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Be warned, this is complex (and a bit dull). Quite useful if you are learning Haematology though...
The healthy vessel wall releases or contains various factors:
- Prostacyclin (PGI2) and nitric oxide (NO). These cause vasodilation and prevent platelet aggregation.
- Plasminogen factor, which causes break down of fibrin.
- Heparin sulphate expression (not sure what that means, but heparin stops clotting).
When there is injury to the vessels there is "reflex vasoconstriction". There is also loss of the antithrombic properties that are released by the undamaged endothelial cells.
This causes platelet adhesion through action of:
- Glycoprotein 1a which binds to collagen.
- Glycoprotein 1b which binds to von Willebrand factor in the plasma, and the vWf in turn binds to collagen.
After adhesion the platelets change shape from discs to spheres and spread along the subendothelium and causes stimulation of Cox, which synthesises TXA2, which stimulates release of ADP and serotonin. The ADP causes a change in the fibrinogen receptor on platelets, allowing them to bind with fibrinogen. The platelets then begin to be bound together using fibrinogen generally found in blood into activated aggregates. This leads to further platelet release, causing a self perpetuating cycle. The serotin and the TXA2 are powerful vasoconstrictors. They are the controlling factors in the bleeding time (if a clot is prevented from forming how long will it take to stop bleeding 2-6 minutes).
Formation of platelets and blood cells. Precursor cells found in bone marrow (adult=axial skeleton, child all bones, in utero=yolk sac, liver, spleen). Pluripotent stem cells proliferate then differentiate into WBC, RBC or platelets.
Differentiation is controlled by growth hormone factors.
Fibrin is broken up by thrombin (factor IIa) into sticky insoluble fibrin monomers. In the presence of factor XIII and Ca2+ the monomers polymerize, making a stable clot. Retraction of platelets subsequently makes the clot to contract and get tougher and more elastic, drawing the edges of the wound together.
Thrombin is not present in plasma, but is produced when prothrombin is activated by factor X, catalysed by factor V. There are two pathways that lead to activation of factor X: intrinsic and extrinsic.
- Takes minutes.
- Activated by collagen.
- Factor XII is activated by exposed macromolecules after tissue damage.
- A cascade results in activation of Factor X, catalysed by factor VIII (with PLD and Ca2+)
- Takes seconds
- Activated by thromboplastin (tissue factor)
- Factor VII combines with tissue factor to activate factor X
- The time this takes is the prothrombin time, and is normally ~14 seconds.
Thrombin binds to thrombomodulin on the endothelial cell surface. This activates protein C with its cofactor protein S. (which inactivates factors VIII and V). Protein C also inactivates an inhibitor of tPa (tissue plasminogen activator). This causes activation of plasminogen (which floats around in the blood) to plasmin. Plasmin digests fibrin and causes the clot to fall apart.
- Time taken for clotting to occur when calcium and thromboplastin are added.
- A prolonged PT shows coagulation factor deficiency, and a short one, an excess of coagulation factors or a deficiency of coagulation inhibitors.
- PT measures the extrinsic pathway.
Partial Thromboplastin Time with Kaolin
- Estimates the degree of anticoagulation induced by heparin for venous thrombosis.
- Long time means the heparin is working.
- It measures the intrinsic pathway.