8- Paediatric Haematology and Oncology Flashcards
Anaemia
Background
- Low haemoglobin in the blood
- Result of underlying disease
pathophysiology of anaemia
- Hb is a protein found in RBC
- transports oxygen from the lungs to cells of the body
- iron is an essential ingredient in creating Hb
types of anaemia
microcytic anaemia
normocytic anaemia
macrocytic anaemia
causes of microcytic anaemia
Thalassaemia
Anaemia of chronic disease
Iron deficiency
Lead poisoning
Sideroblastic anaemia
causes of macrocytic anaemia
Anaemias where the average red cell size is greater than normal (increased MCV)
Megaloblastic
* B12 def
* Folate def
Normoblastic
* Blood cancers
* Alcohol
* Reticulocytes
* Hypothyroidism
* Liver disease
* Azathioprine
causes of normocytic anaemia
(2As and 2Hs)
- Acute blood loss
- Anaemia of chronic disease
- Aplastic anaemia
- Haemolytic anaemia
- Hypothyroidism
general causes of anaemia in children
- physiologic anaemia of infancy
- anaemia of prematurity
- blood loss
- haemolysis
- twin twin transfusion (blood unequally distributed between twins that share a placenta)
symptoms of anaemia
Generic symptoms of anaemia:
- Tiredness
- Shortness of breath
- Headaches
- Dizziness
- Palpitations
- Worsening of other conditions
There are 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
signs of anaemia
Generic signs of anaemia:
- Pale skin
- Conjunctival pallor
- Tachycardia
- Raised respiratory rate
Signs of specific causes of anaemia: - Koilonychia refers to spoon shaped nails, which can indicate iron deficiency
- Angular chelitis can indicate iron deficiency
- Atrophic glossitis is a smooth tongue due to atrophy of the papillae and can indicate iron deficiency
- Brittle hair and nails can indicate iron deficiency
- Jaundice occurs in haemolytic anaemia
- Bone deformities occur in thalassaemia
normal range of Hb
- Depends on age
- Varies significant for the first 6 months as a the child transitions from fetal to adult Hb and adapts to taking oxygen via their lungs rather than placenta
- At puberty values between males and females varies due to menstruation
investigating anaemia
1) FBC
- Hb
- MCV
2) Blood film
3) Reticulocyte cunt
4) Ferritin
5) B12/folate
6) Bilirubin
7) Direct coombs test (autoimmune haemolytic anaemia)
8) Haemoglobinopathies
how can reticulocyte count be helpful
The presence or absence of reticulocytosis ( has the marrow responded normally?)
–> Would expect increase in reticulocyte if marrow was working normally
Reticulocytes
- Immature red blood cells (those which just been released from marrow into blood)
- Slightly LARGER than mature RBC so increase reticulocyte number will increase MCV
- No nucleus, some RNA
- 1% of all RBC
- Take 1 day to mature
Physiologic Anaemia of Infancy
- There is a normal dip in haemoglobin around six to nine weeks of age in healthy term babies.
- High oxygen 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.
BASICALLY: The high oxygen results in lower haemoglobin production.
Anaemia of Prematurity
Premature neonates are much more likely to become significantly anaemic during the first few weeks of life compared with term infants.
The more premature the infant, the more likely they are to require one or more transfusions for anaemia. This becomes more likely if they are unwell at birth, particularly with neonatal sepsis.
Premature neonates become anaemic for a number of reasons:
* 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
Haemolytic disease of the newborn
Pathophysiology
- is a cause haemolysis (red blood cells breaking down) and jaundice in the neonate.
- It is caused by incompatibility between the rhesus D antigens on the surface of the red blood cells of the mother and fetus.
- When a woman that is rhesus D negative (does not have the rhesus D antigen) becomes pregnant, we have to consider the possibility that the fetus will be rhesus D positive (has the rhesus D antigen).
- It is likely at some point in the pregnancy the blood from the fetus will find a way into her bloodstream.
- When this happens, the fetal red blood cells display the rhesus D antigen.
- The mother’s immune system will recognise the rhesus D antigen as foreign and produce antibodies to the rhesus D antigen.
- o The mother has then become sensitised to rhesus D antigens.
- Usually, this sensitisation process does not cause problems during the first pregnancy (unless the sensitisation happens early on, such as during antepartum haemorrhage).
- During subsequent pregnancies, the mothers anti-D antibodies can cross the placenta into the fetus.
- If that fetus is rhesus positive, these antibodies attach themselves to the red blood cells of the fetus and causes the immune system of the fetus to attack its own red blood cells.
- This leads to haemolysis, causing anaemia and high bilirubin levels.
investigations for haemolytic disease of the newborn
Investigations
- Direct coombs test (DCT) can be used to check for immune haemolytic anaemia
Causes of anaemia in older children
The key causes of anaemia in older children are:
- Iron deficiency anaemia secondary to dietary insufficiency. This is the most common cause overall.
