Physiology of Haemostasis

Physiology of Haemostasis Lecture by:

Usi Sukorini

Department of Clinical Pathology

Faculty of Medicine GMU

Yogyakarta

2008

Vessel walls

The vascular intima

1. Innermost vascular lining
   
2. Endothelial cells (endothelium)
   
3. Supporting the endothelial cells
   
4. Basement membrane composed of collagen surrounds endothelium
   
5. Subendothelial connective tissue
   

• Collagen, fibroblast in veins
  
• Collagen, fibroblast, and smooth muscle cells in arteries
  

The vascular intima in haemostasis

Vascular intima of vessel wall is lined by a layer called endothelial cell

Endothelial cells have a smooth, unbroken surface that promotes the fluid passage of blood and prevents turbulence that may otherwise activate platelet and plasma enzymes

Any harmful local stimulus, be it mechanical or chemical, induces vasoconstriction in arterial or arterioles and initiate hemostasis mechanism

Vessel walls

Thrombogenic surface or Procoagulant properties

Procoagulant properties of vascular intima

First, any harmful local stimulus induces vasocontriction in arteries and arterioles

(endothelin = vasoconstrictor))

The SMCs contract, the vascular lumen narrows or closes, and blood flow to the injured site is minimized

Second, the BM and subendothelial connective tissues of arteries & veins are rich in collagen that binds and activates platelets

Third, ECs secrete von Willebrand factor (vWF), a glycoprotein that is necessary for platelets to adhere to exposed subendothelial collagen

Fourth, upon activation, ECs secrete and coat themselves with P-selectin, an adhesion molecules that promotes platelet and leucocyte binding

ECs also secrete immunoglobulin-like adhesion molecules called ICAMs (intercellular adhesion molecules) and PECAM (platelet endothelial cell adhesion molecules) that promote leucocytes binding

Finally, subendothelial cells, that is, smooth muscle cells and fibroblast, support a constitutive surface protein called tissue factor (TF)

Exposed TF activates the plasma coagulation system through factor VII

While damaged vessels have procoagulant properties, the intact vascular intimal layers prevent intravascular thrombosis by several mechanism

Fibrinolytic properties of vascular intima

ECs support fibrinolysis with 2 secretions: TPA (Tissue Plasminogen Activator) and PAI-1 (Plasminogen Activator Inhibitor-1)

Platelet

The blood platelets are fragments of the cytoplasm of the megakaryocyte, hence they are non-nucleated and formed chiefly in the bone marrow

Platelet activation

Platelet adhesion

Release reaction

Platelet aggregation

Platelet secretion/release reaction

The series of platelet events

Platelet adhere to exposed cellular matrix (collagen) at sites of endothelial injury and become activated

Upon activated, platelets secrete granules (ADP) and synthezise TXA2 (Thromboxane A2)

Platelets also exposed phospholipid complexes important in the intrinsic coagulation pathway

Injured or activated endothelial cells release TF to activate the extrinsic coagulation cascade

Released ADP stimulates formation of primary haemostatic plug, which is eventually converted into a larger definitive secondary plug

Fibrin deposition stabilizes and anchors the aggregated platelets