Haematological Disease Flashcards
Define Anaemia in:
- Neonates
- 1 month to 12 month olds
- 1 yr to 12 yr olds
- Neonate: Hb < 140 g/L
- 1-12 month: Hb < 100 g/L
- 1-12 yrs: Hb < 110 g/L
What are the mechanisms behind iron deficiency anaemia?
Main causes of iron deficiency are
o Inadequate intake
▪ Common in infants as additional iron is required for the increased in blood volume accompanying growth
▪ A 1 year old infant requires an intake of iron of ~ 8mg/day (adult male: 9mg/day, adult female: 15mg/day)
o Malabsorption
o Blood loss
What are the sources of iron?
Sources of iron
o Breast milk iron
▪ Low iron content but high absorption (50%)
o Infant formula
o Cow’s milk
▪ Higher iron content but low absorption (10%)
o Solid introduced at weaning e.g. cereals (1% absorption)
Dietary sources of iron
o High in iron
▪ Red meat: beef, lamb
▪ Liver, kidney
▪ Oily fish
o Average iron
▪ Pulses, beans, peas
▪ Fortified cereals with added vitamin C
▪ Wholemeal products
▪ Dark green vegetables: broccoli, spinach
▪ Dried fruit: raisins, sultanas
▪ Nuts and seeds
o Foods to avoid in excess in toddlers
▪ Cow’s milk
▪ Tea: tannin inhibits iron uptake
▪ High-fibre foods: phytates inhibit absorption e.g. in chapatti
o Iron absorption is increased when eaten with food rich in vitamin C
What are the clinical features of iron deficiency anaemia?
Asymptomatic until Hb drops below 60 g/L
Fatigue
Infants will feed more slowly
Explore symptoms of malabsorption
Pale
Pica (inappropriate eating of non-food materials such as soil, chalk and gravel)
What are the clinical features of iron deficiency anaemia?
- Asymptomatic until Hb drops below 60 g/L to 70 g/L
- Fatigue
- Infants will feed more slowly
- Explore symptoms of malabsorption or blood loss
- Pale (tongue, conjunctivae, palmar creases) - unreliable
- Pica (inappropriate eating of non-food materials such as soil, chalk and gravel)
There is evidence the iron anaemia may be detrimental to behaviour and intellectual function
What are the investigations of iron deficiency anaemia?
- Blood
- Low Hb
- Microcytic Hypochromic anaemia (low MCV + MCH)
- Low serum ferritin
- Other main causes of microcytic anaemia
- Beta thalassaemia - request haematinics
- Anaemia of chronic disease e.g. due to CKD
- Note: alpha thalassaemia trait (usually African or Far Eastern ethnicity)- causes microcytic hypo chromic picture but not anaemia
How do we treat iron deficiency anaemia?
- Dietary Advice
- Supplementation with oral iron
- Monitor
What sort of advice should you give for iron deficiency anaemia?
- Dietary advice (increase intake of iron-rich food e.g. dark green vegetables, iron-fortified bread, meat, apricots, prunes and raisins) and consider dietician referral
• ADVICE
o They may experience adverse effects (e.g. dark stools, constipation, diarrhoea, faecal impaction, GI irritation, nausea)
o Discomfort could be minimised by taking the iron supplement with food or reducing dose frequency
o Explain the monitoring requirements
What iron supplements are used in iron deficiency anaemia?
Supplementation with oral iron
o Oral ferrous sulphate 200 mg tablets (2/3 per day)
▪ Should be continued for 3 months after iron deficiency is corrected to allow
stores to be replenished
▪ If not tolerated, consider oral ferrous fumarate or ferrous gluconate
o Monitor to ensure there is an adequate response to treatment
o If failure to respond to treatment, consider other causes
Lissauer’s: Sytron - sodium iron edetate
Niferex - polysaccharide iron complex
How often do we monitor iron deficiency anaemia? How long should treatment last?
