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Haematology and Immunology > Thrombotic Disorder > Flashcards

Thrombotic Disorder Flashcards

1
Q

The elements of homeostasis

A
  1. Primary homeostasis
    - vasoconstriction
    - platelet adhesion
    - platelet aggregation
  2. Blood coagulation
    - insoluble fibrin formation
    - fibrin cross linking
  3. fibrinolysis
    - involves urokinase and tPA interacting with factor XII to convert plasminogen -> plasmin
    - plasmin then converts fibrin to fibrinogen/fibrin degradation products
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2
Q

What is a thrombus?

A

A clot arising in a wrong place

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3
Q

What is a thromboembolism?

A

Movement of a clot along a vessel

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4
Q

Virchows triad

A
  1. stasis
    - bed rest, travel
  2. hypercoagulability
    - pregnancy, trauma
  3. vessel damage
    - atherosclerosis
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5
Q

Types of thrombus

A

Arterial
Venous
Microvascular

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6
Q

What is an arterial thrombosis made up of?

A

White clot

  • platelets
  • fibrin
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7
Q

What does an arterial thrombosis result in?

A

Ischaemia

Infarction

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8
Q

What is arterial thrombosis principally secondary to?

A

Atherosclerosis

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9
Q

Examples of arterial thrombosis

A

Coronary = MI, unstable angina
Cerebrovascular thromboembolism = stroke, TIA
Peripheral embolism = limb ischaemia

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10
Q

Risk factors for arterial thrombosis

A 
Age
smoking
sedentary lifestyle
HTN
DM
obesity 
Hypercholestermia
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11
Q

Treatment of acute presentation of arterial thrombosis

A

Thrombolysis

Antiplatelet/anticoagulation drugs

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12
Q

Prevention of arterial thrombosis

A

Primary
- lifestyle modification
- treatment of vascular risk factors
Secondary

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13
Q

What is a venous thrombosis made up of?

A

Red thrombus

  • fibrin
  • red cells
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14
Q

What does a venous thrombosis result in?

A

back pressure

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15
Q

What is a venous thrombosis principally due to?

A

Stasis

Hypercoagulability

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16
Q

Examples of venous thrombosis

A 
Limb DVT
PE
Visceral venous thrombosis
Intracranial venous thrombosis 
Superficial thrombophlebitis
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17
Q

Risk factors for venous thrombosis (stasis / hypercoagulability)

A 
increasing age
surgery 
obesity 
pregnancy 
hormonal therapy - COCP/HRT 
Immobility
Systemic disease 
FH
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18
Q

Systemic diseases related to venous thrombosis

A 
Cancer
Myeloproliferative neoplasms (MPNs)
Autoimmune diseases (IBD, connective tissue diseases e.g. SLE)
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19
Q

Diagnosis of venous thrombosis

A 
Pretest probability score
- wells score
- Geneva score
D-dimer 
Doppler-USS 
Ventilation/perfusion scan (V/Q)
CT pulmonary angiogram
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20
Q

What is seen on a doppler USS in venous thrombosis?

A

DVT = thromboembosed vein enlarged
Non-compressible
Echogenic material seen

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21
Q

Treatment aims of venous thrombosis

A

Prevention of clot extension
Prevention of clot embolization
Prevent clot recurrent in long term treatment

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22
Q

Treatment of venous thrombosis

A 
Anticoagulants
- LMWH 
- Coumarins (warfarin)
- DOACs
Thrombolysis only in selected cases e.g. massive PE
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23
Q

What does heritable thrombophilia give you an inherited predisposition to?

A

Venous thrombosis

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24
Q

Pathology of Heritable thrombophilia

A 
Common 
- factor V Leiden 
- Prothrombin G20210A
Rare
- antithrombin deficiency 
- protein C / S deficiency
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25
Q

What makes up a microvascular thrombosis?

A

Platelets and/or fibrin

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26
Q

What does microvascular thrombosis result in?

A

Diffuse ischaemia

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27
Q

What is microvascular thrombosis principally due to?

A

Disseminated intravascular coagulation (DIC)

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28
Q

When does DIC occur?

