Haem/Onc Flashcards
Think generally of differenicals for the presentation of anaemia and pallor
again think generally about a presentation of a child with Anaemia and pallor.
What do you want to cover in:
History
Examination
What investigations do you want to order (and why?)
note: ZN protoporphyrin is high as haem binds to zinc in absence of iron
What is sickle cell disease?
- Autosomal recessive. mutation on chromosome 11 - single amino acid substitution (glutamine for valine).
- causes synthesis of an abnormal B globin chain termed HbS instead of HbA
What is most severe form of sickle cell?
Most severe form homozygous sickle Hb HbSS - sickle cell anaemia
Heterozygotes HbAS have sickle cell trait - protects from falciparum malaria - but can get symptomatic sickling if hypoxic
Some patients inherit one HbS and another abnormal haemoglobin (HbC) resulting in a milder form of sickle cell disease (HbSC)
Note; normal haemolgobin is HbAA
Prevalance of sickle cell disease
Around 10% of UK Afro-Caribbean’s are carriers of HbS (i.e. heterozygous). Such people are only symptomatic if severely hypoxic.
1:700 people of african descent
When do symptoms in (homozyous) sickle cell children start to develop and why?
Symptoms develop until 4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin.
most common time to present in childhood is 3months - 6 years
Pathophysiology of sick cell disease
I.E. what happens to cells when 02 is reduced in the bloodstream
- In the deoxygenated state the HbS molecules polymerise and cause RBCs to sickle
HbAS patients sickle at p02 2.5 - 4 kPa
HbSS patients at p02 5 - 6 kPa - Disease from vaso-occlusive crisis/disease (VOD) and haemolysis. ↑ blood viscosity and low flow in small vessels → block and cause infarction. Premature destruction of RBCs → haemolytic anaemia.
What are risks / complications for children with sickle cell disease
young children
older children
young children
* risk of pneumococcla sepsis greatest <3 years
* Infection from encapsulated organisms (if not vaccinated or no phenoxymethylpenicillin prophylaxis)
* parvovirus - aplastic anaemia
* VOD (vaso-occlusive crises) in long bones,
* sleep related Upper airway obstruction due to adenotonisllar hypertrophy -get hypoxia at night - crisis ask about snoring
* stroke
Older children:
* VOD
* avascular necrosis
* stroke.
Give examples of sickle cell crises and problems
- Vasocclusiove crises- dactylitis (trigger: cold, dehyrdation infection etc)
- acute chest syndrome - chest infection precipitates
- sequestration
- stroke
- infections
- aplastic crises - parvovirus B19
- Priapism
- avascular necrosis - e.g. hip, humerus
- renla impairment
- retinopathyy
- ENT- enlarged adenoids/tonsils obstruction
- leg ulcers
- growth and development delay - final height normal
Why is it important to ensure vaccinations are up to date in a child with sickle cell? what prophylaxis is given?
- patients are functionally hyposplenic by 1year
- high risk of infection from Pneumococcus, Meningococcus, and H. influenzae (HiB).
- Ensure vaccination is up-to-date, and give phenoxymethylpenicillin prophylaxis.
How is Sickle cell disease diagnosed?
Clinical suspicion:
* required in unscreened population.
* Routine screening of Afro-Caribbean children prior to anaesthesia.
Haematology:
* Hb 5–9g/dL, reticulocytes ↑, sickle cells on blood film.
* Hb electrophoresis [high-performance liquid chromatography (HPLC)] is definitive test.
Prenatal:
* on fetal RBCs/fibroblasts or newborn screening (UK).
Investigations in acute crises of sickle cell disease?
Lab:
* FBC - Hb low, reticulocytes raised
* blood culture
* U&E
* creatininie
* CRP - raised in sickling / infection
* Group and save
Imaging:
* CXR (i.e. acute chest syndrom)
Management of acute crises of sickle cell?
- Fluids: aim for 150% normal maintenance (PO or IV).
- Analgesia: titrate to severity often opiates if required.
- Antibiotics: broad-spectrum cephalosporin, after blood culture if fever >38°C. Add a macrolide if atypical pneumonia.
- O 2 :to maintain SpO2 >95%. Keep warm.
- Blood transfusion: for aplastic crisis, sequestration, or anaemia;
- Exchange Transfusion: for sequestration, chest syndrome, or stroke.
Maintenacne / Long term management for sickle cell ?
- Avoid precipitators: hypoxia (air travel), cold, dehydration.
- Vaccinations
- Lifetime PO phenoxymethylpenicillin prophylaxis and daily PO folic acid.
- hydroxyurea: may reduce crises and need for blood.
NOTE : Bone Marrow Transplant: if successful, is curative
A blood film is shown to you with leucoystosis, what is a cause of this?
Leukaemia: e.g. Acute lymphoblastic leukaemia
This is the commonest malignancy in childhood.
