2007A10 Explain the mechanisms that prevent blood clotting in intact vessels.
(Do not draw the clotting cascade)

Reason for brakes

·   Once activated, coagulation is self-amplifying and potentially dangerous (e.g. DIC)

·   There must be anticoagulant controls to prevent and limit it

Pathophysiology

Virchow’s triad:

1.    Stasis

2.    Hypercoagulability

3.    Tissue injury

Each anticoagulant mechanisms addresses one or more of these

Continuous laminar flow

·   Keeps coag factors dilute

·   Keeps cells central, plasma peripheral (axial streaming)

·   Keeps vWF globular hence inactive
(Rx: ambulation, sequential calf compression)

Endothelial properties

·   Intact endothelium and glycocalyx = barrier between blood and subendothelium

·   Smooth surface promotes rapid, laminar flow

Reticuloendothelial system

·   Removes activated coagulation factors

Endogenous anticoagulants

·   Normally higher concentrations than procoagulants

·   From the liver

o Antithrombin 3 (AT3)

o Proteins C & S

o α₂-macroglobulin (inhibits thrombin)

·   Expressed by endothelium

o Heparin sulfate: potentiates AT3 1000x, inactivates IIa, IXa, Xa, XIa, XIIa

o Thrombomodulin:

o Tissue factor pathway inhibitor: inhibits TF/VIIa, Xa

·   Secreted by endothelium:

o Nitric oxide -> vasodilatation, ↓platelet activation -> ↓coag

o Prostacyclin -> vasodilatation -> ↑flow -> ↓coag

·   Interaction of the above:

Endogenous fibrinolytics

·   Does not prevent activation but limits propagation