A

Systemic coagulation activation

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29
Q

DIC occurs in what conditions?

A 
Septicaemia
Malignancy 
Eclampsia 
Pancreatitis 
Major trauma 
Pregnancy
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30
Q

What does DIC cause?

A

Tissue ischaemia

  • gangrene
  • organ failure
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31
Q

Examples of vessel wall injury of virchows triad

A 
Trauma or surgery 
Venepuncture
Chemical irritation 
Heart valve disease or replacement 
Atherosclerosis
Indwelling catheters
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32
Q

Causes of hypercoagulable state

A 
Malignancy 
Pregnancy and post partum period
Oestrogen therapy 
Trauma or surgery of lower extremity, hip, abdomen or pelvis
IBD
Nephrotic syndrome 
Sepsis 
Thrombophilia
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33
Q

Causes of circulatory stasis in virchows triad

A 
AF
LVD
Immobility 
Paralysis 
Venous insufficiency or varicose veins 
Venous obstruction from tumour, obesity or pregnancy
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34
Q

Who should thrombophilia testing NOT be offered to?

A

Patients who are continuing on anticoagulation treatment
Patients who have provoked PE or DVT
Not in acute phase (within one month)
On unfractionated heparin

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35
Q

You cannot interpret protein C and S whilst on what? Why?

A

Warfarin

Vitamin K dependent

36
Q

Why cant you perform thrombophilia testing on unfractionated heparin?

A

Interferes with antithrombin levels and other tests

37
Q

Why is pregnancy a hypercoagulable state?

A

Resistance to activated protein C in 2nd and 3rd trimesters
Protein S activity decreases
Fibrinogen and factors II, VII, VIII and X increase
Levels and activity of fibrinolytic inhibitors increase

38
Q

Why is thrombophilia testing in pregnancy less reliable?

A

Already protein S deficient

39
Q

How does protein C work?

A

Activated protein C inactivates Va and VIIIa

40
Q

What is a cofactor of protein C?

A

Protein S

41
Q

Inheritance of protein C deficiency

A

Autosomal dominant

42
Q

Causes of thrombophilia

A

Protein C deficiency
Protein S deficiency
Activated protein C resistance/factor V Leiden
Antithrombin deficiency

43
Q

What is there a risk of in protein C deficiency?

A

Warfarin induced skin necrosis

44
Q

Acquired causes of protein C deficiency

A

Liver disease
Severe infection / septic shock / DIC
Post op state

45
Q

Where is protein C synthesised?

A

Vitamin K dependent synthesis in the liver

46
Q

Inheritance of protein S deficiency

A

Autosomal dominant

47
Q

How does protein S work?

A

Vitamin K dependent cofactor protein S which inactivates factor Va and VIIIa

48
Q

Causes of acquired protein S deficiency

A 
Pregnancy / oral contraceptives
DIC
Acute thromboembolic disease
Nephrotic syndrome 
Liver disease
49
Q

Penetrance of protein S deficiency

A

Variable

Risk increased by factor V leiden

50
Q

What is factor V leiden and how does it work?

A

Mutation on cleavage site of factor V

Do not have appropriate anticoagulant response to activated protein C

51
Q

Inheritance of factor V leiden

A

Autosomal dominant

52
Q

What causes increased risk of clots when have factor V leiden?

A

OCP

53
Q

How does antithrombin work?

A

Inhibits the coagulatiton proteases including IIa, Xa, IXa and XIa

54
Q

What augments antithrombins activity?

A

Heparin

55
Q

Inheritance of antithrombin deficiency?

A

Autosomal dominant

56
Q

Causes of acquired antithrombin deficiency

A

Nephrotic syndrome
Liver disease
DIC

57
Q

How would you treat antithrombin deficiency during pregnancy?

A

LMWH
Stop when labour begins
Continue 6/52 post
Can switch to warfarin

58
Q

What is antiphospholipid syndrome characterised by?