- Blood loss, most frequently from menstruation in older girls
Rarer causes of anaemia in children include:
- Sickle cell anaemia
- Thalassaemia
- Leukaemia
- Hereditary spherocytosis
- Hereditary eliptocytosis
- Sideroblastic anaemia
Management of anaemia
- Depends on cause
- Iron deficiency - iron supplementation
- If severe- blood transfusion
Management of anaemia
- Depends on cause
- Iron deficiency - iron supplementation
- If severe- blood transfusion
Disseminated intravascular coagulation
Background
- Pathological activation of coagulation that occur in response to a variety of severe disease
–>Type of microangiopathic haemolytic anaemia - Thrombo-haemorrhagic condition
Pathophysiology DIC
- Pathological activation of coagulation due to trigger causes numerous microthrombi are formed in the circulation
- Leads to consumption of clotting factors and platelets and a haemolytic anaemia
Triggers of DIC
always a trigger
- Malignancy
- Massive tissue injury e.g. burns
- Infection
- Massive haemorrhage and transfusion
- ABO transfusion reaction
- Obstetric causes- placental abruption, pre-eclampsia, amniotic fluid embolism
Causes of DIC in children
- Neonatal
o Sever asphyxia, sepsis - Older children
o Septicaemia, severe trauma and burns
DIC presentation
- Usually in very ill child
- Oozing and bleeding from venepuncture sites, wounds, mucosal membranes, GI, pulmonary and GU tracts
- Microthrombi causing renal impairment, cerebral dysfunction, localised skin necrosis
- Acute RDS
- Microangiopathic haemolytic anaemia
investigations for DIC
- Clotting tests are affected- raised PT, raised APTT, low fibrinogen and raised D-dimers (fibrin degradation products)
- Challenge to diagnose due to no gold standard test
management of DIC
- Identify the cause and treat
- Support: oxygen, blood transfusion,
- Platelet transfusion : if uncontrolled bleeding
- Coagulation factor replacement e.g. fresh frozen plasma (FFP)
- Use of heparin controversial, but may be needed if large thrombi or significant organ damage from microthrombi
Prognosis of DIC
High mortality due to underlying disease or DIC related haemorrhage or thrombosis
Sickle cell disease
Background
- autosomal recessive condition which causes sickled red blood cells
- Makes RBCs fragile and more easily destroyed -> haemolytic anaemia
sickle cell disease pathophysiology
- Recessive conditions caused by an abnormal beta-globin on chromosome 11
- One copy of the gene results in sickle-cell trait (asymptomatic)
HbF, HbA and HbS
- During the development of a fetus, from 32 to 36 weeks gestation, the production of fetal haemoglobin (HbF) decreases.
- At the same time, adult haemoglobin (HbA) is produced in greater quantities.
- Over time there is a gradual transition from HbF to HbA. At birth, around half the haemoglobin produced is HbF and half is HbA.
- By 6 months of age, very little fetal haemoglobin is produced. Eventually, red blood cells contain almost entirely HbA.
- Patients with sickle-cell disease have an abnormal variant called haemoglobin S (HbS). HbS causes red blood cells to be an abnormal “sickle” shape.
Investigations for sickle cell
- Maternal screening
- Newborn screening heel prick test at 5 days of age
general management of sickle cell
- Avoid dehydration and other triggers of crises
- Ensure vaccines are up to date
- Antibiotic prophylaxis to protect against infection, usually with penicillin V (phenoxymethypenicillin)
- Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of red blood cells. This has a protective effect against sickle cell crises and acute chest syndrome.
- Blood transfusion for severe anaemia
- Bone marrow transplant can be curative
Complications of sickle cell
- Anaemia
- Increased risk of infection
- Stroke
- Avascular necrosis in large joints such as the hip
- Pulmonary hypertension
- Painful and persistent penile erection (priapism)
- Chronic kidney disease
- Sickle cell crises
- Acute chest syndrome
sickle cell relation to malaria
Sickle cell disease is more common in patients from areas traditionally affected by malaria, such as Africa, India, the Middle East and the Caribbean. Having one copy of the gene (sickle-cell trait) reduces the severity of malaria. As a result, patients with sickle-cell trait are more likely to survive malaria and pass on their genes. Therefore, there is a selective advantage to having the sickle cell gene in areas of malaria.
Sickle cell crisis
Umbrella term
- Vaso-occlusive crisis (painful)
- Splenic sequestration crisis
- Aplastic crisis
- Acute chest syndrome
general management of sickle cell crisis
o Have a low threshold for admission to hospital
o Treat any infection
o Keep warm
o Keep well hydrated (IV fluids may be required)
o Simple analgesia such as paracetamol and ibuprofen (NSAIDs should be avoided where there is renal impairment)
o Penile aspiration is used to treat priapism
Vaso-occlusive crisis
Background
is caused by the sickle shaped blood cells clogging capillaries and causing distal ischaemia. It is associated with dehydration and raised haematocrit.
