Clotting Flashcards
What are the 3 phases of haemostasis?
- Vasoconstriction
- Platelet plug formation
- Coagulation
Why does vasoconstricition occur?
It is important as it slows the blood flow to the injured area while the clot is formed?
How does platelet plug formation work?
Platelets encounter damaged vascular surfaces, the platelets change their characteristics.
They swell and assume irregular forms, becomes sticky and adhere to collagen in the tissue and to the von Willebrand Factor.
They then secrete more platelet activating factor (PAF) and thromboxane, these chemicals and ADP activate nearby platelets allowing them to stick to the original platelets.
How is coagulation triggered?
By the extrinsic or intrinsic pathway.
How is the intrinsic pathway triggered?
By contact of blood with negatively charged surfaces such as subendothelial collagen.
How is the extrinsic pathway triggered?
By exposure of blood to tissue factor on the surface of subendothelial cells after vascular injury.
Which pathway if first and faster?
Extrinsic pathway
What pathway is needed for clots of significant enough size to play a role in haemostasis?
Intrinsic pathway
When do the extrinsic and intrinsic pathways converge?
They converge at the level where coagulation factor X is converted to Xa, after this the final common pathway ensues.
What happens in the final common pathway?
Prothrombin goes through proteolytic cleavage and becomes thrombin, this is an enzyme (protease) that will catalyse cleavage of fibrinogen to create the fibrin that will be present in the clot.
What is fibrinolysis?
This is the process by which the clot is removed, the protein plasmin plays a key role.
How does fibrinolysis occur?
Plasminogen is synthesised in the liver and becomes trapped in clots, it then becomes activated in the clot when tissue plasminogen activator (tPA), a urokinase is released.
This converts plasminogen to plasmin which then breaks down the fibrin mesh.
How is tPA secreted?
tPA is released very slowly by damaged endothelium of the blood vessels
What happens to platelets following fibrin degradation by plasmin?
Old activated platelets from the platelet plug are phagocytized and destroyed by macrophages.
What is an APTT?
An activated partial thromboplastin time, an assay commonly used as clinical test of co-agulation.
This assay tests the intrinsic pathway.
What components go into an APTT?
-Platelet poor plasma
-Activators (celite, silica, kaolin)
-Phospholipid
Incubate (37C)
-Calcium
What is the phospholipid/kaolin mimicking in the APTT?
It mimics the negative charges on the platelets and the membrane surface.
What is added to plasma in storage to stop coagulation?
Sodium citrate, this is a calcium chelator and calcium is needed for the clotting process
What is the difference between blood serum and plasma?
Serum is plasma with fibrinogen removed – more specifically, the portion of plasma remaining after coagulation of blood, as the fibrinogen will have been converted to fibrin, this remains in the clot and the serum can be removed.
Why is plasma from lots of donors used in experiments and not just one?
This is to give us an average clotting time and consistent results across the class.
If plasma from individuals was used, there would be a greater range of results, as a volunteer donor could have an abnormal or absent clotting factor.
What does heparin inhibit?
Action of thrombin in final common pathway
What is benzamidine?
Competitive ibhibitor targets protease enzymes in pathway (thrombin) ans slows the overall clotting process.
What does warfarin antagonise?
Vitamin K
What is the structure of hameoglobin?
4 haem groups, 4 polypeptide chains
Why is the liver important in coagulation?
It produces most of the factors needed for coagulation (prothrombin, fibrinogen)
