17 - Haematology Flashcards
What is the structure of fetal haemoglobin and how does it differ from adult haemoglobin?
Two alpha and two gamma subunits rather than two alpha, two beta
Greater affinity for oxygen
When does HbF get replaced by HbA?
- From 32 to 36 weeks HbF production starts to decrease and HbA starts to increase
- At birth around half of each
- By 6 months all of HbF is gone
What is the relevance of HbF and sickle-cell disease?
HbF does not contain beta subunit which is the issue in sickle cell so disease not present/as severe at birth
Can give hydroxycarbamide to increase production of HbF, has a protective effect against sickle cell crisis
What Hb level is anaemia in children?
Varies depending on age but usually Hb<120
What is the most common cause of anaemia in infants and what is the pathophysiology of this?
Physiologic Anaemia of Infancy
Dip in Hb around 6-9 weeks because there is high oxygen delivery to tissues at birth causing a negative feedback so EPO production by kidneys is suppressed so less Hb made by bone marrow
What are some other causes of anaemia in infants?
- Anaemia of prematurity
- Blood loss
- Haemolysis
- Twin to twin transfusion
Why are premature babies more susceptible to anaemia?
Blood tests by doctors remove a large portion of their volume!
- Less time in utero receiving iron from mother
- Red cell creation cannot keep up with rapid growth in first few weeks
- Reduced EPO levels
The more premature the infant the more likely they are to need transfusion for treatment
What are some haemolytic anaemias in infants?
- Haemolytic disease of the new born (ABO or Rh Incompatibilty)
- G6PD deficiency
- Sickle Cell
- Hereditary Spherocytosis
What test can be done to confirm immune haemolytic anaemia?
Direct Coombs Test
plus a haemolytic screen
What are some causes of anaemia in older children, highlighting the most common ones?
- Iron deficiency anaemia due to dietary insufficiency or roundworms
- Blood loss usually due to menstruation
- Sickle cell
- Thalassaemia
- Leukaemia
- Hereditary eliptocytosis
- Sideroblastic anaemia
What are cause of microcytic anaemia? (MCV<70)
- Thalassemia
- Anaemia of chronic disease
- Iron Deficiency
- Lead poisoning
- Sideroblastic
What are causes of normocytic anaemia?
3 A’s, 2 H’s
- Acute blood loss
- Anaemia of Chronic Disease
- Aplastic Anaemia
- Haemolytic
- Hypothyroidism
What are some causes of macrocytic anaemia? (MCV>100)
Megaloblastic
- B12 Deficiency
- Folate Deficiency
Normoblastic
- Alcohol
- Reticulocytosis (from haemolytic anaemia or blood loss)
- Hypothyroidism
- Liver disease
- Azathioprine
What are some symptoms of anaemia?
- Tired
- SOB
- Dizzy
- Palpitations
- Pica and Hair loss for Iron deficiency
What are some signs of anaemia?
- Pale skin
- Conjunctival pallor
- Tachycardia
- Raised respiratory rate
What investigations need to be done for anaemia in children?
- FBC (for Hb and MCV)
- ESR/CRP (for chronic disease)
- Blood film
- Reticulocyte count
- Ferritin (low in iron deficiency)
- B12 and Folate
- Bilirubin (raised in haemolysis)
- Direct Coombs Test
- Haemoglobin electrophoresis
Why do PPIs cause anaemia?
Need stomach acid to keep iron in soluble ferrous form (Fe2+)
When less acid in stomach like in PPIs gets converted to ferric (Fe3+) which is insoluble in duodenum and jejunum
What blood tests are done for iron deficiency?
- Serum iron not accurate as changes throughout day and after protein meal
- TIBC is the total space on transferrin for molecules to bind so TIBC is directly related to amount of transferrin. Both TIBC and transferrin increase in iron deficiency
What is transferrin saturation and what does it tell us?
Transferrin Saturation = Serum Iron/TIBC
Tells us total iron in body, usually around 30% however if less iron in body less is saturation
Fasting sample is best as can increase shortly after each meal rich in iron
Why can ferritin be normal in iron deficiency anaemia?
Ferritin is the stored version of iron
May not be able to get out of the cell!
What is the management of iron deficiency anaemia in children?
- Supplementation with ferrous sulphate or ferrous fumerate. Warn can cause constipation and black stools. Aim for rise of 10 each month
- Ensure adequate Vitamin C and Iron intake. Use fortified milk
- Check for hookworms
- Check for coeliac’s
- Blood transfusions but rare because children can tolerate low Hb levels
How can you spot haemolytic anaemia?
- Evidence of RBC production? (Polychromasia, reticulocytosis.)
- Decreased RBC survival? (Bilirubin raised)
- Intravascular haemolysis? (Haemoglobinuria)
- +ve Coombs’ test?
How does hereditary spherocytosis present?
- Jaundice
- Anaemia
- Gallstones
- Splenomegaly
Aplastic crisis: increased anaemia, haemolysis and jaundice, without the normal response from the bone marrow of creating new red blood cells. No reticulocyte response. This is often triggered by infection with parvovirus.
