than NHL

Question 8

Pathological features of NHL?

Answer 8

• Extranodal involvement is more common than in Hodgkins and these cancers have a less regular pattern of spread, some patients may have leukaemic manifestations
• Extranodal lymphomas are still arising from lymphoid tissue just not the lymph nodes this e.g. lymphoid tissue in the testes or gastrointestinal tract
• 90% are B cell and B cell cancers are usually lower grade, T cells cancers are high grade
• Burkitt lymphoma is a type of B cell NHL that classically presents as massive lymphadenopathy of the jaw in children, it is thought to be related to EBV

Question 9

Management and prognosis of lymphoma in children?

Answer 9

• Treatment is generally with chemotherapy and radiotherapy
• Hodgkins lymphoma has a good cure rate in younger individuals i.e. the paediatric population
• High grade NHL is also potentially curable but low grade harder to cure (paradox of haematological malignancies where high grade is easier to treat)
• There may often be long term toxicity from the treatment including secondary cancers, CVS disease and infertility (mainly with intensive treatments)

Question 10

What is meant by pancytopenia?

Answer 10

• A deficiency of blood cells of all lineages (but generally excludes lymphocytes)
• Pancytopenia is not a diagnosis
• It does not always mean bone marrow failure of malignancy
• It is more a reduction in neutrophils than other white cells

Question 11

2 broad causes of pancytopenia?

Answer 11

reduced production (bone marrow failure)
Hypersplenism (any cause of splenomegaly)

Question 12

List some causes of reduced production/ bone marrow failure?

Answer 12

inherited - Faconi’s anaemia

acquired:
primary - idiopathic aplastic anaemia
myelodysplastic syndrome (not relevant to paeds)
acute leukaemia
secondary - storage disorders, (not relevant to paeds), drug induced aplasia, vitamin deficiency B12 or folate, infections, metastatic cancer

Question 13

List some causes of increased destruction/ splenomegaly?

Answer 13

portal hypertension
rheumatoid arthritis
splenic lymphoma

Question 14

Describe faconis anaemia?

Answer 14

• This is a rare inherited disorder
• It causes bone marrow failure with an aplastic anaemia, congenital anomalies and a pre-disposition to cancer
• Anomalies include: skeletal abnormalities, café au lait macules, endocrine issues, short stature, GI, CVS and renal issues
• The blood production problems often develop between ages 6-8

Question 15

Describe idiopathic aplastic anaemia?

Answer 15

• Auto-immune attack against haemopoietic cells
• There is hypocellularity/ aplasia of the bone marrow
• This can occur in adolescents and young adult

Question 16

Describe drug induced marrow failure?

Answer 16

• Can occur with chemotherapy agents, alcohol, azathioprine, methotrexate and chloramphenicol
• It causes aplasia/ hypocellular marrow

Question 17

Describe B12/ folate deficiency?

Answer 17

• Defects in nuclear maturation can affect all lineages
• Causes a hypercellular marrow

Question 18

Clinical features of pancytopenia?

Answer 18

Features of anaemia, neutropenia, thrombocytopenia
Symptoms relating to the cause of the pancytopenia

Question 19

Establishing the cause of pancytopenia?

Answer 19

• History, including FH
• Clinical findings
• FBC and blood film
• Additional tests: B12/ folate serum, LFTs, virology, auto-antibodies
• Bone marrow examination
• Specialised tests: cytogenetics, NGS, WES (exon testing)

Note:
Marrow will be hypocellular in idiopathic aplastic anaemia, Faconi’s anaemia and drug induced marrow failure
Marrow will be hypercellular in MDS, B12/ folate deficiency and hypersplenism

Question 20

In pancytopenia marrow will be hypo cellular in ___________

it will be hyper cellular in ___________

Answer 20

Marrow will be hypocellular in idiopathic aplastic anaemia, Faconi’s anaemia and drug induced marrow failure
Marrow will be hypercellular in MDS, B12/ folate deficiency and hypersplenism

Question 21

Treatment of pancytopenia?

Answer 21

Can be divided into supportive treatment and treatment based on cause

SUPPORTIVE
* Red cell and platelet transfusions for the anaemia and thrombocytopenia
* Antibiotic prophylaxis/ treatment for neutropenia

• TREATMENT BASED ON CAUSE
• Primary bone marrow malignancy – chemotherapy
• Congenital disease – bone marrow transplant
• Idiopathic aplastic anaemia – immunosuppression
• Drugs – stop drug, consider antidotes
• Viral – treat infection
• B12/ Folate – supplements
• Hypersplenism – treat cause if possible or consider splenectomy

Question 22

Describe hypo and hyper cellular bone marrow causes in pancytopenia?

Answer 22

Hypo:
Faconis (there is bone marrow failure)
Idiopathic aplastic anaemia (again it is bone marrow failure because you are attacking all the cells so there is less of them)
Drug induced (the drug has killed the cells so hypo)
Metastatic disease (destruction of bone marrow by cancer so less cells)
Infection (destruction of bone marrow by infection so less cells)

Hyper:
Acute leukaemia (generally more cells, they just don’t function cause they are leukaemic cells)
MDS (again more cells that don’t function)
B12/ folate (more cells that don’t function)
All causes of increased destruction will result in marrow becoming hypercellular

Question 23

Explain the pathogenesis of sickle cell disease?