Monitoring
o Recheck haemoglobin levels (FBC) after 2-4 weeks of iron supplement treatment
▪ Hb should rise by 10g/L/week
o If the level has risen sufficiently, check again at 2-4 months to ensure that Hb level has normalised
o If it has NOT risen sufficiently, address compliance issues
Once haemoglobin and red cell indices are normal:
▪ Continue iron treatment for 3 months to replenish iron stores
▪ Monitor FBC every 3 months for 1 year
▪ Recheck after another year
What patients should be given a prophylactic dose for iron supplementation?
▪ Recurring anaemia
▪ Iron-poor diet (e.g. vegans)
▪ Malabsorption
▪ Menorrhagia
▪ Gastrectomy
Define red cell aplasia
No red cell production
What are the causes of red cell aplasia?
Causes in children
o Congenital red cell aplasia (Diamond-Blackfan anaemia)
▪ Rare
▪ Family history in 20%, sporadic 80%
▪ Specific gene mutations in ribosomal protein genes implicated in some cases
▪ Most present at 2 months – 3 months age, some present at birth
o Transient erythroblastopenia of childhood
▪ Usually triggered by viral infections
▪ Usually recovers within weeks
o Parvovirus B19 infection
▪ Only causes red cell aplasia in children with inherited haemolytic anaemias
What are the clinical features of Diamond-Blackfan anaemia?
o Symptoms of anaemia
o Some have other congenital anomalies e.g. short stature, abnormal thumbs, microcephaly, cataracts/glaucoma
What are the investigations for red cell aplasia? What results would be expected?
Low reticulocyte count despite low Hb
Normal bilirubin
Negative direct antiglobulin test (Coombs test)
Absent red cell precursors on bone marrow examination
What is the management of red cell aplasia?
• Diamond-Blackfan anaemia
o Oral steroids
o If not responsive to steroids, monthly RBC transfusion
o Some may need stem cell transplantation
• Transient erythroblastopenia of childhood usually recovers
What are the main causes of haemolytic in children? (haemolytic anaemia)
o Immune-mediated haemolytic anaemias are uncommon in children (unlike neonates)
o In children, main causes are intrinsic abnormalities of the red cells
▪ Red cell membrane disorders e.g. hereditary spherocytosis
▪ Red cell enzyme disorders e.g. G6PD deficiency
▪ Haemoglobinopathies e.g. beta-thalassemia major, sickle cell disease
What are the consequences of haemolysis?
o Anaemia
o Hepatosplenomegaly
o Increased unconjugated bilirubin
What are the investigations of haemolysis?
o High reticulocyte count (may appear as polychromasia)
o Unconjugated hyperbilirubinaemia
o High urinary urobilinogen
o Abnormal appearance of red cells on film (e.g. sickle cells, spherocytes)
o Increased red blood cell precursors in the bone marrow
o Positive Coomb’s test if immune cause
How common is hereditary spherocytosis?
1 in 5000 births in caucasians
What is the inheritance pattern of hereditary spherocytosis? What is the mutation?
AD but in 25% no FH
Mutation in genes which encode important red cell membrane proteins such as spectrin or ankyrin.
In HS, the RBCs become spherical in shape because the red cell loses part of its membrane each time it passes through the spleen
How are spherocytes different to normal red blood cells?
Spherocytes are less deformable than normal RBCs and are therefore destroyed prematurely in the spleen
What are the clinical features of hereditary spherocytosis?
Often suspected based on family history
May be asymptomatic
Jaundice
o Usually during childhood
o Intermittent
• Anaemia
o Mild anaemia in childhood
o Hb may fall during infections
Splenomegaly
Aplastic crisis
o Uncommon
o Transient (2-4 weeks)
o Due to parvovirus B19 infections
• Gallstones (due to increase bilirubin excretion)
What are the investigations for hereditary spherocytosis?
• FBC
o Hb:lowornormal
o MCV:lowornormal
o Platelet and WBC: normal
o Raised reticulocytes
Blood film
o Spherocytes
Specific tests
o Dye binding assay
o Osmoticfragility
• Tests for autoimmune haemolytic anaemia (DAT test) as this is also associated with
spherocytes
o Negative in hereditary spherocytosis
What is the management of hereditary spherocytosis?
