Haematology Flashcards
describe the subunits of fetal and adult Hb
Fetal = 2 alpha and 2 gamma subunits
Adult = 2alpha and 2 beta subunits
difference between adult Hb and fetal Hb
Fetal has a greater affinity to oxygen than adult Hb. Oxygen binds to fetal Hb and is more reluctant to let go= steal oxygen away from the mother’s Hb when nearby in the placenta. If the fetal and maternal HB had the same affinity for oxygen, there would be no incentive for the oxygen to switch from the maternal blood to fetal blood.
what happens to fetal Hb at birth
From 32 to 36 weeks gestation, production of HbF decreased. At the same time HbA is produced in greater quantities. gradual transfer HbF to HbA. At birth, around half the Hb produced is HbF and half is HbA. By 6 months of age, very little fetal Hb produced. Eventually, RBC contain entirely HbA.
what is the significance of fetal Hb in Sickle Cell Disease?
In sickle cell disease, a genetic abnormality coding for Beta subunit is responsible for causing the sickle shape of RBC. Fetal Hb does not lead to sickling of RBC because there is no Beta Subunit in the structure.
what is Hydroxycarbamide?
Hydroxycarbamide can be used to increase the production of fetal Hb in sickle cell. This has protective effect against sickle cell crises and acute chest syndrome
what are some causes for anaemia in infancy?
Physiological anaemia of infancy causes most cases in infancy Others:
- Anaemia of prematurity
- Blood loss
- Haemolysis
- Twin-twin transfusion syndrome
Haemolysis is a common cause of anaemia in infancy. No causes in neonate:
- Haemolytic disease of the newborn
- Hereditary spherocytosis
- G6PD deficiency
normal hb values
what is physiological anaemia of infancy?
Normal dip Hb six to nine weeks of age in healthy term babies. High oxygen delivery to tissues caused by the high Hb levels at birth cause negative feedback. Production of EPO in the kidneys is suppressed and subsequently there is a reduction in Hb by the bone marrow. High oxygen results in lower Hb production
what is anaemia of prematurity?
Premature neonates are much more likely to become significantly anaemic during the first few weeks of life compared with term infants. More premature= more likely to require 1 or more transfusions for anaemia. More likely if unwell at birth.
Premature neonates become anaemic for a number of reasons
- Less time utero for iron from mother
- RBC creation cannot keep up with the rapid growth in the first few weeks
- Reduced EPO levels
- Blood tests remove significant proportion of their circulating volume
what is haemolytic disease of the newborn? and what test is relevant?
Where anti d antibodies from the mother cross placenta and if baby is rhesus positive, antibodies attack to fetal RBC and trigger fetal immune system to attack own RBC = haemolysis = anaemia = high bilirubin levels
Direct Coombs test – check for immune haemolytic anaemia - +ve in HDN
what are some causes for anaemia in older children?
- Iron def anaemia secondary to dietary insufficiency- MOST COMMON
- Blood loss- menstruation
RARER INCLUDE:
- Sickle cell anaemia
- Leukaemia
- Hereditary spherocytosis
- Hereditary eliptocytosis
- Sideroblastic anaemia
(Worldwide a common cause of blood loss causing chronic anaemia and iron deficiency is helminth infection, with roundworms, hookworms or whipworms. Common in developing countries & those living in poverty, unusual in the UK. Treatment= single dose albendazole or mebendazole.)
how to we categorise anaemia?
(3 categories)
microcytic
macrocytic
normocytic
what does microcytic mean and what are some causes?
low MCV = small RBC
TAILS - thalassaemia, anaemia of chronic disease, iron deficiency, lead poisoning, sideroblastic anaemia
what does macrocytic mean and what are some causes?
large MCV = large RBC
magaloblastic = impaired DNA synthesis (B12/folate deficiency)
normoblastic - alcohol, reticulocytosis, hypothyroidism, liver disease, azathioprine
what does normocytic mean and what are some causes?
normal MCV = normal RBC
- 3A (Acute blood loss, Anaemia chronic disease, Aplastic anaemia)
- 2H (Haemolytic anaemia, Hypothyroidism)
what are some symptoms of anaemia?
- Tiredness
- SOB
- Headaches
- Dizziness
- Palpitations
- Worsening other conditions
what are some signs and symptoms specific to iron deficiency anaemia?
pica - dietary cravings for things like dirt
hair loss
signs - koilonychia, angular chelitis, atrophic glossitis, brittle hair and nails
what are some signs of anaemia?
