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Biochem 2 > Platelets, von Willebrand factor > Flashcards

Platelets, von Willebrand factor Flashcards

1
Q

Arterial thrombi are also rich in ___

A

platelets

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2
Q

Is Arterial thrombi platelet-dependent or thrombin-dependent?

A

Platelet-dependent

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3
Q

Is Venous thrombosis platelet-dependent or thrombin-dependent?

A

Thrombin-dependent

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4
Q

What is Margination?

A

high number of platelets by the wall, fast flow and red blood cells needed (normal hematocryt!)

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5
Q

What are Platelets?

A

small, non-deformable cells, which are pushed against the wall by red blood cells flowing in the main stream – margination

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6
Q

What is happening here?

A
  1. Primary adhesion
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7
Q

Collagen receptors on platelets
-> What is the role of GpIaIIa?

A

integrin, inactive on resting platelets

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8
Q

Collagen receptors on platelets
-> Characteristics of GpVI

A

Ig-type receptor, does not withstand shear

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9
Q

Collagen receptors on platelets
-> At high shear, what is necessary?

A

At high shear the collagen-von Willebrand factor- GpIb is necessary

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10
Q

Collagen receptors on platelets
-> Is GpIb functional even in resting platelets?

A

At high shear the collagen-von Willebrand factor- GpIb is necessary

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11
Q

Where is von Willebrand Factor synthesized and stored?

A

Endothelial cells synthesize and store it in Weibel-Palade bodies

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12
Q

Describe Structure of von Willebrand Factor – modular structure

A

In globular conformation: only the collagen-binding site in A3 is accessible

Platelet-binding sites (GpIb, GpIIbIIIa), and ADAMTS13-cleavage sites (VWF-cleaving metalloprotease) are hidden

FVIII-binding prolongs the life-time of FVIII in blood

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13
Q

Does A GpIb-Receptor recognize the globular VWF circulating in plasma? Why?

A

A GpIb-Receptor does not recognize the globular VWF circulating in plasma, only if its unfolded upon shear forces – ultralarge, or immobilized on collagen

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14
Q

Characteristics of Platelet activation

A

-i.c.Ca2+↑
-Integrin-aktivation
-secretion of granules(ADP, TXA2)

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15
Q

Platelet adhesion, activation and aggregation
-> What is happening here?

A
  1. secretion: ADP, TromboxánA2, (Serotonin), P-Selectin
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16
Q

Platelet adhesion, activation and aggregation
2. secretion: ADP, TromboxánA2, (Serotonin), P-Selectin
-> Activation: release of granules
-> What happen when releasing gamma-granules?

A
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17
Q

Platelet adhesion, activation and aggregation
2. secretion: ADP, TromboxánA2, (Serotonin), P-Selectin
-> Activation: release of granules
-> What happen when releasing alpha-granules?

A
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18
Q

Platelet adhesion, activation and aggregation
2. secretion: ADP, TromboxánA2, (Serotonin), P-Selectin
-> Activation: synthesis and release of TXA2 (in case of EICOSANOIDs: lipid mediators)

A
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19
Q

Platelet adhesion, activation and aggregation
2. secretion: ADP, TromboxánA2, (Serotonin), P-Selectin
-> Activation: synthesis and release of TXA2 (in case of Cyclooxygenase pathway)

A
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20
Q

What is the role of Aspirin acetylates cyclooxygenase?

A

irreversible inhibition

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21
Q

How can Aspirin acetylates cyclooxygenase cause irreversible inhibition?

A
  1. TXA2-synthesis in platelets inhibited platelet aggregation
  2. PGI2-synthesis in endothelial cells inhibited
    => Platelet aggregation inhibited

PGE2 synthesis in gastric mucosa decreases – acidic erosion, bleeding as a side-effect

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22
Q

Platelet adhesion, activation and aggregation
-> What is happening here?

A
  1. Integrin-activation: GpIIbIIIa, and GpIaIIa
23
Q

What is the structure of integrins?

A

Integrins : the activatable receptors
=> Heterodimers of alpha and beta subunits

24
Q

Describe Conformational states of the integrins

25
What are the 3 Important integrins in hemostasis
Mac1 (aMb2) GpIaIIa (aIIb1) GpIIbIIIa (aIIbb3)
26
Important integrins in hemostasis -> The role of Mac1 (aMb2)?
monocytes, MACs, adhesion and phagocytosis
27
Important integrins in hemostasis -> The role of GpIaIIa (aIIb1)?
collagen receptor on activated platelets, withstands shear forces – stable adhesion
28
Important integrins in hemostasis -> The role of GpIIbIIIa (aIIbb3)?
on activated platelets, RGD sequence recognized, e.g. in fibrinogen, von Willebrand Factor. Important therapeutical target (GpIIbIIIa-blockers)
29
Platelet adhesion, activation and aggregation -> What is happening here?
4. Stable aggregates
30
What are necessary for stable aggregates?
GpIb and GpIIbIIIa
31
GpIb and GpIIbIIIa are necessary for stable aggregates -> What enhance their formation?
high fibrinogen-, VWF-concentrations
32
Agonists for platelet aggregation -> Agonist: Thrombin -> Source?
Coagulation cascade
33
Agonists for platelet aggregation -> Agonist: Thrombin -> Receptors
PAR-1, PAR-4, GpIba
34
Agonists for platelet aggregation -> Agonist: ADP -> Resources?
Platelet delta-Granules
35
Agonists for platelet aggregation -> Agonist: ADP -> Receptors?
P2Y1, P2Y12
36
Agonists for platelet aggregation -> Agonist: collagen -> source?
Extracellular matrix
37
Agonists for platelet aggregation -> Agonist: collagen -> Receptors?
GpIa/IIa, GpIIb/IIIa, GpVI
38
Agonists for platelet aggregation -> Agonist: Thromboxane A2 -> Source?
Synthesis in platelets
39
Agonists for platelet aggregation -> Agonist: Thromboxane A2 -> Receptors?
TxA2R
40
Agonists for platelet aggregation -> Agonist: PAF -> Sources?
Leukocytes
41
Agonists for platelet aggregation -> Agonist: PAF? -> Receptors
PAF-R
42
Agonists for platelet aggregation -> Agonist: Serotonin (5HT)? -> Source?
Platelet delta-Granules
43
Agonists for platelet aggregation -> Agonist: Serotonin (5HT)? -> Receptors
5HT2A
44
Signal transduction in platelets -> What are the factors that contribute to activation?
Increased Ca2+ concentration Decreased cAMP concentration
45
Signal transduction in platelets -> What are the factors that contribute to inhibition?
Increased cAMP concentration
46
Platelet adhesion, activation and aggregation -> What is happening here?
5. Phosphatidyl-serine on the surface: procoagulant platelets
47
Phospholipids in platelet membrane -> The intracellular Ca2+ concentration rises -> What is the consequence?
i.c. Ca2+ rises, which inhibits flippase (aminophospholipid-translocase), and activates scramblase, so PS gets into the outer PL-layer – “procoagulant platelets” – assembly of activation complexes leads to a burst of thrombin generation
48
Benard Soulier syndrome is a deficiency of ___
GpIb
49
Glanzmann thrombasthenia is a deficiency of ___
GIIb/IIIa Receptor
50
von Willebrand disease is a deficiency of ___
vWf
51
An example of cyclooxygenase inhibitor
Acetyl salicylic acid
52
2 examples of ADP antagonists
Ticlopidine Clopidogrel
53
3 examples of "glycoprotein IIb/IIIa antagonists"
Abciximab Eptifibatide Tirofiban

Biochem 2 (38 decks)

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