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Flashcards in MoD Session 5 Deck (136):
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What is haemostasis?

Stopping of haemorrhage within seconds to prevent blood loss

1

What does the success of haemostasis depend on?

Vessel wall
Platelets
Coagulation system
Fibrinolytic system

2

What does a severed artery do in haemostasis?

Contracts to decrease pressure downstream

3

What happens after 5 minutes of an artery being severed?

Fragile primary haemostatic plug of platelets has formed at mouth of vessel to control bleeding

4

What happens ~30 minutes after an artery is severed?

Secondary haemostatic plug forms w/fibrin which becomes organised forming granulation tissue which develops into a tiny scar

5

What do all vessels do to limit blood loss?

Constrict their vessel walls

6

How is a platelet plug formed?

Platelets adhere to the damaged vessel wall and each other

7

What is the platelet release reaction?

ATP --> ADP
ADP and thromboxane A2 cause platelet aggregation
5HT and platelet factor 3 released

8

Which molecules are important in platelet coagulation?

5HT
Platelet factor 3

9

What do platelets do after aggregation?

Coalesce

10

Where are the factors used in the intrinsic coagulation system found?

Within BV

11

What is needed to activate the extrinsic coagulation system?

Exo-BV factors

12

Which factors are activated in the intrinsic coagulation system?

12a --> 11a --> 9a --> 10a

13

Which factors are activated in the extrinsic coagulation system?

3a --> 7a --> 10a

14

How does activation of factor 10a by both the extrinsic and intrinsic coagulation systems cause fibrin formation?

10a --> thrombinogen --> thrombin --> fibrinogen --> fibrin

15

Why does the coagulation system have to be tightly regulated?

There is enough thrombin in 1 ml of blood to convert all the fibrinogen in the body to fibrin

16

How is the coagulation system tightly regulated?

Balance procoagulant and anticoagulant forces

17

What can inhibit the activation of fibrinogen by thrombin?

Anti-thrombin III
Alpha 1 antitrypsin
Alpha 2 macroglobin
Protein C and S

18

What are the effects of inherited antithrombin III or protein C and S deficiencies?

Thrombosis (thrombophilia)

19

What is the fibrinolytic system?

Conversion of plasminogen to plasmin which can dissolve fibrin

20

Give two examples of widely used fibrinolytic therapies.

Streptokinase A
Tissue plasminogen activator (tPA)

21

What is needed for the fibrinolytic system to function?

Plasminogen activators

22

What is activated partial thromboplastin time (aPTT)?

Time taken to generate fibrin from initiation of the intrinsic pathway

23

When is aPTT long?

Haemophilia A and B
Factor deficiencies

24

How do you test aPTT?

Activate factor XII w/out activating factor VII in phospholipid emulsion

25

What is prothrombin time (PT)?

Time taken to generate fibrin from factor VII

26

How do you test PT?

Add thromboplastin, recalcify and wait for fibrin filaments to form

27

When is PT long?

Inherited factor VII deficiency
Liver disease
Warfarin treatment
Sever bleeding/massive transfusion

28

How is a long PT rectified in severe bleeding/massive transfusion?

1:1 mix w/normal plasma

29

What is thrombin time (TT)?

Time taken for fibrinogen --> fibrin in the presence of thrombin

30

How is TT measured?

Add thrombin and calcium and wait for fibrin filaments to form

31

When is a long TT seen?

Deficient fibrinogen
Abnormal fibrinogen
Presence of inhibitor to reaction

32

What does the endothelium secrete?

Anti-thrombotic molecules e.g. Plasminogen activators, prostacyclin, nitric oxide and thrombomodulin

33

What is thrombosis?

Formation of a solid mass of blood w/in circulatory system

34

What does thrombosis occur due to?

Virchow's triad

35

What is Virchow's triad?

Abnormalities of:
Vessel wall
Blood flow
Blood components

36

What can cause abnormalities of the vessel wall?

Atheroma
Direct injury
Inflammation

37

What can cause abnormalities of blood flow?

Stagnation
Turbulence

38

In what circumstances might a patient be hyper-coaguable?

Smoker
Post-partum
Post-op

39

Why can patients who are post-partum have abnormalities of blood components?

Due to over-enthusiastic response to blood loss from childbirth

40

What is given post-op to reduce the risk of abnormalities of blood components causing hyper-coaguability?

Prophylactic treatment

41

How do arterial thrombi appear?

Granular
Pale
Low cell content
Lines of Zahn due to bloodflow - yellow = fibrinous, red = RBCs

42

How do venous thrombi appear?

High cell content
Gelatinous
Deep red
Soft

43

What are the possible outcomes of thrombosis?

Lysis
Propagation
Organisation
Recanalisation
Embolism

44

Why is lysis the best outcome of thrombosis?

Fibrinolytic system is active so can completely dissolute thrombus to re-establish blood flow

45

When is lysis the most likely outcome of thrombosis?

When thrombi are small

46

What can aid lysis of a thrombus and help return bloodflow to an ischaemic area?

