thrombosis

Question 1

how does a disorder of thrombosis usually present?

Answer 1

1. pulmonary embolism
2. deep vein thrombosis

Question 2

what are the symptoms of pulmonary embolism?

Answer 2

• Tachycardia
• Hypoxia
• Shortness of breath
• Chest pain
• Haemoptysis
• Sudden death

Question 3

what is the presentation of deep vein thrombosis

Answer 3

• Painful leg
• Swelling
• Red
• Warm
• May embolise to lungs causing pulmonary embolism
• Post-thrombotic syndrome

Question 4

what factors contribute to thrombosis?

Answer 4

1. blood (dominant in venous thrombosis)
2. vessel wall (dominant in arterial thrombosis)
3. blood flow (dominant in arterial and venous thrombosis)

Question 5

how does vessel wall affect thrombosis?

Answer 5

1. Many proteins active in coagulation are expressed on surface of endothelial cells and their expression altered in inflammation

Question 6

how does blood flow affect thrombosis?

Answer 6

1. Reduced flow (stasis) increases risk of thrombosis
   
   1. Surgery, pregnancy, long haul travel

Question 7

what do the 3 contributory factors to thrombosis make up?

Answer 7

virchow’s triad

Question 8

what is venous thrombosis called?

Answer 8

thrombophilia

Question 9

how does thrombophilia present?

Answer 9

• Thrombosis at young age
• ‘spontaneous thrombosis’- no clear risk factor
• Multiple thromboses
• Thrombosis whilst anticoagulated

Question 10

what can tip the balance towards venous thrombosis?

Answer 10

the decrease in fibrinolytic factors (decrease breakdown clots)

increase coagulant factors & platelets

Question 11

what are the main proteins involved in anticoagulation?

Answer 11

antithrombin

protein c

protein s

• antithrombin inactivates thrombin (F2a) and F10a
• Protein C and Protein S inactivate F5a and F8a

Question 12

what is the treatment of venous thrombosis?

Answer 12

1. Prevention (Thromboprophylaxis)
   
   • Assess and prevent risks
   • Prophylactic anticoagulant therapy
2. Reduce risk recurrence/ extension
   
   • Lower procoagulant factors
     
     • Warfarin, DOACs
   • Increase anticoagulant activity
     
     • Heparin

Question 13

when does anticoagulant therapy have therapeutic effect?

Answer 13

1. Venous thrombosis
   
   1. Initial treatment to minimise clot extension/ embolism (<3months)
   2. Long term treatment to reduce risk of recurrence
2. Atrial fibrillation
   
   1. To reduce risk of embolic stroke
3. Mechanical prosthetic heart valve

Question 14

when can anticoagulant therapy have preventative effects?

Answer 14

(thromboprophylaxis)

Following surgery, during hospital admission, during pregnancy

Question 15

what are the different types of heparin?

Answer 15

• Long chains- unfractionated (UFH)- intravenous administration, short half life
• Low molecular weight (LMWH)- subcutaneous administration

Question 16

what are the actions of unfractionated heparin?

Answer 16

• Enhancement of antithrombin
  
  • Inactivation of throbin (Hep binds AT + thrombin)
  • Inactivation of FXa (hep binds AT only)
  • (Inactivation of FIXa, FXIa, FXIIa)
• Increases APTT

Question 17

what are the actions of low molecular weight heparin?

Answer 17

• Contain pentasaccharide sequence for binding AT
• Predictable dose response in most cases so does not require monitoring -measure anti-Xa as doesn’t change APTT
• Action predominantly against factor Xa with some antithrombin effect

Question 18

what is an examples of a vitamin K antagonist?

Answer 18

warfarin

Question 19

how does warfarin work?

Answer 19

competes with Vit K reduction from epoxide to hydroquinone

reduces the production of functional coagulation factors

induces an anticoagulated state slowly

reversible

Question 20

what is the difficulty of VKA?

Answer 20

narrow therapeutic index and requires monitoring

Question 21

how can VKA be reversed?

Answer 21

• Reversed slowly by vit K administration- takes several hours
• Reversed rapidly by infusion of coagulation factors
  
  • POCC (prothrombin complex concentrate- contains factors II, VII, IX and XI)
  • FFP (fresh frozen plasma)

Question 22

what are the side effects of VKAs?

Answer 22

• Bleeding
• Skin necrosis
  
  • Severe protein C deficiency- 2-3 days after starting warfarin
  • Thrombosis predominantly in adipose tissue
• Purple syndrome
  
  • Disrupted atheromatous plaques bleed
  • Cholesterol emboli lodge in extremities
• Embryopathy
  
  • Chondrodysplasia punctata
    
    • Early fusion of epiphyses
    • Warfarin teratogenic in 1^st trimester

Question 23

what can cause resistance to warfarin?

Answer 23

• Lack of patient compliance
  
  • Measure warfarin levels
  • Proteins induce by vit k absence (PIVKA)
• Diet, increased vit K intake
• Increased metabolism Cyt P450 (CYP2C9)
• Reduced binding (VKORC1)

Question 24

what are some examples of direct oral anticoagulants (DOACS)?

Answer 24

rivaroxaban

apixaban

dabigatran

Question 25

where do DOACs act on the coagulation pathway?

Answer 25

Question 26

what is the difference between warfarin and DOACs?

Answer 26

Question 27

what therapeutic treatment is used in venous thrombosis?

Answer 27

* Initial treatment to minimise clot extension/ emoblisation (\<3month) * DOAC or LMWH for first few days followed by DOAC or warfarin (not started immediately as takes time to work and avoid skin necrosis) * Long term treatment to reduce risk of recurrence * DOAC or warfarin

Question 28

what therapeutic treatment is used in atrial fibrillation?

Answer 28

* To reduce risk of embolic stroke * DOAC or warfarin

Question 29

what therapeutic treatment can be used for mechanical prosthetic heart valve?

Answer 29

* Warfarin (DOACS not effective and should be avoided)

Question 30

when can an anticoagulant preventative be used and what type of drug is more appropriate?

Answer 30

* Lower doses used * Following surgery * LMWH or DOAC * During hospital admission * DOAC not effective for use as medical thromboprophylaxis * LMWH used * During pregnancy * LMWH * DOACs not safe in pregnancy – cross placenta