• Neonates
o Supportive +/- red blood cell transfusion
o Folic acid supplementation
▪ As they have a raised folate requirement secondary to increased RBC production
o Consider phototherapy or exchange transfusion if the baby also has jaundice
• Infants, children and adults
o Supportive care +/- red blood cell transfusion
o Folic acid supplementation (2-5 mg oral OD)
o Splenectomy may be considered with a pre-operative vaccination regimen for encapsulated bacteria (H. influenzae, meningitis C and S. pneumoniae)
▪ Considered if poor growth or troublesome symptoms of anaemia
o Cholecystectomy may be performed because gallstones are common in HS
o Pneumococcal prophylaxis (oral penicillin)
• Aplastic crisis caused by parvovirus B19 requires blood transfusions
What is the prevalence of SCD in England?
1 in 2000 live births
What is the inheritance pattern of SCD? What is the mutation?
AR
HbS forms as a result of a point mutation in codon 6 of the beta globes gene which causes a change in the amino acid encoded from glutamic acid to valine.
Where is SCD the most common?
tropical Africa or the Caribbean, Central India, Middle East
What are the 3 main forms of SCD?
o Sickle cell anaemia(HbSS)
▪ Homozygous for HbS
▪ Have small amounts of HbF and no HbA
▪ Most severe form
o HbSC disease
▪ Inherited HbS from one parent and HbC from the other
▪ HbC mutation is amino acid change from lysine to glutamate at 6th position of beta globin chain
▪ No HbA
o Sickle beta-thalassemia
▪ Inherited HbS from one parent and beta-thalassemia trait from the other
▪ Most patients make no HbA hence have symptoms similar to SCA
▪ In these patients, a mutation of the beta gene blocks production of the normal beta globin chain (beta 0) or reduces its production (beta+)
o Carrier(sickle trait)
▪ Inherited HbS from one parent and a normal beta-globin gene from the other
▪ Approx. 40% of Hb will be HbS
▪ Asymptomatic
Describe the pathogenesis of SCD.
o HbS polymerises within red blood cells forming rigid tubular spiral bodies which deform the RBCs into a sickle shape
o These cells have a reduced life span and are prone to haemolysis, contributing to anaemia
▪ As this haemolysis happens within the vasculature, it is called intravascular haemolysis
▪ Recycling of the haem leads to high levels of unconjugated bilirubin→jaundice
o They can also get stuck in microcirculation resulting in vaso-occlusion and hence ischaemia of an organ
o This is exacerbated by low oxygen tension, dehydration and cold
o Severity can vary based on how much HbF the patient is able to produce (this has some genetic variation)
▪ HbF consists of two alpha and two gamma globin chains so does not include the mutated beta globins
o To counteract the anaemia, bone marrows increases number of reticulocytes produced
▪ This can lead to new bone formation and medullary cavities of the skull can expand outward causing enlarged cheeks and ‘hair-on-end’ appearance on skull X-ray
▪ Extramedullary haematopoiesis can also occur – usually in liver
RBCs can over time clog up the spleen leading to infarction and splenic sequestration
▪ Over time, this can lead to an auto-splenectomy (when spleen scars up with fibrosis)→spleen becomes non-functional
▪ Encapsulated bacteria are normally opsonised and phagocytosed by macrophages in the spleen→become susceptible to these
What are the clinical features of SCD?