What is leukaemia?
Leukaemia is a cancer of immature white blood cells and is the most common type of cancer in children
Leukaemia involves abnormal proliferation and differentiation of leucocytes or their precursor cells.
Most cases of leukaemia are caused by de novo mutations (new mutations which are not inherited). However, there are also genetic syndromes which predispose children to leukaemia.1
Haematopoiesis and development of Leukaemia
explain categories of :
1. acute and chronic leukaemia
2. lymphoid and myeloid leukaemia
Based on where cells originate from and how differenicated the cells are.
Acute: failure of lymphoid or myeloid progenitor cells to differentiate ( lots of very immature cells blast cells)
Chronic: proliferation of cells at a later stage of proliferation
Lymphoid: originated from lymphoid precursors (right side)
Myeloid: myeloid originated from myeloid progenitor
What are the different types of leukaemia?
The types of leukaemia that affect children from most to least common are:
- Acute lymphoblastic leukaemia (ALL) is the most common in children (80%)
- Acute myeloid leukaemia (AML) is the next most common
- Chronic myeloid leukaemia (CML) is rare
Not incl: chronic lymphocytic leukaemia (CLL) v.v.v rare in children.
Explain pathophysiology of leukaemia
Leukaemia is a form of cancer of the cells in the bone marrow. A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell.
How does Leukaemia lead to pancytopenia?
The excessive production of a single type of cell can lead to suppression of the other cell lines, causing underproduction of other cell types.
pancytopenia= combination of low:
- Red blood cells (anaemia),
- White blood cells (leukopenia)
- Platelets (thrombocytopenia)
What is the specific problem / fault in Acute lymphoblastic leukaemia (ALL)?
ALL develops as a result of abnormal proliferation and failed differentiation of B or T lymphoid progenitor cells.
Uncontrolled proliferation of these immature lymphocytes (lymphoblasts) within bone marrow prevents normal haematopoiesis, and the abnormal blasts can spread to infiltrate other organs.
What are some RF for Leukaemia?
Genetic syndromes:
- Down’s syndrome: patients are 30 times more likely to develop ALL, and 150 times more likely to develop AML. The characteristic leukaemia seen in Down’s syndrome is M7 acute megakaryoblastic AML.
- Fanconi anaemia
- Li Fraumeni syndrome
- Ataxia telangiectasia
- Nijmegen breakage syndrome
Other risk factors include:
- Exposure to ionising radiation
- Pesticides
- Viruses such as Epstein-Barr virus (EBV), human immunodeficiency virus (HIV)
Typical symptoms of leukaemia?
Non specific - days - weeks
Fatigue and malaise
Unexplained fever
Failure to thrive
Weight loss
Night sweats
Bone and joint pain: particularly affecting the legs
Dyspnoea: caused by anaemia, mediastinal mass or infection
Dizziness and palpitations
Recurrent and/or severe infections
Fevers
Thrombocytopenia: bleeding tendency (epistaxis, bleeding gums), easy bruising, rashes
Clinical examination
Clinical signs of Leukaemia?
- Weight loss
- Skin: pallor, petechial rash, bruising
- Cardiovascular: tachycardia, flow murmur
- Abdomen: distension, hepatomegaly and/or splenomegaly
- Lymphadenopathy
- testicular swelling
NICE:
red flag clinical SIGNS suggestive of haematological malignancy in children.
An urgent specialist assessment is required if any of the following red flag features are present:
- Unexplained petechiae
- Unexplained hepatosplenomegaly
NICE:
red flag clinical features suggestive of haematological malignancy in children.
An urgent full blood count is required if any of the following red flag features are present:
- Pallor
- Persistent fatigue
- Unexplained fever
- Unexplained persistent infection
- Generalised lymphadenopathy
- Unexplained bruising or bleeding
- Persistent/unexplained bone pain
How does Acute lymphoblastic leukaemia (ALL) tend to present (PASSMED)
Features - those predictable by bone marrow failure:
Features may be divided into those predictable by bone marrow failure:
* anaemia: lethargy and pallor
* neutropaenia: frequent or severe infections
* thrombocytopenia: easy bruising, petechiae
And other features:
* bone pain (secondary to bone marrow infiltration)
* splenomegaly
* hepatomegaly
* fever is present in up to 50% of new cases (representing infection or constitutional symptom)
* testicular swelling
What are differencial diagnoses for leukaemia?
Infective, malignant, autoimmune. haematological
Bedside investigations for leukamia?
- Observations: fever can indicate malignancy or infection, and tachycardia can occur in infection or anaemia.
- Urine dip: infection is an important differential diagnosis.
- ECG: may show tachycardia, and a baseline is useful before cardiotoxic chemotherapy.
