Clinical aspects of thrombosis

Question 1

What is thrombosis

Answer 1

Blood in BVs should be fluid

Inappropriate blood coagulation within a vessel is called thrombosis

Question 2

Appropriate blood coagulation occurs when

Answer 2

Blood escapes from a vessel

-failure of this results in bleeding

Question 3

Types of thrombosis and properties

Answer 3

In the arterial circulation
-high pressure system
-platelet rich
In the venous circulation
-low pressure system
-fibrin rich

Question 4

Arterial thrombosis can cause

Answer 4

MI

Thrombotic stroke

Question 5

Venous thrombosis can cause

Answer 5

Leg deep vein thrombosis (MI)
Pulmonary embolism (PE)

Question 6

Treatment for arterial thrombosis

Answer 6

Antiplatelet drugs

Question 7

Treatment for venous thrombosis

Answer 7

Anticoagulant drugs

Question 8

Formation of arterial thrombosis

Answer 8

Atherosclerotic plaque

• initial fatty streak
• plaque enlargement
• turbulence due to protrusion into lumen
• loss of endothelium and collagen exposure
• platelet activation and adherence
• fibrin meshwork deposition and red cell entrapment
• more turbulence, more platelet and fibrin deposition
• thrombus of layers of platelets, fibrin and red cells

Question 9

Main risk factors for arterial thrombosis

Answer 9

Family history
Diabetes mellitus
Hypertension
Hyperlipidaemia
Smoking
Atrial fibrillation for stroke

Question 10

Other risk factors for arterial thrombosis

Answer 10

Male sex
Polycythaemia, gout
Collagen vascular disease
Lupus anticoagulant, high FVIII, high fibrinogen

Question 11

Management of arterial thrombosis

Answer 11

Stroke and MI are in the top 5 of causes of death.
Lifestyle
-quit smoking
-exercise
-diet
-weight control
Antithrombotics: primary prevention in pts with atrial fibrillation.

Question 12

Treatment options for arterial thrombosis

Answer 12

Antiplatelet agents: start acutely, continue long term
Thombolysis
Invasive
Rehabilitation in all cases
Secondary prevention

Question 13

Antiplatelet agents for arterial thrombosis

Answer 13

Aspirin

Copidogrel

Question 14

Aspirin

Answer 14

Irreversible inhibitor of cyclooxygenase (COX1), inhibiting the production of thromboxane.
Inhibition lasts for the lifespan of platelet: ≈ 1 week.
Risk reduction of non fatal vascular event by 30%.
Risk reduction of fatal vascular event by 15%.

Question 15

Clopidogrel

Answer 15

Irreversible ADP mediated platelet inhibition.
Inhibition lasts for the lifespan of platelet: ≈ 1 week.
Decreases the risk of MI 18%,
Risk of coronary stent thrombosis/recurrent stroke by 30%

Question 16

Thrombolysis indications

Answer 16

MI
stroke within 3 hours,
Life-threatening PE

Question 17

Thombolysis drugs

Answer 17

ALTEPLASE (rt-PA, tissue-type plasminogen activator)
STREPTOKINASE
Others
Main side effect: bleeding

Question 18

Invasive arterial thrombosis treatment

Answer 18

Percutaneous coronary intervention (cardiac stenting)
Combined with 3 – 12 months aspirin + clopidogrel
Coronary artery bypass grafting
Carotid endarterectomy

Question 19

Rehabilitation for arterial thrombosis

Answer 19

Stroke: swallowing, malnutrition, mobilisation

Question 20

Secondary prevention of arterial thrombosis

Answer 20

Lifestyle
-exercise, stop smoking, diet, weight control, safe alcohol use.
Blood pressure control
Cholesterol lowering
Diabetic control
Antithrombotic therapy in stroke associated with atrial fibrillation

Question 21

Atrial fibrillation

Answer 21

Irregularly irregular heart rhythm
4% in >60years, 8% in >80years
Left atrial thrombus
Embolisation leads to stroke
Impaired cardiac output

Question 22

Treatment for atrial fibrillation

Answer 22

DC cardioversion
Heart rate control: Beta blockers, Ca channel blocker, Digoxin, AV junction ablation
Anticoagulation

Question 23

How does atrial fibrillation cause stroke?