Manifests as HbF synthesis reduces ~ 6 months of age
Anaemia
o All have moderate anaemia (Hb 60-100g/L) with clinically detectable jaundice from chronic haemolysis
• Infection
o Susceptible to infection from encapsulated organisms e.g. pneumococci, H influenzae, N meningitidis, Salmonella sp.
o Increased risk of osteomyelitis due to Salmonella
• Painful vaso-occlusive crises
o Cause pain in many organs of the body
o Acute crises can be precipitated by cold, dehydration, excessive exercise or stress, hypoxia or infection
o In late infancy, often presents as hand-foot syndrome
▪ Dactylitis with swelling and pain of the fingers and/or feet from vaso- occlusion
o Acute chest syndrome
▪ Severe form of crises which can lead to severe hypoxia and can require mechanical ventilation and emergency transfusion
o Avascular necrosis of femoral head
• Acute anaemia
o Sudden drop in Hb due to
▪ Haemolytic crises
▪ Aplastic crises
• Parvovirus infection causes temporary cessation of RBC production
▪ Sequestration crises
• Sudden splenic or hepatic enlargement, abdominal pain and circulatory collapse from accumulation of sickled cells in spleen
• Priapism
o Due to vasoocclusion
o Requires prompt treatment with transfusion as it can lead to fibrosis of the corpora cavernosum and erectile impotence
• Splenomegaly
o Common in young children but less frequent in older children
What are the long term problems associated with SCD?
o Short stature and delayed puberty o STROKE and cognitive problems
▪ 1 in 10 children with SCD have a stroke
▪ Can have subtle issues like poor concentration
o Adenotonsillar hypertrophy
▪ Causes sleep apnoea syndrome leading to nocturnal hypoxaemia which can lead to vaso-occlusive crises or stroke
o Cardiac enlargement from chronic anaemia
o Heart failure from uncorrected anaemia
o Renal dysfunction
o Pigment gallstones due to increased bile pigment production
o Leg ulcers (uncommon in children)
o Psychosocial issues
What are the investigations for SCD?
Screened for in newborn blood spot screen
FBC
o Anaemia
o High reticulocytes
• Blood film
o Sickle cells
o Nucleated RBCs
o Howell-Jolly bodies due to hyposplenism
Protein electrophoresis
If presenting with acute chest syndrome take ABCDE approach
o FBC
o CXR
o Oxygen saturation
o ABG
o Blood cultures
What is the prophylaxis of SCD?
o Immunisation against encapsulated organisms (e.g. S. pneumoniae and H. influenzae type B)
o Daily oral penicillin
o Daily oral folic acid
o Vaso-occlusive crises should be minimised by avoiding exposure to cold, dehydration, excessive exercise, undue stress or hypoxia
How do you treat Acute crisis in SCD?
o Oral and IV analgesia
o Good hydration
o Infection should be treated with antibiotics
o Oxygen (if reduced saturation)
o Exchange transfusion is indicated for acute chest syndrome, priapism and stroke
How do you treat chronic problems in SCD?
o Children who have recurrent hospital admission for acute chest syndrome or vaso-occlusive crises could benefit from hydroxycarbamide (stimulates HbF production)
o Monitor for white blood cell suppression (side-effect of hydroxycarbamide)
Splenectomy with immunisation against encapsulated organisms
o Bone marrow transplant may be considered in severe cases
What is the prognosis of SCD?
o Can cause premature death due to complications
o 50% of patients with the most severe form of sickle cell disease will die < 40 years
Define Beta thalassaemia.
Inherited microcytic anaemia caused by mutations of the beta-globin gene leading to decreased or absent synthesis of beta globin
Where is Beta thalassaemia more prevalent?
Higher prevalence In those from Indian subcontinent, Mediterranean and Middle East
What are the 2 main types of beta thalassaemia?
o Beta-thalassemia major (also called transfusion dependent thalassaemia)
▪ Most severe form
▪ HbA cannot be produced due to abnormal beta globin gene - patients inherit 2 copies of abmnormal beta globin from each parent
o Beta-thalassemia intermedia (non transfusion dependent thalassaemia)
▪ Milder form of variable severity
▪ A small amount of HbA and/or large amount of HbF produced
Describe the pathophysiology of beta thalassaemia.
o When there’s a beta-globin chain deficiency, free alpha chains accumulate within RBCs and clump together to form intracellular inclusions which damage the cell membrane
o This leads to haemolysis (RBCs breakdown in bone marrow or are destroyed by spleen)
o Haemolysis leads to
- High unconjugated bilirubin and jaundice
- The excess iron from haemolysis leads to secondary haemochromatosis
- Hypoxia
o The hypoxia leads to extramedullary haematopoiesis
What is the inheritance pattern of beta thalassaemia?
