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Flashcards in Haematology Deck (166)
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1

What does normal adult Hb consist of? (HbA)

4 globin chains- 2 alpha and 2 gamma
4 haem molecules - one in each chain

2

In what chain is there a mutation that leads to sickle cell?

Beta chain

3

What is part of the clinical syndrome of sickle cell disease?

Painful crises
Systemic vasculopathy
End organ damage
Reduced life expectancy

4

What is the pathology behind thalassemia?

Reduced or absent production of beta or alpha chains leading to imbalance in the chains - ineffective erythropoiesis

5

What clinical features may be seen in thalassemia?

Effects of anaemia
Effects of iron overload in those with many transfusions

6

What is the genetic mutation that occurs in sickle cell disease?

Substitution of glutamate by valine in position 6 of the beta globin chain

7

What mode of inheritance is sickle cell disease?

Autosomal recessive

8

Do people who are sickle cell carriers experience symptoms?

No

9

What is the pathophysiology of sickle cell disease?

Polymerisation of the haemoglobin leads to deoxygenation and dehydration and sickling of the RBC leading to vaso-occlusion, infarction and haemolyisis

10

What are precipitating factors for a sickle cell crisis?

Hypoxia
High HbS concentration (possibly via dehydration)
Acidosis
Infection
Skin cooling
Stress

11

What complication can arise post reperfusion after a sickle cell crisis?

Free radical damage

12

What are positive lab findings in sickle cell disease?

Anaemia
Haemolysis- high bilirubin, high LDH, high reticulocytes and undetectable haptoglobin
Blood film showing sickle cells
Hb electrophoresis
Hb solubility test - turns opaque if positive

13

What are the emergency presentations of sickle cell disease?

Acute chest syndrome
Overwhelming sepsis
Painful acute crisis
Acute deterioration of anaemia (aplastic crisis or sequestration)
Acute visual loss
Priaprism
Renal impairment
Acute chest syndrome
Fat embolism syndrome/ multi organ failure
Stroke

14

How does a sickle cell crisis present?

Rapid onset bone pain due to bone marrow infarct
Variable severity and duration - can last hours to weeks
Fever and bone tenderness
+\- swelling, hypertension, tachycardia, tachypnoea

15

How is a sickle cell crisis managed?

Adequate prompt analgesia (usually parental opiates)
Fluids

16

How is acute chest syndrome defined?

Acute illness
New infiltrate on CXR
Respiratory symptoms

17

When is acute chest syndrome more likely?

Surgery/anaesthesia
Pregnancy

18

What are complications from acute chest syndrome?

Increased risk of chronic lung disease and death

19

What is the pathophysiology of acute chest syndrome?

Infection, asthma and hypoventilation leading to hypoxia, inflammation and acidosis
Fat emboli and pulmonary thrombi leading to increased vaso occlusion within pulmonary microvasculature
Creates a vicious cycle

20

What is the immediate management of acute chest syndrome?

Adequate analgesia
Incentive spirometry
O2 therapy
Non invasive ventilation even in the absence of severe hypoxia
Fluids
Antibiotics
Transfusion

21

Why do sickle cell patients get overwhelming hypo splenic sepsis?

Splenic autoinfarction from a very young age leading to functional asplenia

22

What pathogens lead to overwhelming hypo splenic sepsis?

Pneumococcal
Meningococcal
H.influenzae

23

What age does hypo splenic sepsis typically occur?

Over 3 years

24

What is the mortality of splenic sepsis?

50 percent in fulminant disease

25

What are the symptoms of overwhelming splenic sepsis?

Febrile, coma, altered sensorium, seizures

26

What is the treatment for overwhelming splenic sepsis?

Urgent antibiotics
Prophylactic penicillin V

27

What can be done as prophylaxis in overwhelming splenic sepsis?

Prophylactic penicillin V
Vaccination

28

What are the signs and symptoms of sequestration?

Painful enlargement of the spleen
Drop in Hb of 2g per litre or more
High reticulocytes

29

What is the mortality from sequestration?

12 percent

30

What is the recurrence rate of sequestration?

50 percent

31

What percentage of sequestration cases occur in children under 2?

78 percent

32

What virus causes an aplastic crisis?

HPV B19 (common childhood illness)

33

What diseases are caused by HPV B19?

5th disease
Slapped cheek disease

34

What is the pathophysiology of an aplastic crisis?