Tests for Leukaemia?
all: bloods, marrow, CSF, cytogenic anyalysis, imaging
Bloods:
* WCC (up but can be normal)
* Normochromic normocytic anaemia + LOW Platelets
* high urate
* high LDH
Marrow:
* 50-98% nucleated cells will be blasts
CSF
* Pleocytosis with blast forms
* protein high
* glucose low
Cytogenic:
* 80% have genetic abndormalities
Imagine:
* CXR - may be mediastinal lymphadenopathy
Ox handbook specialities p 242
Leukaemia lab investigations :
What looking for in FBC?
- Blast cell proliferation causes raised white blood cell count
- pancytopenia will occur with bone marrow suppression (anaemia and thrombocytopenia are common, while white blood cell count may be variable).
Leukaemia lab investigations :
What looking for on Blood film?
Blood film:
- shows the presence of blast cells (there may be a false negative if blasts are confined to bone marrow).
- Blast cells should normally not be seen in peripheral blood- HIGHLY suspicious for leukaemia if seen on microscopy.
Leukaemia lab investigations :
What looking for on coag profile?
- may be deranged
- may show disseminated intravascular coagulation
Leukaemia lab investigations :
What looking for on kidney and liver function?
- baseline prior to starting chemotherapy.
- Liver tests - may indicate liver infiltration
- Electrolytes can show complications of very high cell turnover such as tumour lysis syndrome (although this is usually seen post-chemotherapy).
Leukaemia lab investigations :
What looking for with lactate dehyrogenase and uric acid?
- Raised lactate dehydrogenase and uric acid: occur with increased cell turnover.
Leukaemia lab investigations :
What looking for with blood cultures?
if presenting with fever/signs of infection
Leukaemia imaging investigations : what and why?
Chest X-ray:
* identify early if a mediastinal mass is present before the child receives any anaesthetic.
* mediastinal mass may be present in T-cell lymphoblastic lymphoma, which overlaps with T-cell ALL, and can cause airway compromise, cardiovascular collapse, and death.
* An X-ray may also show infection, enlarged nodes, and lytic bone lesions.
Echocardiogram:
* prior to starting cardiotoxic chemotherapies.
What are bone marrow aspirations used for in leukaemia care?
- Diagnosis (presence of ≥20% blasts)
- Minimal residual disease analysis after treatment
- Cytogenetics: detects chromosomal aberrations
- Immunophenotyping: uses flow cytometry analysis to characterise the leukaemia blasts
- cytogenetics / immunophenotyping- for disease classification and risk stratification to guide treatment.
Note:
* A trephine biopsy also sometimes done with a second needle, removes a small piece of bone with the marrow inside - looked at under microscope
* LP sometimes done looking for the presence of leukaemic cells in cerebrospinal fluid.
What is minimal residual disease?
At the end of induction chemotherapy, the blast cell count should be ≤5% for patients to be classed as being in remission.
Presence of residual disease (i.e. persistent leukaemic cells) indicates the need for more intensive chemotherapy.
What are the 2 most widely known classifcation systems for leukaemia?
- French-American-British (FAB) classification is based on morphology (the appearance of cells under a microscope) and cytochemical staining of leukaemic cells.
- World Health Organisation (WHO) classification system uses cytogenetics (chromosomal analysis) and immunophenotyping (use of antibodies to detect white blood cell antigens).
how is leukaemia managed?
Chemotherapy is the mainstay of treatment in leukaemia.
Acute lymphocytic leukaemia
stages of chemo
- Induction: intensive 4-6 weeks aims to destroy all leukaemic blast cells. To reduce the risk of tumour lysis syndrome, pre-phase treatment with hydration and allopurinol/rasburicase is given prior to chemotherapy.
- Consolidation and CNS treatment: aim to maintain remission. LP with intrathecal methotrexate aims to prevent spread to the CNS.
- Delayed intensification: aim to remove as many remaining blasts as possible prior to the maintenance phase.
- Maintenance: treatment continues for 2 years in girls, and 3 years in boys. This can involve oral or intravenous chemotherapy, steroids, and intrathecal treatments
What chemo agents used in treating acute lymphocytic leukaemia?
Chemotherapy agents commonly used include:
corticosteroids, vincristine, anthracyclines, asparaginase, cyclophosphamide and cytarabine.
What are the stage of treatment for acute myeloid leukaemia?
- Induction: intensive phase which aims to destroy all leukaemic cells.
- Post-remission treatment: usually involves two further courses of chemotherapy, aiming to destroy residual cells and prevent a recurrence.
Bone marrow tests are repeated following induction, to assess whether remission has been achieved.
What are some other treatements for leukaemia?
- Bone marrow transplant: this is only used in patients with a high risk of disease recurrence, or with recurrence following standard chemotherapy.
- Testicular radiotherapy: used for patients with testicular infiltration.
