Flashcards in 12.7 C Deck (41):
What is hemostasis?
the cellular and noncellular process that prevents blood loss following injury
What are the three main steps of hemostasis?
- platelet plug formation
What gives a hard clot its tensile strength?
Platelet plug formation has what two steps?
- platelet adhesion
- platelet aggregation
What is Von Willebrand Factor?
a plasma protein that binds collagen and links it to Glycoprotein Ib-V-IX
What is glycoprotein Ib-V-IX?
a transmembrane protein found on platelets that binds VWF at the site of injury
Where is Von Willebrand Factor produced?
endothelial cells and platelets
What are Weibel-Palade bodies?
stores of Von Willebrand Factor found in endothelial cells
What are alpha granules?
granules within platelets that store Von Willebrand Factor
Describe the quaternary structure of Von Willebrand Factor.
it forms massive multiers
What is ADAMTS-13?
a protease that cleaves ultra large Von Willeband Factor into its active unit
When Von Willeband Factor is produced, it is in what form?
the ultra large form
Most Von Willeband Factor is produced by what cells?
Von Willeband Factor production in endothelial cells is controlled by what?
- induced hormonally
- but also produced constitutively
Von Willeband Factor has what two functions?
- platelet adhesion
- factor VIII carrier protein which extends the half life
Platelets are cross-linked by what protein?
Describe the structure of fibrinogen?
is bipolar such that it can bind and cross-link two platelets
What are the five most signficant platelet activating factors?
ADP, collagen, thrombin, thromboxane A2, epinephrine
Where is tissue factor found?
on the surface of endothelial cells, fibroblasts, and platelets
How does tissue factor get activated?
by injury to its host cell (fibroblast, endothelial, or platelet)
The coagulation cascade can generally be described as a series of what?
zymogen activation steps
What is the first and last enzyme activated in the coagulation cascade?
tissue factor to thrombin
What enzyme cleaves fibrinogen into a fibrin monomer?
Which coagulation cascade proteins are Vitamin K dependent?
F2, F7, F9, F10
Vitamin K is improtant to the coagulation cascade because it is necessary for what process?
the post-translational gamma-carboxylation of glutamic acid residues, forming gamma-carboxyglutamic acid
Why is post-translational gamma-carboxylation of glutamic acid residues important to the coagulation cascade?
- adds a second negative charge so that the residue can bind calcium
- binding calcium alters the conformation of prothrombin allowing it to insert into a phospholipid membrane on a platelet
How does Warfarin prevent clotting?
by preventing regeneration of the active form of vitamin K
Why is prothrombin insertion into the platelet plasma membrane important?
because only then can it interact with phosphatidylserine, its alloactive cofactor
What happens to phosphatidylserine when a platelet gets activated?
it is flipped to the outer leaflet of the plasma membrane
Phosphatiylserine is flipped to the outer leaflet of a platelet plasma membrane so that what can occur?
assembly of various complexes important to the coagulation cascade
What is a tenase complex?
a complex that forms on platelet membranes in conjunction with PS to generate Factor Xa, which goes on to cleave prothrombin into thrombin
What is a prothrombinase complex?
a complex of Factor Xa and prothrombin (FII) that generates thrombin
What is the name for FII?
What does thrombin do in the coagulation cascade?
it cleaves portions off of fibrinogen to form fibrin monomers which can then spontaneously assemble into multimers
What is the importance of Factor VIIIa in the coagulation cascade?
it catalyzes the transglutaminase reaction, covalently cross-linking D domains of fibrin monomers
What protein is responsible for fibrinolysis?
What is plasminogen?
a zymogen produced by the liver which gets cleaved into plasmin for fibrinolysis
What is t-PA?
the enzyme that cleaves plasminogen into plasmin for fibrinolysis
What are PAI-1 and PAI-2?
enzymes secreted by endothelial cells to inhibit t-PA and thereby inhibit fibrinolysis
What is a2-AP?
a protein secreted by the liver that inhibits plasmin and therefore inhibits fibrinolysis