CVS: Thrombosis

Question 1

What is thrombosis?

Answer 1

Solid mass of blood formed within CVS involving interaction of endothelial cells, platelets and coagulation cascade that impedes blood flow

Question 2

What is the differences between arterial and venous thrombosis?

Answer 2

Arterial:

• Mostly result from atheroma rupture (MI, stroke)
• Platelet-rich ‘white’ thrombosis
• Block downstream arteries

Venous:

• Result from stasis or a hypercoagulant state (DVT)
• Platelet-poor ‘red’ thrombus
• May move to lungs

Question 3

Describe Virchow’s Triad

Answer 3

Development of venous thrombus depend on:

• Changes in normal blood flow
• Alterations in the constituents of blood
• Damage to endothelial layer

Question 4

What are the causes of stasis as per Virchow’s Triad?

Answer 4

• Prolonged immobility (e.g. surgery, travel)
• Stroke
• Cardiac failure
• Pelvic obstruction
• Dehydration
• Hyperviscosity
• Polycythaemia

Question 5

Describe endothelial damage as per Virchow’s Triad

Answer 5

Primary plug:

• When endothelial layer damaged, collagen becomes exposed
• Collagen + Vw factor can bind + activate platelets, platelets enlarge and degranulate, expose a phospholipid surface and express new surface receptors
  
  • Platelets when activated expose a negative phospholipid charge, that aids with secondary haemostasis
• Tissue factor + collagen can stimulate coagulation

Secondary plug:

• Thrombus consists of mesh of platelets + fibrin with entrapped blood cells
• Once thrombin made, cascade of clotting factor activation magnified

Question 6

Describe hypercoagulability in terms of Virchow’s triad

Answer 6

Alterations in constituents of blood components

⬇️Fibrinolytic factors, anticoagulant proteins/activity:

• ARIII deficiency
• Protein C + S deficiencies
• FV Leiden mutation is a thrombophilia (resistance to anticoagulant complex - activates protein C APC)

⬆️Coagulation factors, platelets:

• Malignancy increases clotting factors e.g. tissue factor, FXa, thrombin

Question 7

What components cause blood clots?

Answer 7

4 components:

• Endothelium
• Platelets
• Coagulation
• Fibrinolysis

Question 8

Describe the process of normal haemostasis

Answer 8

• Vessel constriction
• Formation of unstable platelet plug (primary haemostasis)
  
  • Platelet ahesion
  • Plate aggregation
• Stabilisation of plug with fibrin (secondary haemostasis)
  
  • Blood coagulation
• Dissolution of clot and vessel repair
  
  • Fibrinolysis

Question 9

What is the role of platelets in coagulation?

Answer 9

Tissue damage + inflammation leads to endothelium layer becoming exposed.

Circulating Vw factor can bind to receptors on this layer, and so can platelets, which activates further platelets to the site of damage.

Platelets can bind to other platelets at the site of damage, and therefore aggregate forming a fibrin clot

Question 10

What is the role of platelets in fibrinolysis?

Answer 10

Platelet bound fibrinogen promotes fibrinolysis

Question 11

What are the factors involved in blood coagulation?

Answer 11

• Factor 7,8,9, 10, 11, 12 and 2A

Question 12

What are blood coagulation inhibitors and what factors do they inhibit?

Answer 12

Proteins C + S = Activated protein C, inhibits VIIIa and Va

Antithrombin III - Inhibits factors X and 2a (prothrombin)

Question 13

What are the fibrinoloytic factors?

Answer 13

Plasmin, converts fibrin into FDPs

Question 14

What is the clinical importance of above the knee DVT?

Answer 14

50% lead to PE (pulmonary embolism)

Question 15

What are the incidence rates and causes of DVT?

Answer 15

1:1000 annual incidence

• Inherited thrombophilia
• Multifactorial risk

Question 16

Describe symptoms of DVT

Answer 16

• Pain + tenderness of veins
• Limb swelling
• Superficial venous distension
• Increased skin temp
• Skin discolouration

All reflect obstruction to venous drainage

Question 17

Describe the role of valves in blood flow

Answer 17

• Valves in veins prevent backflow of blood
• Contraction of nearby muscles squashes veins, acting as a pump to return blood to heart
• Blood tends to eddy around valves increasing risk of stasis

Question 18

Describe post thrombotic syndrome

Answer 18

• Chronic complication, develops in 20-50% DVT patients
• Results from venous hypertension
• Reduces calf muscle perfusion
• Increases tissue permeability
• Risk increases with obesity + age
• Pain, swelling, oedema
• Redness
• Thickening of skin
• Ulcers in 5-10%

Question 19

What type of medications can prevent venous thrombosis?

Answer 19

Anti-coags (warfarin, heparin , direct oral)

Question 20

What type of medications can reverse venous thrombosis?

Answer 20

Thrombolytics/Fibrinolytics - E.g. plasminogen activators, stretokinase - These ‘dissolve’ blood clots

Question 21

Describe treatments of VTE

Answer 21

Cardiovascularly stable with acute VTE:

• Anticoagulate
  
  • Immediate anticoagulant effect
  • Heparin then warfarin/ DOAC or immediate DOAC - Rivaroxaban or apixaban

Circulatory collapse due to PE:

• Thrombolysis
  
  • Alteplase (tissue plasminogen activator)
  • Streptokinase
  • Followed by heparin and warfarin or other - prevent recurrence

Question 22

What investigations are done pre-treatment for VTE?

Answer 22

• Clotting screen
  
  • Prothrombin time (INR)
  • Partial thromboplastin time
  • Thrombin time
• FBC
• Urea + electrolytes
  
  • Usually part of routine screen - to know creatinine clearance
• Liver function tests - If clinical suspicion of liver disease

Question 23

What are some new types of anticoagulants?

Answer 23

• Indirect Xa inhibitors - enhance antithrombin
  
  • Fondaparinux
  • Idraparinux
• Direct Xa inhibitors ORAL
  
  • Rivaoxaban
  • Apixaba
• Direct thrombin inhibitors ORAL
  
  • Dabigatran

Question 24

Describe proximal DVT and distal DVT

Answer 24

Proximal:

• Higher risk PE and post-thrombotic syndrome (pain, swelling, ulcers)

Distal:

• Rarely cause PE and post-thrombotic syndrome