Thrombosis in the Wrong Place Flashcards
What does coagulation prevent?
→Blood loss
What is coagulation?
→An immunological response
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
Activated when blood is exposed to collagen (or other damaged surfaces or like charged platelets)
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
Begins in the vessel wall.
Damaged endothelial cells release factor III (tissue factor)
What is reverse thrombosis?
→ Fibrinolysis
What happens when tissue is damaged/inflammation?
→ Platelets become activated
→ Fibrinogen turns into fibrin by thrombin
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. Stasis also slows the washout of activated clotting factors and impedes the inflow of clotting factor inhibitor
HYPER-COAGULANT STATE
→ Infection, hereditary or drugs (HRT)
ENDOTHELIAL DAMAGE
→when endothelium gets ripped up is that tissue factor is exposed (which initiates the coagulation cascade).Surgery or cannula
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
Rarely cause post-thrombotic syndrome
→ Proximal has a higher risk of pulmonary embolism and post-thrombotic syndrome
What are the 4 things that can happen to a thrombus?
RESOLUTION
→ thrombolysis activation of fibrinolytic factors may lead to its rapid shrinkage and complete dissolution
EMBOLISM
→ moves to another location + blocks vessel
ORGANIZED
→ becomes covered by endothelium
RECANALISED AND ORGANISED
Holes appear in the thrombus and is covered by endothelium
What is post thrombotic syndrome?
- Inflammation along with damage to the venous valves from the thrombus itself.
- Valvular incompetence combined with persistent venous obstruction inducing a rupture of small superficial veins, subcutaneous hemorrhage and an increase of tissue permeability.
- Pain, swelling, discoloration, and even ulceration follow.
- Proximal DVT
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
Fragmented thrombi from DVTs are carried through progressively larger channels and usually pass through the right side of the heart before arresting in the pulmonary
vasculature
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 clo
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.
→ Particulars inhibits Thrombin and Factor 7.
→ Heparan binds to and activates anti thrombin causing a conformational change .
The activated AT then inactivates thrombin, factor Xa, factor VII and other components of the clotting cascade.
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(a serine protease) activator activates Plasminogen into Plasmin.
→ Plasmin causes Fibrinolysis of the Fibrin Clot into D - Dimers.
→ tPA can be used therapeutically in the treatment 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
Describe the balance between coagulation and fibrinolysis
Endothelial cells express various factors inhibiting coagulation… Nitric Oxide (inhibits platelets) Prostaglandin I2 (inhibits platelet activation) Antithrombin when bound to heparan (inhibits clotting)
If endothelial cells become damaged or inflamed they may favour coagulation, subendothelial cells if disturbed release tissue factor or Von Willebrand factor. Von Willebrand factor (activates platelets) Tissue Factor (Initiates clotting) Clot is broken down by plasmin which is activated from plasminogen by Tissue Plasminogen Activator (tPA)
