thrombosis

Question 1

What is the purpose of coagulation?

Answer 1

Coagulation prevents blood loss
Inflammation activates coagulation, which promotes inflammation
Coagulation is an immunological response

Question 2

Describe arterial thrombosis

Answer 2

Result from atheroma rupture or damage to the endothelium (eg-MI, stroke)

It is a platelet rich, white thrombus (mostly primary haemostasis)

It may block downstream arteries

Question 3

Describe venous thrombosis

Answer 3

• It often results from stasis or a hyper-coagulant state (eg- DVT)
  
  • It is a platelet poor, red thrombus (mostly secondary haemostasis)

It may move to the lungs

Question 4

List some factors/substances that affect the coagulation fibrinolysis balance

Answer 4

• Tissue plasminogen activator: initiates fibrinolysis
• Von Willebrand factor: activates platelets
• Tissue factor: initiates clotting
• Antithrombin: inhibits clotting
• Prostaglandin 12: inhibits platelets
Nitric oxide: inhibits platelets

Question 5

What is Virchow’s Triad?

Answer 5

It describes the 3 categories that contribute to thrombosis:
1. Stasis: static blood lacks kinetic energy and tends to clot
2. Hyper-coagulant state:
Eg- infection, hereditary, drugs (eg-HRT)
3. Endothelial damage
Eg- surgery or cannula

Question 6

What increases the risk of stasis?

Answer 6

Blood tends to swirl around the valves, increasing the risk of stasis

Question 7

What are the 4 possible fates of a thrombus?

Answer 7

1. Resolution
   Fibrinolytic system destroys the whole clot over time
   
   2. Embolism
      Thrombus dislodges and goes to the heart/lungs = DEATH
   3. Organised
      Endothelial cells grow over the clot = makes person more prone to having another one due to the narrowing of the vein
   4. Recanalized and organised
      Thrombus is TOO BIG to grow over it = grow THROUGH it

Question 8

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

Answer 8

Proximal DVT
• Higher risk of pulmonary embolism and post thrombotic syndrome
• This causes pain, swelling and sometimes ulcers
Distal DVT
Rarely causes any problems

Question 9

What does a platelet release when it has been activated?

Answer 9

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

Question 10

What is the final common pathway of the coagulation pathway?

Answer 10

1. Factor Ixa activates factor X by proteolysis to create factor Xa.
   Factor X —–> Factor Xa (VIA PROTEOLYSIS)
   
   2. Factor Xa cleaves prothrombin to form thrombin IIa
   3. Thrombin Iia is a protease that cleaves fibrinogen —> fibrin (insoluble)
   4. Fibrinogen promotes blood clotting by forming bridges between and activating blood platelets through binding to their GpIIb/IIIa surface membrane fibrinogen receptor
   5. Thrombin cleaves factors V and VIII to give Va and VIIIa
   6. Va and VIIIa along with calcium ions form:
      - Tenase complex
      - Prothrombinase complex
      Thee complexes assemble on the charged phospholipid surfaces of activated platelets
      VIIIa and Va amplify the existing reactions making them hard to overpower
   7. Once enough thrombin has been generated, XIII is activated, which crosslinks the fibrin fibres into a solid clot

Question 11

Describe the prothrombinase complex

Answer 11

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 stabilize the complex.
Forming these GLA domains is Vitamin K dependent and can be inhibited by warfarin (rat poison).

Question 12

Describe how the extrinsic pathway can lead to the activation of the final common pathway

Answer 12

1. Tissue factor (TF) is a receptor for VIIa, also bound to a negatively charged surface of platelet phospholipids along with calcium
2. Once activated, VIIa activates Xa and the common pathway is

Question 13

Where are tissue factors found and how are they activated?

Answer 13

TF is present on most subendothelial cells.

They are exposed if the endothelium is damaged, ready for VIIa to bind to and initiate coagulation

Question 14

What is an example of how the extrinsic pathway for coagulation is activated

Answer 14

trauma

Question 15

What is an example of how the intrinsic pathway activates the coagulation pathway

Answer 15

damaged surface

Question 16

When is the intrinsic pathway activated

Answer 16

Activated when you put blood onto a charged surface such as glass

Question 17

Defects can occur differently in the intrinsic and extrinsic coagulation pathway. Describe them

Answer 17

Intrinsic: mutations of enzymes involved in pathway
Extrinsic: defects in factors involved in pathway (larger physiological effect)

Question 18

What is tPA and what can it be used to treat?

Answer 18

Tissue plasminogen activator can be used to treat strokes and myocardial infarctions

Question 19

Describe the process of fibrinolysis via tPA

Answer 19

• Plasminogen is cleaved into plasmin (active form of plasminogen) using tPA
• Plasmin causes fibrinolysis of fibrin clot resulting in the formation of D dimers
D dimers can be used in clinical tests to assess the coagulation system

Question 20

Describe the process of fibrinolysis via antithrombin

Answer 20

• Expressed by endothelial cells and inhibits a lot of the enzymes in the coagulation cascade but thrombin and factor VII in particular
• Heparin binds to the enzyme inhibitor antithrombin III causing a conformational change = activation
The activated antithrombin III then inactivates thrombin, factor Xa and other proteases