TBL 1: The Coagulation Cascade

Question 1

what type of enzymes are most of the active coagulation factors?

Answer 1

serine proteases = they hydrolyze peptide bonds using a serine residue

except XIII which is a transglutaminase and crosslinks and stabilizes fibrin polymers

Question 2

what is the main activator of the intrinsic pathway?

Answer 2

thrombin = IIa

Question 3

what is the main activator of the extrinsic pathway?

Answer 3

tissue factor = III

TF is a protein found:

1. on cells that are normally not in contact with blood like smooth muscle cells in
   the subendothelium and fibroblasts surrounding blood vessels –> vascular injury
   exposes this TF to the blood and initiates the coagulation cascade
2. in “microparticles” – little fragments of cell membrane found in normal blood –> these microparticles have receptors for P-selectin which is a cell adhesion
   molecule that lives in platelets and endothelial cells –> when it’s activated, it flips
   to the outside of the cell membrane, and the microparticles stick to it, and tissue
   factor accumulates in the region of the forming clot
3. on endothelial cells, and on monocytes, when there’s inflammation but not
   under normal resting conditions – otherwise we’d be coagulating all over the
   place

Question 4

what are the functions of thrombin in the coagulation cascade?

Answer 4

1. activates the intrinsic pathway by converting XI to XIa

2. activates factor XIII which crosslinks the fibrin molecules in the platelet plug to create a fibrin mesh

Question 5

how does the coagulation cascade work in the body?

Answer 5

tissue factor kicks off the extrinsic arm of the cascade, but this arm is soon shut
off, and fibrin formation is completed using the intrinsic arm