Background

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