(44) Thrombosis and risk factors Flashcards
(82 cards)
1
Q
What are the 3 components of Virchow’s triad?
A
- blood flow
- vascular endothelium
- blood composition
2
Q
What is the primary pathological abnormality in arterial thrombosis?
A
Atherosclerosis of the vessel wall
3
Q
What do you get in arterial thrombosis?
A
- atherosclerosis
- rupture of atheromatous plaque
- endothelial injury
- platelet aggregation and platelet thrombi
4
Q
In arterial thrombosis, what plays an important role in final vessel occlusion?
A
Platelet aggregation and platelet thrombi
5
Q
What are the risk factors for arterial thrombosis?
A
- smoking
- hypertension
- hypercholesterolaemia
- diabetes
- family history
- obesity
- physical inactivity
- age
- male sex
6
Q
What does the pathogenesis in venous thrombosis involve?
A
- venous stasis
- hypercoagulable state
7
Q
The thrombi in venous thrombosis are composed of what?
A
Predominantly composed of fibrin with a lesser role for platelet accumulation and aggregation
8
Q
Venous thromboembolism (VTE) are frequently unrecognised. What percentage of DVT are clinically silent?
A
80%
VTE is a silent killer
9
Q
In which vein is there a clot in DVT?
A
The femoral vein of the leg
PE in pulmonary artery
10
Q
How many patients with proximal DVT have (asymptomatic) PE?
A
About 50%
11
Q
DVT is found in how many patients with PE?
A
Over 80%
12
Q
What is the incidence of VTE?
A
1 per 1000
13
Q
How many cases of PE present as sudden death?
A
Up to 20%
14
Q
30% of those with VTE develop what?
A
Recurrent VTE in 10 years
15
Q
28% of those with VTE develop what?
A
Post thrombotic syndrome
16
Q
What is the mortality of promptly diagnosed and adequately treated PE?
A
2% (direct)
17
Q
How many deaths does VTE cause in the UK?
A
60,000
32,000 due to hospital admissions, 25,000 preventable
18
Q
How is hospital-acquired VTE defined?
A
Any VTE within 90 days of discharge
- 2/3rds of all VTE
- markedly underestimated
19
Q
Outline the strategies concerning VTE
A
- prophylaxis (consistent risk assessment and appropriate prophylaxis)
- treatment (prompt diagnosis and guideline-led unified care)
20
Q
Describe the care pathway in hospital patients concerning VTE
A
- patient admitted to hospital
- assess VTE risk
- assess bleeding risk
- balance risks of VTE and bleeding and act appropriately
- reassess risks of VTE and bleeding
21
Q
How often should the risks of VTE and bleeding in hospital patients be reassessed?
A
Within 24 hours of admission and whenever the clinical situation changes
22
Q
In hospital patients, the risk of VTE and bleeding should be balanced. What is the appropriate action after this?
A
Offer VTE prophylaxis if appropriate. Do not offer pharmacological VTE prophylaxis if patient has any risk factor for bleeding and risk of bleeding outweighs risk of VTE
23
Q
What are the risk factors for VTE?
A
- active cancer or cancer treatment
- over 60 years
- critical care admission
- dehydration
- thrombophilias
- significant medical comorbidities
- surgery
- major trauma
- personal history of VTE
- use of HRT
- use of oestrogen-containing contraceptive therapy
- varicose veins with phlebitis
- obesity
- pregnancy and postnatal periods
- immobility
- first degree relative with VTE
24
Q
What 2 things must be balanced? (concerning VTE and bleeding)
A
- procoagulants
- anti-coagulants
25
What is involved in pro coagulation?
- platelets
| - clotting factors
26
What is involved in anticoagulation?
