IHL I - Platelet Function (DSA) Flashcards
what stimulates the formation of platelets?
TPO and IL-3
megakaryocytes
release platelets in the bone marrow
stimulated by TPO and IL-3
several thousands/day
lifespan 7-10 days
what stimulates the production of megakaryocyte
SCF, TPO, IL-3, and GM-CSF
stimulate the common myeloid progenitor to form the megakaryocyte
thrombopoietin
stimulation of platelet formation
-produced by liver and kidney
what is the receptor for thrombopoietin
MPL receptor
located on platelets
binding to platelets destroys the TPO (negative feedback)
-more platelets, less megakaryocyte maturation
normal blood concentration of platelets
150-450 x10~9/L
thrombocytopenia
decrease of platelets in the blood
thrombocytosis
high platelet levels in the blood
structure of platelets?
external surface of glycoprotein receptors
tubulin microtubules encircle the disk forming inner skeleton
actin and myosin contractile proteins in the interior
alpha-granules
-vWF, platelet factor 4, TGF-beta1, PDGF, factors 5 and 7, and fibrinogen
dense-core granules:
-ADP, serotonin, histamine, epinephrine, and Ca2+
what are in the alpha granules of platelets?
vWF, platelet factor 4, TFG-B1, PDGF, factors 5 and 8, fibrinogen
what is in dense-core granules
ADP, serotonin, histamine, epinephrine, Ca2+
where are platelets found?
bone marrow (production) blood (permanent residents)
circulating platelets
in the circulating blood
activated???
sequestered platelets
aka marginalized
in pulmonary venous and splenic sinusoids
reserve for platelets and can increase up to 50%
three process of platelet plug formation
adhesion, activation, aggregation
mechanism of platelet adhesion?
binding of platelets to vWF on the endothelium exposed
-normally prevented due to negative charge on platelets and endothelial cells
initiated by increased shearing force
also promoted by release of vWF from alpha granules
mechanism of platelet activation?
binding of vWF triggers G-protein signal transduction via activation of phospholipase C and Ca2+ influx
initiates release reaction:
- exocytosis of dense granules and alpha granules - production of thromboxane A2 - thrombin causes platelet to form filolpod extensions
mechanism of platelet aggregation?
release of ADP, serotonin, thromboxane A2 and Ca2+ activates additional platelets to adhere
promotes platelet aggregation
vWF binds to glycoprotein receptors and activates more platelets while forming bridges between them
additional stuff during aggregation?
activation also changes the Gp IIb/IIIa receptors on the surface and allows them to bind fibrinogen
-allows platelets to form bridges between other platelets via fibrinogen
-results in platelet plug
what promotes clot formation?
release of calcium from activated platelets