Platelet Production and Function Flashcards
1
Q
what kind of cells do megakaryotes develop from?
A
- hematopoietic stem cells
2
Q
where do hematopoietic stem cells reside?
A
- in the bone marrow
3
Q
stem cell gives rise to
A
- early bilineage progenitors that are able to undergo erythrocyte or megakaryocytic differentiation
4
Q
Meg-CFCs begin
A
- endomitosis
5
Q
what happens in endomitosis
A
- DNA replication continues
- neither nucleus nor cell undergoes division
6
Q
what does endomitosis produce?
A
- a polyploid cell
7
Q
after endomitosis, what happens with megakaryoctes?
A
- they undergo cytoplasmic maturation
8
Q
process of cytoplasmic maturation
A
- increase in size
- fill with platelet-specific granules
- expand content of cytoskeletal proteins
- develop invaginated membrane system
9
Q
thrombopoietin function
A
- the physiologically relevant regulator of platelet production
10
Q
what is the TPO receptor
A
- C-Mpl
11
Q
C-Mpl is located on
A
- megakaryocytes
- platelets
12
Q
binding of TPO to its receptor does what
A
- prevents apoptosis of megakaryocytes
- increases their number, size, and ploidy
13
Q
additional of TPO to CD34+ cells in culture results in
A
- majority of cells becoming megakaryocytes
- shedding platelets
14
Q
synthesis of TPO is
A
- static
15
Q
TPO is made in
A
- the liver
16
Q
plasma TPO concentrations are regulated by
A
- platelet production rates
- platelet mass
- MK mass
17
Q
process of TPO regulation
A
- platelets and MKs expression c-Mpl receptors that bind and clear TPO from circulation
- thus regulate free TPO levels
18
Q
integrins are
A
- heterodimeric transmembrane molecules that cells use to both bind to and respond to extracellular matrix proteins
19
Q
integrins composed of
A
- alpha and beta subunits
20
Q
integrins link
A
- extracellular matrix
- intracellular cytoskeleton
21
Q
clustering of integrins leads to
A
- signaling into the cell
22
Q
signaling in the cell also causes
A
- activation of other integrins
23
Q
major platelet glycoproteins that are integrins
A
- a2B1
- A2bB3
24
Q
another name for a2B1
A
- GPIa-IIa
25
GPIa-IIa binds
- collagen
26
another name for a2bB3
- GPIIb-IIIa
27
GPIIb-IIIa binds
- fibrinogen
28
platelet glycoproteins that are not integrins
- GP Ib-IX-V
| - GPVI
29
GP Ib-IX-V binds
- von Willebrand factor
30
GPVI activates
- platelets by binding to collagen
31
platelet plug formation
- adhesion
- activation
- aggregation
- secretion
32
adhesion
- platelets stick to injured vessel wall via GP Ib-IX-V (1b-9-5) binding to vWF
33
activation
- resting platelets come into contact with agonists that bind receptors
- signaling occurs
- platelets change shape, secrete, and activate their GP IIb-IIIa integrins
34
aggregation
- platelets stick to each other via fibrinogen bridges binding to activated GP IIb-IIIa
35
secretion
- platelets release granular contents and potentiate clotting
36
platelet activators examples
- thrombin
- thromboxane
- collagen
- ADP
37
thrombin receptor
- PAR-1
38
type of receptor that PAR-1 is
- GPCR
39
what is the ligand of PAR-1
- it's own proteolyzed N-terminus
40
importance of thrombin
- most potent platelet agonist
41
how is thromboxane produced
- arachidonic acid -> TxA2
| - by COX1
42
COX1 reversibly blocked by
- NSAIDS
43
COX1 irreversibly blocked by
- aspirin
44
thromboxane receptor - type of receptor
- GPCR
45
what keeps the platelets from sticking to normal endothelium?
- nitric oxide
- ecto-ADPase
- prostacyclin
46
nitric oxide
- vasodilator
47
Ecto-ADPase
- chews up ADP to prevent platelet activation
48
how is prostacyclin produced
- arachadonic acid -> prostacyclin
| - via COX-1 and COX-2
49
prostacyclin
- vasodilator
| - inhibits platelet activation
50
membrane of platelets after activation
why?
- turned inside out
| - so the negative charges are on the outside
51
what anchors themselves to the now neg charged platelet membrane?
- coagulation proteins with gamma carboxyl groups
52
qualitative platelets disorders diagnosed by
- a prolonged bleeding time
| - or PFA 100 time
53
PT in platelet qualitative disorders
- normal
54
PTT in platelet qualitative disorders
- normal
55
TT in platelet qualitative disorders
- normal
56
DDX of qualitative platelet disorders
- congenital
| - acquired
57
DDx of congenital qualitative platelet disorders
- Bernard-Soulier
| - Glanzmann's thrombaesthenia
58
Bernard-Soulier defect in
- Ib-IX on platelet surface
59
result of Bernard-Soulier
- no adhesion
60
Ddx of acquired qualitative platelet disorders
- uremia
- drugs
- herbs
- myeloproliferative diseases
61
drugs that induce qualitative platelet disorders
- ASA
| - NSAIDS
62
symptoms of platelet dysfunction
- same defects as primary hemostasis
- petechiae
- mucocutaneous bleeding
63
mucocutaneous bleeding is
- oozing and bruising
64
mucocutaneous bleeding is NOT
- hematomas
| - bleeding into joints
65
abnormal platelet activation results in
- arterial occlusion
66
with splenic enlargement and when platelets go there to hang out, what happens with the TPO levels?
- they stay the same
67
collagen receptors
- GP Ia/IIa
| - GP VI
68
adhesion to collagen mediated by
- GPIa/IIa
69
GPVI acts in complex with
to cause
- FcR gamma
| - platelet activation
70
ADP released by
- damaged RBCs
71
ADP secreted by
- activated platelets
72
ADP receptors
- P2Y12
| - P2Y1
73
type of receptor P2Y12, P2Y1
- GPCR
74
P2Y12 target of
- anti platelet drugs
75
Glanzmann's defect in
- IIb/IIIa
76
result of Glanzmann's
- no aggregation
