Thrombosis

Question 1

Why does coagulation occur (as in, what is its purpose)?

Answer 1

• Coagulation prevents blood loss.
• Inflammation activates coagulation and coagulation promotes inflammation.
• Coagulation is an immunological response.

Question 2

Describe both arterial and venous thrombosis.

Answer 2

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

Question 3

List some factors/substances that affect the coagulation-fibrinolysis balance.

Answer 3

• 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

Question 4

What is Virchow’s Triad, and what are its three components?

Answer 4

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

Question 5

How are the valves involves in stasis?

Answer 5

Blood tends to eddy around the valves, increasing the risk of stasis.

Valves prevent blackflow of blood

Question 6

What are the four possible fates of a thrombus?

Answer 6

• 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

Question 7

What is the difference between a proximal DVT and a distal DVT?

Answer 7

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.

Question 8

What does a platelet release when it has been activated?

Answer 8

The activated platelet releases thromboxane A2 (TxA2) and adenosine diphosphate (ADP); these induce receptors for fibrinogen.

Question 9

Describe the common pathway.

Answer 9

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.

Question 10

Describe the prothrombinase complex.

Answer 10

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).

Question 11

What is Haemostasis?

Answer 11

The stopping of blood flow - coagulation

Question 12

What is Thrombosis?

Answer 12

Formation of blood clot inside a blood vessel that obstructs the flow of blood

Question 13

What is Primary and Secondary Haemostasis

Answer 13

Primary Haemostasis is aggregation of platelets

Secondary Haemostasis is conversion of fibrinogen into fibrin

Surface of platelets important component of coagulation process

Question 14

Describe the steps of Fibrinolysis and Anticaogulants

Answer 14

1. Aggregation of platelets
2. Fibrinogen converted into Fibrin mesh
   - done by Thrombin - which is a protease
3. Thrombin itself converted from Prothrombin
   - prothrombin is the culmination of a cascade of similar activation steps

Question 15

What is Deep Vein Thrombosis?

Answer 15

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

Question 16

What is Post Thrombotic Syndrome?

Answer 16

Inflammation along with damage to venous valves from thrombus itself

valvular incompetence combined with persistent venous obstruction

• pain
• swelling
• discolouration
• even ulceration follow

Question 17

Explain the steps involved in Platelet Adherence

Answer 17

• von Willebrand factor on sub-endothelial cells activate platelets
• circulating Von Williebrand factor may bind to exposed subendothelial cells
• activated endothelial cells can also express von Willebrand factor

Question 18

What happens during Platelet Activation

Answer 18

• Activated platelets rekease Thromboxane A2 and Adenosine Diphosphate (ADP)
• which induces receptors for fibrinogen ( GPIIb/Illa)

These bind to receptors on adjacent platelets and increase expression of the glycoprotein complex GPIIb/Illa

Question 19

What happens during Platelet Aggregation

Answer 19

• Fibrinogen acts as a tether, holding platelets together.
• This is aggregation.
• Fibrinogen is the soluble precursor to fibrin and is in the circulation.

Question 20

What happens during Platelet Substrate for Coagulation?

Answer 20

• Once a clump of platelets aggregate they form a negatively charged surface which is required for coagulation.
• Coagulation involves the conversion of fibrinogen to fibrin and then crosslinking of the fibrin clot