Blood – Platelets Flashcards
What is the shape of platelets?
disc-shaped
Do platelets have nuclei?
no
What allows for platelet shape alteration?
pseudopodia
What are the 2 types of granules in platelets?
- alpha granules
- dense granules
What do alpha granules contain?
- coagulation factors
- procoagulants (ie. factor V, vWF)
- platelet-derived growth factor
- adhesion molecules
What do dense granules contain?
- ADP
- ATP
- Ca2+
- serotonin
What is thrombopoietin?
liver hormone
What does thrombopoietin do?
- stimulates megakaryocyte (precursors to platelets) production in bone marrow
- produces clotting factors
What type of replication is thrombopiesis?
endomitotic synchronous nuclear replication – replicating DNA without cell division occurring
Thrombopoiesis
When does cytoplasmic granulation occur?
- occurs at any stage during maturation
- the earlier granulation occurs, the fewer amount of platelets will be produced
What is thrombopoiesis?
generation of platelets
How does platelet formation (thrombopoiesis) occur?
- endomitotic synchronous nuclear replication – megakaryocyte maturation
- cytoplasmic granulation
- cell fragments (platelets) break off from edges of megakaryocytes
Where does platelet formation occur?
(after release from cells) occurs in bone marrow or quickly following entry into circulation
What does a normal hemostatic response do?
acts to arrest bleeding following injury to vascular tissue
What are the 3 hemostasis responses?
- reaction of blood vessels (vasoconstriction)
- immediate response to vascular injury - primary hemostasis (platelet plug)
- occurs quickly, but not sufficient - secondary hemostasis (clot formation)
What is secondary hemostasis?
clot formation – network of stable fibrin that is laid on top of platelet plug
Hemostatic Vasoconstriction
What are the 2 components of the hemostatic vasoconstriction response?
- local contractile response (vasoconstrictionm and increased tissue pressure)
- release of humoral substances
Hemostatic Vasoconstriction
What does increased tissue pressure do?
helps compress vessels and reduce their diameter
Hemostatic Vasoconstriction
What does vasoconstriction do?
reduces diameter of vessels – blood less likely to flow there
Hemostatic Vasoconstriction
What is a neurogenic spasm?
rapid, but short lasting (~60 seconds) response
Hemostatic Vasoconstriction
What is a myogenic spasm?
longer lasting response (20-30 minutes)
Hemostatic Vasoconstriction
What are the 3 humoral substances released?
- serotonin – released from activated platelets
- endothelins – released from injured endothelium
- clotting factors – blood coagulation cascade reactions
What does serotonin do?
promotes vasoconstriction
What does endothelin do?
promotes vasoconstriction
What does exposure due to damaged blood vessel result in?
contact between substances that do not normally occur
Platelet Plug Formation
- Platelets adhere to:
- von Willebrand factor (vWF), mediated by glycoproteins on platelet surface (GpIb)
- exposed collagen fibers in vascular wall
- Activated platelets undergo conformational change (pseudopodia formation), and release:
- alpha granules (clotting factor V, fibrinogen, vWF)
- dense granules (ADP, ATP, serotonin, Ca2+)
- ADP and fibrinogen are responsible for initiation of platelet aggregation
- ADP stimulates release of thromboxane A2 (from activated platelets), which acts as potent vasoconstrictor and potentiates platelet aggregation (positive feedback)
- more platelets = more release of thromboxane A2 - Results in formation of unstable hemostatic (platelet) plug
- plug may be sufficient to stop bleeding in small vascular injuries
- plug formation is localized due to ADP-induced prostacyclin and NO release
Role of Prostaglandins
What does prostacyclin (PGI2) do?
inhibition of platelet aggregation in intact vessels
Role of Prostaglandins
What does thromboxane A2 (TXA2) do?
activation of platelet aggregation in damaged vessels
Role of Prostaglandins
How might aggregation and adhesion be prevented?
reduction of free cytosolic Ca2+ due to high cAMP levels
Role of Prostaglandins
What is there an enhanced production of in activated platelets? What does this do?
enhanced production of TXA2
- decreases level of cAMP → impacts Ca2+ in cell
- helps enhance aggregation of platelets
Role of Prostaglandins
What does the pathway in healthy, intact endothelial cells do?
results in production of prostacyclin, which is released from endothelial cells
- prostacyclin acts on activated platelets to increase amount of cAMP
- increases Ca2+ levels to help prevent release of TXA2-mediated response
- results in less vasoconstriction, and less aggregation
Role of Prostaglandins
Where is Cox found?
endothelial cells
Role of Prostaglandins
What does release of prostacyclin do?
helps stop activated platelets from aggregating in that region
- if platelets are not activated, loss of prostacyclin does not have as big of an impact
Role of Prostaglandins
What does Cox do?
if prone to clotting (aggregation of platelets), reducing activity of Cox in platelet itself will help prevent aggregation (prevent platelet plug formation)
What is baby aspirin (aspirin 81)?
Cox (cyclo-oxygenase) inhibitor
What is the goal of the coagulation cascade?
create stable fibrin formation (clot) to strengthen platelet plug and complete the seal
What is the main requirement for the coagulation cascade?
production of thrombin – acts on fibrinogen (factor I) to promote fibrin clot formation