AR
What are the clinical features of beta thalassaemia?
• Severe anaemia + jaundice
o Transfusion dependent
o From 3 months to 6 months of age (until this point HbF is produced and this process uses up the alpha chains)
o Fatigue, shortness of breath, pallor, fatigues easily
- Faltering growth/growth failure
- Extramedullary haemopoiesis
o Prevented by regular transfusions
o If no transfusions→hepatosplenomegaly and bone marrow expansion (causes maxillary overgrowth and skull bossing described as chipmunk faces)
▪ Skull Xray shows ‘hair-on-end’ appearance
rarely seen in high income countries
What are the investigations of beta thalassaemia?
• FBC
o Microcyticanaemia
• Peripheral blood smear
o Microcytic, hypochromic RBCs
o Target cells
• Haemoglobin electrophoresis
o Low HbA
o Increases in HbF and HbA2
What is the treatment of beta thalassaemia major?
- Beta-thalassemia major is FATAL without regular blood transfusions
- The transfusions aim to maintain the Hb concentration > 95-100 g/L to reduce growth failure and prevent bone deformation
- Repeated blood transfusion can cause iron overload
- This can lead to cardiac failure, liver cirrhosis, diabetes, infertility and growthfailure
- To prevent this, all patients are treated with iron chelation
- Chelators include SC desferrioxamine or oral deferasirox
- Good compliance with transfusion and chelation is associated with a high probability of surviving beyond 40 years
- Bone marrow transplantation is the only cure for beta-thalassemia major
- However, this is reserved for children with an HLA-identical sibling
What are the complications of long-term blood transfusions in children?
o Iron deposition
▪ Heart→cardiomyopathy
▪ Liver→cirrhosis
▪ Pancreas→diabetes
▪ Pituitary gland→delayed growth and sexual maturation
▪ Skin→hyperpigmentation
o Antibody formation (10%)
▪ Allo-antibodies to transfused RBCs in the patient make finding compatible blood very difficult o Infection (very rare now)
▪ Hepatitis A, B, C
▪ HIV
▪ Malaria
▪ Prions
o Venous
▪ Often traumatic in young children
▪ Central venous access device, e.g. Portocath, may be required but these predispose to infection
When should prenatal diagnosis of beta thalassaemia be considered?
Prenatal diagnosis
o Prenatal diagnosis via chorionic villus sampling and genetic counselling should be offered to parents who are heterozygous for beta thalassaemia
What are the clinical features, investigations and management of beta thalassaemia trait?
Heterozygotes are asymptomatic
A blood film will show microcytic hypochromic red cells
o This can lead to confusion between beta-thalassaemia trait and iron deficiency anaemia
o However, beta-thalassaemia trait has NOT got a low ferritin
Anaemia may be mild or absent
RBC is usually increased
MOST IMPORTANT DIAGNOSTIC FEATURE: Raised HbA2 (~5%) on high performance liquid chromatography (HPLC)
How many alpha globin genes do healthy individuals have?
4
What happens in alpha thalassaemia major?
o Aka Hb Barts hydrops fetalis
o Mostsevereform
o Caused by deletion of all four alpha-globin genes
o NO HbA can be produced
o Presents in mid-trimester with fetal hydrops (oedema and ascites) due to foetal anaemia
o ALWAYS fatal in utero or within hours of delivery
o Diagnosis is made by high-performance liquid chromatography which shows only Hb Barts
What happens in HbH disease?
o Occurs when THREE of the alpha-globin genes are deleted
o Affected children have mild-moderate anaemia
o Some patients may be transfusion-dependent
What happens in alpha-thalassaemia trait?
o Deletion of one or two alpha-globin genes
o Usually asymptomatic
o Red cells may be microcytic and hypochromic
What are the causes of anaemia in the newborn?
