YK Goh How does the endothelium prevent coagulation Vascular Surgery

Q: How does the endothelium prevent coagulation in the normal

vascular system - Intravascular anticoagulants?

Endothelial surface factors:

1. Smoothness of the endothelial cell surface

o Prevents activation of the intrinsic clotting system (Factor XII and platelets)
2. A layer of glycocalyx on the endothelium
o Glycocalyx is a mucopolysaccharide adsorbed to the surfaces of the
endothelial cells
o Which repels clotting factors and platelets
o Thereby preventing activation of clotting
o Binds to antithrombin III removes thrombin
3. A protein bound with the endothelial membrane (Thrombomodulin)
o Thrombomodulin binds to thrombin
This slows the clotting process by removing thrombin
o Thrombomodulin-thrombin complex activates a plasma protein, protein C
Protein C acts as an anticoagulant by inactivating activated Factors
V and VII
Factor V accelerates the protease accelerates prothrombin
activation
Factor VII complexes with TF to activate Factor X

Lysis of blood clots

o Vascular endothelium very slowly release a powerful activator called tissue
plasminogen activator (t-PA)
After the clot has stopped bleeding, eventually converts plasminogen
to plasmin
Removes remaining unnecessary blood clot
When the endothelial wall is damage, its smoothness and its glycocalyx-
thrombomodulin layer are lost
o Which activates both Factor XII and the platelets
Setting off the intrinsic pathway of clotting
o If Factor XII and platelets come in contact with the subendothelial collagen,
activation is even more powerful

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YK Goh How does the endothelium prevent coagulation Vascular Surgery

EXTRA:
Other aspects of the endothelium that prevent coagulation

Endothelium controls the extravasation of fluid, solutes, hormones,

macromolecules as well as platelets and blood cells
o Guarantees the availability of appropriate amounts of clotting factors and
platelets (not in excess when not needed)
o Involvement of endothelium in the conversion and catabolism of vasoactive
agents
Histamine, bradykinin, vasopressin and thrombin
o Endothelium plays an important role in the control of perfusion of specific
tissues and blood tension by local vasoregulation
If endothelium activated by vasoactive agents, they release VWF and t-PA
o VWF is only synthesized in the endothelium
o VWF promotes binding of platelets
o t-PA enhances control by fibrinolysis
Endothelium prevents exposure of Tissue Factor to Factor VII (Extrinsic pathway)
VWF cut into smaller multimers by action of metalloproteinase ADAMTS13 on the
surface of endothelium
Platelet activation is counteracted by prostacyclin and prostaglandin E2
o Which are liberated from endothelium after stimulation by vasoactive agents
and thrombin
Prostacyclin is produced by the endothelium of large vessels
Prostacyclin is enhanced by nitric oxide
Endothelial cells from smaller vessels produce predominantly
prostaglandin E2
Endothelium produces nitric oxide by nitric oxide synthase (eNOS) - antithrombotic
o NO production is rapidly enhanced after exposure of endothelial cells to
vasoactive agents

Resources:

Guyton and Hall Textbook of Medical Physiology

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233666/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617895/

http://circ.ahajournals.org/content/126/9/1127