Infection of red cell precursors in the marrow leading to pre red cell aplasia - giving low reticulocytes

35

What can be seen on blood tests with aplastic crisis?

Hb nadir 15 days post infection

36

What is the management of an aplastic crisis?

Urgent blood transfusion

37

Which chromosomes are effected in beta thalassemia?

11 and 16

38

What is the pathophysiology of beta thalassemia?

Lack of production of beta chains so increased alpha chain inclusion which is toxic to red cell progenitors
Leads to ineffective erythropoiesis

39

What is the clinical syndrome of beta thalassemia?

Severe anaemia - leads to growth failure and plasma volume expansion (probably leading to worsening anaemia)
Bone marrow expansion - gives thalassemia facies and hairy skull on X-ray, also causes bone disease, poor dentition and extramedullary erythropoiesis

40

What is the prognosis of beta thalassemia?

Death in first to second decade without transfusion

41

How is beta thalassemia managed?

Regular transfusions to maintain Hb over 10/dl
Be aware of iron overload (haemosiderosis)

42

What is the clinical sequelae of iron overload?

Cardiac failure
Arrhythmia
Cardiomyopathy
Pituitary - impaired growth and infertility
Hypoparathyroidism
Hepatic cirrhosis
Hypogonadism
DM

43

How can iron status be assessed?

Serum ferritin - although is an acute phase reactant so non specific
TIBC
Liver biopsy - invasive
Cardiac and liver MRI (gold standard)

44

What is the gold standard way of assessing iron status?

Cardiac and liver MRI

45

How does liver MRI grade iron status?

Liver (mg/g dry weight)
Normal15

46

How does a cardiac MRI grade iron status?

Cardiac (msec)
Normal >20
Moderate 10-20
Severe

47

Name some iron chelation agents?

Desferoxamine (continuous infusion)
Deferiprone (oral)
Deferassirox (oral)

48

Which features in the history may point to iron overload?

Short stature
Splenectomy
Osteoporosis
Amenorrhoea
Hair loss

49

How many alpha globin chains does a normal person have?

4, 2 from each parent

50

What is the pathophysiology in alpha thalassemia?

Reduced production of alpha chains so increased beta chains but these are less toxic that increased alpha chains

51

What different genotypes are relevant to alpha thalassemia?

Normal - 2 alpha on each chromosome
Silent carrier - single alpha deletion on one chromosome
Alpha plus thalassemia trait - single alpha deletion on each chromosome
Alpha 0 thal trait - double alpha deletion on one chromosome

52

What is HbH?

Beta tetramers- non functional

53

What is HbBarts?

Y tetramers

54

Which ethnic groups are high risk for Alpha 0 thalassemia?

China
South East Asia
East Mediterranean
Middle East

55

What is the clinical syndrome of alpha thalassemia trait?

Asymptomatic
Low or very low MCV/MCH with no evidence or iron deficiency
Definitive diagnosis with genetic testing

56

What mode of inheritance is alpha thalassemia?

Mendelian codominant

57

What happens in the event of homozygous alpha 0 thalassemia?

Incompatible with life
Hydrops fetalis

58

What is the genotype for HbH disease?

A single alpha deletion on one chromosome with a double alpha deletion on the other

59

What are the clinical features of HbH disease?

Microcytic/hypochromic anaemia of variable severity
HbH inclusion bodies
Tendency for iron overload

60

What is the clinical picture for thalassemia intermedia?

Significant anaemia but not transfusion dependent
Increased iron absorption so risk of iron overload disproportionate to transfusion history

61

What are common examples of thalassemia intermedia?

1. Beta thal major with alpha thal trait so less beta and alpha imbalance
2.Beta thal trait with triplicate alpha chains so more alpha and beta imbalance

62

What is the purpose of heel prick antenatal screening test?

To identify significant haemoglobinopathy including sickle cell and offer penicillin prophylaxis, immunisation and parent education

63

How much haemoglobin is made daily and lost daily?

1ml made, 1ml lost

64

What can cause a normocytic anaemia?

Haemolytic
Bone marrow disorder
Hypersplenism
Acute blood loss
Anaemia of chronic disease

65

What can cause a macrocytic anaemia?

B12 and folate deficiency
Liver disease
Hypothyroidism
Reticulocytosis

66

What can lead to normocytic anaemia with a high Hct?

Thalassemia

67

What can lead to a microcytic anaemia with a low Hct?