- Reduced red blood cell production
- Haemolytic anaemia (increased red cell destruction)
- Blood Loss
- Anaemia of Prematurity
Describe reduced red blood cell production in newborns?
o TWO main causes (both are rare):
▪ Congenital infection with parvovirus B19
▪ Congenital red cell aplasia (Diamond-Blackfan anaemia)
o Hb is low
o Red cells look normal
o Reticulocyte count is low o Bilirubin is normal
Describe haemolytic anaemia (increased red cell destruction)
o Either due to antibodies destroying red cells or due to an intrinsic abnormality of the red cell
o Main causes:
▪ Immune (haemolytic disease of the newborn)
▪ Red cell membrane disorders (e.g. hereditary spherocytosis)
▪ Red cell enzyme disorders (e.g. G6PD deficiency)
▪ Abnormal haemoglobins (e.g. alpha-thalassaemia major)
o Increased reticulocyte count (as red blood cell output is increased in an attempt to compensate for increased destruction)
o Increased unconjugated bilirubin
o Haemolytic disease of the newborn (immune haemolytic anaemia) is due
to antibodies against blood group antigens o Mostimportantantibodies:
▪ Anti-D (rhesus)
• This occurs if the mother is RhD-negative but the baby is RhD positive
▪ Anti-A
▪ Anti-B
▪ Anti-Kell
o This can be diagnosed using Coombs test
▪ NOTE: it is only positive in antibody-mediated
o MOST COMMON causes of non-immune haemolytic anaemia in neonates:
▪ G6PD deficiency
▪ Hereditary spherocytosis
Describe blood loss in newborns.
o Main causes:
▪ Feto-maternal haemorrhage (occult bleeding into the mother)
▪ Twin-to-twin transfusion
▪ Blood loss around the time of delivery (e.g. placental abruption)
o Diagnostic clues:
▪ Severe anaemia
▪ Raised reticulocyte count
▪ Normal bilirubin
Describe anaemia of prematurity
o Main causes:
▪ Inadequate EPO production
▪ Reduced red cell lifespan
▪ Frequent blood sampling whilst in hospital ▪ Iron or folic acid deficiency
How do you manage haemolytic disease of the newborn?
• Prevention
o Anti-D immunoglobulin
- Given at 28 and 34 weeks and at birth
can be given as a single dose (1500IU) between 28 and 30 weeks
• Baby:
o Resuscitation
- A to E approach particularly if preterm, anaemic or hydropic
o Exchange transfusion Indicated if:
- • Bilirubin rapidly rising (>8-10 μmol/l/hr) despite adequate phototherapy
- • Severe hyperbilirubinaemia insufficiently responsive to phototherapy and supportive care
- • Significant anaemia (Hb <100 g/l)
o Phototherapy
- Do not delay if baby thought to clinically have significant jaundice
- Transcutaneous bilirubin measurement can be taken to confirm/ if unsure
o IVIG
Only for immune haemolysis
o Follow-up
Check for late anaemia at 4-6 weeks
• Consider folate supplementation to protect against this Hearing screen
• Parent:
o Should be counselled on recurrence of HDN in subsequent pregnancies
Define haemophilia
Most common severe inherited coagulation disorder inherited with an X-linked recessive inheritance pattern, resulting from the deficiency of a coagulation factor
How common are haemophilia A and B?
o Haemophilia A: deficiency of clotting factor VIII
▪ 1 in 5000 male births
o Haemophilia B: deficiency of clotting factor IX
▪ 1 in 30,000 male births
How common is a FH of haemophilia in these patients?
⅔ of newly diagnosed infants have a FH of haemophilia and ⅓ sporadic.
What are the clinical features of haemophilia?
- Can be graded as severe, moderate or mild depending on how much of the factor is produced
- Severe disease involves recurrent spontaneous bleeding into joints and muscles → Can lead to crippling arthritis if not treated
- Many of these children have large bruises from trivial pressure → may lead to the suspicion of NAI
- Most present in first year of life when they start to walk, and fall over - develop muscle and joint bleeds
- 40% of cases present in neonatal period with intracranial haemorrhage, bleeding post- circumcision or prolonged bleeding from heel prick and venepuncture sites
What are the investigations on haemophilia?
