Disorders of blood coagulation Flashcards
Why does blood clot ?
Defence mechanism following injury or trauma:
Keep blood in +Keep pathogens out
Blood loss is stopped through formation of a plug made of platelets and fibrins.
What are the two main processes of Haemostasis?
Primary and Secondary
Describe blood clotting simply
Platelets and fibrinogen circulate in the blood (inactive form)
Damage to vessel wall will trigger clotting (collagen is exposed in blood)
Aggregated platelets +fibrin mesh
Endothelium is usually anticoagulant process
Describe primary haemostasis
(Platelet aggregation and platelet plug formation)
1;The endothelium will continuously release small amounts of von Willebrand factor which circulates in the blood.
- Endothelial cells also store von Willebrand factor in Weibel-Palade bodies(storage granules) for release when stimulated
- If collagen is exposed to blood following endothelium damage , von Willebrand Factor will bind to it.
- Platelets express receptors for both collagen and von Willebrand Factor and become activated when these proteins bind to them. Activated platelets express functional fibrinogen receptors which are required for aggregation.
Describe secondary haemostasis
(Activation of clotting components)
- Tissue factor expressed by nearly all sub-endothelial cells activates the coagulation cascade to initiate a minor burst of thrombin.Factor FVIIa binds to Tissue factor which leads to the conversion of prothrombin to thrombin.
- Thrombin activates receptors on platelets as well as endothelium amplifying platelet aggregation and initiating release of stored von Willebrand factor from endothelial cells.
Describe the amplification of Thrombin
Thrombin activates two cofactors :Factor VIIIA and Factor Va which form calcium ion dependent complexes on the surface of platelets with Factor IXa (tenase complex) and Factor Xa (prothrombinase complex).
2.These complexes will accelerate production of Factor Xa and thrombin. This is the amplification stage of the coagulation cascade.
\the greatly increased production of thrombin via tenase and prothrombinase contributes to the process.Thrombin will convert fibrinogen to the fibein mesh.
What is Fibrinolysis?
This is the breakdown of the fibrin in blood clots
Describe Fibrinolysis
- Plasminogen inactivated to plasmin by tissue plasminogen activator t-PA(expressed on surface of endothelial cells)
- Plasmin degrades the fibrin mesh to fibrin degradation products which can be cleared
Describe the Antithrombin natural anticoagulant pathway
Too much coagulation can be a problem.
Antithrombin (AT) is a serpin (serine protease inhibitor).
Its activity is enhanced by binding heparan binding sites on endothelial cells.
Major checkpoint to inhibit coagulation (thrombin) Ixa,Xa.Its heparan binding domain is the basis of the anticoagulant activity of heparin which increases the activity of ATIII.
Describe the Protein C/S anticoagulant pathway
Protein C/S are natural anticoagulant plasma proteins.
Protein C is activated by thrombin bound to thrombomodulin(TM) on endothelial cells to form activated protein C (APC).
Protein S is an APC cofactor which helps binding to cell surfaces for e.g platelets. APC degrades cofactors FVa and FVIIIa(part of tenase and prothrombinase complex).
What are three disorders of blood coagulation?
What are the three components in which defects occour ?
Haemophilia
Thrombophilia
Disseminated intravascular coagulation
- Coagulation proteins
- Platelets
- Endothelium
Describe Haemophilia
Failure to clot leading to haemorrhage
- Mutations in coagulation factors (haemophilia A/B)
- Platelets disorders(Von willebrand disease-required to activate platelets in primary haemostasis)
- Collagen abnormalities(fragile blood vessels and bruising)
Describe Thrombophilia
Excessive clotting leading to thrombosis
- Inherited (Mutations in coagulation factors(DVT)
- Acquired(Malignancy increases clotting factors (DVT)
Describe dissemintated intravascular coagulation (DIC)
This is whole body clots
Infection
Depletion of clotting factors and platelets leads to bleeding.
This can also happen in sepsis when the body’s response to an infection injures its tissues and organs
Describe the mutations of Haemophilia
Haemophilia A (80% of cases) Mutated FVIII(8) Haemophilia B Mutated FIX (9) Von Willebrand disease Inherited defect/deficiency in vWF (No platelet adhesion/aggregation)
