Formation of the Platelet Plug
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In the coagulation cascade, glycoprotein receptors have two subunits, α, and β, which are responsible for platelet aggregation and adhesion.
They are present on the platelet plasma membrane and undergo a conformational change upon platelet activation, allowing them to adhere to each other. These GP IIb/IIIa inhibitors bind to the receptor and prevent fibrinogen and von Willebrand factor (vWF) from binding to the receptors.
Integrillin has a half-life, elimination of 2.5 hours, and the onset of action occurs in 1 hour with a duration of action of 4 hours. It is 25% protein-bound and has a Vd of 185 to 260 mL/kg. Its excretion is via the urinary system. It has a renal clearance of 55 to 58 mL/kg/hr.
Tirofiban has a half-life of 2 hours, and its duration of action is 4 hours. It is 65% protein-bound, and its Vd is 22 to 42. About 65% of tirofiban clearance is through urine and 25% through feces. Its clearance is 213 to 314 mL/min. It is dialyzable.
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Platelets bind to cellular and extracellular matrix constituents of the vessel wall and tissues through specific membrane receptors
Glycoprotein receptors on the platelet plasma membrance have two subunits, α, and β. They are responsible for platelet aggregation and adhesion.
The platelets undergo a conformational change upon of the glycoprotein receptors, allowing them to adhere to each other.
Vascular injury exposes von Willebrand Factor (vWF), normally located between the endothelium and the basement membrane.
Platelets quickly adhere to the site of injury by binding to von Willebrand factor primarily and to exposed subendothelial collagen to a lesser extent through specific platelet membrane collagen receptors
- Platelet plug formation is activated by a glycoprotein called Von Willebrand factor (vWF), which is found in plasma. (?)
- When platelets come across the injured endothelium cells, they change shape, release granules and ultimately become ‘sticky’. Platelets express certain receptors, some of which are used for the adhesion of platelets to collagen. When platelets are activated, they express glycoprotein receptors that interact with other platelets, producing aggregation and adhesion. Platelets release cytoplasmic granules such as adenosine diphosphate (ADP), serotonin and thromboxane A2. Adenosine diphosphate (ADP) attracts more platelets to the affected area, serotonin is a vasoconstrictor and thromboxane A2 assists in platelet aggregation, vasoconstriction and degranulation. As more chemicals are released more platelets stick and release their chemicals; creating a platelet plug and continuing the process in a positive feedback loop. Platelets alone are responsible for stopping the bleeding of unnoticed wear and tear of our skin on a daily basis. This is referred to as primary hemostasis.[5][7]
Inhibitors
[These GP IIb/IIIa inhibitors bind to the receptor and prevent fibrinogen and von Willebrand factor (vWF) from binding to the receptors.
Integrillin has a half-life, elimination of 2.5 hours, and the onset of action occurs in 1 hour with a duration of action of 4 hours. It is 25% protein-bound and has a Vd of 185 to 260 mL/kg. Its excretion is via the urinary system. It has a renal clearance of 55 to 58 mL/kg/hr.
Tirofiban has a half-life of 2 hours, and its duration of action is 4 hours. It is 65% protein-bound, and its Vd is 22 to 42. About 65% of tirofiban clearance is through urine and 25% through feces. Its clearance is 213 to 314 mL/min. It is dialyzable.
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Platele adhesion is enhanced by release of von Willebrand factor (vWF).
von Willebrand factor (vWF) resides in the plasma, subendothelial matrix, and storage granules within endothelial cells and platelets.1
It is in megakaryocytes. Platelets come from megakaryocytes.
vWF is a multimer composed of repeating subunits that create several binding sites for the proteins with which it interacts.
Platelets and vWF will combine to form a plug at the site of injury.
Circulating vWF bind with collagen and Factor VIII as well as other endothelial substances, allowing the platelet plug to adhere to the area of injury.