• APTT: usually prolonged
o Mixing study will show APTT corrected (suggesting clotting factor deficiency)
Factor VIII and IX assay
FBC usually normal
PT normal
What is the management of Haemophilia?
- Recombinant factor 8 concentrate for haemophilia A
- Recombinant factor 9 concentrate for haemophilia B
- Acute bleeds are treated with factor concentrates and
- anti-fibrinolytics (e.g. amniocaproic acid, tranexamic acid)
- NOTE: these should be given by prompt IV infusion whenever there is any bleeding
- Analgesia and physiotherapy may be required for deep bleeds into muscles and joints
- Orthopaedic and pain team review may also be necessary
- In patients with haemophilia, the following should be AVOIDED (NAI)
- IM injections
- Aspirin
- NSAIDs
- Replacement therapy should be given at HOME to avoid delay in treatment
- Prophylactic factor 8 is given to all children with severe haemophilia A to further reduce the risk of chronic joint damage
- Desmopressin (DDAVP) may be useful in mild haemophilia A as it stimulates the endogenous release of factor 8 and vWF.
What are the complications of treatment of haemophilia?
Define Von Willebrand Disease.
Inherited bleeding disorder due to either a qualitative or quantitative abnormality of von Willebrand factor
What is the inheritance pattern of vWD?
AD - multiple different mutations implicated
What are the types of vWD?
o Type 1 (60-80%) usually mild and not diagnosed until puberty or adulthood
o Type 2 and 3 have more severe symptoms
What are the clinical features of vWD?
- Bruising
- Excessive, prolonged bleeding after surgery
- Mucosal bleeding such as epistaxis and menorrhagia
- Soft tissue bleeding such as large haematomas and haemarthroses are uncommon (unlike haemophilia)
What are the investigations for vWD?
PT: within reference range in VWD
APTT may be mildly prolonged
FBC usually normal
vWF antigen < 0.30 IU/mL
vWF assay < 0.30 IU/mL
What is the management of vWD?
Depends on type and severity
Type 1 vWD can be treated with DDAVP
o NOTE: it should be used with caution in children < 1 year old, because it can cause hyponatraemia and may precipitate seizures
More severe types of vWD have to be treated with plasma-derived factor 8 concentrate
Things to AVOID in vWD:
o IM injections
o Aspirin
o NSAIDs
Define Immune Thrombocytopenia Purpura (ITP)
Autoimmune haematological disorder characterised by isolated thrombocytopenia in the absence of an identifiable cause
What is the incidence of ITP?
Most common cause of thrombocytopenia in children (4 per 100,000 per year)
What is the pathophysiology of ITP?
o Usually caused by destruction of circulating platelets by antiplatelet IgG autoantibodies
o Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex
o This reduces platelet count
o May be accompanied by compensatory increase of megakaryocytes in the bone marrow
What are the clinical features of ITP?
- Most children present between 2-10 years
- Onset tends to be 1-2 weeks after a viral infection (may also occur after a vaccination)
- Typically more acute presentation than in adults
- Children develop petechiae, purpura and/or superficial bleeding
- May have epistaxis and mucosal bleeding
- Intracranial bleeding is a rare but serious complication
What are the different durations of ITP?
- Newly-diagnosed: Duration ≤ 3 months
- Persistent ITP: Duration 3-6 months
- Chronic ITP: ≥ 6 months
What are the investigations of ITP?
Diagnosis of exclusion
In younger children, a congenital cause (e.g. Wiskott-Aldrich syndrome or Bernard-Soulier syndrome) should be considered
Keep an eye out for atypical clinical findings such as:
o Anaemia
o Neutropaenia
o Hepatosplenomegaly
o Marked lymphadenopathy
o NOTE: in the case of abnormal clinical findings, bone marrow examination should be conducted to exclude acute leukaemia or aplastic anaemia
• NOTE: bone marrow examination is required before treatment with steroids because the steroid treatment could temporarily mask the diagnosis of acute lymphoblastic leukaemia (ALL)
What is the management of ITP?
