Whitehead 3-10 hemostasis Flashcards
first responders to site of bleeding
platelets
What keeps platelets quiescent?
epithelial cells
Which factors mobilize platelets
ADP, Collagen from sub-intimal layer, Von Willebrand factor (like a fishing line that captures platelets)
describe platelets
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.
Glanzmann Thromasthenia
Platlet Receptor disorder. missing an integrin, prevents it from stabily binding to site of damage
Bernard Soulier
Platelet receptor disorder. unable to recruit other factors. bar fight victim example.
Scott syndrome
platelet membrane disorder. unable to flip phosphotidyl serine. anionic flipping
granulopathy
Gray platelet syndrome, ARC, Hermansky Pudlak
platelet cytoskeleton disorders
Wiskott-Aldrich, Myosin defects
When is a bleeding disorder life-threatening
child birth menses injury surgery tooth extractions
What are coagulation factors?
serine proteases that are released from the liver and activated when needed (inactive form= zymogen)
Describe fibrinogen
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
Describe thrombin.
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
Gla domain
2 carboxylic acids. gamma- carboxyglutamate domain, common in coagulation factors, Ca++ binding to activate it in platelet membrane
Kringle domain
3 conserved disullfide bonds
How does Coumadin work?
It is a Vit K mimetic. Vit K helps Gla domain of prothrombin bind Ca++ more tightly, so less activated thrombin in circulation.
Factor X
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
Tenases
Activate factor ten. Tissue factors released in response to damage.
Factor VII
Always present at low levels in plasma, further activated by tissue factor (Factor III)
Intrinsic pathway
Complex of VII, IX Tenases. Connected to the Contact Pathway (Factor XI and XII).
What molecules are Clotting pathway dependent on
Ca++ and phospholipids. Ca++ allows to localize to the phophotidyl serines on platelets.
Petechia
bleeding in the mucous membranes, general abnormal bleeding
Heparin
activated thrombin inhibitor antithrombin, kelates Ca++ ions
Ways that clot formation is stopped
Blood flow mediated dilution, serine protease inhibitors, heparin/antithrombin, Protein C/Protein S/ thrombomodulin (negative feedback created by thrombin), hirudin (leeches, ticks)