- CNS treatments: chemotherapy drugs may be injected intrathecally (via lumbar puncture), and occasionally radiotherapy is used for infiltration following relapse.
Supportive measures for leukaemia treatment?
- Education for families
- Broad-spectrum antibiotics urgently for children (suspect neutropenic sepsis).
- Prophylactic antimicrobials: particularly co-trimoxazole (to prevent pneumocystis jirovecii) in ALL, and antifungals in AML.
- Blood transfusions.
- Allopurinol (prevention of tumour lysis syndrome).
- Insertion of a central venous catheter for chemotherapy and blood sampling.
- Granulocyte-colony stimulating factor (G-CSF): to support cell counts (e.g. prolonged neutropenia).
- Psychosocial support, educational support, advice about financial support for families
What are some early complications of leukaemia?
- Neutropenic sepsis
- Thrombocytopenia: bleeding, stroke, haemorrhage (lung or gastrointestinal)
- Blast cell lysis
- Leucostasis: stroke, pulmonary oedema, heart failure
- CNS infiltration: seizures, stroke
What are some therapy - related complications of leukaemia?
- Corticosteroid side effects: behavioural issues, weight gain
- Neutropenic sepsis
- Tumour lysis syndrome
- Mucositis, gastrointestinal inflammation
- Renal and hepatic toxicity
- Neurotoxicity
- Venous thromboembolism
- Alopecia
Long term coomplications of leukaemia?
- Secondary cancers
- Avascular necrosis (a complication of high-dose steroids)
- Cardiotoxicity (e.g. secondary to anthracycline treatment)
- Reduced growth hormone: short stature and obesity
- Fertility issues
What is tumour lysis syndrome?
Oncological emergency caused by lysis of tumour cells, either due to chemotherapy treatment or sometimes spontaneously in highly proliferative tumours.
- electrolyte imbalances hyperphosphataemia, hyperkalaemia, hypocalcaemia, hyperuricaemia.
Clinical manifestations include:
* Acute kidney injury
* Cardiac arrhythmias
* Nausea and vomiting
* Seizures.
treatment for tumour lysis syndrome?
Aggressive hydration, rasburicase or allopurinol, and haemofiltration or dialysis.
G6PD deficiency should be excluded before giving rasburicase as it increases the risk of haemolytic crisis.
Prophylactic: hydration and allopurinol are important prior to chemotherapy.
Prognosis for leukaemia?
Poor prognosis factors for ALL?
Overall cure rate in ALL is 85-90%
The best prognosis is in children aged between 1 and 10 years.
Poor prognostic factors for ALL:
* age < 2 years or > 10 years
* WBC > 20 * 109/l at diagnosis
* T or B cell surface markers
* non-Caucasian
* male sex
What are rough ranges for normal haemaglobin levels in children by age?
TOM: vary by local haem labs but to show how values vary around age
Haemaglobin levels: what is the significance of the 6 month mark?
Haemaglobin levels vary significantly for the first 6 months as the child transitions from fetal to adult haemoglobin and adapts to taking oxygen from the air rather than the placenta.
Causes of Anaemia in infancy?
- Physiologic anaemia of infancy - most common cause
- anaemia of prematurity
- blood loss
- haemolysis
- twin-twin transfusion
Hameolysis - also a common cause see below for cuases of haemolysis of a neonate:
* Haemolytic disease of the newborn (ABO / rhesus incompatability)
* Hereditory spherocytosis
* G6PD deficiency
What is physiologic anaemia of infancy?
Pathophysiology
- normal dip in haemoglobin 6-9 weeks
- high 02 delivery to the tissues caused by the high haemoglobin levels at birth cause negative feedback.
- Production of erythropoietin by the kidneys is suppressed and subsequently there is reduced production of haemoglobin by the bone marrow.
- The high oxygen results in lower haemoglobin production.
Why does anaemia of prematurity happen?
What reasons make being an anaemic neonate more likely?
- the more premature the child the more likely to be anaemic compared to term infant - need transfusions
- especially in unwell at birth (especially neonatal sepsis)
Causes:
* Less time in utero receiving iron from the mother
* Red blood cell creation cannot keep up with the rapid growth in the first few weeks
* Reduced erythropoietin levels
* Blood tests remove a significant portion of their circulating volume
What happens in haemolytic disease of the newborn?
Haemolysis and jaundice caused by incompatibility between the rhesus antigen on the surface of the RBC on mother and fetus.
rhesus antigen vary on individuals and different from ABO blood group - Rhesus D antigen is most important
What is the significance of a rhesus D negative woman getting pregnant?
- Posisibility the fetus will be rhesus D positive (has the antigen)
- mothers immune system will regnosise as foreign and produes antibodies = sensitised
When does sensisitsation usually happen i.e. in what pregnancy might rhesus status become an issue?