A

Venous thrombosis
Arterial thrombosis
Miscarriage

59
Q

Lab evidence of antiphospholipid antibodies (aPL)

A

Anticardiolipin antibodies

Lupus anticoagulant

60
Q

What can antiphospholipid syndrome be assosiated with?

A

SLE

61
Q

When does HIT usually appear?

A

Within 10 days of initiation

62
Q

What does HIT stand for?

A

Heparin induced thrombocytopenia

63
Q

What commonly drops on initiation of heparin (non immune)?

A

Platelets

64
Q

What types of heparin is there an increased incidence of HIT with?

A

Longer duration heparin

Unfractionated heparin

65
Q

Even though there is low platelets in HIT, what is there a high risk of?

A

Thrombosis 50-75%

66
Q

Treatment of PE

A

Immediate start of dalteparin
Start warfarin for 3 MONTHS
Continue dalteparin until INR in target range

67
Q

Typical blood picture of DIC

A

Low platelets
Prolonged APTT, prothrombin and bleeding time
Fibrin degradation products often raised
Schistocytes due to microangiopathic haemolytic anaemia

68
Q

Typical blood picture of warfarin administration

A

Prothrombin time prolonged
APTT normal
Bleeding time normal
Platelet count normal

69
Q

Typical blood picture of aspirin administration

A

Prothrombin time normal
APTT normal
Bleeding time prolonged
Platelet count normal

70
Q

Typical blood picture of heparin

A

Prothrombin time normal or prolonged
APTT prolonged
Bleeding time normal
Platelets normal

71
Q

What NOAC is preferred for patients with renal impairment due to minimal renal drug clearance?

A

Apixaban

72
Q

How long is warfarin treatment carried on for in a provoked DVT (e.g. recent surgery)?

A

3 months

73
Q

How long is warfarin treatment carried on for in an unprovoked DVT?

A

6 months

74
Q

What is factor V Leiden?

A

Activated protein C resistance

75
Q

If a patient presents with symptoms of a DVT of the calf, but the wells score is 1, what must be done next?

A
  1. D dimer. If +ve, order…..

2. Doppler USS of leg

76
Q

What are oral contraceptives a known risk factor for?

A

Thrombosis

77
Q

If a patient is on OCP and needs to undergo surgery, how long before the surgery should the pill be stopped and why is this done?

A

4 weeks before surgery

To prevent a pulmonary embolism

78
Q

If a patient is suspected of having a DVT, what should be performed?

A

two level DVT-wells score

79
Q

Features of the two level DVT wells score that count for 1 point each

A

Active cancer (ongoing, within 6 months or palliative)
Paralysis, paresis or recent plaster immobilisation of lower extremities
Recently bedridden for 3 days or more, or major surgery within 12 weeks requiring general or regional anaesthesia
Localised tenderness along the distribution of the deep venous system
Entire leg swollen
Calf swelling at least 3cm larger than asymptomatic side
Pitting oedema confined to symptomatic leg
Collateral superficial veins (non varicose)
Previously documented DVT

80
Q

What two level DVT wells score feature gives a score of -2?

A

An alternative diagnosis is at least as likely as DVT

81
Q

Clinical probability simplified score of the wells score

A

DVT likely - 2 points of more

DVT unlikely - 1 point or less

82
Q

What should be done if a DVT is likely (i.e. 2 or more points)?

A

Proximal leg vein USS within 4 hours
If -ve - D dimer

If cannot perform USS within 4 hours, D dimer should be performed and a LWMH administered (USS should be done within 24 hours)

83
Q

What should be done if a DVT is unlikely (I.e. 1 point or less)?

A

D dimer.
If +ve, arrange proximal leg USS within 4 hours
If USS cannot be performed under 4 hours, LWMH should be given (USS must be carried out within 24 hours)

84
Q

Treatment of DVT

A

Initially after diagnosis - LWMH or fondaparinux (at least 5 days or INR sorted. If active cancer - 6 months)
Warfarin within 24 hours diagnosis (for 3 months provoked, 6 months unprovoked)

85
Q

Should compression stockings be offered routinely to all patients with DVT?

A

NO

Haematology and Immunology (18 decks)

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