Chapter 4: Platelet adhesion, activation, and aggregation

Question 1

What is hemorrhage?

Answer 1

Bleeding / the loss of blood

Question 2

True/false: a hemorrhage is the external bleeding of the body

Answer 2

False, it is both internal and external

Question 3

What are possible causes of hemorrhage? (don’t learn by heart, just for illustration)

Answer 3

Damage to blood vessels, defective clot formation, in chronically congested tissues, trauma, atherosclerosis, or inflammatory or neoplastic erosion of a vessel wall

(this is in order of what is most common)

Question 4

The risk of hemorrhage is increased in a wide variety of clinical disorders. What are these clinical disorders collectively called?

Answer 4

Hemorrhagic diatheses

Question 5

Hemorrhage may be external or accumulate within a tissue. How is internal hemorrhage called?

Answer 5

Hematoma

Question 6

Large bleeds into body cavities are described variously according to location. What are some locations (just for illustration)

Answer 6

hemothorax, hemopericardium, hemoperitoneum, or hemarthrosis

Question 7

How are minute (1 to 2 mm in diameter) hemorrhages into skin, mucous membranes, or serosal surfaces called?

Answer 7

Petechiae

Question 8

What are some causes of petechiae? (illustration)

Answer 8

Low platelet counts (thrombocytopenia), defective platelet function, and loss of vascular wall support, as in vitamin C deficiency

Question 9

How are slightly larger (3 to 5 mm) hemorrhages called?

Answer 9

Purpura

Question 10

What are some causes of purpura? (illustration)

Answer 10

Purpura can result from the same disorders that cause petechiae, as well as trauma, vascular inflammation (vasculitis), and increased vascular fragility

Question 11

What are are larger (1 to 2 cm) subcutaneous hematomas (colloquially called bruises) called?

Answer 11

Ecchymoses

Question 12

Ecchymoses usually display different colours. Explain briefly how this occurs

Answer 12

Extravasated red cells are phagocytosed and degraded by macrophages; the characteristic color changes of a bruise result from the enzymatic conversion of hemoglobin (red-blue color) to bilirubin (blue-green color) and eventually hemosiderin (golden-brown).

Question 13

So, to summarize, what are the different sizes and their names of hemorrhages?

Answer 13

• hematoma: external / accumulation within tissue
• petechiae: 1-2mm
• purpura: 3-5mm
• ecchymoses: 1-2cm

Question 14

Until how many percent of rapid blood loss, have little impact in healthy adults?

Answer 14

20%

Question 15

Does great blood loss, at a slow rate have a high impact on healthy adults?

Answer 15

Nope

Question 16

What can great losses of blood cause?

Answer 16

Hemorrhagic (hypovolemic) shock

Question 17

True/False: Chronic or recurrent external blood loss always culminates in iron deficiency anemia as a consequence of a loss of iron in hemoglobin

Answer 17

False! External bleeding (peptic ulcer/mentstrual bleeding) often leads to anemia, but, ironically, iron is efficiently recycled from phagocytosed red cells, so internal bleeding (e.g., a hematoma) does not lead to iron deficiency

Question 18

What is the pathologic counterpart of hemostasis?

Answer 18

Thrombosis

Question 19

PLEASE look at fig 4.5

Answer 19

Yes ma’am

Question 20

What are the general sequence of events leading to hemostasis at a site of vascular injury (4 steps)?

Answer 20

1. Arteriolar vasoconstriction
2. Primary hemostasis: the formation of the platelet plug
3. Secondary hemostasis: deposition of fibrin
4. Clot stabilization and resorption

These steps are named in the following questions to refer to where in the process we are (you’ll see)

Question 21

How is arteriolar vasoconstriction mediated and then augmented? (step 1)

Answer 21

It is mediated by reflex neurogenic mechanisms and augmented by the local secretion of factors such as endothelin, a potent endothelium-derived vasoconstrictor.

Question 22

Disruption of the endothelium exposes subendothelial von Willebrand factor (vWF) and collagen, which promote … (step 2)

Answer 22

platelet adherence and activation

Question 23

Activation of platelets results in a dramatic shape change. How does this change look like? (step 2)

Answer 23

from small rounded discs to flat plates with spiky protrusions that markedly increased surface area

Question 24

When the platelets are activated, they do not only change shape, but they also secrete something. What is this ‘something’? And what does this do? (step 2)

Answer 24

secretory granules (that recruit additional platelets, which undergo aggregation to form a primary hemostatic plug)

Question 25

Vascular injury exposes tissue factor at the site of injury. What is this tissue factor? (step 3)

Answer 25

Tissue factor is a membrane-bound procoagulant glycoprotein that is normally expressed by subendothelial cells in the vessel wall, such as smooth muscle cells and fibroblasts

Question 26

What does the tissue factor do? (step 3)

Answer 26

Tissue factor binds and activates factor VII, setting in motion a cascade of reactions that culiminates in thrombin generation

Question 27

What does thrombin cleave? (step 3)

Answer 27

Thrombin cleaves circulating fibrinogen into insoluble fibrin, creating a fibrin meshwork

Question 28

What else does thrombin, besides cleaving fibronogen, do? (step 3)

Answer 28

It is a potent activator of platelets, leading to additional platelet aggregation at the site of injury

Question 29

Fill in: Polymerized fibrin and platelet aggregates undergo contraction to form a solid, … that prevents further hemorrhage. (step 4)

Answer 29

permanent plug

Question 30

What are counterregulatory mechanisms? (step 4)

Answer 30

tissue plasminogen activator, t-PA made by endothelial cells

Question 31

Why are counterregulatory mechanisms formed? (step 4)

Answer 31

To limit clotting to the site of injury, so that it can eventually lead to clot resorption and tissue repair

Question 32

So, for overview purposes, what are the steps (in detail) of homeostasis?