- protein C
- protein S
- anti-thrombin III
- fibrinolytic system
27
Give some general advice concerning hospital patients and VTE
- do not allow the patients to become dehydrated unless clinically indicated
- encourage patients to mobilise as soon as possible
- do not regard aspirin or other anti-platelet drugs as prophylaxis for VTE
28
Describe the pressure differences at different parts of the leg (Doppler)
```
upper thigh = 8mmHg
lower thigh = 10mmHg
popliteal = 8mmHg
calf = 14mmHg
ankle = 18mmHg
```
29
What are the pharmacological prophylaxis for VTE?
- "low dose" low molecular weight heparin
- fondaparinux (synthetic pentasaccharide)
- newer anticoagulants (rivaroxaban, dabigatran)
30
Which drug is a direct inhibitor of factor Xa? (an anticoagulant)
Rivaroxaban (apixaban)
31
Which drug is a direct thrombin inhibitor? (an anticoagulant)
Dabigatran
32
What is fondaparinux?
An anticoagulant medication chemically related to low molecular weight heparins
- a synthetic pentasaccharide
33
What are low molecular weight heparins?
Class of anticoagulant medications - used in the prevention and treatment of venous thromboembolism
34
What is the Wells score/Wells criteria used for?
Used for clinical prediction
- diagnosing DVT
- diagnosing PE
35
What is a D-dimer test used for?
Used to help exclude thrombus (exclude DVT/VTE)
36
What does a positive D-dimer indicate?
The presence of an abnormally high level of cross-linked fibrin degradation products in your body. Shows there has been significant thrombus formation and breakdown in the body, but it does not identify the location or cause. An elevated D-dimer may be due to a VTE or DIC but it may also be due to a recent surgery, or trauma, infection etc
A negative result practically rules out thrombosis
37
What is a D-dimer?
A fibrin degradation product, present after a clot is degraded by fibrinolysis.
- contains D fragments of the fibrin protein
38
What do you look for on ultrasound to detect DVT?
- loss of flow signal
- intravascular defects
- non-collapsing vessels in the venous system
Duplex scanning with compression will aid to detect any thrombus
39
Is ultrasound useful for diagnosing thrombi?
Highly sensitive and specific for diagnosing DVT
40
What types of scans can be used for diagnosing DVT?
- ultrasound
- spiral/multislice CT
- VQ scan
41
What might a V/Q mismatch indicate?
A potential pulmonary embolism
42
Describe how low molecular weight heparin (LMWH) is used in treatment for VTE?
- doses fixed by body weight
- usually once a day by s/c injection
- treat for at least 5 days
- overlap with warfarin until INR >2.0 for 2 consecutive days
43
Give 2 examples of LMWH and how they are used
- enoxaparin 1.5mg/kg subcutaneous one daily
| - tinzaparin 175u/kg subcutaneous once daily
44
Describe the treatment pathway for uncomplicated DVT/PE in whom pregnancy excluded
- suspected DVT/PE (check contraindication to anticoagulation)
- treat with single dose LMWH (sub cut - see enoxaparin dosing chart)
- confirm diagnosis
- LMWH (min. 5 days)
- start warfarin (see dosing chart)
- start patient-held anticoagulant book + inpatient warfarin chart
- overlap warfarin and heparin until 2 therapeutic INR results (>2)
45
What should you use instead of LMWH if there is a need for quick anticoagulation or the rapid reversal of is required?
Unfractionated heparin intravenously
46
Name a parenteral anticoagulant
Fondaparinux
47
What does parenteral mean?
Administration by injection
48
Name an oral anticoagulant
- rivaroxaban
- apixaban
- dabigatran
49
Name a direct thrombin inhibitor
Dabigatran
50
Name anticoagulants that have direct anti-Xa activity
- rivaroxaban
- apixaban
- endoxaban
51
What does NOAC stand for?
New oral anticoagulant
52
How much does the dose of warfarin vary?
40 fold
53
How do the does of NOACs vary?
- dose is uniform in most patients
- no need for routine monitoring: predictable effect
- all agents have dose reduction recommend in specific populations
54
In which groups is the dose of NOAC recommended to be lowered?
- very elderly
- renal impairment
- for VTE prevention
- for AF
55
Do NOACs have a slow of fast onset of action?