- Usually second pregnancy
- IMPORTANT unless early sensitisation i.e antepartum haemorrhage
- AB cross placenta and attach to the RBC of fetus causing the immune system of fetus to attack its own RBCs.
- leads toL haemolysis, anaemia and high bilirubin levels
What test for immune hameolytic anaemia?
Direct Coombs test (DCT) will be positive.
What are causes of anaemia in older children?
- Iron deficiency anaemia -dietary insufficiency is most common
- Blood loss, i.e. menstruation
Rarer causes :
* Sickle cell anaemia
* Thalassaemia
* Leukaemia
* Hereditary spherocytosis
* Hereditary eliptocytosis
* Sideroblastic anaemia
Globally:
* helminth infection, with roundworms, hookworms or whipworms in developing countries. Treatment = single dose of albendazole or mebendazole.
How do you categorise anaemia?
- Microcytic anaemia (low MCV indicating small RBCs)
- Normocytic anaemia (normal MCV indicating normal sized RBCs)
- Macrocytic anaemia (large MCV indicating large RBCs)
What are causes of microcytic anaemia?
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
What are causes of normocytic anaemia?
There are 3 As and 2 Hs for normocytic anaemia:
A – Acute blood loss
A – Anaemia of Chronic Disease
A – Aplastic Anaemia
H – Haemolytic Anaemia
H – Hypothyroidism
Causes of Macrocytic anaemia?
megaloblastic or normoblastic.
Megaloblastic = impaired DNA synthesis preventing the cell from dividing normally and grows into a large, abnormal cell i.e. vitamin deficiency
Megaloblastic anaemia is caused by:
* B12 deficiency
* Folate deficiency
Normoblastic macrocytic anaemia is caused by:
* Alcohol
* Reticulocytosis (usually from haemolytic anaemia or blood loss)
* Hypothyroidism
* Liver disease
* Drugs such as azathioprine
Symptoms of Anaemia?
There are many generic symptoms of anaemia:
- Tiredness
- Shortness of breath
- Headaches
- Dizziness
- Palpitations
- Worsening of other conditions
Symptoms specific to iron deficiency anaemia?
- Pica describes dietary cravings for abnormal things such as dirt and can signify iron deficiency
- Hair loss can indicate iron deficiency anaemia
What are some general and specific signs for certain anaemias?
Generic signs of anaemia:
* Pale skin
* Conjunctival pallor
* Tachycardia
* Raised respiratory rate
Signs of specific causes of anaemia:
* Koilonychia -spoon shaped nails- iron deficiency
* Angular chelitis - iron deficiency
* Atrophic glossitis is a smooth tongue due to atrophy of the papillae - iron deficiency
* Brittle hair and nails- iron deficiency
* Jaundice occurs in haemolytic anaemia
* Bone deformities occur in thalassaemia
Investigations for anaemia?
Initial Investigations:
- Full blood count for haemoglobin and MCV
- Blood film
- Reticulocyte count
- Ferritin (low iron deficiency)
- B12 and folate
- Bilirubin (raised in haemolysis)
- Direct Coombs test (autoimmune haemolytic anaemia)
- Haemoglobin electrophoresis (haemoglobinopathies)
- Reticulocytes are immature red blood cells. A high level of reticulocytes in the blood indicates active production of red blood cells to replace lost cells. This usually indicates the anaemia is due to haemolysis or blood loss.
How common is neonatal jaundice?
60% of term infants and 80% of preterm infants
Neonatal jaundice is caused by hyperbilirubinaemia - how would you classify hyperbilirubinaemia
unconjugated (divided into physiological or pathological)
or
conjugated (always pathological).
High levels of unconjugated bilirubin can lead to what?
acute harmful effects as well as long term damage if left untreated - kernicterus.
(type of brain damage that can result from high levels of bilirubin in a baby’s blood. It can cause athetoid cerebral palsy and hearing loss. Kernicterus also causes problems with vision and teeth and sometimes can cause intellectual disabilities.)
Can Jaundice in a baby be normal? Whats it called? What are some causes?
yes can be normal
Causes:
* Increased red blood cell breakdown: in utero the fetus has a high concentration of Hb (to maximise oxygen exchange and delivery to the fetus) that breaks down releasing bilirubin as high Hb is no longer needed
- Immature liver: not able to process high bilirubin concentrations
What is the time course of Physiological Jaundice?
Starts: day 2-3
peaks: day 5
usually resolved by day 10.
The baby remains well and does not require any intervention beyond routine neonatal care.
What is lymphoma? How is it categorised
Lymphoma is a malignancy of the lymphatic system. This includes lymph nodes, the spleen, the thymus and the bone marrow.
It is commonly divided into Hodgkin’s lymphoma and non-Hodgkin’s lymphoma.
