Thrombotic Disorder Flashcards
1
Q
The elements of homeostasis
A
- Primary homeostasis
- vasoconstriction
- platelet adhesion
- platelet aggregation - Blood coagulation
- insoluble fibrin formation
- fibrin cross linking - fibrinolysis
- involves urokinase and tPA interacting with factor XII to convert plasminogen -> plasmin
- plasmin then converts fibrin to fibrinogen/fibrin degradation products
2
Q
What is a thrombus?
A
A clot arising in a wrong place
3
Q
What is a thromboembolism?
A
Movement of a clot along a vessel
4
Q
Virchows triad
A
- stasis
- bed rest, travel - hypercoagulability
- pregnancy, trauma - vessel damage
- atherosclerosis
5
Q
Types of thrombus
A
Arterial
Venous
Microvascular
6
Q
What is an arterial thrombosis made up of?
A
White clot
- platelets
- fibrin
7
Q
What does an arterial thrombosis result in?
A
Ischaemia
Infarction
8
Q
What is arterial thrombosis principally secondary to?
A
Atherosclerosis
9
Q
Examples of arterial thrombosis
A
Coronary = MI, unstable angina
Cerebrovascular thromboembolism = stroke, TIA
Peripheral embolism = limb ischaemia
10
Q
Risk factors for arterial thrombosis
A
Age smoking sedentary lifestyle HTN DM obesity Hypercholestermia
11
Q
Treatment of acute presentation of arterial thrombosis
A
Thrombolysis
Antiplatelet/anticoagulation drugs
12
Q
Prevention of arterial thrombosis
A
Primary
- lifestyle modification
- treatment of vascular risk factors
Secondary
13
Q
What is a venous thrombosis made up of?
A
Red thrombus
- fibrin
- red cells
14
Q
What does a venous thrombosis result in?
A
back pressure
15
Q
What is a venous thrombosis principally due to?
A
Stasis
Hypercoagulability
16
Q
Examples of venous thrombosis
A
Limb DVT PE Visceral venous thrombosis Intracranial venous thrombosis Superficial thrombophlebitis
17
Q
Risk factors for venous thrombosis (stasis / hypercoagulability)
A
increasing age surgery obesity pregnancy hormonal therapy - COCP/HRT Immobility Systemic disease FH
18
Q
Systemic diseases related to venous thrombosis
A
Cancer Myeloproliferative neoplasms (MPNs) Autoimmune diseases (IBD, connective tissue diseases e.g. SLE)
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
20
Q
What is seen on a doppler USS in venous thrombosis?
A
DVT = thromboembosed vein enlarged
Non-compressible
Echogenic material seen
21
Q
Treatment aims of venous thrombosis
A
Prevention of clot extension
Prevention of clot embolization
Prevent clot recurrent in long term treatment
22
Q
Treatment of venous thrombosis
A
Anticoagulants - LMWH - Coumarins (warfarin) - DOACs Thrombolysis only in selected cases e.g. massive PE
23
Q
What does heritable thrombophilia give you an inherited predisposition to?
A
Venous thrombosis
24
Q
Pathology of Heritable thrombophilia
A
Common - factor V Leiden - Prothrombin G20210A Rare - antithrombin deficiency - protein C / S deficiency
25
What makes up a microvascular thrombosis?
Platelets and/or fibrin
26
What does microvascular thrombosis result in?
Diffuse ischaemia
27
What is microvascular thrombosis principally due to?
Disseminated intravascular coagulation (DIC)
28
When does DIC occur?
Systemic coagulation activation
29
DIC occurs in what conditions?
```
Septicaemia
Malignancy
Eclampsia
Pancreatitis
Major trauma
Pregnancy
```
30
What does DIC cause?
Tissue ischaemia
- gangrene
- organ failure
31
Examples of vessel wall injury of virchows triad
```
Trauma or surgery
Venepuncture
Chemical irritation
Heart valve disease or replacement
Atherosclerosis
Indwelling catheters
```
32
Causes of hypercoagulable state
```
Malignancy
Pregnancy and post partum period
Oestrogen therapy
Trauma or surgery of lower extremity, hip, abdomen or pelvis
IBD
Nephrotic syndrome
Sepsis
Thrombophilia
```
33
Causes of circulatory stasis in virchows triad
```
AF
LVD
Immobility
Paralysis
Venous insufficiency or varicose veins
Venous obstruction from tumour, obesity or pregnancy
```
34
Who should thrombophilia testing NOT be offered to?
Patients who are continuing on anticoagulation treatment
Patients who have provoked PE or DVT
Not in acute phase (within one month)
On unfractionated heparin
35
You cannot interpret protein C and S whilst on what? Why?
