Haematology/oncology Flashcards
How does the structure of a foetus haemoglobin differ from that of an adult haemoglobin?
Foetus haemoglobin has two alpha and two gamma subunits
Adult haemoglobin has two alpha and two beta subunits
When does HbF become HbA?
HbF production decreases from 32 to 36 weeks gestation and at the same time HbA is produced, over time there is a gradual transition from HbF to HbA.
By 6 months, very little fetal haemoglobin is produced.
What can be used as a treatment in sickle disease?
In sickle cell disease, a genetic abnormality coding for the beta unit of haemoglobin is responsible for the sickle shape of the red blood cells.
Fetal haemoglobin does not lead to sickling as there is no beta unit, there is only gamma and alpha.
HYDROXYCARBAMIDE can be used to increase the production of fetal haemoglobin in patients with sickle cell anaemia.
What is anaemia?
A low level of haemoglobin in the blood.
What should you always check if the patient has a low haemoglobin?
The mean cell volume as this helps you identify the underlying cause.
What are the causes of anaemia in infancy?
Physiologic anaemia of infancy (most common) Anaemia of prematurity Blood loss Haemolysis (break down of RBCs) Twin- twin transfusion
What is the cause of haemolysis in infancy?
Haemolytic disease of the newborn (ABO/rhesus incompatibility)
Hereditary spherocytosis
G6PD deficiency
What is physiologic anaemia of infancy?
There is a normal dip in haemoglobin around 6-9 weeks of age in healthy term babies. There is high haemoglobin at birth and therefore high oxygen delivery to the tissues, this then causes negative feedback and there is a reduced production of EPO by kidneys and hence reduced haemoglobin and red blood cells by the bone marrow.
What are the reasons that premature babies are more likely to have anaemia?
. They have less time in utero receiving iron from the mother
. RBC creation cannot keep up with the rapid growth in the first few weeks
. Reduced EPO
. Blood tests remove a significant portion of the circulating volume
How can you check for haemolytic disease of the newborn?
Direct coombes test
What are the most common causes of anaemia in older children?
Iron deficiency anaemia
Blood loss
Others; sickle cell anaemia, thalassaemia, leukaemia, hereditary spherocytosis, hereditary elliptocytosis, sideroblastic anaemia.
What is a common cause of blood loss causing chronic anaemia, worldwide?
Helminth infection with roundworms, hookworms, whipworms
What are the causes of microcytic anaemia?
TAILS T= thalassaemia A= anaemia of chronic disease I= iron deficiency anaemia L= lead poisoning S= sideroblastic
What are the causes of normocytic anaemia?
3As and 2Hs A= acute blood loss A= anaemia of chronic disease A= aplastic anaemia H= haemolytic anaemia H= hypothyroidism
Macrocytic anaemia can be megaloblastic or normoblastic, what is megaloblastic anaemia?
Megaloblastic is where there is impaired DNA synthesis and the cell cant divide normally, rather than dividing it grows into a large and abnormal cell. It is caused by vitamin deficiency (B12/ folate)
What are the causes of normoblastic macrocytic anaemia?
Alcohol
Hypothyroidism
Liver disease
Azathioprine
What are the symptoms of anaemia?
Fatigue SOB Headaches Dizziness Palpitations
What are the symptoms specific to iron deficiency anaemia?
Pica
Hair loss
What are the signs of anaemia?
Pale skin, conjunctival pallor, raised RR, tachycardia
Koilonychia Angular cheilitis Atrophic glossitis Brittle hair and nails All indicate iron deficiency anaemia
Jaundice indicates haemolytic disease of newborn
Bone deformities indicate thalassaemia
What investigations would you do for anaemia?
FBC for haemoglobin and MCV Blood film Reticulocyte count Ferritin B12 and folate Bilirubin (raised in haemolysis) Direct coombes test (positive in autoimmune haemolytic anaemia) Haemoglobin electrophoresis (for haemoglobinopathies like thalassaemia and sickle cell anaemia)
What would a high level of reticulocytes in the blood indicate?
Indicates active production of RBC to replace lost cells and usually indicates the anaemia is due to haemolysis or blood loss.