Answer 23

1. Blood pools in atria
2. Blood clot forms
3. Blood clot breaks off
4. Blood clot travels to brain and blocks a cerebral artery causing a stroke

Question 24

Venous thromboembolism

Answer 24

DVT –> PE –> pulmonary hypertension (or death) –> chronic PE (can lead to death)
DVT –> deep vein insufficiency –> post-thrombotic syndrome –> leg ulcers

Question 25

Formation of venous thrombosis

Answer 25

``` *Virchow's triad* Clotting factors and blood -hypercoagulability (inherited or acquired) Vessel wall -vascular damage (acquired) Flow -stasis (acquired) ```

Question 26

Risk factors for venous thrombosis

Answer 26

Heritable Aquired Mixed

Question 27

Heritable risk factors for venous thrombosis

Answer 27

``` Antithrombin deficiency Protein C deficiency Protein S deficiency Factor V Leiden Prothrombin mutation 20210 A Dysfibrinogenaemia Homocysteinuria ```

Question 28

Acquired risk factors for venous thrombosis

Answer 28

``` Age Previous VTE Antiphospholipid syndrome Paralysis/ immobility Major trauma/ surgery Malignancy Pregnancy Chemotherapy HRT Combined oral contraceptive pill Obesity Paroxysmal nocturnal haemoglobinuria Heparin induced thrombocytopenia ```

Question 29

Mixed risk factors for venous thrombosis

Answer 29

``` Raised FVIII Raised FIX Raised XI Raised fibrinogen Hyperhomocysteinaemia ```

Question 30

Heritable thrombophilias typically associated with

Answer 30

idiopathic VTE at young age

Question 31

Incidence of venous thrombosis

Answer 31

``` 1 in 1000 overall Higher in older age 3 in 10.000 age 40 26 in 10.000 age 80 -therefore, presence of a heritable thrombophilia only gives a small increase in absolute risk ```

Question 32

How many pts with a strong family history is a thrombophilic defect identified

Answer 32

Only 50%

Question 33

Risk factors for venous thrombosis

Answer 33

``` COCP Increases with age Pregnancy FV Leiden Immobilisation without prophylaxis Hospitilisation -multifactorial disorder occurring through the interplay of one or more genetic and/or environmental risk factors when a critical thrombotic threshold is reached ```

Question 34

Assessing risk for venous thrombosis in pts

Answer 34

risk for each patient must be assessed by looking for individual risk factors present

Question 35

Hospitilisation as risk factor for venous thrombosis

Answer 35

150 fold increased risk compared to community

Question 36

Epidemiology hospitalised pts and venous thrombosis

Answer 36

Venous thromboembolism in hospitalised patients causes 25,000 – 32,000 deaths each year in the UK Many of these deaths are preventable with thromboprophylaxis 5 times the number of deaths of acquired hospital infections

Question 37

Reducing risk of venous thromboembolism in hospital

Answer 37

Undergo assessment of VTE and bleeding risk using criteria in the ‘national tool’ Be offered verbal and written information on VTE prevention as part of admissions process Have VTE and bleeding risk reassessed with 24hrs of admission to hospital If at risk of VTE, be offered prophylaxis in accordance with NICE guidance Be offered verbal and written information on VTE prevention as part of discharge process Where appropriate be offered extended prophylaxis in accordance with NICE guidance

Question 38

Venous thombosis prevention strategies

Answer 38

Adequate hydration Early mobilisation Mechanical prophylaxis Chemical prophylaxis prevents 50 – 70% of VTE

Question 39

Mechanical prophylaxis (venous thrombosis prevention)

Answer 39

All surgical patients at risk of VTE Graduated elastic compression hosiery Intermittent pneumatic compression (flowtron boots or foot pumps)

Question 40

Chemical prophylaxis (venous thrombosis prevention)

Answer 40

Low molecular weight heparin | Direct oral anticoagulants

Question 41

Risk assessment and dental surgery

Answer 41

NICE guidance for adults (18 years and older) admitted to hospital as inpatients or formally admitted to a hospital bed for day-case procedures. Do not routinely offer pharmacological or mechanical VTE prophylaxis to patients undergoing a surgical procedure with local anaesthesia by local infiltration with no limitation of mobility. All other patients must be risk assessed on admission (or at pre-assessment clinic) and reassessed within 24 hours

Question 42

Acute VTE - treatment options

Answer 42

Anticoagulation Thrombolysis Thrombectomy Inferior vena cava (IVC) filter

Question 43

Long-term VTE - treatment options

Answer 43

Anticoagulation | Stockings

Question 44

Duration of treatment of VTE

Answer 44

3 months after provoked event Long term after 2nd idiopathic thrombosis Long term after 1st life threatening PE Consider long term after 1st idiopathic thrombosis depending on risk factors for recurrence and bleeding

Question 45

Duration of treatment of VTE

Answer 45

3 months after provoked event Long term after 2nd idiopathic thrombosis Long term after 1st life threatening PE Consider long term after 1st idiopathic thrombosis depending on risk factors for recurrence and bleeding

Question 46

Summary - venous thrombosis

Answer 46

Multifactorial disease Associated with significant mortality/morbidity Prevention essential, especially in hospital setting Treatment mainly with anticoagulants -optimum duration debated -associated with increased risk of bleeding

Question 47

Summary of thrombosis

Answer 47

Both venous and arterial thrombosis have high morbidity and mortality. Prevention is essential in both Treatment is with systemic anticoagulation in venous thrombosis and antiplatelet agents in arterial thrombosis