Streptokinase A

47

Why is propagation when an outcome of thrombosis?

Progressive spread of thrombosis which is distal in arteries and proximal in veins

48

How does a thrombus change as it moves during propagation?

Increases in size with increasing venous diameter

49

What is organisation as an outcome of thrombosis?

Reparative process where ingrowth of fibroblasts and capillaries keep lumen unobstructed

50

What process is organisation as a result of thrombosis like?

Formation of granulation tissue

51

What is recanalisation?

One or more channels formed through organising thrombus which re-establish blood flow

52

Is previous bloodflow usually matched after recanalisation?

No, recanalisation is usually incomplete

53

What is embolism as an outcome of thrombosis?

Where part of the thrombus breaks off and travels through bloodstream to a distant site

54

What is the passage of an embolism in a vein?

Encounters larger vessels until it reaches the heart where it passes through to pulmonary circulation and becomes trapped

55

What is the passage of an embolism in an artery?

Encounters smaller vessels until it becomes trapped

56

What origin does pulmonary embolism always have?

Venous

57

What are the effects of arterial thrombosis?

Ischaemia
Infarction

58

What do the effects of arterial thrombosis depend on?

Site and collateral circulation

59

What are the effects of venous thrombosis?

Congestion
Oedema from obstruction causing high hydrostatic pressure
Ischaemia
Infarction if tissue pressure is high enough to occlude artery

60

What is an embolism?

Blockage of a BV by solid, liquid or gas at a site distant from its origin

61

>90% of emboli are what type?

Thrombo-emboli

62

How do thrombo-emboli from the heart enter renal, mesentric and other arteries?

Via the aorta

63

Where do thrombo-emboli in the brain originate from?

Atheromatous carotid arteries

64

Where do thrombo-emboli caused by an atheromatous abdominal aorta end up?

Arteries of the legs

65

What types of emboli are there apart from thrombo-emboli?

Air
Amniotic fluid
Nitrogen
Medical equipment
Tumour cells

66

What can embolism lead to which requires amputation?

Coagulation necrosis

67

Why can an amputation due to embolism have to be more proximal than the necrotic tissue?

Remaining tissue has increased metabolic demand which the blood supply cannot support

68

What can cause the formation of a thrombo-emboli in the heart?

MI
AF

69

How can carotid endarctorectomies decease the risk of cerebral embolism?

Strip carotid arteries of atheroma so decrease risk of thrombus formation

70

Why must a patient who has presented with a fracture who then goes on to develop SoB and neurological symptoms be treated quickly?

They have a fat embolism which has blocked vessels in the brain causing small haemorrhages

71

How does fracture of a long bone cause fat embolism?

2-6 days after break bone marrow cells die and release fat into the surrounding broken BV

72

Why does fat embolism cause neurological symptoms?

The fat can squeeze through arterial-venous anastomoses in the lungs and therefore enter the arterial system where it is most noticeable in the brain as it causes small haemorrhages

73

What two causes other than long bone fracture can cause fat embolism?

Adipose tissue damage
Biochemical disturbance

74

What type of embolism would injection of an oily drug into a vein cause?

Iatrogenic

75

What are the predisposing factors for DVT?

Immobility - lack of calf muscle pumping
Post-op
Pregnancy and post-partum
High oestrogen type contraceptives
Severe burns
Cardiac failure
Disseminated cancer

76

What is Trossaeu syndrome?

Where tumour cells secrete coagulation factors

77

Can DVT be prevented?

No, you can only reduce the risk in identified high-risk patients

78

What is used for prophylaxis in patients with a high risk of DVT?

SC heparin
Heparin derivatives w/low molecular weight
ED stockings
Inflatable boots in surgery

79

What treatment is given for DVT?

IV heparin followed by oral warfarin

80

What does IV heparin followed by warfarin take a few days to act?

Have to irreversibly inhibit all enzyme molecules

81

What method does DVT treatment usually follow?

Prevention of thrombus propagation, not breaking it down

82

What determines the outcome of pulmonary embolism?

Size of embolism

83

What are the effects of a massive pulmonary embolism?

If it causes >60% decrease in bloodflow it is rapidly fatal as it often completely blocks the pulmonary trunk

84

What are the effects of a medium sized pulmonary embolism?

Medium sized BV are blocked causing SoB with or without a cough
Blood stained sputum can be caused due to development of a pulmonary infarct

85

What effects does a minor pulmonary embolism cause?

Asymptomatic or minor SoB due to peripheral pulmonary artery blocking

86

What do recurrent pulmonary emboli cause?

Pulmonary hypertension

87

How fast does the fibrinolytic system destroy blood clots?

At the same rate at which they are formed

88

Why does it not matter that a severed vein will not contract as a severed artery does in haemostasis?

Pressure in them is already low

89

Which step of haemostasis do patients with a platelet count of <1x10^9/L lack?

Formation of a primary haemostatic plug

90

Which step of haemostasis do haemophiliacs lack?

