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Flashcards in Haematological Disorders Deck (139):
1

When is HbF very low in healthy children - when is it not?

By age 1
Increased proportions of HbF are indicators of severe inherited disorders of haemoglobin production - haemoglobinopathies

2

Hb at birth

14-21.5g/dl to compensate for low oxygen concentration in fetus

3

What happens to Hb after birth

Falls over first few weeks of life, mainly due to reduced red cell production, to 10g/dl at 2 months of age

4

What happens to Hb after birth in pre-term babies?

It has a steaper fall to a mean of 6.5-9g/dl at 4-8 weeks chronological age

5

What are the iron, B12 and folic acid stores like in term and preterm infants at birth and after birth?

Iron, B12 and folic acid are adequate at birth in term and preterm babies
However in preterm babies stores of iron and folic acid are lower and are depleted more quickly leading to deficiency after 2-4months if recommended daily intakes are not maintained by supplements

6

Anaemia value in neonate

Hb less than 14g/dl

7

Anaemia value in 1-12months old

Hb less than 10g/dl

8

Anaemia value in 1-12 years

Hb less than 11g/dl

9

What is red cell aplasia

Complete absence of red cell production

10

What is ineffective erythropoeisis?

Red cell production is normal/increased rate but differentiation or survival of red cells is defective

11

What are the main causes of iron deficiency anaemia x3

Inadequate intake (common in infants)
Malabsorption
Blood loss

12

Which milk is not good for maintaining infant iron levels?

Cows milk because it has a higher iron content than breast milk but only 10% of the iron is absorbed
Therefore infants should not be fed unmodified cows milk

13

At what Hb level do children become symptomatic with anaemia?

6-7g/dl

14

How do children with iron deficiency anaemia present?

Pica- eating non-food materials such as soil, chalk, gravel or foam rubber

15

What are indicators on blood tests of iron deficiency anaemia

Microcytic, hypochromic anaemia (low MCV and MCH)
Low serum ferritin

16

Management of iron deficiency anaemia in infants?

Increase oral iron intake with supplementation - Sytron or Niferex are best tolerated preparations
Or just increase iron rich foods

17

What are the 3 main causes of red cell aplasia in children?

1) Diamond-Blackfan anaemia - congenital red cell aplasia
2) Transient erythroblastopenia of childhood
3) Parvovirus B19 infection in children with haemolytic anaemia

18

Diagnostic features of red cell aplasia x4

Low reticulocyte count despite normal Hb
Normal bilirubin
Negative direct antiglobulin/Coombs test
Absent red cell precursors on bone marrow examination

19

What is Diamond-Blackfan anaemia?

It is a rare congenital disease of red cell aplasia

20

Inheritance of Diamond-Blackfan anaemia

20% family history - remaining 80% are sporadic mutations
RPS (ribosomal protein) genes implicated in some cases

21

Presentation of Diamond-Blackfan anaemia

Most present at 2-3 months of age but 25% present at birth

22

Features of Diamond-Blackfan anaemia x2

Anaemia
Also congenital abnormalities such as short stature or abnormal thumbs

23

Treatment of Diamond-Blackfan anaemia x2

Oral steroids
Monthly red cell transfusions for children not responsive to steroids

24

What is transient erythoblastopenia of childhood?

Red cell aplasia usually triggered by viral infections
Same haemotological features as D-Blackfan anaemia

25

Prognosis of transient erythroblastopenia of childhood

Always recovers - usually within several weeks (hence differs from d-blackfan)

26

Inheritance of transient erythroblastopenia of childhood

No family history

27

When does haemolysis lead to anaemia?