How is haemolytic anaemia caused by hereditary spherocytosis diagnosed and managed?
Ix
- Flow cytometric analysis of eosin-5-maleimide (EMA) binding to red cells
- Blood film and Reticulocyte count
Mx
- Folate supplement
- Splenectomy leads to increased RBC survival
- Cholecystectomy for gallstones
What is G6PD deficiency and the pathophysiology behind the presentation of this disease?
- X linked recessive (usually affects males)
- Haemolytic crises that are triggered by infections, medications or fava beans (broad beans)
- G6PD enzyme is responsible for helping protect cells from damage by reactive oxygen species (ROS). A deficiency in G6PD makes RBCs more vulnerable to ROS, leading to haemolysis in red blood cells. Periods of increased stress, with a higher production of ROS, can lead to acute haemolytic anaemia
How is G6PD deficiency diagnosed and managed?
Ix
- Blood film: Heinz Bodies (inclusions of denatured bodies)
- G6PD enzyme assay
Mx
- Avoid triggers, e.g broad beans, antimalarials, and this will stop jaundice and other symptoms
What is the pathophysiology of Thalassemia?
(image important for chromosomes)
Autosomal recessive
Defect in the protein chains that make up haemoglobin, can be alpha or beta
FBC are more fragile and break down more easily so splenomegaly.
Bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia. This causes susceptibility to fractures and pronounced forehead and cheekbones
What are some signs and symptoms of thalassemia?
- Microcytic anaemia
- Fatigue
- Pallor
- Jaundice
- Gallstones
- Splenomegaly
- Poor growth and development
- Pronounced forehead and malar eminences
How is Thalassemia diagnosed?
- FBC: microcytic anaemia.
- Haemoglobin electrophoresis
- DNA testing to look for the genetic abnormality
Pregnant women offered a screening test for thalassaemia at booking
Why do children with Thalassemia develop iron overload and how does this present?
Due to recurrent transfusions and increased absorption of iron in the gut in response to anaemia
- Fatigue
- Liver cirrhosis
- Infertility
- Impotence
- Heart failure
- Arthritis
- Diabetes
- Osteoporosis and joint pain
How is iron overload managed in thalassemia?
- Serum ferritin monitored to check for iron overload
- Limit transfusions
- Iron chelation with Desferroxamine
What is the epidemiology of sickle cell disease?
NHS sickle cell and thalassaemia (SCT) screening programme found the incidence of sickle cell disease is 1 in 2,449 in the UK with a carrier risk of 1 in 89
Usually people of Western African origin
Having HbS provides immunity against Plasmodium Falciparum
What is the epidemiology of sickle cell disease?
NHS sickle cell and thalassaemia (SCT) screening programme found the incidence of sickle cell disease is 1 in 2,449 in the UK with a carrier risk of 1 in 89
Usually people of Western African origin
Having HbS provides immunity against Plasmodium Falciparum
What is the pathophysiology of sickle cell disease?
Autosomal Recessive affecting beta globin gene
HbS allele due to substitution from GAG to GTG causing glutamic acid to be substituted with valine.
Cam one HbS allele and a different faulty beta globin allele other than HbS (HbSβ-thalassaemia)
HbS prone to ‘sickling’.. In the deoxygenated state the HbS tetramers bind to each other and begin to polymerise, which distort the shape of the red blood cell. These sickle cells prone to haemolysis and can cause vast-occlusion
What are some signs and symptoms of sickle cell anaemia?
History
- Acute pain symptoms from vaso-occlusion – hallmark of sickle cell disease. May be precipitated by hypoxia, infection, strenuous exercise, dehydration. Usually back, legs, knees, arms, chest and abdomen
- Dactylitis – painful inflammation of a digit (finger or toe)
- Family history
Examination
- Pallor, lethargy due to anaemia
- Jaundice due to haemolysis
- Fever
- Tachycardia, tachypnoea
- Digital redness, swelling and pain
- Splenomegaly
What are the complications of sickle cell anaemia?
(both acute and chronic)
- Anaemia
- Increased risk of infection
- Stroke
- Avascular necrosis consider if vasoocclusive crisis lasting more than 7/7
- Pulmonary hypertension
- Priapism
- Chronic kidney disease
- Sickle cell crises
- Acute chest syndrome
- Retinopathy
How is sickle cell disease managed in general?
- Avoid dehydration and other triggers of crises
- Ensure vaccines are up to date
- Antibiotic prophylaxis usually with penicillin V (phenoxymethypenicillin)
- Hydroxycarbamide to protect against crises and acute chest syndrome as this stimulates HbF which doesn’t sickle
- Folate supplementation
- Blood transfusion for severe anaemia to keep HbS<30%
- Bone marrow transplant can be curative
- Education on prevention, for example avoiding excessive alcohol consumption or strenuous exercise,
What are some examples of sickle cell crises and some triggers for this?
- Vaso-occlusive Crisis (AKA painful crisis): priapism
- Splenic Sequestration
- Aplastic
- Acute Chest syndrome
How are sickle cell crises managed in general terms?