What causes iron deficiency?
Loss of iron- bleeding like heavy menstruation
Inadequate iron absorption through crohns or coeliac
Dietary insufficiency
How can PPIs (ie: omeprazole) lead to iron deficiency anaemia?
Acid in the stomach is needed to keep the iron in soluble ferrous (Fe2+) form, if theres no acid then it stays in the insoluble ferric form.
Where is most iron absorbed?
In the duodenum or the jejunum.
How does iron travel around the blood?
Iron travels around the blood as ferric ions (Fe3+) bound to a carrier protein called transferrin.
What is the form that iron takes when it is deposited and stored in cells?
Ferritin
Extra ferritin is released from cells when there is inflammation such as: with infection or cancer
Can a patient with normal ferritin levels still have iron deficiency anaemia?
Yes because they may have reasons to have high ferritin, like infection.
What other tests in iron deficiency anaemia can be used other than ferritin?
Serum iron- however this is not very helpful as fluctuates
Total iron binding capacity- marker of how much transferrin is in the blood
transferrin saturation- gives a good indication of the total iron in the body
How can you treat iron deficiency?
Iron can be supplemented by ferrous sulphate or ferrous fumarate, this slowly corrects the iron deficiency however oral iron can cause constipation and black coloured stools.
What is leukaemia?
Cancer of a particular line of the stem cells in the bone marrow which causes unregulated production of certain types of blood cells.
What are the types of leukaemia?
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic myeloid leukaemia
What is the pathophysiology behind leukaemia?
Leukaemia is a form of cancer on the cells in the bone marrow. A genetic mutation in one of the precursor cells in the bone marrow leads to an excessive production of a single type of abnormal white blood cell. The excessive production of a single type of cell can lead to suppression of the other cell lines, causing underproduction of other cell types which results in pancytopenia.
Combination of: Low WBCS (leukaemia) Low RBCS (anaemia) Low platelets (thrombocytopenia)
What are the risk factors to leukaemia?
Radiation exposure with abdo xray during pregnancy
Certain conditions which predispose to a higher risk of developing leukaemia- downs syndrome, kleinfelter, noonan, fanconis.
What is the presentation of leukaemia?
Persistent fatigue Unexplained fever Failure to thrive Weight loss Night sweats Pallor (anaemia) Petechiae and abnormal bruising Unexplained bleeding Abdominal pain Generalised lymphadenopathy Unexplained or persistent bone or joint pain Hepatosplenomegaly
How do you diagnose leukaemia?
Refer any child with unexplained petechiae or hepatomegaly for an immediate specialist assessment
FBC- shows anaemia, leukopenia, thrombocytopenia and high numbers of abnormal WBCs
Blood film- shoes blast cells
Bone marrow biopsy
Lymph node biopsy
Further tests for staging... CXR CT Lumbar puncture Genetic analysis and immunophenotyping of abnormal cells.
What is the management of leukaemia?
MULTI DISCIPLINARY TEAM
Primarily treated with chemo
Other therapies= radiotherapy, bone marrow transplant, surgery
What are the complications of chemo?
Failure to treat the leukaemia Stunted growth and development Immunodeficiency and infections Neurotoxicity Infertility Cardiotoxicity Secondary malignancy
What is idiopathic thrombocytopenic purpura?
Condition characterised by idiopathic thrombocytopenia (low platelet count) causing a purpuric rash.
What is the presentation of idiopathic thrombocytopenic purpura?
Bleeding
Bruising
Petechial or purpuric rash
What is the difference between petechial or purpuric rash?
Petechial= pin prick spots (around 1mm) of bleeding under the skin Purpura= more than 10mm of blood collected, ecchymoses, non blanching lesions.
What is the treatment of idiopathic thrombocytopenic purpura?
Condition can be confirmed by doing an urgent FBC for the platelet count
Other causes of the low platelet count should be excluded- heparin induced thrombocytopenia, leukaemia.
Around 70% of patients will remit spontaneously within 3 months
Treatment may be required if the patient is actively bleeding or there is severe thrombocytopenia (platelets below 10).. . Prednisolone . IV immunoglobulins . Blood transfusions if required . Platelet transfusions if required
Why do platelet transfusions only work temporarily?
