Sg1E2: Vocabulary: Platelets

Front 1

platelet structure

Back 1

Are disc-shaped, anucleate cell fragments that are shed from megakaryocytes in the bone marrow into the blood stream.

Front 2

platelet role

Back 2

They play a critical role in normal hemostasis, by forming the hemostatic plug that initially seals vascular defects, and by providing a surface that recruits and concentrates activated coagulation factors.

Front 3

what does platelet function depend on?

Back 3

Their function depends on several glycoprotein receptors, a contractile cytoskeleton, and two types of cytoplasmic granules

Front 4

α-Granules (platelets)

Back 4

have the adhesion molecule P-selectin on their membranes and contain:
1. fibrinogen,
2 fibronectin,
3. factors V and VIII,
4. platelet factor 4 (a heparin-binding chemokine),
5. platelet-derived growth factor (PDGF),
6. transforming growth factor-β (TGF-β).

Front 5

Dense (or δ) granules (platelets)

Back 5

contain:
1. ADP and ATP
2. ionized calcium
3. histamine
4. serotonin
5. epinephrine.

Front 6

T/F α-Granules and delta granules are prothrombic

Back 6

true

Front 7

platelet adhesion, glycoprotein Ib (GpIb), von Willebrand disease, Bernard-Soulier syndrome

Back 7

1. 2nd step of hemostasis: platelets sticking to exposed subendothelial ECM at a site of vascular injury.
2. Platelet adhesion to ECM is mediated largely via interactions with vWF
3. Although platelets can also adhere to other components of the ECM, vWF-GpIb associations are necessary to overcome the high shear forces of flowing blood.

Front 8

vWF

Back 8

1. acts as a bridge between platelet surface receptors (e.g., glycoprotein Ib [GpIb]) and exposed collagen
2. this occurs during Platelet adhesion to ECM at site of vascular injury

Front 9

how do we know vWE mediated adhesion of platelets to ECM at vascular injury site are important?

Back 9

genetic deficiencies of vWF (von Willebrand disease) or its receptor (Bernard-Soulier syndrome) result in bleeding disorders

Front 10

platelet secretion (release reaction) is induced via what process?

Back 10

1. a process that releases alpha and delta-granules after platelets stick to exposed subendothelial ECM.
2. Various agonists can bind platelet surface receptors and initiate an intracellular protein phosphorylation cascade ultimately leading to degranulation.

Front 11

What does the release reaction (platelet secretion) ultimately result in?

Back 11

1. Release of the contents of alpha -granules is especially important, since calcium is required in the coagulation cascade
2. ADP is a potent activator of platelet aggregation
3.. ADP also begets additional ADP release, amplifying the aggregation process

Front 12

What changes to the cell surface does platelet activation lead to?
why is this important?

Back 12

1. negatively charged phospholipids (particularly phosphatidylserine) on their surfaces.
2. These phospholipids bind calcium and serve as critical nucleation sites for the assembly of complexes containing the various coagulation factors.

Front 13

platelet aggregation

Back 13

1. a multitude of new platelets stick to the relatively few platelets already sticking to the ECM
2. follows adhesion and granule release

Front 14

what are the 6 components of the process that amplifies and stabilizes the initial platelet adhesion to of the exposed subendothelial ECM at a site of vascular injury?

Back 14

1. platelet aggregation
2. thromboxane A2 (TxA2)
3. protease-activated receptor
4. platelet contraction
5. thrombin
6. fibrin

Front 15

thromboxane A2

Back 15

1. vasoconstrictor
2. in addition to ADP, it is A2 is an important platelet-derived stimulus that amplifies platelet aggregation, which leads to the formation of the primary hemostatic plug

Front 16

via what 2 mechanisms does thrombin stabilize the platelet plug?

Back 16

1. thrombin binds to a protease-activated receptor on the platelet membrane and in concert with ADP and TxA2 causes further platelet aggregation
- This is followed by platelet contraction which constitutes the definitive secondary hemostatic plug.
2. thrombin converts fibrinogen to fibrin in the vicinity of the platelet plug, functionally cementing the platelets in place.

Front 17

Platelet contraction

Back 17

1. An event that is dependent on the platelet cytoskeleton that creates an irreversibly fused mass of platelets
2. Cnstitutes the definitive secondary hemostatic plug

Front 18

conformational change in the platelet GpIIb-IIIa (Gp=glycoprotein) receptors

Back 18

1. Induces binding to fibrinogen, a large protein that forms bridging interactions between platelets that promote platelet aggregation
2. triggered by platelet activation by ADP

Front 19

Glanzmann thrombasthenia

Back 19

1. bleeding disorder
2. inherited deficiency of GpIIb-IIIa

Front 20

Clopidogrel = Plavix

Back 20

1. therapeutic agents that blockes platelet aggregation by interfering with thrombin activity
2. blocks ADP binding

Front 21

synthetic antagonists or monoclonal antibodies that block platelet aggregation (GpIIb-IIIa receptor)

Back 21

Binding to the GpIIb-IIIa receptors

Front 22

fibrin split products (FSP):

Back 22

1. proteins produced when plasmin degrades fibrin.
2. FSP are an important signal of inappropriate fibrin formation, as in disseminated intravascular coagulation (DIC), a dangerous condition.