Iron deficiency
Lead poisoning
Anaemia of chronic inflammation
Sideroblastic

68

What acute compensatory mechanisms are there for anaemia?

Right shift of 2,3 DPG curve
Increased cardiac output through SV and HR
Redistribution of blood flow

69

What are the chronic compensatory mechanisms for heart failure and how do they lead to worsening heart failure?

Chronic severe anaemia ➡️ peripheral vasodilation ➡️ decreased BP ➡️ raised neurohormones like catecholamines, RAA, natriuretic peptide, AVP ➡️ decreased blood flow and GFR ➡️ increased salt and water retention ➡️ raised plasma volume and extracellular volume ➡️ increased workload of the heard leading to LV remodelling and dysfunction and increased LV mass ➡️ worsening heart failure

70

How does alcoholic liver disease lead to a macrocytic anaemia?

Excess cholesterol

71

What type of anaemia does myelodysplasic syndrome lead to?

Macrocytic

72

What are the complications of DVT?

Increased risk of recurrence
Post thrombotic syndrome
Pulmonary hypertension

73

What are mechanical methods for VTE thromboprophylaxis?

Graduated compression stockings
Intermittent pneumatic compression

74

What are pharmacological methods of thromboprophylaxis?

Unfractionated heparin 5000 u bd or qds
Or fondaparinux

75

What are complications due to heparin?

Heparin induced thrombocytopenia
Renal excretion - patients may have renal impairment
Lack of reversibility
Bleeding

76

Which clotting factor does dabigatron inhibit?

Thrombin (IIa)

77

What factor does rivaroxaban inhibit?

Xa

78

Which clotting factor does apixaban inhibit?

Xa

79

The new type anticoagulants should not be given when?

Pregnancy

80

What are the contraindications to graduated compression stockings?

Known peripheral vascular disease
Leg and buttock pain on exercise
Previous or planned revascularisation surgery
Leg oedema where stockings cannot be fitted
Skins abnormalities including dermatitis, gangrene and recent skin grafts

81

How should VTE be treated?

Anticoagulant therapy to treat and to prevent prophylaxis
1. Immediate therapy with LMWH
2. Overlap with warfarin until INR in the therapeutic range which is a minimum of 5 days
3. Stop heparin and continue warfarin for 3m

82

What should the target INR be with warfarin?

2-3

83

What the two enantiomers of warfarin?

R (less active) and S (more active)

84

What is the half life of warfarin?

36 hours

85

Which organ metabolises warfarin?

The liver

86

What is the mechanism of warfarin?

Vitamin K antagonist that stops factor II, VII, and X and protein C and S production from hepatocytes

87

Which should warfarin not be given in pregnancy?

Teratogenic and increased bleeding risk

88

Which enzyme metabolises R warfarin?

CYP2C19
CYP1A2
CYP3A4

89

Which enzyme metabolises S warfarin?

CYP2C9

90

How many times more potent is S warfarin than R warfarin?

3-5x

91

Which enzyme does warfarin inhibit?

VKORC1 that normally converts vitamin K hydroquinone to vitamin K epoxide

92

Which enzyme normally converts vitamin K epoxide back to vitamin K hydroquinone?

Gamma glutyl carboxylase

93

What percentage of dabigatran is renally cleared?

80 percent

94

What is malaria?

Systemic tropical parasitic infection of the red blood cells caused by plasmodium spp and transmitted by the female anopheles mosquito

95

Which species of plasmodium is most common?

Falciparum

96

Which species of plasmodium lead to uncomplicated relapsing pneumonia?

Viral
Ovals

97

Which species of plasmodium leads to uncomplicated non relapsing malaria?

Malariae

98

Which species of plasmodium causes monkey malaria?

Knowlesi- restricted to certain parts of South East Asia

99

Which is the female anopheles mosquito active?

Dusk to dawn

100

How else other than mosquito bite can malaria be spread?

Congenital
Blood transfusion

101

What is the incubation period for malaria?

7-30 days (shorter for P.falciparum and longer for P.malariae)

102

What is "airport malaria"?

Mosquitos stored in aircrafts and luggage that affect people that have not travelled

103

How many cases are there world wide of malaria?

200 million

104

Which area of the world brings in the most malaria cases in travellers returning to the UK?