The antibodies against platelets will begin destroying transfused platelets as soon as they are infused.
What advice can be given for patients with thrombocytopenia?
Avoid contact sports
Avoid IM injections and procedures such as lumbar punctures
Avoid NSAIDS, aspirin and blood thinning medication
Advice on managing nosebleeds
Seek help after any injury that may cause internal bleeding- car accidents or head injuries
What is sickle cell anaemia?
Sickle cell anaemia is a genetic condition that causes sickle (crescent) shaped RBC.
What is the pathophysiology of sickle cell anaemia?
Fetal haemoglobin F is usually replaced by haemoglobin A at around 6 weeks of age, patients with sickle cell disease have an abnormal variant called HbS. HbS causes RBC to have an abnormal sickle shape.
What is the genetic inheritance of sickle cell anaemia?
Sickle cell anaemia is an autosomal recessive condition where there is an abnormal gene for beta globin on chromosome 11. One copy of the gene results in sickle cell trait
Two abnormal copies of the gene are required for sickle cell disease
What are the complications of sickle cell anaemia?
Anaemia Increased risk of infection Stroke Avascular necrosis in large joints such as hip Pulmonary hypertension Painful and persistent penile erections (priapism) CKD Sickle cell crises Acute chest syndrome
What is the management of sickle cell anaemia?
Avoid dehydration and other crises triggers
Ensure that the vaccines are up to date
Abx prophylaxis to protect against infection, usually penicillin V
HYDROXYCARBAMIDE (stimulates production of fetal haemoglobin (HbF))
Blood transfusion for severe anaemia
Bone marrow transplant (this can be curative)
What can cause a sickle cell crises?
They can occur spontaneously or be triggered by infection, dehydration, cold, significant life events
What is vaso occlusive crisis?
This is also known as painful crisis and is caused by the sickle shaped blood cells clogging the capillaries causing distal ischaemia, it is associated with dehydration and raised haematocrit. It can cause priapism in men by trapping blood in the penis (urological emergency- treat with aspiration of blood).
What is splenic sequestrian crisis?
Caused by red blood cells blocking blood flow within the spleen. It causes an enlarged and painful spleen. The pooling of blood in the spleen can lead to severe anaemia and circulatory collapse (hypovolaemic shock).
What is an aplastic crisis?
This occurs in sickle cell patients
It is where there is a temporary loss in the creation of new blood cells and is triggered by an infection with parvovirus B19.
Aplastic crisis leads to significant anaemia, management is supportive with blood transfusions if necessary and usually resolves spontaneously within a week.
What is thalassaemia?
This is a genetic defect in the protein chains that make up haemoglobin. Normal haemoglobin has 2 alpha and 2 beta chains, if there is a defect in the alpha chains then this is alpha thalassaemia, if there is a defect in the beta chains then this is beta thalassaemia.
It is autosomal recessive
What are the features of thalassaemia?
In patients with thalassemia, the red blood cells are more fragile and break down more easily. The spleen acts as a sieve to filter the blood and remove older blood cells. In patients with thalassemia the spleen collects all the destroyed RBC resulting in splenomegaly.
Bone marrow expands to produce extra RBC- prominent forehead and malar eminences (cheek bones).
Will have general signs and symptoms of anaemia... . Fatigue . Pallor . Jaundice . Gallstones . Splenomegaly . Poor growth and development . Pronounced forehead and malar eminences
How do you diagnose thalassaemia?
FBC shows a microcytic anaemia
Haemoglobin electrophoresis is used to diagnose globin abnormalities
DNA testing is used to look for the genetic abnormality
Why does iron overload occur in thalassaemia?
It occurs as a result of the faulty creation of RBC, reccurent transfusions, increased absorption of iron in the gut un response to anaemia.
What does iron overload in thalassaemia lead to?
It leads to similar effects of haemochromatosis: Fatigue Liver cirrhosis Infertility Impotence Heart failure Arthritis Diabetes Osteroporosis and joint pain
