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:
- 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:
- 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
- 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)
- 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.
Valves prevent blackflow of blood
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 another location and blocks vessel eg. 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.
What does a platelet release when it has been activated?
The activated platelet releases thromboxane A2 (TxA2) and adenosine diphosphate (ADP); these induce receptors for fibrinogen.
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).
What is Haemostasis?
The stopping of blood flow - coagulation
What is Thrombosis?
Formation of blood clot inside a blood vessel that obstructs the flow of blood
What is Primary and Secondary Haemostasis
Primary Haemostasis is aggregation of platelets
Secondary Haemostasis is conversion of fibrinogen into fibrin
Surface of platelets important component of coagulation process
Describe the steps of Fibrinolysis and Anticaogulants
- Aggregation of platelets
- Fibrinogen converted into Fibrin mesh
- done by Thrombin - which is a protease - Thrombin itself converted from Prothrombin
- prothrombin is the culmination of a cascade of similar activation steps
What is Deep Vein Thrombosis?
When venous return is blocked, the affected organs become congested with fluid
Increased pressure so more filtration
Risk associated : thrombosis may become dislodged and make its return to the heart
