Whitehead 3-10 hemostasis

Question 1

first responders to site of bleeding

Answer 1

platelets

Question 2

What keeps platelets quiescent?

Answer 2

epithelial cells

Question 3

Which factors mobilize platelets

Answer 3

ADP, Collagen from sub-intimal layer, Von Willebrand factor (like a fishing line that captures platelets)

Question 4

describe platelets

Answer 4

anucleate fragments of cells. football shapes that grow filapodia and then spread out when activated to cover damaged sites, recruit fellow platelets, stimulate repair and growth of endothelium, damaged tissues. Bind to collagen. ADP receptors that respond to cellular damage.

Question 5

Glanzmann Thromasthenia

Answer 5

Platlet Receptor disorder. missing an integrin, prevents it from stabily binding to site of damage

Question 6

Bernard Soulier

Answer 6

Platelet receptor disorder. unable to recruit other factors. bar fight victim example.

Question 7

Scott syndrome

Answer 7

platelet membrane disorder. unable to flip phosphotidyl serine. anionic flipping

Question 8

granulopathy

Answer 8

Gray platelet syndrome, ARC, Hermansky Pudlak

Question 9

platelet cytoskeleton disorders

Answer 9

Wiskott-Aldrich, Myosin defects

Question 10

When is a bleeding disorder life-threatening

Answer 10

child birth menses injury surgery tooth extractions

Question 11

What are coagulation factors?

Answer 11

serine proteases that are released from the liver and activated when needed (inactive form= zymogen)

Question 12

Describe fibrinogen

Answer 12

Factor I. designed to oligomerize. when zymogen is cleaved, protein-protein interactions to make chains, then Factor XIII creates covalent isopeptide interactions glutamine to lysine to crosslink that structure

Question 13

Describe thrombin.

Answer 13

Factor II. Makes fibrinogen to fibrin. Has typical coagulation zymogen domains Gla and Kringle, which are cleaved when activated. Self-cleaving. Activates the PAR receptor of platelets that have been recruited but not fully activated at the site

Question 14

Gla domain

Answer 14

2 carboxylic acids. gamma- carboxyglutamate domain, common in coagulation factors, Ca++ binding to activate it in platelet membrane

Question 15

Kringle domain

Answer 15

3 conserved disullfide bonds

Question 16

How does Coumadin work?

Answer 16

It is a Vit K mimetic. Vit K helps Gla domain of prothrombin bind Ca++ more tightly, so less activated thrombin in circulation.

Question 17

Factor X

Answer 17

Part of the Common Pathway (starts with Factor X, ends in fibrin). Forms complex with Factor V that cleave prothrombin. Uses its Gla domain to bond to phosphotidyl serine in platelet membrane

Question 18

Tenases

Answer 18

Activate factor ten. Tissue factors released in response to damage.

Question 19

Factor VII

Answer 19

Always present at low levels in plasma, further activated by tissue factor (Factor III)

Question 20

Intrinsic pathway

Answer 20

Complex of VII, IX Tenases. Connected to the Contact Pathway (Factor XI and XII).

Question 21

What molecules are Clotting pathway dependent on

Answer 21

Ca++ and phospholipids. Ca++ allows to localize to the phophotidyl serines on platelets.

Question 22

Petechia

Answer 22

bleeding in the mucous membranes, general abnormal bleeding

Question 23

Heparin

Answer 23

activated thrombin inhibitor antithrombin, kelates Ca++ ions

Question 24

Ways that clot formation is stopped

Answer 24

Blood flow mediated dilution, serine protease inhibitors, heparin/antithrombin, Protein C/Protein S/ thrombomodulin (negative feedback created by thrombin), hirudin (leeches, ticks)

Question 25

Ways that clot is reversed/dissolved

Answer 25

plasminogen (causes thrombin to dissolve)–> plasmin, urokinase (plasminogen activator), steptokinase

Question 26

Plasmin

Answer 26

cuts at crosslinks of fibrin, causes it to dissipate

Question 27

What are some examples of anticoagulants and how do they work

Answer 27

aspirin and plavix. work by disallowing platelet from becoming active.