What is lymphoma? How is it categorised
Lymphoma is a malignancy of the lymphatic system. This includes lymph nodes, the spleen, the thymus and the bone marrow.
It is commonly divided into Hodgkin’s lymphoma and non-Hodgkin’s lymphoma.
Hodgkin’s - Reed-Sternberg cells ( from B lymphocytes.)
Non-Hodgkin’s - T or B lymphocytes, disease is high or low grade, includes the lymphoblastic lymphomas that are similar to ALL.
Epidiemiology of Lymphoma?
- accounts for over 10% of childhood cancers
- more common in boys
- more common in older children, teenagers and young adults
Pathophysiology of lymphoma?
- genetic alterations which trigger the abnormal proliferation of lymphocytes.
- Unknown underlying cause of lymphoma but chromosomal abnormalities have been identified which are associated with subtypes of lymphoma and can indicate prognosis.
- infection, genetic factors and environmental exposures all potentially involved
What features distinguish lymphoma from leukaemia?
Lymphoma:
* malignant cells are mature lymphocytes, and they arise within sites outside of the bone marrow (e.g. lymph nodes).
Leukaemia:
* develops from immature blasts and arises within the bone marrow.
Exception:
* less common lymphoblastic lymphomas (B-cell lymphoblastic lymphoma, and T-cell lymphoblastic lymphoma), which develop from immature precursor lymphoblasts similarly to leukaemia.
* distinguished by the degree of bone marrow infiltration by blasts; <25% bone marrow involvement is lymphoma
What are some risk factors for lymphoma?
- Epstein-Barr virus
- immunosuppressed patients (transplant)
- previous treatment for cancer
What are some risk factors for lymphoma?
- Epstein-Barr virus
- immunosuppressed patients (e.g. solid organ transplant, immunosuppressant drugs)
- HIV
- previous treatment for cancer
How might a patient with lymphoma present ?
Painless, progressive lymphadenopathy (develops over weeks-months)
History of “B symptoms” such as:
* Weight loss
* Night sweats
* Fevers
non-specific symptoms of malignancy:
* lethargy
* anorexia
What might you find on examination of a patient with lymphoma?
- Non-tender, firm, matted lymph nodes (more likely to be malignant)
- Hodgkin’s: often cervical, supraclavicular, axillary
- Non-Hodgkin’s: more rapidly growing bulky lymphadenopathy
- Mediastinal mass: may cause severe effects such as SVC obstruction, effusions, or airway obstruction
- Abdomen: splenomegaly, hepatomegaly, abdominal mass
- Skin: T cell lymphomas including mycosis fungoides, jaundice
- Testicular mass
- Neurological: weakness, sensory abnormalities, features of raised intracranial pressure
What are some symptoms indicating extranodal involvement in lymphoma? (more common in non-hodgkinsons)
- Bone marrow: symptoms of anaemia, infections, easy bruising/bleeding.
- Abdo: bloating, early satiety, pain, unable to pass stools and vomiting if obstructed.
- Retroperitoneal lymphadenopathy: urinary retention.
- Skin: new skin lesions (such as mycosis fungoides), or jaundice.
- Testicular swelling
- CNS: behavioural change, headache, confusion, nausea and vomiting, seizures, weakness, sensory changes.
Differencials for lymphoma?
- Reactive lymphadenopathy - always ask about infection hx in children (more likely to be tender, fluctuant if abscess formed) INFECTION MOST COMMON CAUSE OF LYMPHADENOPATHY IN CHILDREN
- Leukaemia - ‘Bulky’ consider if signs and symptoms of anaemia / thrombocytopenia
What are bedside investigations for lymphoma?
Observations:
* fever due to malignancy / infection,
* RR + SpO2 assess for mediastinal disease.
Swabs:
* infective causes of lymphadenopathy
Urine dip:
* exclude infection if febrile
(ECG)
* chest disease may cause effects such as pericardial effusions and obtaining a baseline ECG is useful to have prior to starting cardiotoxic chemotherapies.
Lab investigations for lymphoma?
FBC:
* pancytopenia or leukaemic presentation – leukaemia (important differential diagnosis) will cause anaemia, thrombocytopenia, and usually a raised WBC.
Urea and electrolytes (U&E):
* baseline pre chemotherap
* electrolytes can show tumour lysis syndrome if rapid cell turnover occurs (HIGH LDH and urate)
LFT:
* baseline pre chemotherapy
* derangement - hepatic involvement.
* Low albumin= worse prognosis.
Monospot test:
* exclude Epstein-Barr virus infection
ESR:
* raised- worse prognosis
Hepatitis B/HIV tests:
* risk of hepatitis reactivation with rituximab treatment
G6PD:
* deficiency should be identified before commencing rasburicase as it can cause a haemolytic crisis.
What imaging for lymphoma?
Chest X-ray:
* mediastinal mass arising from the lymph nodes or thymus, intrathoracic lymph nodes, or effusions.