When the bone marrow can no longer increase red cell production to compensate for the premature destruction of red cells

28

Main causes of haemolytic anaemias in children? What is uncommon children

Intrinsic abnormalities of RBCs (membrane and enzyme disorders and haemoglobinopathies)
Immune haemolysis is uncommon

29

What does haemolysis from increased RBC breakdown lead to? x4

Anaemia
Hepatomegaly and splenomegaly
Increased blood levels of unconjugated bilirubin
Increased urinary urobilinogen

30

Diagnostic clues to haemolytic anaemia x4

Increased reticulocyte count
Unconjugated bilirubinaemia and urinary urobilinogen
Abnormal appearance of red blood cells on film (spherocytes, sickle shaped or very hypochromic)
Increased red blood cell precursors in bone marrow

31

Incidence of hereditary spherocytosis

1 in 5000 live births in caucasians

32

Inheritance of hereditary spherocytosis

Usually autosomal dominant inheritance - BUT in 25% there is no family history and it is sporadic mutation

33

What is pathology of hereditary spherocytosis?

Mutation in gene for protein in red blood cell membrane - therefore RBC looses part of its membrane when it goes through the spleen
Therefore reduced surface-to-volume ratio and cell becomes spherical
Therefore less deformable than normal RBC and destruction of microvasculature of spleen

34

What are the clinical features of hereditary spherocytosis? x5

Clinical manifestations vary and patients can be completely asymptomatic or present during childhood or be intermittent - but can have:
- Jaundice
- Anaemia
- Mild-moderate splenomegaly
- Aplastic crisis with parvovirus B19
- Gallstones

35

Management of hereditary spherocytosis x2

Many have mild and therefore only require folic acid supplementation
Splenectomy is beneficial but only indicated if poor growth or troublesome symptoms - usually deferred until after 7 years old because of risk of sepsis

36

Management of aplastic crisis in hereditary spherocytosis

Usually requires 1 or 2 blood transfusions over 3-4 weeks whilst no red blood cells are produced

37

What is incidence of Glucose-6-phosphate dehydrogenase deficiency?

G6PD is commonest red cell enzymopathy - affects 100million people worldwide
10-20% of individuals from central africa, mediterranean and the middle east and far east

38

What is pathology of G6PD deficiency?

G6PD is an enzyme required to prevent oxidative damage to red cells - therefore red cells lacking the enzyme are susceptible to oxidant-induced haemolysis

39

Inheritance of G6PD deficiency?

It is x-linked therefore predominantly affects males. Heterozygous females are usually clinically normal and homozygous females (or one deletion + one mutation) will be affected

40

Clinical presentation of G6PD in children x2

1) Neonatal jaundice - onset in first 3 days of life - severe
2) Acute haemolysis precipitated by infection, certain drugs, fava beans (broad beans) and naphthalene (mothballs)

41

Details of haemolysis in G6PD - where does it occur and what does it cause x4

Mostly intravascular
Causes fever, malaise, passage of dark urine
Rapid fall in Hb

42

Diagnosis of G6PD

Between episodes almost all patients have a completely normal blood picture therefore diagnosis by looking at G6PD activity
During an episode G6PD may be misleadingly high due to increased reticulocyte production

43

Management of G6PD

Parents should be given advice about signs of acute haemolysis and provided with a list of what to avoid
Transfusions are rarely required even for acute episodes

44

When do B-thalassaemias present?

Delayed until after 6months of age when most of HbF (no B chains) has been replaced by HbA (with B chain)

45

Prevalence of sickle cell disease

1 in 2000 live births in UK

46

What does sickle cell disease encompass?

Sickle cell anaemia, sickle cell trait, HbSC disease and Sickle B-thalassaemia

47

What is HbSC disease?

One HbS and one HbC from other parent - HbC is point mutation in B-globin therefore also have no HbA

48

Features of sickle B-thalassaemia

Also have no normal B chains therefore no HbA and similar symptoms to sickle cell anaemia

49

Features of sickle cell trait?

