Introduction to Hemostasis

Question 1

What are primary and secondary hemostasis?

Answer 1

Primary hemostasis is the initial response to vascular continuity and involves the formation of a platelet plug at a site of injury.

Secondary hemostasis is the generation of a fibrin clot, generally overlying a platelet plug

Question 2

Normal, healthy endothelium acts to prevent thrombosis by inhibiting platelet activation. How does it achieve this? (Three compounds)

Answer 2

Endothelium makes PGI2 (prostayclin) which prevents platelet activation. It also exso expresses adenosine diphosphatase to metabolize ADP into AMP, and produces NO to decrease platelet aggregation.

Question 3

How does normal healthy endothelium prevent coagulation?

Answer 3

It is coated wtih heparan sulfate, which inactivates some coagulation factors, and expresses surface thrombomodulin which redirects thrombin towards anticoagulant effects.

Question 4

How does normal healthy endothelium act vasodilatory?

Answer 4

Endothelial cells take up vasoactive substances, like serotonin, to limit activity
and NO production

Question 5

After vascular injury, what induces transient vasoconstriction in muscular vessels?

Answer 5

Endothelin peptide, histamine,thromboxane A2 others

Question 6

During primary hemostasis, circulating platelets get exposed and then adhere to subendothelial collagen via two types of receptors, becoming activated.

Answer 6

Collagen – von Willebrand factor – platelet vWF receptor

collagen—platelet collagen receptors (gpIa/IIa, gpVI)

Question 7

Where is von Willebrand Factor found?

Answer 7

platelet alpha granules and endothelial cell Weibel-Palade bodies

Question 8

vWF form large multimers. How does this promote hemostasis?

Answer 8

They unfold under shear stress to expose the binding sites for the platelets, then forming an adhesive bridge between subendothelial collagen and platelet glycoprotein Ib (GpIb)

Question 9

When circulating platelets bind vWF and collagen and are activated, what do they do?

Answer 9

1. change shape to be flatter and spread to increase surface area (may extend filopods)
2. granule release: ADP, TxA2, which recruits more platelets

Question 10

What are the Alpha and Delta granules released by platelet activation?

Answer 10

Alpha:
-P selectin
GpIIbIIIa, GPIbalpha

• fibronectin
• Factor V, vWf, fibrinogen

PDGF, other growth factors

Delta: dense bodies
ADP and ATP
Ca2+, Mg 2+
polyphosphate
histmaine, serotonin

Question 11

How does histamine affect bleeding?`

Answer 11

It’s a vasoconstrictor, it prevents bleeding.

Question 12

Primary hemostasis is balanced by two compounds, one produced by endothelium and one produced by platelets. Explain.

Answer 12

Prostacyclin, produced by endothelium, prevents platelet activation and aggregation. Thromboxane A2, produced by platelets, is a strong platelet activator. This balance localizes the platelet aggregation and makes the clot happen where it needs to.

Question 13

Of the platelet produced compounds ADP and thromboxane, which binds what?

Answer 13

1. ADP bindsactivating platelet and endothelial purine receptors, including P2Y12
2. Thromboxane binds platelet thromboxane receptor, and is the most powerful platelet activator.