CT/MRI/PET scans:
* for staging purposes e.g/ full body CT
Ultrasound of the liver and spleen
Is biopsy needed for lymphoma?
Lymph node biopsy is necessary for definitive diagnosis under GA
* excision or a partial biopsy
* bone marrow biopsy can be done for staging / detect infiltration
What staging is used for lymphoma?
Hodgkins: Ann Arbor classification
Non Hodgkins: St Jude classification- more extranodal involvement
Teach me Paeds has the below:
What could be some immediate management needed
for emergencies
mediastinal mass with potential airway compromise:
* high dose steroids and airway support
Superior vena cava obstruction (SVCO)
* stenting of veins to keep them patent
* will usually resolve with treatment of the underlying malignancy.
tumour lysis syndrome
* intense hydration
* Allopurinol or rasburicase
Treatment of Hodgkin’s lymphoma?
- chemotherapy
Other:
* Radiotherapy is used in <50% children. A PET scan is used to assess response after 2 cycles of chemotherapy, and patients with ongoing PET avidity will receive adjuvant radiotherapy.
* Lymphocyte-predominant HL has less intensive treatment (due to a slower growth rate); usually surgery or low-dose chemotherapy is sufficient.
Treatment for non-Hodgkin’s lymphoma?
- Chemotherapy
The specific regimen will be based on the type of disease and staging
Other :
* Biologics: Rituximab (anti CD20 antibody) is the standard of care in high-risk mature B-cell NHL.
* Radiotherapy is used rarely in addition to chemotherapy.
* Bone marrow transplant (BMT): high dose chemotherapy with BMT can be used for relapsed patients.
* Lymphoblastic lymphoma is treated according to chemotherapy protocols for ALL.
Lymphoma: some short term compliations due to:
1. condition related
2. treatment related
Lymphoma: long term complications related to treatment?
Secondary cancers
cardiotoxicity
pulmonary toxicity
renal impairment
growth impairment
infertility
Prognosis of Lymphoma?
- 90% of patients with Hodgkin’s lymphoma
- > 90% of children with Non-Hodgkin’s lymphoma achieve remission.
BUT:
* long-term effects of treatment need long-term follow-up as well as assessing for recurrence
What is the characteristic histological finding in Hodgkin’s lymphoma?
Reed-Sternberg cells and is derived from B lymphocytes.
What does the spleen do?
- produces protective humoral antibodies
- involved in the production and maturation of B and T cells and plasma cells
- Removes unwanted particulate matter (eg, bacteria)
- Acts as a reservoir for blood cells, especially white cells and platelets.
How might a splenectomy occur ( 3 )?
i.e. planned
- Planned- prophylactically to prevent later complications.
- Traumatic- accident or during surgery
- Autosplenectomy- physiological loss (i.e.hyposplenism) - eg, sickle cell anaemia (chronic damage to the spleen results in atrophy), coeliac disease, dermatitis herpetiformis, essential thrombocythaemia and ulcerative colitis
What are some causes of hyposplenism?
- splenectomy
- sickle-cell
- coeliac disease (30% are)
- dermatitis herpetiformis
- Graves’ disease
- systemic lupus erythematosus
- amyloid
- Essential thrombocythaemia and ulcerative colitis
What are some indications for a surgeical splenectomy?
Trauma:
* 25% of injuries are iatrogenic.
Spontaneous rupture:
* massive splenomegaly (eg, infectious mononucleosis) and is often precipitated by minor trauma.
Hypersplenism:
* hereditary spherocytosis or elliptocytosis, immune thrombocytopenia.
Neoplasia:
* lymphoma or leukaemic infiltration.
With other viscera:
* total gastrectomy, distal pancreatectomy.
Other indications:
* splenic cysts, hydatid cysts, splenic abscesses.
Complications of splenectomy?
- Thromobocytosis - peaks 7-19 days give aspirin if very hight
Overwhelming infection:
* encapsulated bacteria e.g. ‘NHS’ Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.
Blood film results for someone with hyposplenism?
- target cells
- Howell-Jolly bodies
- Pappenheimer bodies
- siderotic granules
- acanthocytes
How do you manage a patient with hyposplenism
medical only
- Immunisations
* S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended.
* pneumococcal
* meningococcal groups A, C, W, Y and B - Antibiotic prophylaxis
* e.g. oral phenoxymethylpenicillin or macrolides e.g. erythromycin
* have a reserve at home take when signs of infection i.e. pyrexia, shivering and seek help
How do you manage a patient with hyposplenism
non-medical: alerts, advice and counselling on precautions to take
The British Committee for Standards in Haematology recommends:
- give pts written information and carry a card to alert health professionals to the risk of overwhelming infection. Patients should wear an alert bracelet or pendant.