About 40% HbS - do not have symptoms but are carriers and can pass on to children

50

Pathology of sickle

HbS polymerises forming stiff sickle shape with can get trapped in microcirculation - causing vaso-occlusion and therefore ischaemia
Exacerbated by low O2 tension, dehydration and cold

51

Clinical features of sickle x7

Anaemia (moderate 6-10g/dl)
Infection
Painful vaso-occlusive crises
Acute anaemia (eg. in crises)
Priapism
Splenomegaly
Long term problems

52

Types of infection risk in sickle

Infection from encapsulated organisms such as pnemococci and haemophilus influenzae
Increased osteomyelitis by salmonella
Due to hyposplenism and microinfarction in spleen in infancy

53

When is sepsis risk greatest in sickle

In early childhood - post-spleen destruction in infancy

54

Where is most commonly affected in painful crises of sickle x2

Bones of limbs and spines
Chest most serious as leads to hypoxia

55

What can cause acute anaemia in sickle? x3

Haemolytic crises (sometimes associated with infections)
Aplastic crises (B19)
Sequestration crises (sudden splenic or hepatic enlargement due to accumulation of sickled cells in spleen)

56

What needs to be done if priaprism in sickle

Urgent treatment with exchange transfusion as may lead to fibrosis in corpora cavernosa and erectile impotence

57

What age is splenomegaly common in sickle?

Common in younger children but not older children

58

What are long-term problems for sickle?x 6

Stroke and cognitive problems
Adenotonsillar hypertrophy - causing sleep aponea syndrome
Cardiac enlargement, heart failure - from anaemia
Renal dysfunction
Pigment gallstones
Leg ulcers

59

Prophylaxis in sickle? x3

Fully immunised against pneumococcal, haem infl type B and meningococcus infections
Daily oral penicillin throughout childhood
Folic acid

60

Lifestyle managements in sickle

Avoid cold, dehydration, excessive exercise, undue stress or hypoxia

61

Treatment of acute sickle crisis x4

Oral or IV analgesia
Good hydration
Antibiotics for infection
Oxygen if O2 sats reduced

62

Which 3 acute sickle crisis require exchange transfusion in sickle?

Priaprism, acute chest crisis and stroke

63

Common painful presentation of sickle in childhood?

Hand-foot syndrome due to dacylitis causing swelling and pain in fingers and/or feet from vaso-occlusion

64

Management for children with recurrent sickle crises? x2

Hydroxyurea which increases HbF concentration
requires monitoring for white blood cell suppression

If this doesn't work then bone marrow transplant can be offered

65

Cure rate in sickle with bone marrow transplant

Cure rate is 90%
5% risk of fatal transplant-rated complications

66

How is sickle diagnosed early

Guthrie heelprick test at birth

67

SC disease difference from sickle anaemia x3

Have fewer painful crises but may develop proliferative retinopathy in adolescence - therefore check eyes periodically
Also prone to osteonecrosis of hips and shoulders

68

Where is B-thalassaemia common

Indian subcontinent, mediterranean and middle east

69

Two different types of b-thalassaemia?

Major and intermedia- intermedia is milder

70

Clinical features of b-thalassaemia x3

Severe anaemia - transfusion dependant from 3-6months of age
Failure to thrive/grow
Extramedullary haemopoiesis - prevented by transfusions but if no transfusions then hepatosplenomegaly and bone marrow expansion - classic facies with maxillary overgrowth and frontal bossing

71

Management of b-thalassaemia

Lifelong transfusions
Can lead to iron overload therefore iron chelation with desferrioxamine or deferasirox from age 2-3

72

Cure for b-thalassaemia

Bone marrow transplantation (90-95% success with HLA matched identical twin)

73

B-thalassaemia trait features x3

Usually asymptomatic
Hypochromic and microcytic red cells
Anaemia mild or absent

74

What happens in a-thalassaemia major

All four a-globin genes are deleted therefore hydrops fetalis - death in utero or within hours of birth
Can only survive with intrauterine transfusions and then lifelong

75

What happens in HbH disease - a-thalassaemia

Three a-globin chains deleted
Mild-moderate anaemia but occasionally they are transfusion dependant

76

Features of alpha-thalassaemia trait

1 or 2 chain deletions
Usually asymptomatic
Anaemia is mild or absent

77

What can b and a-thalassaemia traits be confused with?

Diagnostically they can be confused with mild iron deficiency

78

What is immune haemolytic anaemia of the newborn due to?

