Haemostasis Flashcards
How does a clot form (simple overview)?
-Vessel wall becomes damaged
=Injured endothelial cells actively promote clot formation via exposure of subendothelial collagen and release of tissue factor
-Von Willebrand factor (circulating protein) binds to components in blood vessel wall
-Capture platelets to activate coagulation factor cascade (exposure to ADP and thrombin) = recruit even more platelets
=Thrombus/ plug
=Clot dissolved to restore blood flow (fibrinolysis)
What is primary haemostasis?
-Involves the interactions between vessel wall, platelets and vWF to produce the initial barrier to blood loss, the primary haemostatic plug
Actions in primary haemostasis
- Vasoconstriction (immediate)
- Platelet adhesion (seconds)
=via vWF and collagen
=Produce and release thromboxane A to cause vasoconstriction to reduce blood flow to damaged area
=Platelets activated through various agonists then release further agonists like ADP for further activation - Platelet aggregation (minutes)
=Platelet to platelet linkages formed through binding of mainly soluble fibrinogen to activated Gp2b/3a on adjacent cells
=Strengthened when fibrinogen converted to fibrin
What is secondary haemostasis?
-Involves coagulation factors acting in concert to generate fibrin to strengthen the primary haemostatic plug
=Key enzyme: thrombin
Phases of in vivo coagulation
- Initiation: generates a small amount of thrombin from tissue factor and Factor VII interactions.
- Amplification: Thrombin causes positive feedback with large scale generation of thrombin on platelet surfaces
- Propagation: thrombin cleaves fibrinogen to fibrin. The clot is stabilised by cross-links via Factor XIIIa
What regulates secondary haemostasis?
Inhibitors (antithrombin, protein C, protein S)
Actions in secondary haemostasis timeline
- Activation of coagulation factors (seconds)
- Formation of fibrin (minutes)
What is fibrinolysis?
-A process which degrades the fibrin-bound clot to prevent vascular occlusion and remove the clot once the wound has healed
Actions in fibrinolysis (timeline)
- Activation of fibrinolysis (minutes)
- Lysis of the plug (hours)
Key enzyme in fibrinolysis
-Fibrinolytic plasmin (fibrin-splitting protease).
=Generated from plasminogen via activators such as tissue plasminogen activator (tPA) from endothelial cells.
=Plasmin fibrin into fibrin degradation products such as DDimers.
=Fibrinolysis also needs to be regulated via inhibitors like anti-plasmin.
Where do drugs act in haemostasis?
-Antiplatelet drugs: primary haemostasis
-Anticoagulant drugs: secondary
-Thrombolytic drugs: fibrinolysis
Von Willebrand Factor
This multimeric plasma protein binds to exposed collagen and is crucial for platelet adherence and activation
What is coagulation?
Mechanisms leading to the conversion of soluble fibrinogen to insoluble fibrin.
Describe the coagulation system
-The coagulation system consists of a cascade of proteolytic enzymes called coagulation factors.
-The suffix “a” refers to the
activated factor.
-These factors are synthesised in the liver, though Factor V is also made in endothelium and platelets.
-Synthesis of Factors II, VII, IX and X is Vitamin K dependent
What to involve in a bleeding history
-Have you bled?
=Challenges: birth, operations, dentistry, trauma
=Pattern: primary vs secondary (examination)
-PMH (liver disease)
-Family (haemophilia, vWD)
-Drugs (warfarin, DOA, aspirin)