Sub Saharan Africa (1 in 5 cases)

105

Describe the malaria life cycle

Mosquito- mosquito ingests a bloody meal containing gameocytes. Gameocytes undergo sexual reproduction in the mosquito's mid gut and produce thousands of sporozoites. Sporozoites migrate to the mosquito salivary gland and initiate another cycle when transmitted to the human host.
Liver- sporozoites enter hepatocytes via blood and develop into schizonts that contain several daughter cells known as merozoites (with P.vivax and P.ovale some sporozoites enter a dormancy period called hypnozoites and may remain as such for years). Schizonts rupture leading to release of merozoites into blood.

106

What are global vector control methods for malaria?

Insecticide treated nets
Indoor residual spray
Genetically modified mosquitos

107

What personal protective measures can be done against malaria?

DEET based insect repellent
Insecticide treated bed nets
Clothing

108

Why must a combination of prophylaxis be taken for malaria?

No regime is 100 percent effective
Based on countries malaria species and resistance patterns

109

How can non-falciparum malaria be treated?

Chloroquine
Eradication therapy for liver stages of vivax and ovale with primaquine (avoid in severe G6PD deficiency and pregnancy)

110

What antibiotic should be replaced in pregnancy and children in malaria treatment and why?

Replace doxycycline with clindamycin as greater chance of complications

111

If you doubt the species of plasmodium, how should you treat it?

As P.falciparum

112

What is the pathogenesis of malaria?

Infected red blood cells adherence to host endothelium causes:
Microvascular occulsion
Metabolic derangement and metabolic acidosis
Intravascular haemolysis due to schizont rupture evoking vigorous cytokine response

113

How should falciparum malaria be treated?

1. Parasitaemia less than 2% and no signs of severity:
Oral quinine sulphate +\- doxycycline
Oral artemether and lumefantlin (riamet and co-artem)
Oral atovaquone and proguanil (Malarone)
2. Parasitaemia greater than 2% +\- signs of severity
Involve ITU or HDU
iv quinine dihydrochloride (needs ECG and glucose monitoring)
iv artesunate (unlicensed use in EU)

114

What is the clinical presentation of malaria?

Fever
Headache and muscle aches
Diarrhoea
Vomiting
Foreign travel (last 12m for falciparum and longer for other types)
Malaria prophylaxis?
Pregnancy- high risk for complications

115

Which type of blood film is more sensitive in diagnosing malaria generally?

Thick

116

Which type of blood film is better for finding the exact species in malaria?

Thin

117

Which type of blood film is better for determining the level of parasitaemia in malaria?

Thin

118

What is seen with P.falciparum on LM?

Numerous fine ring forms
Double chromatin dots
Red cells not enlarged

119

What is seen with P.vivax on LM?

Enlarged red cells
Developing and thick signet ring forms

120

What is seen with P.ovale on LM?

Oval shape trophozoite
Comet like red cell
Enlarged red cell

121

What is seen with P.malariae on LM?

Broad band form in red blood cell
Red cells not enlarged

122

What is seen with P.knowlesi on LM?

Ring stages resemble falciparum
Mature stages indistinguishable from malariae
Molecular methods needed to confirm diagnosis

123

What are the rapid tests for plasmodium antigens?

1. Histidine rich protein 2 (HRP2)
2. Plasmodium lactate dehydrogenase (pLDH)

124

What the non infectious complications of blood transfusions?

ABO incompatible
DHTR (other red cell antibodies e.g. Rh and kell)
FNHTR
urticarial rash
IgA deficiency (anaphylaxis)
PTP
TRALI
Immunomodulation
TA
GVHD

125

What are the non immune complications of a blood transfusion?

Iron overload
Fluid overload (TACO)

126

What percentage of people are each blood group?

A - 42%
B - 9 %
AB - 3%
O - 46%

127

What is the most common blood group?

O

128

How does ABO mismatch lead to complement activation?

Haemolysis leads to C5b-9, thromboplastic substances and release of histamine and other vasoactive amines. These cause cytokines to be released resulting in decreased blood pressure (causing shock and renal failure). The processes also increase coagulation (leading to DIC), inflammation and increased vascular permeability.

129

Why does an acute haemolytic reaction occur?

Wrong blood group leading to immediate complement mediated lysis

130

What is the clinical picture of an acute haemolytic reaction?

Can be fatal soon after starting transfusion
Shock , high fever, kidney failure, death

131

How should an acute haemolytic reaction be managed?

Stop transfusion
Iv fluids to maintain blood pressure
FBC, coagulation screen and chemistry
Repeat blood group
Return blood unit to blood bank
Blood cultures
Treat DIC and admit to ITU

132

How long after a transfusion does an acute haemolytic reaction occur?