(image is important)
SUPPORTIVELY
- Pain relief every 30 minutes
- Refer to haematology
- Treat any infection
- Keep warm
- Keep well hydrated (IV fluids may be required)
What investigations are done for all sickle cell crises?
- FBC reticulocyte count
- Group and save
- Biochemistry: LDH, U&Es, LFTs, Bone
- Septic screen: blood cultures (if fever), chest x-ray, MSU
- Bone x-rays: rarely needed, for suspected osteomyelitis
How are vasoocclusive crises managed?
Due to sickle cells blocking capillaries and causing distal ischaemia
- Analgesia: review regularly
- Oxygen
- IV fluids
- Antibiotics if infection
- Aspiration if priapism
How is splenic sequestration managed as a sickle cell crisis? (NOT DONE)
- Sickle cells block blood flow in spleen so becomes painful and enlarged
- Pooling of blood can cause severe anaemia and hypovolaemic shock
- Do FBC and urgent cross match
- Blood transfusions and Fluid resuscitation
- Splenectomy if recurrent crises
What is an aplastic crisis in sickle cell and how is it managed?
- Temporary loss of the creation of new blood cells
- Triggered by Parvovirus B19 so do Parvovirus PCR
- Do FBC and crossmatch
- Blood transfusions and resolves within a week
How is acute chest syndrome diagnosed and managed?
Usually have fever, chest pain, wheezing, hyperaemia, cough, respiratory distress
Ix
- CXR: new infiltrates
- ABG
- Infection screen
- FBC, G+S, CRP, U+Es
Management (Medical Emergency)
- Antibiotics or antivirals for infections
- Blood transfusions via Red Cell exchange urgently
- Incentive spirometry encourages effective deep breathing to prevent atelectasis
- Artificial ventilation with NIV or intubation may be required
What vaccines are given to patients with sickle cell, how often and why?
Spleen damage by auto-infarction can increased susceptibility to infections
- Seasonal influenza vaccines – yearly
- Pneumococcal vaccines – every 5 years
- Hepatitis B vaccine – if receiving regular blood transfusions
- Men C and HiB
Also given prophylactic penicillin V
What are some causes of hyposplenism?
- Splenectomy
- Autosplenism e.g sickle cell or coeliac’s
(learn image)
How long should someone who is asplenic be on prophylactic antibiotics?
At least 2 years after surgery
Lifelong if high risk (children)
What education do you need to give to parents/children who are hyposplenic?
- Need to carry splenectomy card
- Must contact GP if become unwell or go to A and E if deteriorate
- Must keep up to date with vaccines and have annual flu jab
- Must have chemoprophylaxis in malaria areas
- Risks with mosquito and animal bites
What is the main indication for hydroxycarbamide in sickle cell?
Increases the level of fetal haemoglobin so less sickling
What are some causes of DIC in children?
What investigations should you do to diagnose DIC and what will they show?
- Platelet count: low
- INR: raised
- Fibrinogen: low
- PT: raised
- D-Dimer
How is DIC managed in children?
- Refer to haematology
- Treat cause e.g NEC, Sepsis
- Give Vit K
- Platelet transfusion
- Fresh plasma (FFP) and cryoprecipitate
- Heparin or Protein C depending on if thrombotic or fibrinolytic
• If bleeding still continues, consider exchange transfusion.
What is idiopathic thrombocytopenia purpura and how does it present?
Type 2 hypersensitivity reaction where antibodies are made against platelets. Often triggered by viral illness
- Non blanching rash (purpura) over 24-48h
- Bleeding (gums, epistaxis, menorraghia)
- Bruising
- History of viral illness
- Under 10
What investigations need to be done for ITP diagnosis?
IT IS A DIAGNOSIS OF EXCLUSION
- FBC/blood film for platelet count – thrombocytopenia should ONLY abnormality
- Coagulation screen – normal
- Bone marrow examination
Need to rule of meningitis, heparin induced thrombocytopenia and leukaemia
What is the prognosis of ITP?
- 75% resolve spontaneously within three months
- 5‐15% becomes persistent or chronic (lasting > 12 months), especially if over 10
- Intracranial haemorrhage is a rare but serious consequence
What is some general advice to give to a parent/child with mild ITP?
Safe to live with petechiae and low platelet count
- Avoid contact sports with high risk of head injury and trauma
- Helmets for scooters and bikes
- Avoid IM injections and lumbar punctures
- Avoid NSAIDs, aspirin and blood thinning medications
- Advice on managing nosebleeds
- OCP for menstruating girls
- Seek help after any injury that may cause internal bleeding e.g car accident
What is the treatment for acute ITP?
- Prednisolone
- IVIG if life threatening bleeding
- Blood transfusions if required
- Platelet transfusions only work temporarily because antibodies against platelets will begin destroying the transfused platelets
When does ITP not need to be treated?
- No active bleeding
- Controlled epistaxis (stops in <20mins with gentle pressure)
- Bruising
- Petechiae
In anaemia what is the direct coombs test for?
To work out if haemolytic is due to immune mediated or non-immune mediated reaction
What are some causes of haemolytic anaemia in children?
What are the causes of megaloblastic anaemia in children?
