Platelet Structure and Function Flashcards
Primary hemostasis
Platelets-adhesion, activation, aggregation (AAA)
Secondary hemostasis
Coagulation cascase-3D network of fibrin, platelets, and RBCs to form fibrin clot
Clot removal, vessel wall restored
Fibrinolysis
Platelets form by fragmentation at the end of cytoplasmic processes extending from these cells
Megakaryocytes
Where are platelets produced?
In bone marrow
Normal platelet life span
10 days
At any one time, 1/3 of platelets are resting in this organ
Spleen (also a little in liver)
Normal platelet count
145,000-450,000 / ul
Like RBC, platelets do not contain?
Unlike RBCs, platelets contain?
no nucleus, mitochondria in cytoplasm
How and where are old platelets removed?
In spleen and by kupffer cells in the liver
Platelets contain many important glycoprotein surface receptors. List the 4 important ones:
- VWF receptor
- Thrombin receptor
- Fibrinogen receptor
- ADP receptor
GP1b/IX/V
Von Willebrand receptor
This ligand facilitates adhesion, the “glue” between platelets and subendothelium
Von Willebrand Factor
G-coupled protein platelet receptor
ADP receptor
ligand responsible for initial platelet shape change, binds ADP receptor
P2Y1
ligand responsible for completion of platelet aggregation, binds ADP receptor
P2Y12
Activates platelets through a family of unique protease-activated receptors (PAR)
Thrombin, binds to thrombin receptor
When does Thromboxane A2 (TxA2) synthesis occur?
platelet activation. promotes aggregation
In addition to glycogen stores, the central area of platelet cytoskeleton contains what two types of granules?
Dense and alpha granules
Platelet cytoskeleton contains what type of tubular system?
Dense. Contain microtubules (maintain shape) and actin filaments (maintain shape and platelet contraction)
Platelet cytoskeleton contains what type of canalicular system?
Open, vesicles continuous with outer plasma membrane
Main function of platelets (3)
Blood clotting, repair blood vessels, prevent blood loss
In addition to serving as a cofactor in platelet adhesion, VWF is also a carrier for what?
Factor VIII, has other functions
What type of granule ca you not see under conventional light microscopy (requires EM)
Dense granules
Specific receptor exposure, glycoprotein IIb/IIIa, occurs during this phase
Activation
What are glycoprotein IIb/IIIa’s primary ligands?
Von Willebrand factor and fibrinogen
This receptor is present on platelet surface but inaccessible to ligands, needs to be activated.
ADP, ATP, serotonin, and calcium are in this granule
Dense granules
Growth factors, proteoglycans, coagulation proteins, adhesive glycoproteins, and P-selectin are in this granule
Alpha granules
Can see these granules under conventional light microscopy
Alpha granules
Platelet shape change occurs during this phase
Activation
Granule release occurs during this phase
Activation
TxA2 synthesis occurs during this phase
Activation
Phospholipid exposure occurs during this phase
Activation
What do Phosphatidylserine and Phosphatidylethanolamine provide during phospholipid exposure?
The negative charge for a catalytic surface for fibrin clot formation
These activating complexes require calcium ions for binding of coagulation factors
Tenase and prothrombinase complexes
TxA2 is involved in activating other platelets. What pathway produces TxA2? What initiates the pathway?
The arachidonic acid pathway produces TxA2. Platelet activation initiates the arachidonic acid pathway.
COX inhibitors
Inhibit TxA2 formation, an example is aspirin. This is why older people take baby aspirin to decrease risk of stroke. Essentially keep platelets quiet
Formation of platelet cluster
Aggregation
What is the glue during aggregation?
Fibrinogen
What is the role of thrombin in platelet pro-coagulant activity?
Recruits additional activated platelets to clot and stimulates conversion of fibrinogen to fibrin (helps stabilize fibrin clot)
How do platelets promote vessel repair?
Release growth factors
These two growth factors play a major role in connective tissue repair and regeneration.
PDGF (platelet derived growth factor)
TGF-beta (transforming growth factor)
Thrombocytopenia
Decreased platelet count (bleeding)
Thrombocytosis
Increased platelet count
What is the thrombocytosis paradox?
Increased platelet count usually implies clotting, but sometimes thrombocytosis is due to bleeding. If you have disfunctional platelets, they either don’t adhere, activate, aggregate etc. properly. This is an example of mixed quantitative and qualitative.
In a platelet aggregation test, epinephrine, ADP, Collagen, Arachidonic Acid, and Ristocetin are all examples
Agonists (platelets are exposed to these ligands, and if they aggregate, ere is an increase in light transmission)
During platelet aggregation test, you can see a biphasic pattern. What are the primary and secondary wave due to?
Primary wave: activation of GPIIb/IIIa integrin
Secondary wave: platelet granule release
What is TxA2 involved in?
activating other platelets
