Disorders Of Blood Coagulation Flashcards
Why are blood clots important?
Blood loss is stopped by formation of. Plug composed of platelets and fibrin
Must remain localised
What is haemostasis?
Endothelium in blood vessels normally maintains a anticoagulant surface
When Damage to vessel wall triggers clotting Causes Platelets and fibrinogen aggregate forming a mesh
Primary and secondary haemostasis occur independently at the same time
What occurs during PRIMARY haemostasis?
- Endothelium continuously releases small amount of Von Willabrand factor, which circulates in the blood. - - Endothelial cells store Von willabrand factor in Weibel-palade bodies for release when appropriately stimulated.
- If collagen becomes exposed to blood due to endothelial damage, Von willabrand factor binds to it
- Platelets express receptors for both collagen and Von willabrand factor.
- When von willabrand factor and collagen bind to thee receptors platelets become activated
- Activated platelets express functional fibrinogen receptor, which are required for aggregation
What occurs during SECONDARY haemostasis?
- Tissue factor is expressed by most sub-endothelial cells
- Tissue factor activates the coagulation cascade to initiate a minor burst of thrombin that can then be amplified
- Tissue factor binds to factor 7a
- Factor 7a then activates factor 10a
- Factor 10a then induces the initial trickle of thrombin from prothrombin
- Thrombin activates receptors on platelets as well as endothelial cells - amplifying platelet aggregation and initiating release of stores Von willabrand factor from endothelial cells.
- Thrombin activates 2 co factors (8a + 5a) which form calcium ion dependent complexes on the surface of platelets with 10a - this complex accelerates the production of factor 10a and thrombin
- The increase in the production of thrombin contributes considerably to the process where thrombin will convert fibrinogen to the fibrin mesh.
Describe how thrombin is produced?
Prothrombase is converted to thrombin using tenase
What is fibrinolysis?
- Plasminogen is activated to plasmin (proteolitic enzyme) by plasminogen activator (t-PA)
- Plasmin degrades the fibrin mesh to fibrin degradation products (eg. D dimer)1 which can be cleared.
This prevents blood clots from growing and becoming problematic.
What is antithrombin?
A serpin (serine protease inhibitor) found on heparin binding sites of endothelial cells
It inhibits the activity of thrombin and factor 10a.
Activity greatly enhanced by heparin binding sites on endothelial cells
- it’s HEPARAN binding domain is the basis of the anticoagulant activity of heparin
- heparin enhances the activity of anticoagulant
Major checkpoint to inhibit coagulation
What are examples of natural anticoagulants in the body?
- antithrombin
- protein C and protein S
How do protein C and protein S function to prevent coagulation?
Natural anticoagulant plasma protiens
Plasma C:
- activated by thrombin (bound to thrombomodulin) on endothelial cells
- form activated protein C (APC)
- degrades cofactors 8a and 5a
Plasma S:
- APC cofactor
- helps complex bind to cell surfaces
What molecular components of blood clotting are effected in blood clotting disorders?
Coagulation proteins
Platelets
Endothelium
What is haemophilia?
Failure to-clot leading to haemorrhage
What are the three causes of haemophilia?
- mutations in coagulation factors (haemophilia A and B)
- platelet disorders (Von willebrand disease)
- collagen abnormalities (fragile blood vessels and bruising)
What is thrombophillia?
Excessive clotting leading to thrombosis
What are the 2 causes of thrombophillia?
- inherited: mutations in coagulation factors (DVT)
- acquired: malignancy increases clotting factors (DVT)
What is disseminated intravascular coagulation (DIC)?
Whole body clots
