Haemostatics and Blood Clotting

More importantly, damaged endotheilial cells release certain chemicals: 

Thromboxanes 

these act on the tunica media and cause the vessel to constrict 

Endothelins.

Short proteins which act on the tunica media causing the vessel to constrict. 

Normally occurs following damage to small vessels in the body.

Reduces blood loss for several minutes to hours during which time other homeostatic mechanisms go into action.

Vascular spasm can be caused by pain via neural routes as blood vessels are surrounded by many pain receptors.

Haemostatics = “To arrest bleeding”

   There are three major haemostatic mechanisms in the human body, what are they?

Useful for plugging small tears in blood vessels 

The Platelet PLug is initially quite loose but becomes quite tight when reinforced by fibrin threads 

Can stop blood loss completely if the tear in the blood vessel is small. 

When a blood vessel is damaged, collagen fibres become exposed 

Blood flows over the damaged area which causes the release of Von Willband Factor 

This factor coats the exposed collagen fibres and platelets adhere to it. 

Platelets are able to adhere to the factor due to the presence of integrins. 

These are proteins and glycoproteins that sit n the surface of the platelets. 

As the platelets bind to the Von Willieband Factor they may become activated and in tuen produce ither factors/responses. 

This phase is called the platelet release reaction. 

1 - Von Willebrand adheres to exposed collagen 

2 - Platelets adhere to the VW factor 

3 - Platelets ahdered to the VW factor activate other enzymes which also assist in the platelet release reaction. 

Thromboxane - Further platelet aggregation and vasoconstriction 

Adenosine Diphosphate - Further platelet aggregation and vasocomstriction 

Serotonin - further platelet aggregation and vasoconstriction. 

Platelet activating factor - further platelet aggregation 

Integrin - makes the platelets already present "stickier" (more likely to adhere to each other) 

Fibrinogen - Facilitates the platelets cross linking and forming the platelet plug

Extrinsic Pathway 

- Occurs outside of the blood following damage to tissues

Intrinsic Pathway

- Occurs within the blood and follows on from platelet plug formation 

The Common Pathway 

- The intrinsic and extrinsic pathways converge at the point where an enzyme called Prothrombinase is activated 

- From here onwards the mechanismis reffered to as the common pathway.

Normal clotting depends on adequate Vitamin K 

Although not involved in actual clot formation it is required fir the synthesis of clotting factors. 

Pt's suffering from disorders that effect Vitamin K are at risk of uncontrolled bleeding. 

The consolidation or tightening of the fibrin clot 

Fibrin threads attached to the damaged sirfaces of the blood vessel gradually contract due to platelets pulling on them

As the clot retracts it pulls the edges of the damaged vessel closer together 

Thus the risk if haemorrage is further decreased. 

The fibrinolytic system regulates the clotting process

It also dissolves clots at the site of damage once the damage has been repaired.

There are 2 major mechanisms:

- Anti-Thrombin, aids in clot dissoloution 

- The Plasmin Pathway (Fibrinolysis) 

Context, 

Despite the advances in trauma care, haemorrhage still kills alot of people. 

Dependant on the source the figures range bewtween 25% and 45%.

Haemorrhage generally kills within the first 4 hours of the point of injury. 

Haemorrhage is the leasding cause in potentially preventable death. 

Coagulopathy - excessive infusion 'haemodilites' blood and its clotting factors

Acidosis - The coagulation process becomes impaired from excessive acidosis 

Hypothermia - The Coagulation process becomes impaired by hypothermia (low body temperature)

This is an ever developing area of research 

Well established - 'Resuscitation associated' coagulopathy (aka the lethal triad)

- hypothermia 

-acidosis

-coagulopathy

More novel 'ATC' "Acute Traumatic Coagulopathy) 

- up to 30% of trauma pt's arrive at the MTC with this. 

More novel, SHINE , Shock Indcuced Endothlialopathy. 

First demonstrated, scientifically, in 2007. 

Combines a number of factors 

- coagulation factor deficency (Hypocoagulopathy)

-- inactivation of factors 5, 7 and 10 in the clotting cascade (refer to notability on coagulation date 09/11/2020)

-- because of activated protein C, for which the exact mechanism isnt fully understood 

--... may be to do with the inflammatory response to trauma 

Increased fibrinolysis (hyperfibrinolysis) 

- plasmin breaks down fibrin threads and clots

- plasminogen (inactive) is convertedin to plasmin by t-PA (tissue plasminogen activator)

- the "sympathetic" response to trauma may result in increased production of t-PA from the endothelium. 

- Sometimes called endothelial dysfinction 

- results in increased endotheilial permeability and decreased circulating volume becuase of the damage to the Glycocalyx. 

- An emerging area of science again not fully understood 

- Because of the release if catecholamines 

-- i.e. to do with the sympathtic response to trauma.