In 80% of children, the disease is acute, benign and self-limiting
It will resolve spontaneously within 6-8 weeks
Most children can be managed at home→conservative management with repeat FBC in 5-7 days
Treatment is indicated if there is evidence of major bleeding (e.g. intracranial or gastrointestinal) or persistent minor bleeding that affects daily life (e.g. excessive epistaxis)
Life- or Organ-threatening bleeding
o IVIG + corticosteroid + platelet transfusion
o Antifibrinolytics may be used
Newly Diagnosed Child
o Asymptomatic or Minor Bleeding
▪ Observation (most will achieve a normal platelet count eventually)
▪ Most manifestations are limited to the skin
o Major Bleeding
▪ Corticosteroids
▪ IVIG OR anti-D immunoglobulin
Child with Chronic Disease (Chronic ITP) (20%)
o Mycophenolatemofetil
o Rituximab
o Eltrombopag (thrombopoietin agonist) o 2nd line: splenectomy
o Screen for SLE
Define disseminated intravascular coagulation.
Acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi (via fibrin deposition in microvasculature) and depletion of platelets and coagulation factors
What are the causes of DIC?
o Severe sepsis or shock due to circulatory collapse e.g. meningococcal septicaemia
o Extensive tissue damage from trauma or burns
What is the pathophysiology of DIC?
o In DIC, the process of haemostasis goes into overdrive
o Multiple clots form in small and medium-sized vessels serving various organs leading to ischaemia
o All this clotting consumes platelets and clotting factors
o Without enough platelets, other parts of the body start to bleed even with the slightest damage to the blood vessel walls
o The clots are also broken down via fibrinolysis, causing release of fibrin degradation products into the circulation
o So there is too much clotting as well as not enough clotting
What are the clinical features of DIC?
- Bruising
- Purpura
- Haemorrhage
- Purpura fulminans may occur (a rare syndrome of intravascular thrombosis and haemorrhagic infarction of the skin)
What are the investigations of DIC?
• DIC should be suspected when the following abnormalities coexist:
o Thrombocytopaenia
o Prolonged PT
o Prolonged APTT
o Low fibrinogen
o Raised fibrinogen degradation products and D-dimers
o Microangiopathic haemolytic anaemia
o There is also usually a marked reduction in naturally occurring anticoagulants (e.g. protein C, protein S and antithrombin)
• There is no single reliable test to diagnose DIC
What is the management of DIC?
- Treat underlying cause (usually sepsis)
- Supportive care e.g. FFP, cryoprecipitate, platelets
- Restoration of physiological coagulation pathways (e.g. using heparin)
- Replacement therapy - replacement of platelets and coagulation factors
- protein C concentrates may be used, particularly in severe meningococcal septicaemia
- chronic DIC may require heparin and tranexamic acid
How should you manage a patient that presents with bruising?
If there is active bleeding, admit to hospital
Consider non-accidental injury – red flags:
o Bruises are on a child who is not yet independently mobile (crawling, cruising, or walking).
o Bruises have indicative features - unusually large, multiple sites or in clusters, similar shape and size, patterned in the shape of a hand print, ligature, stick, tooth, grip, or implement (such as a belt).
o Bruises are found in indicative places-any non-bony part of the body or face (including the eyes, ears, cheeks, back, abdomen, buttocks, arms, and genitalia).
o Explanation for the bruising is implausible, inadequate, or inconsistent
o Delay in presentation.
• If no suspicion of NAI:
o Consider leukaemia if unexplained petechiae, hepatosplenomegaly, high WBC on FBC
o Urgent referral for neuroblastoma if periorbital bruising, palpable abdominal mass
o Further investigations to detect underlying cause
What are the typical bleeding patterns for plt disorder and coagulation factor disorders