7 to 10 days post transfusion

133

Why does a delayed haemolytic reaction occur?

Due to red cell antibodies such as Rh system, Kell, Fya, Jkb etc

134

How is a delayed haemolytic transfusion reaction diagnosed?

Positive direct antiglobulin test

135

What is the clinical picture of a delayed haemolytic transfusion reaction?

Starts 7 to 10 days post transfusion
Jaundice
Failure of Hb to rise

136

When does a febrile non haemolytic transfusion reaction occur?

During or after transfusion

137

What is seen clinically with FNHTR?

Rise in temperature more than 1C (fever) +\- rigors

138

Is FNHTR life threatening?

No but must exclude wrong blood group and infection

139

What process has lowered the incidence of FNHTR?

Leucodepletion of blood and platelets

140

What is seen in an allergic reaction to transfusion products?

Either urticarial rash (+\- wheeze) or anaphylaxis

141

Why does an urticarial rash occur?

Hypersensitivity to one of the plasma proteins

142

What is the clinical picture of anaphylaxis?

Life threatening soon after wheeze has started
Increased wheeze/asthma
Shock (tachycardia with low BP)
Laryngeal or facial oedema
May be related to IgA deficiency

143

Which antibody deficiency is linked to anaphylaxis?

IgA

144

What pulmonary complications are linked to transfusion?

Transfusion associated circulatory overload (TACO)
Transfusion related acute lung injury (TRALI)

145

Who is at risk of TACO?

Elderly
Pre existing heart disease
Very small patients with high volume transfusion

146

Why does TRALI occur?

Transfused anti leukocyte antibodies in donor plasma reacts with the patients white blood cells

147

What is seen on X-ray with TRALI?

Bilateral pulmonary infiltrate

148

How is TRALI managed?

Supportively with ventilation

149

Does diuretics improve TACO or TRALI?

TACO as it is fluid overload

150

What is the pulmonary arterial pressure in TACO vs TRALI?

Over 18mmHg in TACO and less than or equal to 18mmHg in TRALI

151

What are some of the other rare immune complications that can occur in transfusion?

Post transfusion purpura (PTP)
Transfusion associated graft vs host disease
TA-GVHD

152

When does PTP occurs?

7-10 days after transfusion of blood or platelets

153

What causes PTP?

HPA1 negative patients form antibodies after transfusion or pregnancy
After further transfusion there is destruction of one's own platelets

154

Is transfusion associated graft vs host disease always fatal?

Yes, but rare

155

Why does transfusion associated graft vs host disease occur?

Mediated by viable lymphocytes in donor blood or platelets (prevented by irradiation)

156

How is TA-GVHD avoided?

Avoid by HLA matching or use blood from first degree relative

157

Who is prone to TA-GVHD?

Very immunosupressed such as bone marrow transplant, on fluidarabine, Hodgkin's disease, foetus needing intrauterine infusion, congenital immunodeficiency

158

How are observations done during a transfusion?

Baseline
Every 15 mins
Hourly after transfusion had ended

159

Which framework has been put in place to ensure better use of blood products?

HSC 2007/01

160

Which viruses are commonly spread through transfusion?

Hepatitis: HPV, HBV, HCV, HDV (HDV needs HBV to survive)

161

Other than transfusion, what are other ways HBV, HIV and HCV be transmitted?

HBV - intravenous drugs, sexually (homosexuals more prone), vertically
HIV - sexually (homosexuals more prone) >intravenous drugs, vertically
HCV - intravenous drugs>>sexually, vertically

162

Why is HBV more likely in blood transfusion related infections?

The initial period of 3-4months post infection the HBsAg is negative so must exclude high risk donors

163

What is prion disease?

Mad cow disease
Transmission through blood and sheep in humans
Cannot diagnose with blood test only biopsy

164

What steps have been taken to reduce the incidence of blood transfusion related prion disease?

Leucodepletion
U.K. Plasma not used for fractionating
Imported FFP for all patients born after 1996
Any recipient of blood after 1980 barred from donation

165

What are the complications of bacterial contamination into blood products?

Can be fatal
Bacterial sepsis - especially if endotoxin produced e.g. Gram negative rods (E.coli)
Shock, kidney failure and death

166

How can bacterial contamination of blood products be reduced?

Stringent cleansing of donor skin