Answer 23

• HbS (sickle cell Hb) results from a single base mutation (point) at codon 6 in beta globin gene that substitutes glutamine to valine
• HbS polymerises if exposed to low O2 levels for a prolonged period which distorts the RBC and damages the membrane
• The sickle gene is most common in Africans but is also found in Middle East, India and Southern Europe
• Sickling of cells is initially reversible but with repeated sickling cells lose membrane flexibility and become irreversibly sickled
• Sickling can produce a shortened red cell survival and impaired passage of cells through the microcirculation leading to obstruction of small vessels and tissue infarction

Question 24

Explain what is meant by sickle cell trait, why is it common in some areas and what are the implications?

Answer 24

HbAS)
* One normal, one abnormal gene
* This is an asymptomatic carrier state and there 300M worldwide
* Sickle cell trait is very predominant in areas where malaria is endemic because it provides improved survival against malaria so was an evoluntionary advantage
* There are few clinical features as HbS levels are too low to polymerise
* Cells may sickle in severe hypoxia, dehydration and physical extertion and care should also be taken in pregnancy and anaesthesia
* Blood film is normal, there is mainly HbA, HbS < 50%

Question 25

What is meant by sickle cell disease/ anaemia?

Answer 25

* HbSS * HbS > 80%, no HbA

Question 26

Presentation of sickle cell disease/ anaemia?

Answer 26

* Symptoms begin between 3 months and 6 months of age when HbF levels are falling * Babies may present with anaemia, jaundice, pallor, lethargy, growth restriction and general weakness * Splenomegaly may be present in infancy and childhood but recurrent splenic infarcts can then cause autosplenectomy (the spleen shrivels up), children then have increased susceptibility to infections by encapsulated bacteria e.g. strep pneumonia * Anaemia is present because cells repeatedly sickle, them become weakened resulting in premature destruction * Jaundice can be present because there is intravascular haemolysis so increased bilirubin

Question 27

What is meant by sickle cell crisis?

Answer 27

* Vaso-occlusive crisis can occur when there is obstruction of the microcirculation by sickled red blood cells causing ischaemia * It may be precipitated by cold, infection, dehydration, exertion or ischaemia * This may present with swollen painful joints, tachypnoea, neurological signs, acute abdo distention and pain, loin pain, priapism, hyphaemia and retinal occlusion * Large vessels can also be involved causing thrombotic strokes, acute sickle chest syndrome and placental infarction

Question 28

Investigations for sickle cell disease?

Answer 28

* Sickle cell disease is screened for in the newborn heelprick test in the UK * FBC and blood film * Sickling of red cells on blood film with 2% sodium metabisulphite or sickle solubility test * Haemoglobin analysis by electrophoresis is needed to confirm the diagnosis, there is no HbA, 80-95% HbSS and 2-20% HbF * Should also do renal function, LFTs and lung function tests to allow for baseline and monitoring

Question 29

Management of sickle cell crisis?

Answer 29

* Opiates * Hydration * Rest * Oxygen * Antibiotics if evidence of infection * In severe crisis do a red cell exchange transfusion (venesect-transfuse-venesect-etc)

Question 30

Long term management of sickle cell disease?

Answer 30

* Parental and patient education: avoidance of situations that can precipitate crises e.g. cold, dehydration, exhaustion, early treatment and recognition of infection * Folic acid and zinc supplementation * Manage hyposplenism with prophylactic penicillin and pneumococcal meningococcus, flu, hepatitis B and HiB vaccines * Hydroxycarbamide (note teratogenic) can be used to reduce the severity of the disease by inducing HbF production, hydroxyrurea can also be used * Regular transfusions may be needed in some cases

Question 31

Explain what DIC is/ pathogenesis?

Answer 31

* Syndrome that arises due to systemic activation of coagulation either by release of pro-coagulant material such as tissue factor or via cytokine pathways as part of the inflammatory response * Such systemic activation leads to widespread generation and deposition of fibrin in vessels leading to thrombosis and multi-organ failure * As there is so much fibrin deposition there is then increased fibrinolysis which can cause haemorrhage * The large consumption of platelets and coagulation factors also then results in increased bleeding tendency * Essentially there is a paradox where there is widespread thrombosis which then causes a tendency to bleed

Question 32

List some triggers of DIC?

Answer 32

* Malignancy (especially leukaemias) * Sepsis * AHTR (acute haemolytic transfusion reaction) * Placental abruption * Snake bites * Trauma * Burns * Surgery

Question 33

Presentation of DIC?

Answer 33

* Usually shocked and very ill * The patient is usually shocked and very ill * The patient may be bleeding from mouth, nose, venepuncture site, widespread ecchymoses (bleeding underneath the skin) * Thrombotic events can involve any organ but the skin, brain and kidneys are most common

Question 34

Investigations for DIC?

Answer 34

* Low platelets * High fibrin degradation productions including D-dimer * PT elevated * Fibrinogen levels low

Question 35

Management of DIC?

Answer 35

* Use of blood components and treatment of underlying condition * Transfusion of platelets, FPP or cryoprecipitate (clotting factors) may be indicated