- Patients should be aware of the potential risks of overseas travel, particularly with regard to malaria and unusual infections - eg, those resulting from animal bites.
- Patient records should be clearly labelled to indicate the underlying risk of infection. Vaccination and re-vaccination status should be clearly and adequately documented.
How do you manage a patient with hyposplenism
non-medical: alerts, advice and counselling on precautions to take
The British Committee for Standards in Haematology recommends:
- give pts written information and carry a card to alert health professionals to the risk of overwhelming infection. Patients should wear an alert bracelet or pendant.
- Patients should be aware of the potential risks of overseas travel, particularly with regard to malaria and unusual infections - eg, those resulting from animal bites.
- Patient records should be clearly labelled to indicate the underlying risk of infection. Vaccination and re-vaccination status should be clearly and adequately documented.
What is pancytopenia?
diagnosed by a full blood count showing the combination of: anaemia, thrombocytopenia, and leukopenia.
Causes of pancytopenia?
Causes of decreased marrow haematopoetic function
- chemotherapy and radiotherapy (the pancytopenia may be transient).
- Vitamin B12 and folate deficiency.
- Marrow infiltration by haematological malignancies (leukaemias or lymphomas).
- Myelofibrosis, in which there is progressive marrow fibrosis.
- Multiple myeloma (a plasma cell dyscrasia).
- Parvovirus infection in haemolytic disease (such as sickle cell anaemia).
Causes of pancytopenia?
Inherited causes of marrow failure
The most common causes include:
* Fanconi’s anaemia (an autosomal recessive condition)
* dyskeratosis congenita (an X-linked condition).
Causes of pancytopenia?
Increased destruction/sequestration of blood cells peripherally
This is seen in conditions affecting the liver (such as hepatitis B/C, autoimmune hepatitis, and cirrhosis).
Causes of panyctopenia
Immune destruction of blood cells
This occurs in drug-induced pancytopenia (secondary to, for example, Sulphonamide or Rifampicin).
What is DIC (Disseminated intravascular coagulation)
DIC is the pathological activation of blood coagulation pathways that occurs in response to a variety of severe diseases.
All, or some may simultaneously occur:
- Consumption of platelets and clotting factors → abnormal bleeding.
- Activation of intravascular thrombosis with both macro- and microthrombi formation, leading to endorgan damage.
- Widespread activation of fibrinolysis, leading to further bleeding.
- MAHA -Microangiopathic hemolytic anemia (‘RBCs destroyed in fibrin mesh’).
Causes of DIC can be divided by age in paediatrics.
Causes of DIC in neonates?
common and less common
Common:
* severe asphyxia
* sepsis.
Less common:
* severe IUGR,
* Respiratory distress syndrome
* aspiration
* pneumonitis
* NEC
* Rh isoimmunization
* dead twin
* severe haemorrhage
* purpura fulminans
* profound hypothermia.
Causes of DIC can be divided by age in paediatrics.
Causes of DIC in older children?
common and less common
Common:
* septicaemia (60%)
* severe trauma
* burns.
Less common:
* profound shock
* hepatic failure
* anaphylaxis
* severe blood transfusion reactions.
How does DIC present in a child?
DIC usually occurs in the setting of a profoundly sick child.
- Oozing and bleeding from venepuncture sites, wounds, mucosal membranes, and GI, pulmonary, and GU tracts.
- Microthrombi causing renal impairment, cerebral dysfunction, and localized skin necrosis.
- ARDS - acute respiratory distress syndrome (life threatening fluid leaks into lungs)
- MAHA - microangiopathic hameoltyic anaemia
NOTE: MAHA = RBC destruction in microvasculature + thrombocytopenia due to platelet activation and consumption.
Investigations for DIC results: specifially bloods related to coagulation and clotting
- Platelets ↓
- fibrinogen ↓ (<1g/L),
- PT ↑
- APTT ↑
- TT ↑
- FDPs ↑ (>80mg/mL) or D-dimers (non-specic, but useful in monitoring progress).
ibrinogen degradation products (FDPs). D-dimer is a specific fragment.
Management of DIC
Immediate
* identify and vigorously treat underlying cause.
Supportive care:
* O2
* IV fluids for shock
* blood transfusion.
Platelets:
* Platelet transfusion if uncontrolled bleeding or pre-procedure to ma
Coagulation factors to control bleeding
* e.g. FFP (prolonged PT and ative bleeding)
* cryoprecipitate if fibrinogen <500mg/L.
Seek expert advice from a paediatric haematologist - heparin can be used for large thrombi - controversial
Prognosis of DIC
high mortality, due to either the underlying disease or DIC-related haemorrhage or thrombosis.
Lightening learning Immune Thrombocytopenia (ITP)
What, presents, causes to cover in history
Child with ALL, what are the stages of chemotherapy they will go through ?
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