Thrombosis Flashcards
Why does coagulation occur (as in, what is its purpose)?
Coagulation prevents blood loss.
Inflammation activates coagulation and coagulation promotes inflammation. Coagulation is an immunological response.
Describe both arterial and venous thrombosis.
ARTERIAL THOMBOSIS:
- they mostly result from an atheroma rupture or damage to the endothelium (eg. MI, stroke)
- it is a platelet-rich, ‘white’ thrombosis; it’s mostly primary haemostasis
- it may block downstream arteries
VENOUS THROMBOSIS:
- it often results from stasis or a hyper-coagulant state (eg. DVT)
- it is a platelet-poor, ‘red’ thrombus; it is mostly secondary haemostasis
- it may move to the lungs
List some factors/substances that affect the coagulation-fibrinolysis balance.
- tissue plasminogen activator: initiates fibrinolysis
- von Willebrand factor: activates platelets
- tissue factor: initiates clotting. These are usually underneath the endothelial cells, but during inflammation or tissue dammage, they are exposed.
- antithrombin: inhibits clotting
- prostaglandin I2: inhibits platelets
- nitric oxide: inhibits platelets
What is Virchow’s Triad, and what are its three components?
It describes the three categories that are thought to contribute to thrombosis. These three categories are:
- STASIS: static blood lacks kinetic energy and tends to clot
- HYPER-COAGULANT STATE: eg. infection, hereditary, drugs (eg. HRT). Some people may inherent clotting factors that are slightly more prone to clotting.
- ENDOTHELIAL DAMAGE: eg. surgery or cannula
How are the valves involves in stasis?
Blood tends to eddy around the valves, increasing the risk of stasis.
What are the four possible fates of a thrombus?
- RESOLUTION: where the fibrinolytic system destroys the whole clot over time
- EMBOLISM: where the thrombus dislodges and goes to the heart/lungs, causing death
- ORGANISED: where the endothelial cells just grow over the clot; this makes the person more prone to having another one due to the narrower vein
- RECALANISED AND ORGANISED: where the thrombus is so big you can’t grow over it, but you can grow through it.
What is the difference between a proximal DVT and a distal DVT?
With a proximal DVT, there is a higher risk of a pulmonary embolism and post-thrombotic syndrome (causing pain, swelling, and sometimes ulcers).
With a distal DVT, it rarely causes a pulmonary embolism or post-thrombotic syndrome.
Distinction between them is around the knee. distal - they’re not as bad, as they’re smaller clots, formed in smaller blood vessels. But then the proximal one breaks off, he vessels are getting larger as it goes back to the heart, but the pul. vessels are smaller - seriousness depends on how much of the lungs is blocked.
Describe the common pathway.
The common pathway pathway reactions run at a trickle and are easily overpowered by inihibitors.
1) Factor IXa activates Factor X by proteolysis to create Factor Xa.
2) Factor Xa (FXa) cleaves prothrombin to form thrombin (FIIa).
3) Thrombin (FIIa) is a protease that cleaves fibrinogen into fibrin. Fibrinogen is a large molecule that’s present in plasma - once cleaved, it becomes insoluble fibrin.
4) Thrombin cleaves Factors V and VIII to give FVa and FVIIIa. This is known as amplification, as FVIIIa and FVa amplify the existing reactions, making them harder to overpower.
5) FVa and FVIIIa together with the plasma Ca2+ form the:
- Tenase complex - FVIIIa + FIXa = FXa
- Prothrombinase complex - FVa + FXa = thrombin
These complexes assemble on the charged phospholipid surfaces in the activated platelets.
Fibrinogen also promotes blood clotting by forming bridges between, and activating, blood platelets through binding to their GpIIb/IIIa surface membrane fibrinogen receptor.
Describe the prothrombinase complex.
The negative surface of the activated platelet causes calcium, prothrombin and Factor Xa and Va to bind. This makes the prothrombinase complex. These components all bind by a particular domain of glutamic acids (GLA); they stabilise the complex.
Forming these GLA domains is Vit K dependent and can be inhibited by warfarin (rat poison).
Briefly describe 2 main steps in blood clot formation.
Primary - Aggregation of platelets.
Secondary - Fibrinogen converted into fibrin mesh by thrombin which is a protease.
What is sepsis? and what is a cannula?
Sepsis is a condition that arises when the body’s response to infection causes injury to its own tissues and organs. In extreme sepsis, all the vascular lining is coagulable, so all the coagulation will occur at the same time – which is usually the thing that kills you.
Cannula - a thin tube inserted into a vein or body cavity to administer medication, drain off fluid, or insert a surgical instrument.
How do leg muscles increase venous return? and what happens if there is a blockage?
When you move, there is contraction of nearby muscles
squashes veins, acting as a pump
to return blood to the heart.
If venous return is blocked, the affected organ becomes congested with fluid. increased pressure so more filtration.. ~ The risk is that . the thrombosis might become dislodged and make its way back to the heart.
Outline the steps in platelet activation.
- von Willebrand factor on subendothelial cells activates platelets.
- Circulating Von Willebrand factor may bind to exposed subendothelial cells.
- Activated endothelial cells can also express von Willebrand factor.
Outline the steps in platelet agrregation
- The activated platelet releases thromboxane A2 (TxA2) and adenosine diphosphate (ADP); these induce receptors for fibrinogen.
- These bind to receptors on adjacent platelets and increase expression of the glycoprotein complex GPIIb/IIa.
- Fibrinogen acts as a tether, holding platelets together (this is not blood coagulation).
- Once you have a clump of platelets, they form a negatively charged surface which is required for coagulation.
