Disorders of Blood coagulation Flashcards
Why does our blood clot
- Keeps blood in
- Keeps pathogens out
Clotting is localised as we want blood to flow and not clot everywhere
What are blood clots made out of
Platelets and fibrin
Describe how a blood clot forms
- Platelets and fibrinogen circulate the blood ready to go
- When there is damage to a vessel wall it triggers clotting
- Platelets aggregate and a fibrin mesh is formed
Endothelium in blood vessels normally maintains an anticoagulant surface
Injury exposes collagen to come into contact with blood components to activate clotting
What are the 2 main processes in haemostasis
Primary and Secondary
Describe the steps in primary haemostasis
- Endothelial cells continuously release small amounts of von Willebrand factor into the blood
- If collagen comes in contact with vWF when the endothelium breaks it binds to it
- Platelets have vWF and collagen receptors, when there is a break platelets bind to the sub-endothelial collagen and get activated
- Activated platelets express functional fibrinogen receptors which are needed in aggregation
Describe the steps involved in secondary haemostasis
- Tissue factor which is expressed by sub-endothelial cells activates the coagulation cascade to initiate a minor burst of thrombin.
- FVIIa bind to TF and leads to the conversion of prothrombin to thrombin
- Thrombin activates receptors on platelets and the endothelium which amplifies platelets aggregation and initiating release of vWF
Explain the amplification step of the clotting cascade
- Thrombin activates 2 cofactors: Factor VIIIa and Factor Va, which form calcium ion-dependant complexes on platelet surfaces with factor IXa and factor Xa.
- These complexes greatly accelerate the production of factor Xa and thrombin
- Thrombin will convert fibrinogen to the fibrin mesh
Describe the process of fibrinolysis
- Plasminogen is activated to plasmin by tissue plasminogen activator (t-PA)
- Plasmin degrades the fibrin mesh to fibrin degradation products which can be cleared
Explain how antithrombin is a natural anticoagulant
Antithrombin (AT) is a serpin
(serine protease inhibitor)
Activity is greatly 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
Explain how Protein C&S are a natural anticoagulant
Protein C and protein 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
APC degrades cofactors FVa and FVIIIa
What are the defects in the key component of clotting
- Coagulation proteins
- Platelets
- Endothelium
List some clotting disorders
Haemophilia - failure to clot leading to haemorrhage:
- Mutations in coagulation factors (haemophilia A and B)
- Platelet disorders (von Willebrand disease)
- Collagen abnormalities (fragile blood vessels and bruising)
Thrombophilia – excessive clotting leading to thrombosis:
- Inherited: mutations in coagulation factors (DVT)
- Acquired: malignancy increases clotting factors (DVT)
Disseminated intravascular coagulation (DIC) – whole body clots:
- Infection
- Depletion of clotting factors and platelets leads to bleeding
What defects can cause excessive clotting
Factor V Leiden mutation:
- Resistance to APC
- FVa is not inactivated
- Increases risk of DVT
Antithrombin deficiency:
- Thrombin, IXa and FXa are not inactivated
- Increases risk of DVT
Protein C&S deficiency:
- Increases risk of DVT
What can cause deep vein thrombosis
Development of a venous thrombus depends on:
- Alterations in the constituents of the blood
- Changes in normal blood flow
- Damage to the endothelial layer
What are some symptoms of DVT
- Pain & tenderness of veins
- Limb swelling
- Superficial venous distension
- Increased skin temperature
- Skin discoloration
All reflect obstruction to the venous drainage
Increased risk of pulmonary embolism
