Lec. 48 Platelet Plug Flashcards
Two components to a thrombus
Platelet Plug: aggregation of platelets to plug the injury, called primary hemostasis
Fibrin Clot: coagulation factor proteases aggregate and produce thrombin, thrombin makes fibrin monomers that are cross linked to form a meshwork around the platelet plug, called secondary hemostasis
Where are platelets produced?
Produced from megakaryocytes in bone marrow
What is thrombocytopenia?
low platelet count
less than 1x10^5/mL
What prevents resting platelets from adhering to each other or the vessel wall?
A negatively charged glycocalyx
What organelles do platelets have and not have?
Platelets lack a nucleus, but they do have mitochondria and lysosomes.
What granules do platelets have?
Dense granules: several per cell, store Ca2+ and ADP
Alpha granules: 50-80 per cell, store von Willebrand Factor, fibrinogen, coagulation factor V
Two membranous structures that play an important role in platelet function
Canalicular system: invaginations in the plasma membrane of platelets, provides surface area for vesicular trafficking
Dense tubular system: network of ER in the platelet, stores Ca2+ and releases it during activation
What is the function of glycoproteins in platelet adhesion, and what three types are there?
Glycoproteins are integrins that are essential for the binding of platelets to each other and the damaged endothelial wall.
1) GPIb: binds to von Willebrand Factor
2) GPIa & GPVI: bind to collagen
3) GPIIb/IIIa: bind to vWF or fibrinogen
What happens to a platelet when it is activated?
Conformational changes in the cell surface receptors (glycoproteins)
Degranulation: granules are released into extracellular space, signals other platelets, facilitated by canalicular system
Change in cell shape: microtubules contract to change cell from disc shape to spiny spheres with pseudopods or filopodia
Cell receptors on platelets bind to what ligands that activate the platelets?
Epinephrine
ADP
Thrombin
TXA2
What ligands are released from platelets after they are activated?
Phospholipase A2 which results in the synthesis of TXA2
Degranulation releases platelet activators such as ADP
How does GPVI activate platelets?
Binds collagen in the subendothelia and activates platelets through tyrosine-kinase coupled receptors.
Interaction between Thrombin and PAR (protease activated receptor)
Thrombin is a protease that cleaves a small portion of a protein off the tail of a GCPR located on the surface of platelets called PAR. This tail becomes a tethered ligand that activates it’s own receptor and stimulateGalpha-q related signaling. This is a strong activator of platelets.
What two molecules are in the subendothelial layer and are essential for the initial adhesion of platelets at the site of injury?
Collagen & vWF
How does vWF tether platelets to collagen?
vWF can bind to both collagen and platelet integrin receptors (GPIb) to tether the two together.