Secondary Haemostasis Flashcards
What is secondary haemostasis?
The formation of a stable fibrin clot (coagulation).
What is the need for secondary haemostasis (why are the actions of primary haemostasis insufficient)?
A platelet plug is sufficient for a very small vessel injury but in larger vessels it will fall apart. Fibrin formation stabilises the plug.
What does thrombin do?
Cleaves the soluble protein fibrinogen to form the insoluble protein fibrin which stabilises the platelet plug.
Where are most clotting factors synthesised? What are the exceptions?
The liver. The exceptions are factor VIII and VWF, which are made by endothelial cells. VWF is also made in megakaryocytes and incorporated into platelet granules.
What are factors II (prothrombin), VII, IX and X dependant on and what for?
They are dependant on Vitamin K for carboxylation of their glutamic acid residues, which is essential for the function of these clotting factors.
The process of blood coagulation involves a number of steps that are activated in sequence. Each step is characterised by the conversion of what into what? How is this done?
The conversion of an inactive zymogen (proenzyme) into an active clotting factor by the splitting of one or more peptide bonds and exposure of the active enzyme site, e.g. prothrombin into thrombin (Factor II into Factor IIa)
Factors V and VIII are what?
Co-factors
Many clotting factors are thought to work on the exposed what?
Phospholipid surface of platelets, which helps to localise and accelerate these reactions.
What allows activated clotting factors to bind to the phospholipid surfaces of platelets?
Calcium ions.
What triggers the initiation of coagulation?
The exposure of Tissue Factor (TF) on the surface of endothelial cells and leukocytes and on most extravascular cells in an area of tissue damage. (TF is not usually exposed to the blood under normal physiological conditions, as a result blood only encounters at sites of vascular injury).
What does the binding of TF to factor VIIa lead to?
The activation of factors IX to IXa and X to Xa.
What does the activation of factors IX and X lead to?
This leads to the activation of prothrombin (factor II) to generate a small amount of thrombin (factor IIa). This phase (starting from the initial binding of TF to VIIa) is known as the initiation phase.
What happens in the amplification phase?
The small amount of thrombin produced mediates the activation of the co-factors V and VIII, the zymogen factor XI and platelets.
What happens in the propagation phase?
Factor XI converts factor IX to IXa, which in combination with factor VIIIa, amplifies the conversion of factor X to Xa (from the initiation phase) and there is consequently a rapid burst in thrombin generation, which cleaves the circulating fibrinogen to form the insoluble fibrin clot.
What is the overall series of reactions to form a fibrin clot? (HARD)
- TF binds to VIIa, leading to the activation of IX to IXa and X to Xa.
- This leads to the activation of prothrombin (factor II) to produce a small amount of thrombin (factor IIa)
- Thrombin mediates the activation of the co-factors V and VIII, the zymogen factor XI and platelets.
- Factor XI converts more factor IX to IXa, which in combination with factor VIIIa, amplifies the conversion of factor X to Xa, leading to a burst in thrombin production.