Presentation
Symptoms are typically pain, fever and those of the triggering infection. It can cause priapism in men by trapping blood in the penis, causing a painful and persistent erection.
- This is a urological emergency and is treated with aspiration of blood from the penis.
Acute Chest Syndrome
A diagnosis of acute chest syndrome requires:
- Fever or respiratory symptoms, with:
- New infiltrates seen on a chest xray
Acute chest syndrome can be due to
infection (e.g. pneumonia or bronchiolitis) or non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli).
Management
Acute chest syndrome is a medical emergency with a high mortality. It requires prompt supportive management and treatment of the underlying cause:
- Antibiotics or antivirals for infections
- Blood transfusions for anaemia
- Incentive spirometry using a machine that encourages effective and deep breathing
- Artificial ventilation with NIV or intubation may be required
Aplastic Crisis
Aplastic crisis describes a situation where there is temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19.
It leads to significant anaemia. Management is supportive with blood transfusions if necessary. It usually resolves spontaneously within a week.
Splenic sequestration crisis
Splenic sequestration crisis is caused by red blood cells blocking blood flow within the spleen.
Presentation
This causes an acutely enlarged and painful spleen. The pooling of blood in the spleen can lead to severe anaemia and circulatory collapse (hypovolaemic shock).
Management
Splenic sequestration crisis is considered an emergency.
- Management is supportive, with blood transfusions and fluid resuscitation to treat anaemia and shock.
- Splenectomy prevents sequestration crisis and is often used in cases of recurrent crises. Recurrent crises can lead to splenic infarction, resulting in susceptibility to infections.
role of spleen
major role in reticuloendothelial system
o Producing antibodies, B and T cells and plasma cells
o Filtered opsonised pathogens for phagocytosis
o Reservoir for blood cells e.g. WBC and platelets
Asplenia
absence of spleen due to congenital anomaly or surgical procedure
Hyposplenism
reduced or absent function of spleen, impairing capacity to prevent bacterial infections
causes of splenectomy
1) Planned e.g. neoplasia
2) Traumatic e.g. accident or surgery
3) Auto splenectomy
- Physiological loss of spleen function e.g. hypersplenism’s
- Sickle cell
- Coeliac
- Essential thrombocytopenia
- UC
Indication for splenectomy
- Trauma
- Spontaneous rupture e.g. caused by splenomegaly due to infectious mononucleosis
- Hypersplenism – immune thrombocytopenia
- Neoplasia
Complication of splenectomy
- Thrombocytosis ->Increased risk of VTE, but prophylactic aspirin may be given if very high
- Infection by encapsulated bacteria
o Streptococcus pneumonia
o Haemophilus influenzae
o Neisseria meningitis’s
Investigations for hyposplenism
- Blood film: features of hyposplenism include Howell-Jolly bodies, Pappenheimer bodies, target cells and irregular contracted red blood cells.
- Imaging techniques: ultrasound, CT scanning, and MRI scanning.
- Other investigations, which will depend on the clinical context.
Complications of hyposplenism
- Increased risk of NHS encapsulated bacterial infections
- Increased risk of severe falciparum malaria
management of hyposplenism
Immunisations
- H.influzenae type B
- Influenza virus
- Pneumococcal
- Meningococcal ACWY and B
Antibiotic prophylaxis
- For those at high risk of pneumococcal infections
- Types:
Phenoxypenicillin
Macrolides
Risk factors for high risk hyposplenism
- Age <16 years or >50 years.
- Poor response to pneumococcal vaccination.
- Previous invasive pneumococcal illness.
- Underlying haematological malignancy resulting in splenectomy (increased risk if immunosuppressed).
Pancytopenia
Background
- Low levels of RBC, WBC and platelets
o RBC- oxygen delivery
o WBC- immune
o Platelets- haemostasis - Increases risk of infection and bleedings
pancytopenia causes
Causes usually unknown
- Cancer e.g. acute leukaemia’s, chemotherapy or radiation
- Genetic conditions
- Vitamin B12 and folate deficiency
- Autoimmune conditions which attack the bone marrow
- Some medicines e.g. antiseizure, antibiotics
presentation of pancytopenia
Anaemic symptoms
- Weakness
- Fatigue
- Rapid heart rate
- SoB
- Pale skin
Low WBC
- Frequent infections
Low platelets
- Petechiae
- Bleeding from the gums or nose, blood in faeces or urine, heavy bleeding from cut
- Heavy menstruation in female
- Easy bruising
Investigation for pancytopenia
Bloods
- Full blood count
- Blood culture
- Clotting/coagulation studies
- Group and cross-match blood
- U&Es
- CRP
Bone marrow biopsy