Antibodies against blood group antigens - most important are anti-D, anti-A or anti-B (ABO blood group)
Mother is always negative and baby is always positive therefore mother makes antibodies against baby's blood group

79

Diagnostic tool for immune haemolytic anaemia

Coombs test (direct anti-globulin) positive - only positive in antibody mediated anaemias

80

Which haemolytic anaemias commonly present in neonatal period

Mostly due to G6PD deficiency or hereditary spherocytosis
Haemoglobinopathies rarely present with clinical features in neonatal period (but are detected on Guthrie)

81

What is aplastic anaemia?

Bone marrow failure
- reduction or absence of all 3 main lineages in bone marrow

82

What does aplastic anaemia lead to?

Peripheral blood pancytopenia - reduction of all blood cell types

83

What causes aplastic anaemia?

Many are "idiopathic" because specific cause cannot be found
Some can be inherited
Some can be acquired (viruses eg. hepatitis, drugs or toxins)

84

Clinical presentation of aplastic anaemia? x3

Anaemia due to reduced RBC
Infection due to reduced WBC
Bruising and bleeding due to thrombocytopenia

85

What is Fanconi anaemia?

Most common inherited aplastic anaemia

86

Inheritance of Fanconi anaemia?

Autosomal recessive condition

87

Clinical features of Fanconi anaemia other than directly due to blood cells?

Majority of children also have congenital abnormalities including short stature, abnormal radii and thumbs, renal malformations and pigmented skin lesions

88

How does Fanconi anaemia present?

Can present either with signs of bone marrow failure (not usually until age 5-6) or congenital abnormalities

89

Management of Fanconi anaemia?

Bone marrow transplantation from healthy sibling because can progress to acute myeloid leukaemia

90

What is Shwachman-Diamond syndrome?

Rare bone marrow failure - autosomal recessive disorder

91

What features are present in Shwachman-Diamond syndrome? x3

Signs of bone marrow failure
Also pancreatic exocrine failure and skeletal abnormalities

92

Risk with Fanconi anaemia and Shwachman-Diamond syndrome?

Both can advance to acute leukaemia

93

What is a good way to establish if new onset bleeding disorder is acquired or inherited?

If previous surgical procedures or dental extractions were uncomplicated - suggests acquired

94

What sort of bleeding disorder is associated with mucous membrane bleeding and skin haemorrhage?

Platelet disorders or von Willebrand disease

95

What sort of bleeding disorder is associated with bleeding into muscles or joints?

Haemophilia

96

What sort of disorder is associated with scarring and delayed haemorrhage

Disorders of connective tissue such as Marfans syndrome, osteogenesis or factor XIII deficiency

97

Clotting factors in neonate?

Levels of all (except FVIII and fibrinogen) are lower and preterm infants have even lower values - therefore have to compare with values for gestational age

98

How are haemophilia a and b inherited?

Both have x-linked recessive inheritance therefore only affect males

99

Deficiency in haemophilia a

FVIII deficiency

100

Deficiency in haemophilia b

FIX deficiency

101

Which haemophilia is more common

haemophilia a is a lot more common

102

Different types of both haemophilias

Disorder is graded as severe, moderate or mild

103

Features of severe haemophilia

Recurrent spontaneous bleeding into joints and muscles - leads to crippling arthritis if not properly treated
Present usually towards end of 1st year when starting to crawl and walk

104

How can haemophilia present if presents before crawling/walking age?

Can present in neonatal period (40%) with intracranial haemorrhage, bleeding post-circumcision or prolonged oozing from heel prick and venepuncture sites

105

Inheritance of severity of haemophilia?

Severity usually remains constant within a family

106

Acute management of haemophilia

Recombinant factor VIII or IX is given IV whenever there is acute bleeding
Usually raising level to 30% of normal is enough

107

When do factor levels need to be raised above 30% of normal in haemophilia?

Major surgery or life threatening bleeds - require raising to 100% and then maintained at 30-50% for 2 weeks to prevent secondary bleed

108

Prophylactic treatment for severe haemophilia a

Prophylactic FVIII - usually begins at age 2-3 years, given 2/3x per week

109

Prophylactic treatment of mild haemophilia a

Desmopressin may allow mild haemophilia a to be managed without blood products
Ineffective in haemophilia b

110

What is von Willebrand disease?