Warfarin
| Vitamin K dependent
36
Why cant you perform thrombophilia testing on unfractionated heparin?
Interferes with antithrombin levels and other tests
37
Why is pregnancy a hypercoagulable state?
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
Why is thrombophilia testing in pregnancy less reliable?
Already protein S deficient
39
How does protein C work?
Activated protein C inactivates Va and VIIIa
40
What is a cofactor of protein C?
Protein S
41
Inheritance of protein C deficiency
Autosomal dominant
42
Causes of thrombophilia
Protein C deficiency
Protein S deficiency
Activated protein C resistance/factor V Leiden
Antithrombin deficiency
43
What is there a risk of in protein C deficiency?
Warfarin induced skin necrosis
44
Acquired causes of protein C deficiency
Liver disease
Severe infection / septic shock / DIC
Post op state
45
Where is protein C synthesised?
Vitamin K dependent synthesis in the liver
46
Inheritance of protein S deficiency
Autosomal dominant
47
How does protein S work?
Vitamin K dependent cofactor protein S which inactivates factor Va and VIIIa
48
Causes of acquired protein S deficiency
```
Pregnancy / oral contraceptives
DIC
Acute thromboembolic disease
Nephrotic syndrome
Liver disease
```
49
Penetrance of protein S deficiency
Variable
| Risk increased by factor V leiden
50
What is factor V leiden and how does it work?
Mutation on cleavage site of factor V
| Do not have appropriate anticoagulant response to activated protein C
51
Inheritance of factor V leiden
Autosomal dominant
52
What causes increased risk of clots when have factor V leiden?
OCP
53
How does antithrombin work?
Inhibits the coagulatiton proteases including IIa, Xa, IXa and XIa
54
What augments antithrombins activity?
Heparin
55
Inheritance of antithrombin deficiency?
Autosomal dominant
56
Causes of acquired antithrombin deficiency
Nephrotic syndrome
Liver disease
DIC
57
How would you treat antithrombin deficiency during pregnancy?
LMWH
Stop when labour begins
Continue 6/52 post
Can switch to warfarin
58
What is antiphospholipid syndrome characterised by?
Venous thrombosis
Arterial thrombosis
Miscarriage
59
Lab evidence of antiphospholipid antibodies (aPL)
Anticardiolipin antibodies
| Lupus anticoagulant
60
What can antiphospholipid syndrome be assosiated with?
SLE
61
When does HIT usually appear?
Within 10 days of initiation
62
What does HIT stand for?
Heparin induced thrombocytopenia
63
What commonly drops on initiation of heparin (non immune)?
Platelets
64
What types of heparin is there an increased incidence of HIT with?
Longer duration heparin
| Unfractionated heparin
65
Even though there is low platelets in HIT, what is there a high risk of?
Thrombosis 50-75%
66
Treatment of PE
Immediate start of dalteparin
Start warfarin for 3 MONTHS
Continue dalteparin until INR in target range
67
Typical blood picture of DIC
Low platelets
Prolonged APTT, prothrombin and bleeding time
Fibrin degradation products often raised
Schistocytes due to microangiopathic haemolytic anaemia
68
Typical blood picture of warfarin administration
Prothrombin time prolonged
APTT normal
Bleeding time normal
Platelet count normal
69
Typical blood picture of aspirin administration
Prothrombin time normal
APTT normal
Bleeding time prolonged
Platelet count normal
70
Typical blood picture of heparin
Prothrombin time normal or prolonged
APTT prolonged
Bleeding time normal
Platelets normal
71
What NOAC is preferred for patients with renal impairment due to minimal renal drug clearance?
Apixaban
72
How long is warfarin treatment carried on for in a provoked DVT (e.g. recent surgery)?
3 months
73
How long is warfarin treatment carried on for in an unprovoked DVT?
6 months
74
What is factor V Leiden?
Activated protein C resistance
75
If a patient presents with symptoms of a DVT of the calf, but the wells score is 1, what must be done next?
1. D dimer. If +ve, order.....
| 2. Doppler USS of leg
76
What are oral contraceptives a known risk factor for?
Thrombosis
77
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?
4 weeks before surgery
| To prevent a pulmonary embolism
78
If a patient is suspected of having a DVT, what should be performed?
two level DVT-wells score
79
Features of the two level DVT wells score that count for 1 point each
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
What two level DVT wells score feature gives a score of -2?
An alternative diagnosis is at least as likely as DVT
81
Clinical probability simplified score of the wells score
DVT likely - 2 points of more
| DVT unlikely - 1 point or less
82
What should be done if a DVT is likely (i.e. 2 or more points)?
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
What should be done if a DVT is unlikely (I.e. 1 point or less)?
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
Treatment of DVT
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
Should compression stockings be offered routinely to all patients with DVT?
NO
