3.3.3 Coagulation and Fibrinolysis Flashcards
What is hemostasis?
The cellular and noncellular process that prevents blood loss following blood vessel injury
What are the three steps in hemostasis?
- Platelet plug formation
- Coagulation
- Fibrinolysis
What are the two steps of platelet plug formation?
- Platelet adhesion
- Platelet aggregation
What are the three proteins that play an important role in platelet adhesion? What are their functions?
- Collagen
- Von Willebrand Factor (VWF) - binds subendothelial collagen
- Glycoprotein Ib-V-IX - surface protein of platelets that binds VWF
What the two possible sites for synthesis of VWF?
- Endothelial cells (Weibel-Palade bodies) - Constitutive and inducible
- Platelets (stored in alpha granules)
Describe the quaternary structure of VWF found in plasma. What enzyme is important in processing VWF in plasma?
Multimers w/ varying MW (600 kD to 20,000 kD)
ADAMTS-13: protease that cleaves ultra large VWF multimers into smaller sizes
What type of cell is this? What is the green arrow pointing to? What does this structure store?
Platelet, alpha body, stores VWF
What the top and bottom arrows pointing to?
Top: platelet
Bottom: VWF coated surface
Aside from platelet adhesion, what is an important function of VWF?
Factor VIII carrier protein (VWF extends the half-life of FVIII from 2 hrs to 12 hrs)
What allows monomeric platelets to aggregate?
Platelet agonist
What protein is used in platelet cross-linking?
Fibrinogen
What are some platelet agonists? (5)
ADP, collagen, thrombin, thromboxane A2, epinephrine
What step follows platelet plug formation in hemostasis?
Fibrin clot formation
What the three coagulation pathways in-vitro?
Intrinsic, Extrinsic, and Common
What are the three contact activation factors?
HMWK, PK (prekallikrein), FXII
Which factor is thrombin?
FIIa
Which enzyme in the coagulation pathway converts fibrinogen to fibrin?
FIIa (thrombin)
Draw the three in-vitro coagulation pathways.
What are the four major differences b/t the in-vivo coagulation pathway and the in-vitro coagulation pathway?
- Renamed pathways (Extrinsic to initiation, intrinsic to propagation)
- Removal of the contact activation factors (HMWK, PK, FXII)
- Emphasis on the role of thrombin (goes back to work on the first physiological step in the initiation pathway which is FXI, activates critical allosteric activators)
- Presence of FXIIIa, which is activated by thrombin
Map out the propagation and initiation pathways.
What are the vitamin K dependent coagulation proteins
Factors II, VII, IX, X (coagulation)
Protein C and protein S
Vitamin K plays an important role in what process in these proteins?
Post-tln gamma-carboxylation of glutamic acid residues, forming gamma-carboxyglutamic acid (gla)
Interaction with what ion with these gla residues allows for a conformational change?
Ca++
What happens to PS (phosphatidylserine) during platelet activation?
PS residues flip flops from the inner leaflet to the outerleaflet. The flip flopping of the PS residues allows for the activation fo FX and FII (prothrombin)
