1) Platelet structure & function Flashcards
2 functions of hemostasis
- stop bleeding
- maintain blood in fluid form
breakdown of a clot
fibrinolysis
function of plasmin
digests fibrinogen & fibrin (fibrinolysis)
pinpoint bleeding from arterioles, venules
petechiae
bruises/bleeding from veins
ecchymoses
nosebleed
epistaxis
mucocutaneous bleeding
platelets deficient or defective
joint bleeding
factor deficiency
presents with both mucocutaneous bleeding and joint bleeding
DIC
clot formation on the interior of an intact vessel
thrombosis
the ———– effect is disturbed when there is stagnation of blood flow
endothelial anticoagulant
normal VECs are ————–, so clots do not form
thromboresistant
inactive coag proteins in circulation
zymogens
VECs, plasma components and platelets normally repel each other because…
they are negatively charged
vasoconstrictors
- serotonin
- TXA2
- endothelin-1
vasodilator
prostaglandin (PGI2)
tissue factor is also called…
thromboplastin
t-PA
tissue plasminogen activator
dissolves fibrin clot
inactivates and clears thrombin
activates protein C coag inhibitor
thrombomodulin
clots mainly form in…
arterioles & venules
for normal function, need at least —— plt
100
plt <20
at risk for spontaneous bleed
plt >20, <50
at risk for hemorrhage during surgery, trauma
plt >50, <100
minimal risk of hemorrhage during surgery
platelets have ———– (nonspecific) granules
azurophilic
platelets last…
7-10 days
distribution of platelets in body
70% in circulation
30% in spleen reserves
splenomegaly — plt in PB
↓
stages of plt development
- HSC
- CFU-GEMM
- CFU-Meg
- BFU-Meg
- Megakaryoblast
- Promegakaryocyte
- (Meta)megakaryocyte
- Platelet
regulates all stages of plt development
thrombopoietin (TPO)
TPO is made by the…
liver
spleen
kidneys
TPO binds to ——- on plts/megas, which renders it unable to stimulate proliferation (negative feedback)
CD110
DNA count doubles but there is no cell division
results in polyploidy cells
endomitosis
megakaryocytes
DMS
demarcation membrane system
membranes form all throughout mega cytoplasm, which will become platelets
blast → mature plt takes — days
5
characteristics of megakaryoblast
- 20-45 μm
- single round or oval nucleus
- 1-2 nucleoli
- blunt protrusions (blebs)
- scant cytoplasm
- no granules
characteristics of promegakaryocyte
- more cytoplasm
- multiple nuclei
- 20-80 μm
- reddish granules
- demarcation membranes begin to form
characteristics of megakaryocyte
- multiple nuclei
- 30-100 μm
- many small uniform granules, reddish blue
- demarcation system
what happens once the mega reaches maturity and is ready to produce plts?
membrane ruptures
nuclei are engulfed by macrophages
RR for megas on BM
1-4 megas/100 nucleated cells
plt shape at rest
discoid
4 plt zones
- peripheral zone
- structural zone
- organelle zone
- membrane systems
parts of plt peripheral zone
glycocalyx (GPs)
phospholipid membrane
vWF, thrombin and ristocetin receptor
GPIb/IX
CD42b/c
GPIb/IX
fibrinogen receptor
GPIIb/IIIa
hidden in resting plts and appears on activation
GPIIb/IIIa
CD41/61
GPIIb/IIIa
parts of plt structural zone
- cytoskeleton
- microtubules
- protein network
function of plt microtubules
contract during stimulation
allows for degranulation, and ↑ surface area
plt protein network consists of…
actin and myosin
parts of plt organelle zone
- mitochondria
- glycogen (source of energy)
- granules
3 types of plt granules
- dense bodies
- alpha granules
- lysosomal granules
contained in dense bodies
ADP
ATP
serotonin
Ca2+
contained in alpha granules
PF4
PDGF
(alpha granules/dense bodies) are more numerous
alpha granules
contained in plt lysosomal granules
microbicidal enzymes
proteases
hydrolases
OCS
open cannalicular system
2 plt membrane systems
- OCS
- DTS
function of OCS
- from surface to interior
- plt storage and secretion
DTS
dense tubular system
function of DTS
Ca2+ storage
Bernard-Soulier disease
↓ or dysfunctional GPIb/IX
2 types of plt adhesion problems
Bernard-Soulier disease
von Willebrand disease
activation of plt leads to externalization of ——— and …
GPIIb/IIIa
secretion of granules’ contents
precursor to TXA2
arachidonic acid
TXA2 synthesis requires enzyme ———-
causes…
cyclooxygenase
degranulation & vasoconstriction
action of aspirin
inhibits TXA2 synthesis
most potent plt activator
thrombin
2 types of plt aggregation problems
Glanzmann thrombasthenia
↓ fibrinogen
Glanzmann thrombasthenia
↓ or dysfunctional GPIIb/IIIa
hepatin neutralizer
PF4
promotes smooth muscle growth
helps heal wounded tissue
PDGF