Secondary haemostatic plug formation as they have normal platelets but can't produce fibrin

91

What are the five platelet activators?

Collagen surfaces within extravascular areas
Thrombin
ADP released by activated platelets and injured RBC
Adrenaline
Some prostaglandins

92

What do activates platelets do?

Swell into sticky spiny spheres and die

93

How do platelets adhere to other surfaces?

Stick to von Willebrand factor which is concentrated on the subendothelial basement membrane

94

What is the subendothelium?

The basement membrane or collagen where the endothelium is removed

95

What acts as glue between platelets in aggregation?

Fibrinogen

96

What factors do platelets secrete to help the platelet plug to grow?

Fibrinogen
ADP
Thromboxane A2 - powerful platelet aggregator

97

What are most of the circulating molecules which act to activate thrombin?

Proenzymes

98

Give two examples of cofactors used in blood clotting.

Phospholipids
Calcium

99

What is clot retraction?

When platelets cling to fibrin filaments and pull by their actin-myosin system as they die

100

What is the purpose of clot retraction?

Toughen clot by squeezing out fluid?
Helps to pull sides of small wounds together

101

What happens to fibrinolytic activity after surgery?

Drops for 7-10 days

102

What is urokinase?

A plasminogen activator found in urine

103

Why is the vascular wall not passive?

The arterial media contracts and the subendothelium traps platelets

104

Why does smoking cause hypercoaguability of blood?

Activates Hageman factor (factor XII)

105

Why are platelets in the veins more concentrated along the endothelium?

They are the smallest formed elements in the blood

106

How does a parietal thrombus compare to an occlusive thrombus?

Parietal - restricts lumen of vessel
Occlusive - fills and obstructs lumen

107

What is the most important mechanism for limiting spread of thrombus?

Blood flow

108

How do thrombi form in a vein?

Platelets catch in an eddy behind a valve, form an aggregate, settle on the wall and stick to other platelets as they pass by

109

What do arterial thrombi tend to remain?

Parietal

110

When do occlusive arterial thrombi tend to occur?

Over an atherosclerotic plaque that has cracked open

111

How can thrombi and post-mortem clots be distinguished?

Thrombi = laminated w/lines of Zahn, opposed to intimal surface
Clots = rubbery and shiny, not laminated, not attached to intima

112

What is a vegetation?

2-3 cm long thrombus on a cardiac valve

113

Why do vegetations usually occur on the valves of the left heart?

Exposed to greater pressure and therefore microtrauma so exposed subendothelial tissue is thrombogenic

114

What can happen the vegetations?

They can become infected

115

How does aspirin work as an antithrombogenic?

Irreversibly acetylates an enzyme of prostaglandin metabolism in platelets so they cannot produce thromboxane A2, inhibiting haemostatic plug formation

116

What is a saddle emboli?

Large emboli that becomes lodged astride the bifurcation of the pulmonary artery

117

Where do approximately 80% of pulmonary emboli arise?

In thrombi in the deep veins of the thigh and popliteal vein

118

How does atrial fibrillation lead to thrombi formation?

Decreased atrial contraction --> dilatation of the left atrium --> stagnation of blood in atrium --> thrombus

119

How do paradoxical emboli bypass the lungs?

Small emboli pass through arterio-venous anastomoses in the pulmonary circulation
Larger emboli pass through defects in the IV septum or formaen ovale during straining which increases pressure in right side of heart

120

What is a paradoxical embolus?

Arise in systemic veins but embolism in systemic arteries

121

What is atheroma?

Gruel-like necrotic material in atherosclerotic plaques released into the blood when the plaque breaks open

122

When might an atherosclerotic plaque break open?

Spontaneously
During surgery
During catheterisation

123

Why do patients with emboli of atheroma present with abdominal pain?

The intestine is often affected

124

How does air embolism arise after trauma or the neck and chest?

During inspiration in the upright position veins draw in air due to their negative pressure

125

What approximate amount of air will cause a fatal air embolus?

100 ml

126

How can air embolism arise in labour?

Enter uterus and be forced into veins open during uterine contraction

127

What happens to air emboli from the lungs when they reach the heart?

Gather in right heart as a frothy mass that stops circulation

128

Why is nitrogen a particular problem when a diver resurfaces too quickly and releases dissolved gases into the body as bubble?

It is fat soluble and can result in persistent bubbles in lipid-risk tissues e.g. CNS

129

How is the bends treated?

Prompt recompression

130

How does amniotic fluid cause embolism?

Enters circulation through a tear in amniotic membranes

131

What can amniotic fluid embolism cause?

Sudden respiratory distress and collapse

132

What is amniotic fluid embolism a complication of?

Labour and Caesarean section

133

Why can emoblisation not occur in veins?

Blood runs from smaller to larger vessels so injects will o through heart and embolism pulmonary arteries

134

Why does venous flow favour stenosis?

It is slow

135

What can be seen in the lungs of IV drug abusers?

Microscopic foreign bodies e.g. talcum