(this is also discussed in more detail later! this is a v important flashcard, i recommend looking at pic 4.5)

Answer 32

Normal hemostasis. (1) After vascular injury, local neurohumoral factors induce a transient vasoconstriction. (2) Platelets bind via glycoprotein Ib (GpIb) receptors to von Willebrand factor (VWF) on exposed ECM and are activated, undergoing a shape change and granule release. Released ADP and thromboxane A2 (TXA2) induce additional platelet aggregation through platelet GpIIb-IIIa receptor binding to fibrinogen, and form the primary hemostatic plug. (3) Local activation of the coagulation cascade (involving tissue factor and platelet phospholipids) results in fibrin polymerization, “cementing” the platelets into a definitive secondary hemostatic plug. (4) Counterregulatory mechanisms, mediated by tissue plasminogen activator (t-PA, a fibrinolytic product) and thrombomodulin, confine the hemostatic process to the site of injury.

Question 33

Which cells play the most important role in homeostasis and thrombosis?

Answer 33

Endothelial cells, they regulate everything!

Question 34

The following sections describe roles of platelets, coagulation factors and endothelium in hemostasis in greater detail

Answer 34

Okay

Question 35

Fill in: Platelets play a critical role in hemostasis by forming the … that initially seals vascular defects and by providing a surface that binds and concentrates activated coagulation factors

Answer 35

primary plug

Question 36

Where do platelets come from?

Answer 36

They are shed by megakaryocytes

Question 37

The function of platelets depends on several glycoprotein receptors, a contractile cytoskeleton, and two types of cytoplasmic granules. What are these two types of granules?

Answer 37

Alpha- and delta (δ, dense) granules

Question 38

What do alpha-Granules contain?

Answer 38

α-Granules have the adhesion molecule P-selectin on their membranes and contain proteins involved in coagulation, such as fibrinogen, coagulation factor V, and vWF, as well as protein factors that may be involved in wound healing, such as fibronectin, platelet factor 4 (a heparin-binding chemokine), platelet-derived growth factor (PDGF), and transforming growth factor-β

Question 39

What do delta (dense) granules contain?

Answer 39

Dense (or δ) granules contain adenosine diphosphate (ADP) and adenosine triphosphate, ionized calcium, serotonin, and epinephrine.

Question 40

After a traumatic vascular injury, platelets encounter constituents of the subendothelial connective tissue, such as vWF and collagen. On contact with these proteins, platelets undergo a sequence of reactions that culminate in the formation of a ….

Answer 40

platelet plug

Question 41

How is platelet adhesion mediated?

Answer 41

vWF acts as a bridge between the platelet surface receptor glycoprotein Ib (GpIb) and exposed collagen

Question 42

Because of adhesion, platelets rapidly change shape. What is this change accompanied by?

Answer 42

• Alterations in glycoprotein IIb/IIIa (increase affinity for fibrinogen),
• Translocation of negatively charged phospholipids (particularly phosphatidylserine) to the platelet surface

(These phospholipids bind calcium and serve as nucleation sites for the assembly of coagulation factor complexes)

Question 43

Which two events are often referred to as ‘platelet activation’?

Answer 43

Secretion of granule contents and the change of shape of platelets

Question 44

Platelet activation is triggered by a number of factors. What are the two most important of these?

Answer 44

the coagulation factor thrombin and ADP

Question 45

How does thrombin activate platelets?

Answer 45

Through a special type of G-protein– coupled receptor referred to as a protease-activated receptor (PAR), which is switched on by a proteolytic cleavage carried out by thrombin

Question 46

What does ADP do?

Answer 46

Recruiting!
ADP is a component of dense-body granules; thus, platelet activation and ADP release begets additional rounds of platelet activation, a phenomenon referred to as recruitment.

Question 47

What do activated platelets produce? And what is it?

Answer 47

The prostaglandin thromboxane A2 (TXA2), a potent inducer of platelet aggregation

Question 48

What inhibits platelet aggregation and produces a mild bleeding defect by inhibiting cyclooxygenase, a platelet enzyme that is required for TXA2 synthesis?

Answer 48

Aspirin

Question 49

Platelet aggregation follows their activation. The conformational change in glycoprotein IIb/IIIa that occurs with platelet activation allows binding of fibrinogen. What is this firbinogen?

Answer 49

A large bivalent plasma polypeptide that forms bridges between adjacent platelets, leading to their aggregation.