thrombosis Flashcards
What is the purpose of coagulation?
Coagulation prevents blood loss
Inflammation activates coagulation, which promotes inflammation
Coagulation is an immunological response
Describe arterial thrombosis
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
Describe venous thrombosis
- 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
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 12: inhibits platelets
Nitric oxide: inhibits platelets
What is Virchow’s Triad?
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
What increases the risk of stasis?
Blood tends to swirl around the valves, increasing the risk of stasis
What are the 4 possible fates of a thrombus?
- Resolution
Fibrinolytic system destroys the whole clot over time- Embolism
Thrombus dislodges and goes to the heart/lungs = DEATH - Organised
Endothelial cells grow over the clot = makes person more prone to having another one due to the narrowing of the vein - Recanalized and organised
Thrombus is TOO BIG to grow over it = grow THROUGH it
- Embolism
What is the difference between a proximal DVT and a distal DVT?
Proximal DVT
• Higher risk of pulmonary embolism and post thrombotic syndrome
• This causes pain, swelling and sometimes ulcers
Distal DVT
Rarely causes any problems
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
What is the final common pathway of the coagulation pathway?
- Factor Ixa activates factor X by proteolysis to create factor Xa.
Factor X —–> Factor Xa (VIA PROTEOLYSIS)- Factor Xa cleaves prothrombin to form thrombin IIa
- Thrombin Iia is a protease that cleaves fibrinogen —> fibrin (insoluble)
- Fibrinogen promotes blood clotting by forming bridges between and activating blood platelets through binding to their GpIIb/IIIa surface membrane fibrinogen receptor
- Thrombin cleaves factors V and VIII to give Va and VIIIa
- 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 - Once enough thrombin has been generated, XIII is activated, which crosslinks the fibrin fibres into a solid clot
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 stabilize the complex.
Forming these GLA domains is Vitamin K dependent and can be inhibited by warfarin (rat poison).
Describe how the extrinsic pathway can lead to the activation of the final common pathway
- Tissue factor (TF) is a receptor for VIIa, also bound to a negatively charged surface of platelet phospholipids along with calcium
- Once activated, VIIa activates Xa and the common pathway is
Where are tissue factors found and how are they activated?
TF is present on most subendothelial cells.
They are exposed if the endothelium is damaged, ready for VIIa to bind to and initiate coagulation
What is an example of how the extrinsic pathway for coagulation is activated
trauma
What is an example of how the intrinsic pathway activates the coagulation pathway
damaged surface
When is the intrinsic pathway activated
Activated when you put blood onto a charged surface such as glass
Defects can occur differently in the intrinsic and extrinsic coagulation pathway. Describe them
Intrinsic: mutations of enzymes involved in pathway
Extrinsic: defects in factors involved in pathway (larger physiological effect)
What is tPA and what can it be used to treat?
Tissue plasminogen activator can be used to treat strokes and myocardial infarctions
Describe the process of fibrinolysis via tPA
• 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
Describe the process of fibrinolysis via antithrombin
• 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