Rapid onset of action
initiation may be done directly with rivaroxaban and apixaban with no need for LMWH
56
Briefly describe the management of the first episode of proximal vein DVT or PE
Treat for 3-6 months
For warfarin, target INR = 2.5
57
Briefly describe the management of recurrent episodes of VTE
Treat with long term anticoagulation
58
Briefly describe the management of proximal DVT or PE that has occurred in the absence of reversible risk factor
Consider long term anticoagulation
59
How should the target INR change in recurrent VTE on therapeutic anticoagulation
Increase target INR to 3.5 for warfarin
60
In which conditions should you consider long term anticoagulation?
For recurrent episodes of VTE, and in proximal DVT or PE that has occurred in the absence of reversible risk factor
61
What does INR show?
The higher the INR, the thinner the blood
The lower the INR, the thicker the blood
1 = normal blood
62
Define thrombophilia
Familial or acquired disorders of the haemostatic mechanism which are likely to predispose to thrombosis
Inherited abnormalities must co-segregate with clinical thrombosis in the pedigree
63
Give an alternative definition of thrombophilia
Patients who develop VTE
- spontaneously
- of disproportionate severity
- recurrently
- at an early age
64
Name 6 heritable thrombophilias
- antithrombin deficiency
- protein C deficiency
- protein S deficiency
- activated protein C resistance/FV Leiden
- dysfibrinogenaemia
- prothrombin 20210A
65
Name a type of acquired thrombophilia
Antiphospholipid syndrome (APS - also known as Hughes syndrome)
66
What are the clinical features of thrombophilia?
- DVT
- PE
- superficial thrombophlebitis
- thrombosis of cerebral, axillary, portal, mesenteric veins
- arterial thrombosis (APS, only)
- coumarin induced skin necrosis (PC deficiency)
- obstetric complications: foetal wastage (APS)
67
What converts fibrinogen to fibrin?
Thrombin
68
What converts prothrombin to thrombin?
Factor Va
69
What does the activated protein C/protein S complex?
Degrades factors Va and VIIIa by proteolysis
70
What does the factor V Leiden mutation cause?
Protein C is unable to inactivate factor Va when the factor V Leiden mutation is present
71
Factor V Leiden is associated in most cases with which mutation?
A single point mutation in the factor V gene: G to A1691
72
What amino acid change occurs in factor V Leiden?
Arg506 is replaced by Gln (glutamine), rendering FV relatively resistant to cleavage by APC
73
What is the most common familial thrombophilia?
Factor V Leiden
74
Geographically, where is factor V Leiden found?
5-8% European population are heterozygous
Not found in Far East and Africa
75
What increased risk do heterozygotes of factor V Leiden have of venous thrombosis?
3-5 fold OR for venous thrombosis
76
What increased risk do homozygotes of factor V Leiden have of venous thrombosis?
30-50 fold OR for venous thrombosis
77
What is prothrombin 20210A?
- point mutation in 3' untranslated region of prothrombin gene
- associated with increased prothrombin levels
- 3 fold increase in venous thrombosis
78
Geographically, where do prothrombin 20210A occur?
- occurs in 1-2% health UK population
| - rare in Asia and Africa
79
What is antiphospholipid syndrome?
An autoimmune, hypercoagulable state caused by antiphospholipid antibodies. Predisposed to thrombi in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia
80
How is antiphospholipid syndrome defined?
Antiphospholipid antibodies (lupus anticoagulant or anticardiolipid antibody) on at least 2 occasions 8 weeks apart in association with venous thrombosis or arterial thrombosis or recurrent foetal loss
May be primary or secondary
81
For selected patients with arterial events of recurrent miscarriage, which thrombophilia screening tests should you do?
Antiphospholipid antibody screen only
82
In which situations should you not do thrombophilia screening?
In acute VTE
When the patient is already on anticoagulants
Pregnancy and oral contraceptive pills also have an effect
