Thrombosis Flashcards
What does coagulation prevent?
Prevents blood loss
What does inflammation activate?
Inflammation activates coagulation and coagulation promotes inflammation
What type of response is coagulation?
Coagulation is an immunological response
What is primary haemostasis?
Primary haemostasis is the aggregation of platelets
What is secondary haemostasis?
Secondary haemostasis is the conversion of fibrinogen into fibrin
Surface of what is an important component in coagulation?
The surface of platelets is an important component in the process
What do anticoagulants prevent?
Prevent thrombosis
What does fibrinolysis reverse?
Reverses thrombosis
What is fibrinogen converted into and by what?
Fibrinogen is converted into a fibrin mesh by thrombin which is a protease
What is thrombin converted from?
Prothrombin
What does arterial thrombosis most result from?
Mostly result from atheroma rupture or damage to the endothelium (e.g. MI, stroke)
What type of thrombosis is arterial thrombosis?
Platelet-rich “white” thrombosis
o Mostly primary
What can arterial thrombosis do?
May block downstream arteries
What does venous thrombosis often result from?
Often results from stasis or a hyper-coagulant state
What type of thrombosis is venous thrombosis?
Platelet-poor “red” thrombus
o Mostly secondary
Where can venous thrombosis move to?
May move to lungs
What is usually being inhibited?
Usually coagulation is being inhibited
What is coagulation inhibited by?
o Prostaglandins
o Antithrombin and Heparan
o Nitric Oxide
What does the tissue plasminogen activator cleave?
Cleaves plasmin into D dimer (a fibrin degradation product)
What does vonWillebrand factors activate?
activates platelets and makes them clump together
What does tissue factor initiate?
Initiates clotting
What is Virchow’s triad?
Stasis-Static blood lacks kinetic energy and tends to clot
Endothelial damage-Surgery
Hyper-coagulant state-Infection/sepsis
What do valves do in veins?
Valves in veins prevent backflow of blood
what do nearby muscles of the veins do?
Contraction of nearby muscles squashes veins, acting as a pump to return blood to
the heart
What does blood do around valves?
Blood tends to eddy around the valves increasing the risk of stasis
Why does DVT occur?
If venous return is blocked, the affected organ becomes congested with fluid
What happens to pressure in DVT?
There is increased pressure so there is more filtration
What risk is there in DVT?
The risk is that the thrombosis might become dislodged and make its way back to
the heart
What is the fate of thrombus?
- Resolution
- Embolism
- Organised
- Recalled and organised
What is there a higher risk of in proximal DVT and what are the symptoms?
Higher risk of pulmonary embolism and post-thrombotic
syndrome
- Pain, swelling, maybe even ulcers
What does distal DVT rarely cause?
- Rarely cause pulmonary embolism
- Rarely causes post-thrombotic syndrome
What can a small venous thrombus cause?
A slight VQ(ventilation perfusion) mismatch or small infarct zone
what can a large venous thrombus cause?
A saddle embolism blocking both pulmonary arteries
What activates platelets?
Von Willebrand factor on subendothelial cells activates platelets
What do circulating VWF bind to?
Circulating VWF may bind to exposed subendothelial cells
What can also express VWF?
Activated endothelial cells can also express VWF
What do activated platelets release and what do these bind to?
The activated platelets release Thromboxane A 2 (TxA 2 ) & Adenosine diphosphate
(ADP) which induce receptors for fibrinogen
- These bind to receptors on adjacent platelets and increase the expression of the
glycoprotein complex GPIIb/IIIa
What else can platelets be activated by?
Platelets can also be activated by thrombin, collagen and many other mediators
What does fibrinogen act as?
Fibrinogen acts as a tether holding the platelets together (this is not blood
coagulation)
What is fibrinogen?
Fibrinogen is the soluble precursor to fibrin and is in the circulation
What do a clump of platelets form?
Once you have a clump of platelets, they form a negatively charged surface which is
required for coagulation
Coagulation pathway process
See notes
What is the GLA domain?
GLA domain is 10-12 glutamic acids in the N-terminus of the
molecule converted to gamma-carboxyglutamic acid (Gla)
What is the formation of gamma-carboxyglutamic acid dependent on?
Vitamin K dependent process
What inhibits the production of carboxygutamic residues?
warfarin inhibits production of carboxygutamic
residues
Extrinsic pathway
See notes
What is the intrinsic pathway activated by?
Activated when you put blood onto a charged surface such as glass
Defects in extrinsic vs inttinsic pathway
Defects in the factors of the extrinsic pathway have far larger physiological effects than
mutations in the enzymes of the intrinsic pathway
What can inhibit clotting?
Antithrombin inhibits clotting in the first place
What is the clot broken down by?
The clot is broken down by plasmin which is activated from plasminogen by tPA
What are some thrombolytic agents used for?
Some of these thrombolytic agents such as tissue plasminogen activator and related
compounds are used to treat strokes and myocardial infarctions
How its anti-thrombin activated?
Heparin binds to the enzyme inhibitor antithrombin III (AT), causing a conformational
change that results in its activation
What does activated AT do?
activated AT then inactivates thrombin, factor Xa and other proteases
What is AT expressed by and what does it do?
AT is expressed by the endothelial cells and inhibits a lot of the enzymes in the
coagulation cascade but thrombin and FVII in particular
