Aim of Coagulation
To produce sufficient thrombin to rapidly convert soluble fibrinogen into insoluble mass of fibrin
Coagulation cascade must be localised & limited to site of tissue injury
Three phases
1. Immediate Control of Blood Loss
Vascular Phase
- damage to blood vessel triggers reflex vasoconstriction
Platelet phase
- damage blood vessels release serotonin and adrenalin
- stimulates vasoconstriction and platelet aggregation
- platelets release thromboxane A2
- stimulates further platelet formation
- platelets form plug
2. Clot Formation
Formation of fibrin
- red cells & platelets bound together by strands of fibrin
- final common pathway is Factor X activation
- factor X converts Prothrombin to Thrombin
- thrombin converts Fibrinogen to Fibrin
Intrinsic System
- started by activation of factor XII
- secondary to exposed subendothelium
- HMWK & PreKallikrein-->Kallikrein
- ends with activation factor X
Extrinsic System
- tissue Thromboplastins
- released by tissue damage
- activate factor VII
- activates factor X
3. Removal of Clots
Fibrinolytic enzymes remove clot as vessel wall repaired e.g plasmin
Platelets
Function
- when subendothelial structures are exposed to flowing blood, platelets adhere to subendothelial VWF & collagen
- platelets then release granules
- ADP & Thromboxane A2
- potentiates aggregation & stimulates vasoconstriction
Bleeding time
BP cuff inflated to 40 mm Hg & incision made
- time until bleeding ceases is noted
- normal < 9 minutes
Prolonged with
- platelet count < 50,000/mm
- platelet function impaired (NSAIDs, aspirin)
- von Willebrand Disease
Thrombolytics
Prostacyclin
- produced in vessel walls
- has antithrombotic effect
- high intimal concentration discourages luminal obstruction by platelets
- antagonist effect to TXA2
Antithrombin III
- circulating protease
- binds & inhibits Thrombin
- inhibits II, IXa, Xa, XIa, XIIa
- ↑ APTT (Intrinsic)
- heparin globally increases its activity
- LMWH only works against Xa
Protein C & S
- Vit K dependent
- natural anti - Thrombolytics
- activated by Thrombin
- familial lack rare ++ 1: 16 000
- decreased amount associated with spontaneous DVT
Tissue Plasminogen Activator
- converts plasminogen to plasmin
- plasmin degrades fibrin
- e.g. streptokinase, urokinase, TPA