- Pale skin
- Conjunctival pallor
- Tachycardia
- Raised RR
what investigations are done for anaemia?
- FBC for Hb and MCV
- Blood film
- Reticulocyte count
- Ferritin (low iron deficiency)
- B12 and folate
- Bilirubin (raised in haemolysis)
- Direct Coombs test (autoimmune haemolytic anaemia)
- Hb electrophoresis (haemaglobinopathies)
- Reticulocytes (high in blood loss or haemolysis as active production to replace lost cells)
how is anaemia managed?
Depends underlying cause. Severe require blood transfusions.
Iron=iron supplementation.
what are the 3 broad causes of iron deficiency anaemia?
dietary insufficiency - most common
loss of iron
inadequate absorption
where in the gut is iron absorbed?
Iron absorbed in the duodenum and jejunum. Requires the acid in the stomach to keep the iron in soluble ferrous (Fe2+) form. Less acid in the stomach = changes to insoluble Ferric 3+ Meds such as PPI can interfere with iron absorption. Crohns or coeliac also affect the duodenum and jejunum- reduced absorption.
what does iron travel as in the blood and on what?
Iron travels in blood as ferric ions (FE3+) on transferrin
what is ferritin and what is its significance?
form iron takes when deposited and stored in cells
released from cells in inflammation such as infection or cancer.
- Low = highly suggestive or iron deficiency anaemia
- High= hard to interpret as inflammation or overload.
- Normal ferritin can have iron def anaemia, particularly if they have reasons to have raised such as inflammation.
what is transferrin saturation?
indication of total iron in body
how is iron deficiency anaemia managed?
Treating underlying cause and correcting anaemia. In children the underlying cause is usually dietary deficient, so dietician input important.
Can supplement with ferrous sulphate or fumarate. This slowly correct iron deficiency. Oral iron causes constipation and black coloured stools. Unsuitable if malabsorption the cause of anaemia.
Blood transfusions are rarely necessary. Children generally able to tolerate a low Hb well and can be given time to correct their anaemia.
what is leukaemia?
Cancer of a particular line of stem cells in the bone marrow. Causes unregulated production of certain typed of blood cells. Types of leukaemia can be classified depending on how regularly they progress (chronic slow and acute is fast) and the cell line that is affected (myeloid- Granulocytes, monocytes, macrophages, and dendritic cells (DCs) or Lymphoid)
what are the 3 types of leukaemia? which is most common?
- Acute lymphoblastic Leukaemia (ALL) most common in children
- Acute Myeloid Leukaemia (AML) is the next most common
- Chronic Myeloid Leukaemia RARE
what age groups are ALL and AML common in?
- ALL peaks 2-3yrs
- AML peaks aged under 2 years
what is the pathophysiology of leukaemia?
A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white cell. The excessive production of one cell can lead to suppression of the other cell lines, causing underproduction of the other cell types= Pancytopenia which is a combination of low:
- RBC (anaemia)
- WBC (leukopenia)
- Platelets (thrombocytopenia)
what is pancytopenia?
Pancytopenia which is a combination of low:
- RBC (anaemia)
- WBC (leukopenia)
- Platelets (thrombocytopenia)
what are some risk factors for leukaemia?
- radiation exposure (main risk)
- Down’s syndrome
- Klinefelter syndrome
- Noonan syndrome
- Fanconi’s anaemia
how does leukaemia present?
- Persistent fatigue
- Unexplained fever
- Failure to thrive
- Weight loss
- Night sweats
- Pallor
- Petechiae (abnormal bruising from thrombocytopenia)
- Unexplained bleeding- thrombocytopenia
- Abdo pain
- Generalised lymphadenopathy
- Unexplained or persistent bone or joint pain
- Hepatosplenomegaly
how is leukaemia diagnosed?
Refer unexplained petechiae or hepatomegaly for immediate specialist assessment – NICE reccomendation
Urgent FBC w/in 48Hr
To establish diagnosis:
- FBC- anaemia, leukopenia, thrombocytopenia, and high no of abnormal WBC
- Blood film- blast cells- precursors to circulating cells
- Bone marrow biopsy
- Lymph node biopsy
Further for staging:
- CXR
- CT scan
- LP
- Genetic analysis and immunophenotyping of the abnormal cells
how is leukaemia managed?
Paediatric oncology MDT
Primarily treated w/ chemotherapy
Others:
- Radiotherapy
- Bone marrow transplant
- Surgery
what are some complications of leukaemia?
