CVS: Thrombosis Flashcards
What is thrombosis?
Solid mass of blood formed within CVS involving interaction of endothelial cells, platelets and coagulation cascade that impedes blood flow
What is the differences between arterial and venous thrombosis?
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
Describe Virchow’s Triad
Development of venous thrombus depend on:
- Changes in normal blood flow
- Alterations in the constituents of blood
- Damage to endothelial layer
What are the causes of stasis as per Virchow’s Triad?
- Prolonged immobility (e.g. surgery, travel)
- Stroke
- Cardiac failure
- Pelvic obstruction
- Dehydration
- Hyperviscosity
- Polycythaemia
Describe endothelial damage as per Virchow’s Triad
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
Describe hypercoagulability in terms of Virchow’s triad
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
What components cause blood clots?
4 components:
- Endothelium
- Platelets
- Coagulation
- Fibrinolysis
Describe the process of normal haemostasis
- 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
What is the role of platelets in coagulation?
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
What is the role of platelets in fibrinolysis?
Platelet bound fibrinogen promotes fibrinolysis
What are the factors involved in blood coagulation?
- Factor 7,8,9, 10, 11, 12 and 2A
What are blood coagulation inhibitors and what factors do they inhibit?
Proteins C + S = Activated protein C, inhibits VIIIa and Va
Antithrombin III - Inhibits factors X and 2a (prothrombin)
What are the fibrinoloytic factors?
Plasmin, converts fibrin into FDPs
What is the clinical importance of above the knee DVT?
50% lead to PE (pulmonary embolism)
What are the incidence rates and causes of DVT?
1:1000 annual incidence
- Inherited thrombophilia
- Multifactorial risk
Describe symptoms of DVT
- Pain + tenderness of veins
- Limb swelling
- Superficial venous distension
- Increased skin temp
- Skin discolouration
All reflect obstruction to venous drainage
Describe the role of valves in blood flow
- 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
Describe post thrombotic syndrome
- 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%
What type of medications can prevent venous thrombosis?
Anti-coags (warfarin, heparin , direct oral)
What type of medications can reverse venous thrombosis?
Thrombolytics/Fibrinolytics - E.g. plasminogen activators, stretokinase - These ‘dissolve’ blood clots
Describe treatments of VTE
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
What investigations are done pre-treatment for VTE?
- 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
What are some new types of anticoagulants?
- Indirect Xa inhibitors - enhance antithrombin
- Fondaparinux
- Idraparinux
- Direct Xa inhibitors ORAL
- Rivaoxaban
- Apixaba
- Direct thrombin inhibitors ORAL
- Dabigatran
Describe proximal DVT and distal DVT
Proximal:
- Higher risk PE and post-thrombotic syndrome (pain, swelling, ulcers)
Distal:
- Rarely cause PE and post-thrombotic syndrome
