Thrombosis Flashcards
What does coagulation prevent?
→Blood loss
What is coagulation?
→An immunological response
What do anticoagulants prevent?
→ Thrombosis
What are the steps for the contact activation pathway?
Factor 12 → activated factor 12
activated factor 12 → Activated factor 11
Activated factor 11 → Activated factor 9
Activated factor 9 → Activated factor 10
Pro thrombin → Thrombin
What is the intrinsic pathway activated by?
→ Damaged surfaces
What are the steps for the extrinsic pathway?
Factor 7 → activated factor 7
Tissue factor → activated factor 10
Prothrombin → Thrombin
What is the extrinsic pathway activated by?
→ trauma
What is reverse thrombosis?
→ Fibrinolysis
What happens when tissue is damaged/inflammation?
→ Platelets become activated
→ Fibrinogen turns into fibrin
What does arterial thrombosis result from?
→ Atheroma rupture or damage to the endothelium
What is arterial thrombosis described as?
→ Platelet rich ‘white’ thrombosis
What can arterial thrombosis do to arteries downstream?
→ May block arteries downstream
What does venous thrombosis result from?
→ From stasis or a hypercoagulant state DVT
What is venous thrombosis described as?
→ Platelet poor ‘red’ thrombosis
What can venous thrombosis do?
→ move to the lungs
What do endothelial cells express?
→ Factors inhibiting coagulation
What does tissue plasminogen activator do?
→ Activates Plasminogen to Plasmin
→ Plasmin carries out lysis of the clot to D Dimers.
What do subendothelial cells release if they are disturbed?
→ Tissue factor
→ Von Willebrand Factor
What is Virchow’s triad?
STASIS
→ Static blood lacks kinetic energy and tends to clot
HYPER-COAGULANT STATE
→ Infection, hereditary or drugs (HRT)
ENDOTHELIAL DAMAGE
→Surgery or cannula
What do valves do?
→ Prevent backflow of blood
How is blood returned to the heart in veins?
→ Contraction of nearby muscles squash veins
What does blood do around valves?
→ Tends to eddy around valves which increases the risk of stasis
What is DVT?
→ If a venous return in blocked the affected organ becomes congested with fluid
What is the difference between distal DVT and proximal DVT?
→ Distal rarely causes pulmonary embolism
→ Proximal has a higher risk of pulmonary embolism
What are the 4 things that can happen to a thrombus?
RESOLUTION
→ thrombolysis
EMBOLISM
→ moves to another location + blocks vessel
ORGANIZED
→ becomes covered by endothelium
RECANALISED AND ORGANISED
What happens with a small venous thrombolus?
→ Slight VQ mismatch or small infarct zone
What happens with a large venous thrombolus?
→ Saddle embolism blocks both arteries
→ can cause rapid death
How does platelet adherence happen?
→ VWF on subendothelial cells activates/binds platelets
→ Circulating VWFs may bind to exposed subendothelial cells
→ Activated endothelial cells can express VWF
How does platelet activation happen?
→ Platelets release thromboxane A2 and ADP
→ Thromboxane A2 and ADP induce receptors for fibrinogen
→Platelets can also be activated by thrombin and collagen
What holds platelets together?
→ Fibrinogen acts as a tether holding platelets together
What is required platelet wise for successful coagulation?
→Negatively charged platelet surfaces
→ Charged phospholipids are required
How does the common pathway happen?
→ Factor 9A activates factor 10 by proteolysis to make factor 10A
→ factor 10A cleaves prothrombin to form thrombin
→thrombin (protease) cleaves fibrinogen into fibrin
→ Fibrinogen becomes insoluble fibrin
→ Thrombin cleaves factor 5 and 8 to give 5A and 8A
What is the tenase complex?
→ 8A + 9A = 10 A
What is the prothrombinase complex?
→ 5A + 10A = Thrombin
How does fibrinogen promote blood clotting ?
→ Forms bridges between and activates platelets through binding to GPIIB fibrinogen receptors
What does warfarin inhibit?
→ production of carboxyglutamic residues
→ by inhibiting vitamin K
How does a solid clot form?
→ Once enough thrombin has been generated
→ Factor 13 is activated which cross-links the fibrin fibres into a solid clot
What is the common pathway?
→ The bulk of the coagulation pathway
How is the common pathway initiated via the extrinsic?
→TF is a receptor for Factor 7A
→ Bound to a -vely charged surface of platelet phospholipids along with calcium
→Once activated Factor 7A activates Factor 10A and the common pathway starts
Where is TF present?
→ Present on most sub-endothelial cells
When is TF exposed?
→ When the endothelium is damaged
How does anti thrombin work?
→ Inhibits clotting in the first place.
→ Inhibits many enzymes in coagulation cascade.
→ Particulary inhibits Thrombin and Factor 7.
→ Heparan binds to and activates anti thrombin.
Why are d dimers measured clinically?
→ measured to see the level of thrombolysis
→ Degradation products of thrombuses are D dimers
Describe Tissue Plasminogen Activator and its’ function:
→ Tissue Plasminogen activator activates Plasminogen into Plasmin.
→ Plasmin causes Fibrinolysis of the Fibrin Clot into D - Dimers.
→ tPA can be used therapeutically in the treatement of clots.
→ tPA is an inherent anti thrombolytic
What exactly does the Plasmin break down during lysis of the clot?
→ It breaks down the fibrin cross linkages between the platelets.
What do ADP and Thromboxane A2 do?
→ Induce receptors for fibrinogen GP2B and GP3A
What is endocrine?
→ hormone released and moves somewhere else in the body
What is paracrine?
→A cell releases a hormone and it goes to the adjacent cell
What is autocrine?
→ releases a hormone that activates itself
Why is it called the coagulation cascade?
→ Amplification of the signal at each step
→Multiple steps where you can inhibit the process
→Small amounts of activated factors can have a big effect
How is factor 10 bound to the -vely charged phospholipids and what is needed for this?
→ Factor 10 is bound to the -vely charged phospholipid by the GLA domain
→ To make the GLA domain vitamin K is needed