- Failure to treat the leukaemia
- Stunted growth and development
- Immunodeficiency and infections
- Neurotoxicity
- Infertility
- Secondary malignancy
- Cardiotoxicity
what is the prognosis for leukaemia?
Overall cure rate for ALL is around 80%, but prognosis depends on individual factors. Outcomes less positive AML
what is immune thrombocytopenia?
a condition characterised by idiopathic thrombocytopenia causing a purpuric rash.
what is the pathophysiology of immune thrombocytopenic purpura and what type of hypersensitivity reaction is it?
type 2 hypersensitivity reaction
Caused by production of antibodies that target and destroy platelets. This can happen spontaneously, or it can be triggered by something, such as viral infection.
how does immune thrombocytopenic purpura present?
Usually present U10yo. Often there is a hx of a recent viral illness. Onset over 24-48Hrs:
- Bleeding
- Bruising
- Petechial or purpuric rash- bleeding under the skin
what are petechiae, purpuras and eccymoses?
- Petechiae- pin-prick spots (around 1mm) bleeding under the skin.
- Purpuras are larger (3-10mm) spots of bleeding under skin.
- Ecchymoses (>10mm)
they are all non-blanching
how is immune thrombocytopenic purpura managed?
Urgent FBC for the platelet count
Other values on the FBC should be normal/ Other causes should be exclude - Heparin induced thrombocytopenia and leukaemia
Severity management depends how far the platelet count falls. Usually no treatment required as platelets return to usual. Around 70% remit spontaneously in 3/12
Treatment may be required if pt is actively bleeding or severe thrombocytopenia (platelets below 10)
- Prednisolone
- IVIg
- Blood transfusions if required
- Platelet transfusions only work temporarily as ab will destroy again
- Splenectomy
Key education and advice is necessary:
- Avoid contact sports
- Avoid IM injections and procedures such as LP
- Avoid NSAIDs, aspirin and blood thinning medications
- Advice on managing nosebleeds
- Seek help after any injury that may cause internal bleeding- eg car accidents or head injuries
what are the complications of ITP?
- Chronic ITP
- Anaemia
- Intracranial and subarachnoid haemorrhage
- GI bleeding
what is sickle cell anaemia?
genetic condition that causes sickle shaped RBC which are more easily destroyed leading to haemolytic anaemia
what is the abnormal variant of Hb in sickle cell anaemia?
HbS
what is the inheritance of sickle cell?
Autosomal recessive where there is an abnormal gene for beta-globin on chromosome 11.
One copy of the gene results in sickle-cell trait - usually asymptotic but 2=disease.
what is the significance of sickle cell in malaria?
More common in areas of Malaria= Africa, India, the Middle East and the Caribbean. Having 1 copy reduces severity of Malaria. As a result= selective advantage.
how is sickle cell diagnosed?
Pregnant women at risk of being carriers of the sickle cell gene are offered testing during pregnancy.
Sickle cell disease is also tested for on the newborn screening heel prick test at 5 days of age.
what is thalassaemia?
genetic defect in the protein chains that make up Hb
- Hb has 2 alpha chains and 2 beta chains - Defect in alpha = alpha thalassaemia, defect in beta = beta thalassaemia - both conditions are autosomal recessive.
what is hereditary speherocytosis?
RBC are sphere shaped, making fragile and easily destroyed when passing through the spleen
autosomal dominant
what is hereditary elliptocytosis?
- Very similar to hereditary spherocytosis except the RBC are ellipse shaped.
- Also autosomal dominant.
- Presentation and management are very similar.
what will be seen on blood film of G6PD deficiency?
Heinz bodies may be seen on a on blood film. Heinz bodies are blobs of denatured haemoglobin (“inclusions”) seen within the red blood cells.
what is lymphoma?
cancer in the lymphatic system
cancerous cells proliferate within the lymph nodes and cause lymph nodes to become abnormally large = lymphadenopathy
what is a Reed-Sternberg cell?
Key finding from lymph node biopsy in patients with Hodgkin’s lymphoma.
They are abnormally large B cells that have multiple nuclei that have nucleoli inside them.
appearance of face of owl with large eyes
what is Ann Arbor Staging?
used for both NHL and HL
important to note whether the affected nodes are above or below the diaphragm
- Stage 1: Confined to one region of lymph nodes.
- Stage 2: In more than one region but on the same side of the diaphragm (either above or below).
- Stage 3: Affects lymph nodes both above and below the diaphragm.
- Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver.