Quantitative or qualitative deficiency of vWF

111

What does vWF do? x2

Faciliates platelet adhesion to damaged endothelium
Acts as carrier protein for FVIII

112

Pathology of vWD?

Defective platelet plug formation and also deficient in FVIII

113

Inheritance of vWD?

Autosomal dominant

114

Presentation age of vWD?

Commonest subtype - type 1 (60-80%) usually fairly mild and often not diagnosed until puberty or adulthood

115

Clinical features of vWD? x3

Bruising
Excessive, prolonged bleeding after surgery
Mucosal bleeding such as epistaxis and menorrhagia

116

Management of mild vWD?

Mild can often be managed with desmopressin

117

When do you need to be careful using desmopressin?

Need to be used with caution in children under 1 because can cause hyponatraemia due to water retention and may cause seizures if fluid intake is not strictly regulated

118

Treatment of more severe vWD?

Treated with plasma derived FVIII concentrate (recombinant does not contain vWF therefore no good)

119

What should be avoided in haemophilia and vWD patients? x3

IM injections, aspirin and NSAIDs

120

What is the definition of thrombocytopenia?

Platelet count below 150 x10-9/L

121

Definition and presentation of severe thrombocytopenia

Platelets below 20 x 10-9/l
Risk of spontaneous bleeding

122

Definition and presentation of moderate thrombocytopenia

Platelets 20-50
Risk of excess bleeding during operations or trauma but low risk of spontaneous bleeding

123

Definition and presentation of mild thrombocytopenia

Platelets 50-150
Low risk of bleeding unless there is a major operation or severe trauma

124

What can thrombocytopenia result in? x4

Bruising, petechiae, purpura, mucosal bleeding (nose, gums)

125

What is immune thrombocytopenia? (ITP)

Commonest cause of thrombocytopenia in childhood - caused by destruction of circulating platelets by antiplatelet IgG autoantibodies

126

Typical presentation of ITP and age

Present between ages of 2 and 10 with onset often 1-2 weeks after viral infection

127

Clinical features of ITP x5

Most children have a short history of days/weeks of
Petechiae, purpura and/or superficial bleeding
Can also cause mucosal bleeding and epistaxis

128

Rare complication of ITP

Intracranial bleeding - rare but serious - mainly in those with a long period of severe thrombocytopenia

129

Diagnosis of ITP

Diagnosis of exclusion
Examine bone marrow to exclude aplastic anaemia or leukaemia

130

Management of ITP

80% of children have benign self-limiting disease - remitting within 6-8 weeks
But if persistent bleeding then oral prednisolone, IV anti-D or IV immunoglobulin
Platelet transfusions only for life-threatening haemorrhage

131

What is chronic ITP

20% in whom the platelet count remains low 6months after diagnosis

132

Management of chronic ITP

Supportive mostly
Drugs only for chronic bleeding
Monoclonal antibodies and other new drugs

133

What is disseminated intravascular coagulation? (DIC)

Disorder characterised by coagulation pathway activation leading to fibrin deposition in microvasculature and consumption of coag factors and platelets and therefore bleeding

134

Commonest causes of DIC x3

Severe sepsis or shock due to circulatory collapse (meningococcal septicaemia), or extensive tissue damage from trauma or burns

135

Clinical features of DIC x3

Bruising, purpura and haemorrhage

136

Management of DIC

Treat underlying cause whilst providing intensive care
Can give fresh frozen plasma, platelets and cryoprecipitate

137

EG's of prothrombotic disorders x4

Protein C and S deficiency
Antithrombin deficiency
Factor V Leiden

138

When do prothrombotic disorders present?

C and S heterozygotes - mostly in second or third decade and rarely in childhood
C and S homozygotes rare - thrombosis and widespread haemorrhage and purpura in neonatal period

139

Most common cause of thrombosis in children

95% of venous thromboembolic events in childhood are secondary to underlying disorder with hypercoagulable state